- Research article
- Open access
- Published: 17 July 2018
Cognitive Behavioural Therapy for schizophrenia - outcomes for functioning, distress and quality of life: a meta-analysis
- Keith R. Laws 1 ,
- Nicole Darlington 1 ,
- Tejinder K. Kondel 2 ,
- Peter J. McKenna 3 &
- Sameer Jauhar 4
BMC Psychology volume 6 , Article number: 32 ( 2018 ) Cite this article
The effect of cognitive behavioural therapy for psychosis (CBTp) on the core symptoms of schizophrenia has proven contentious, with current meta-analyses finding at most only small effects. However, it has been suggested that the effects of CBTp in areas other than psychotic symptoms are at least as important and potentially benefit from the intervention.
We meta-analysed RCTs investigating the effectiveness of CBTp for functioning, distress and quality of life in individuals diagnosed with schizophrenia and related disorders. Data from 36 randomised controlled trials (RCTs) met our inclusion criteria- 27 assessing functioning (1579 participants); 8 for distress (465 participants); and 10 for quality of life (592 participants).
The pooled effect size for functioning was small but significant for the end-of-trial (0.25: 95% CI: 0.14 to 0.33); however, this became non-significant at follow-up (0.10 [95%CI -0.07 to 0.26]). Although a small benefit of CBT was evident for reducing distress (0.37: 95%CI 0.05 to 0.69), this became nonsignificant when adjusted for possible publication bias (0.18: 95%CI -0.12 to 0.48). Finally, CBTp showed no benefit for improving quality of life (0.04: 95% CI: -0.12 to 0.19).
CBTp has a small therapeutic effect on functioning at end-of-trial, although this benefit is not evident at follow-up. Although CBTp produced a small benefit on distress, this was subject to possible publication bias and became nonsignificant when adjusted. We found no evidence that CBTp increases quality of life post-intervention.
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The first use of cognitive therapy to help people with schizophrenia was in 1952 [ 1 ]. Beginning somewhat later, with Kuipers et al. [ 2 * ], over 60 randomised controlled trials (RCTs) have subsequently examined the efficacy of Cognitive Behavioural Therapy for psychosis (CBTp). These trials have typically looked at the effectiveness of CBTp in improving the core symptoms of schizophrenia i.e., positive symptoms, or delusions and hallucinations measured separately, and in some cases negative symptoms. Recent meta-analyses of these trials have converged on finding symptomatic improvement that is in the small range (e.g. [ 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. The most comprehensive of these meta-analyses - that of Jauhar et al. [ 7 ] - additionally found no effectiveness against positive symptoms in trials with blinded outcome assessments.
Over a decade ago, Birchwood and Trower [ 10 ] introduced the phrase ‘quasi-neuroleptic’ to describe the symptom-focused approach of CBTp. They argued that this view of CBTp was inappropriate and that the intervention was more likely to have a distinctive profile of effects that are complementary to rather than substituting for drug treatment. Such a view appears to be reflected in the two principal clinical guidelines in use in the UK, the National Institute for Care and Health Excellence (NICE) and the Scottish Intercollegiate Guidelines Network (SIGN). Thus, NICE [ 11 ] states that “The aims of psychological & psychosocial interventions in psychosis & schizophrenia are numerous. These should include interventions to improve symptoms but also those that address vulnerability, which are embedded in developmental processes. The aims, therefore, include: reduction of distress associated with psychosis symptoms… promoting social and educational recovery; reducing depression and social anxiety … and relapse prevention (p.32).” Similarly, SIGN [ 12 ] states: “The aim [of CBTp] is to help the individual normalise and make sense of their psychotic experiences, and to reduce the associated distress and impact on functioning (p.55)”. Similar sentiments are expressed in guidelines from elsewhere in the world, e.g. the Royal Australian and New Zealand College of Psychiatrists [ 13 ].
Nevertheless, the effect of CBTp on non-symptomatic outcomes in schizophrenia has been relatively less investigated than its effect on symptoms. Nearly 10 years ago, Wykes et al. [ 14 ] carried out a series of meta-analyses that included 15 trials which evaluated functioning. The pooled effect size was significant (Glass’s Δ = 0.38: 95% CI 0.15 to 0.60); however, analysing the trials by study quality (as measured using a unitary scale for this) revealed a large and significant difference in effect size between high and low-quality trials (0.15 vs. 0.51). They did not examine effect sizes for any follow-up period. Several meta-analyses of functioning were also carried out by the National Collaborating Centre for Mental Health (NCCMH) ( http://www.rcpsych.ac.uk/workinpsychiatry/nccmh.aspx ) for the purposes of the 2009 NICE guideline. These analyses assessed data relating to specific functioning scales and for all scales combined; examining effects at end-of-treatment and follow-up as well as against ‘treatment as usual’ (TAU) or other active controls (such as befriending or supportive counselling). The standardised mean difference (SMD) revealed that CBTp had no significant impact on functioning compared to TAU (K = 6: - 0.14, 95% CI -0.45 to 0.17), but at 12-month follow up was marginally significant (K = 4: -0.20, 95% CI-0.41 to − 0.00). When CBTp was contrasted with active controls, a medium effect emerged at the end-of-treatment (K = 3: SMD -0.50, 95% CI -0.84 to − 0.16); there was no meta-analysis against active controls at follow-up. The small numbers of trials analysed however, limits the reliability of findings from some of the NICE meta-analyses. The other main limiting factor concerning the meta-analyses by Wykes et al. [ 14 ] and NICE [ 11 ], is that the data in both are now a decade old.
NICE [ 11 ] also reported on a small number of trials measuring quality of life and found no significant advantage for CBTp compared to supportive counselling at the end of treatment (K = 3) (SMD 0.01, 95% CI –0.19 to 0.21) or for follow-up at either 52 weeks (K = 2; SMD -0.18, 95% CI -0.10 to 0.47) or 78 weeks (K = 1; SMD 0.40, 95% CI -0.17 to 0.98). In their Cochrane review of CBTp versus other psychosocial interventions, Jones et al. [ 6 ] included only one trial that examined quality of life [ 15 ] and no differential effect of CBTp was found either at end of treatment or follow-up in this trial. No meta-analysis appears to have examined the effects of CBTp on distress.
The aim of the series of meta-analyses reported here was to determine whether evidence shows that CBTp improves aspects of the patient experience beyond symptom-reduction. Based on there being enough trials to permit meaningful pooling of data, we selected three outcome variables: functioning, distress and quality of life.
We initially considered the 52 RCTs retreived by Jauhar et al. (2014), which covered the period of 1993 (the date of the first published trial of cognitive behavioural therapy in schizophrenia) to March 2013. We also searched the trials previously excluded by Jauhar et al. These studies were supplemented with a systematic search of the literature using PubMED and Scopus to identify RCTs of CBTp between the dates of March 2013 and April 2018. Searches were unrestricted regarding language and whether material was published or unpublished. We also searched through reference sections of papers that were considered eligible. Multiple searches were conducted using the following terms and combinations of terms:
“Cognitive Behavioural Therapy” AND “Psychosis” AND “Randomised controlled trial”.
“Cognitive Behavio*” AND “Psychosis” AND “Randomi*”.
“Cognitive Behavio*” AND “Psychosis” AND “RCT”.
“CBT” AND “Psychosis” AND “RCT”.
“CBT” AND “Psychosis” AND “Randomi*”.
“Cognitive Behavio*” AND “schizo*”.
“CBT” AND “Schizo*”.
“Cognitive Behavio*” AND “Schizo*” AND “RCT”.
“Cognitive Behavio*” AND “Schizo*” AND “Random*”.
“CBT” AND “Schizo*” AND “Randomi*”.
“CBT” AND “Schizo*” AND “RCT”.
This search produced a further 16 studies. All 69 studies were then hand-searched by one of us (ND) for the outcome measures of interest and counter-checked by another (KRL).
Our inclusion criteria paralleled those used by Jauhar et al. [ 7 ], Wykes et al. [ 14 ], NICE [ 11 ] and the Cochrane Collaboration [ 6 ]. Thus, studies were included if a majority of the patients had a diagnosis of schizophrenia, schizoaffective or non-affective functional psychosis, either made clinically or according to diagnostic criteria. Trials could use any measure of functioning, distress or quality of life (for details, see below). Studies also had to include a parallel control group of any type, i.e. waitlist, TAU or an intervention designed to control for the non-specific effects of psychotherapy. We excluded non-randomised trials and those which used inappropriate randomisation methods (e.g. allocation by alternation or by availability of the intervention). The four non-randomised trials that were located all also used non-blinded outcome assessment and were low in overall quality (see [ 16 , 17 , 18 , 19 ]).
Determination of what types of therapy constituted CBTp was relatively broad and followed Jauhar et al. [ 7 ] – those that incorporated additional elements of therapy, such as motivational interviewing, family engagement, behaviour therapy and social skills training, were also included. Following previous meta-analyses, we did not include studies that delivered CBT as part of a multicomponent package of care that involved several other interventions (sometimes referred to as integrated treatment or similar). We included trials using both individual and group CBTp.
For functioning, trials used a variety of clinician-assessed rating scales which included: the Global Assessment of Functioning scale (GAF: [ 20 ]); the Social and Occupational Functioning Assessment Scale (SOFAS: [ 21 ]); the Global Assessment Scale (GAS: [ 22 ]); the Multnomah Community Ability Scale (MCAS: [ 23 ]); and the Life Skills Profile (LSP: [ 24 ]). Other scales considered to be includable were the Social Functioning Scale (SFS: [ 25 ]), the Role Functioning Scale (RFS: [ 26 ]), the Social Behaviour Schedule (SBS: [ 27 ]), the Independent Living Skills Survey (ILSS: [ 28 ]), and the Personal and Social Performance Scale (PSP: [ 29 ]).
Studies were included if they measured the distress associated with the symptoms of psychosis. Outcomes relating to depression and anxiety alone were not included as these were considered to represent symptomatic measures. Where articles provided more than one outcome measure for distress, ‘total distress’ scores were used. Measures included: the ‘distress’ domain within the Psychotic Symptom Rating Scale (PSYRATS: [ 30 ]); the Global Severity Index (GSI: [ 31 ]); and a questionnaire using a Likert scale ([ 32 * ]: On a scale from 0 to 10, how bothered are you when you experience (specific hallucination) [or think about (specific delusion)]?).
The quality of life measures used in trials included: the Quality of life scale (QLS: [ 33 ]); the World Health Organisation Quality Of Life Scale (WHOQOL-BREF: [ 34 ]); the Quality of life, Enjoyment and Satisfaction Questionnaire (Q-LES-Q: [ 35 ]); the Modular System for quality of life (MSQoL: [ 36 ]); and the Manchester Short Assessment of Quality of Life (MANSA: [ 37 ]).
Pooled effect sizes for the data were created using Comprehensive Meta-analysis, version 2 [ 38 ]. A random-effects model was used in all analyses. Effect sizes were derived from the post-intervention (or follow-up) scores using Hedges g (i.e. the standardized mean difference using group means divided by the pooled standard deviation: Eq. 1 ) and corrected for the tendency towards overestimation in small studies ([ 39 ] Eq. 2 ). When these data were not available in a paper, authors were contacted. Effect sizes are described using Cohen’s convention: an effect size of 0.20 was considered small, 0.50 moderate, and 0.80 large.
Heterogeneity was examined with Q and I 2 statistics. An I 2 value of 0–40% suggests that heterogeneity may not be important, 30–60% may represent moderate heterogeneity, 50–90% may represent substantial heterogeneity, and 75–100% may represent considerable heterogeneity (see [ 40 ]). Publication bias was examined using Duval and Tweedie’s [ 41 ] trim and fill technique, which aims to estimate the number of missing studies within an analysis and the effect that those studies might have on outcomes. Moderator analyses, where feasible, followed Jauhar et al. [ 7 ] and so, included comparisons of blind vs non-blind outcome-assessment and the use of active control vs treatment as usual. The latter categorical comparisons were conducted using a method analogous to ANOVA.
Thirty-six RCTs (37 samples) met our inclusion criteria (See Fig. 1 ), some measuring more than one outcome. Twenty-six samples assessed functioning, 8 assessed distress and 10 quality of life. See Table 1 for excluded studies and main reason for exclusion.
Flow chart outlining study selection
Functioning was assessed in 25 trials (with 26 samples: see Additional file 1 ) providing a total of 1579 participants (780 received CBTp and 799 were in the control condition). Of the 26 samples, 17 compared CBTp to treatment as usual (TAU), while the remaining 9 compared it to another intervention (psychoeducation, befriending, cognitive remediation, social activity therapy, supportive therapy, goal focused supportive contact). The majority of studies used individual therapy (22/25 - only [ 54 * – 56 * ], and used group therapy).
The pooled effect size for functioning across 26 samples was 0.25 (95%CI: 0.14 to 0.33, p < .001, positive sign indicates CBTp better than control). The studies were moderately heterogeneous ( Q [ 25 ] = 50.66, p < .001) with an I 2 value of 50.66 (see forest plot in Fig. 2 ). Duval and Tweedie’s Trim and Fill [ 41 ] analysis revealed no evidence of publication bias. We re-ran the analysis removing one outlier trial [ 57 * ], which was the only one that revealed significantly worse functioning post CBT – this increased the effect size to 0.28 (95%CI .15 to .41) p < .001; Q [ 24 ] =39.52, p = .02, I 2 = 39.27.
Forest plot for post-intervention scores on functioning. Note. Edwards et al. [ 58 * ] had intervention groups (Clozapine + CBT [CZ + CBT] and Thioridazine + CBT [TDZ + CBT] and two control groups i.e. Clozapine and Thioridazine respectively
Forest plot for follow-up scores on functioning. Note. F = follow-up
Blind vs nonblind assessment
We compared 19 studies where assessors were blinded (masked) to treatment condition with 7 where assessment was not blinded (unmasked) to the treatment group. The unmasked trials revealed a small and significant effect size of 0.29 (95% CI: 0.10 to 0.48, p < .001); and the studies had low nonsignificant heterogeneity (Q = 6.94 [ 6 ], p = .33: I 2 = 13.59). The masked trials revealed a small significant effect size of 0.22 (95% CI: 0.02 to 0.42, p = .03); these 19 studies were moderately heterogeneous (Q = 58.45 [ 18 ], p < .001; I 2 = 58.45).
Active versus non-active control
We compared 19 trials using treatment as usual (TAU) as a control versus 7 trials using active control conditions. The effect size for TAU was significant at 0.26 (95%CI .08 to .43), p = .01; and showed low-moderate heterogeneity (Q = 34.83, df = 18, p = .01; I 2 = 47.65). The effect size for trials with an active control was nonsignificant at 0.22 (95%CI -0.07 to 0.52, p = .14); and showed moderate heterogeneity (Q = 16.25, df = 6, p = .012; I 2 = 63.07). The effect sizes from trials using TAU and active control did not significantly differ (Q = 0.03, df = 1, p = .86).
Follow-up data were available in 16 of the trials, with a median follow-up time of 12 months (range 3–18 months). Follow-up assessments involved 792 participants (393 CBTp and 399 controls) and retention was high with over 91% of the CBT and control participants examined at end-of-trial being assessed at follow-up.
The pooled effect size for CBTp on functioning at follow-up was nonsignificant 0.10 [95%CI -0.07 to 0.28], p = .23 (see Fig. 3 ). The samples showed low heterogeneity (Q = 21.78, df = 15, p = .11; I 2 = 31.12). Most trials used blind assessment (K = 13: g = 0.12–0.08 to 0.32) and did not differ significantly in effect size (Q = 0.14, df = 1, p = .71) from nonblind trials (K = 3 g = 0.04–0.33 to 0.42) with both being nonsignificant.
Distress was analysed in 8 studies (see Additional file 2 ) with a total sample size of 465 (235 receiving CBTp and 230 in control conditions). Of these studies, 7 were against a treatment as usual (TAU) and 1 was against a waitlist control. Most trials (7/8) used individual therapy with only [ 59 * ] using group therapy.
The pooled effect size was significant at 0.37 (95% CI 0.05 to 0.69, p = .02). The studies were heterogeneous (Q (7) = 17.27, p = .01) with an I 2 value of 60.51 suggesting moderate-high levels of true heterogeneity amongst the studies. The forest plot is shown in Fig. 4 .
Forest plot for post-intervention scores on distress
Duval and Tweedie’s trim and fill bias analysis [ 41 ] imputed 3 trials (see Fig. 5 ). When the meta-analysis was adjusted for this potential bias, the new effect size reduced and became nonsignificant ( g = 0.18, 95% CI: -0.12 to 0.48).
Funnel plot for distress (white dots are published trials & black dots imputed missing trials)
Most trials were non-blind and these showed a significant distress reduction (K = 6, g = 0.43[95% CI 0.20 to 0.66]); however, the two blind trials [ 60 * , 61 * ] produced a nonsignificant effect (0.19 [95% CI -0.72 to 1.10]).
- Quality of life
Quality of life was assessed in 10 samples from 9 trials (see Additional file 3 ) with a total sample size of 592 (293 received CBTp and 299 in the control condition. Of these studies, 1 was against an active control condition (psychoeducation/befriending), 7 were against a treatment as usual (TAU condition), and 2 were against a waitlist control. Three trials used group therapy ([ 59 * , 62 * , 63 * ], and) – the remaining 7 samples used individual therapy.
CBTp had no significant impact on quality of life, with an effect size close to zero at 0.04 (95% CI: -0.12 to 0.19, p = .66). The studies were not heterogeneous ( Q (9) = 7.19, p = .62) with an I 2 value of 0. The forest plot in Fig. 6 presents the effect sizes for each trial, showing that none of the individual trials significantly improved QoL; both group (K = 3 g = 0.15 95% CI -0.22 to 0.51) and individual therapy were nonsignificant (K = 7, g = 0.01 95% CI -0.17 to 0.19) and I 2 was zero in both.
Forest plot for post-intervention scores on quality of life
When publication bias was examined, Duval and Tweedie’s trim and fill [ 41 ] imputed 1 missing effect size. With the analysis adjusted for this, the new effect size was reduced slightly (g = 0.01, 95% CI: -0.15 to 0.16).
The five trials examining QoL under blind conditions had a nonsignificant mean effect size of 0.06 [95% CI -0.24 to 0.36, p = .69], as did the three trials assessing QoL without blinding (0.16 [95%CI -0.20 to 0.52] p = .39); two further studies were unclear about blinding ([ 63 , 64 * ] was presented blind, however raters correctly guessed 70% of the group assignments).
As noted in the introduction, while more than a dozen meta-analyses have examined whether CBTp reduces the positive and negative symptoms of schizophrenia, non-symptomatic outcomes have been somewhat neglected. Two previous meta-analyses – both now a decade old – have examined the impact of CBTp on functioning [ 11 , 14 ] but ours is the first to examine the impact of CBTp across a range of non-symptomatic outcomes, including: functioning at end-of trial and follow-up and the impact on quality of life and distress. Although a small benefit of CBTp for functioning emerged at end-of-trial, this was non-significant at follow-up. In 8 trials, CBT was found to produce a small significant reduction in distress; however, evidence of potential publication bias led to the imputing of 3 studies, halving the effect size and making it non-significant. The effect was also moderated by blinding – significant distress reduction was only found in trials using non-blind outcome assessment. Quality of life was unaffected by CBTp and indeed, none of 10 samples documented a significant benefit.
With respect to functioning, our effect size of 0.25 (95% CI 0.14 to 0.33) for functioning is considerably smaller than the 0.38 effect size reported by Wykes et al. [ 14 ] in their meta-analysis of 15 trials - indeed, the Wykes et al. [ 14 ] effect size falls beyond the upper end of our 95% confidence intervals. One possible reason for this reducing effect size is that 12 of 14 RCTs published since Wykes et al’s 2008 [ 14 ] meta-analysis – and since NICE [ 11 ] published their current guidance on CBTp - have produced nonsignificant outcomes. Importantly, more recent studies also included large well-controlled trials (e.g [ 65 * ]). Furthermore, our analysis of follow-up data derived from 16 samples revealed that CBT did not significantly improve functioning. This latter finding contrasts with the findings reported by NICE; it seems likely that this reflects the fact that the current meta-analysis is much larger - involving four times as many trials. Our findings provide an important update on the multiple meta-analyses carried out for NICE (2009), which was on small numbers of trials and produced mixed findings. NICE have still failed to update their meta-analyses, which contain no trials post-2008; and so, it might seem an appropriate time to update their analyses and potentially, their recommendations given the findings here. The repeated decisions by NICE to not update CG178 with any trials post-2008 has also been remarked upon in meta-analyses and indeed, by the Chair of SIGN [ 7 , 66 ].
With an effect size that was close to zero, we found no suggestion that CBTp improves quality of life in people diagnosed with schizophrenia. Our findings accord with earlier smaller analyses of quality of life by NICE [ 11 ] and the Cochrane Collaboration [ 6 ], both of which found no evidence of CBTp being efficacious for this outcome. Although the current number of trials remains quite small (K = 9 and 10 samples), we found little to suggest that missing trials or methodological factors - such as blinding or type of control group - were playing any role in this null finding. Indeed, every published trial has reported a nonsignificant effect of CBTp on quality of life; particularly noteworthy is one trial by van der Gaag et al. [ 64 * ] which had large numbers (109 CBTp and 97 controls) and an effect size of zero.
Despite CBTp being promoted as effective against distress by both NICE [ 11 ] and SIGN [ 12 ], this outcome has received surprisingly little interest from triallists. Only 8 in 67 RCTs that met our eligibility criteria reported distress as an outcome and this was always as a secondary measure. Although significant at 0.37, the effect size for distress was prone to potential publication bias and when adjusted for three potentially missing trials, became small and nonsignificant at 0.18. Also noteworthy is that several RCTs assessing distress had small samples and so their power to detect true (small) effects is likely to be low. Following Button et al. [ 67 ], it is possible to derive the median statistical power of each study in the meta-analyses to obtain the overall effect size (using the mean effect sizes as the best estimate of likely true effect size). Doing this revealed that the power in CBTp trials assessing distress was low at .22, whereas those for quality of life and functioning were somewhat better but still underpowered at .50 and .64 respectively. The low level of power also accords with the evidence of potential publication bias in trials measuring distress; and may reflect the publishing of unreliable small trials with positive, but not negative results. Future studies of distress would need four times the current mean sample size of 40 per group to reliably detect the effect size reported in existing trials. Only one trial, that of Birchwood et al. [ 61 * ], comes close to the sample size required, and this found increased distress following CBTp. Clearly adequate powering is essential in future trials – not only to accurately ascertain if CBTp reduces distress, but to eliminate any possibly that it may increase distress in some patients.
Our meta-analysis is the first to assess whether CBTp improves quality of life or reduces distress in individuals diagnosed with schizophrenia. We also present an updated meta-analysis assessing the impact of CBTp on functioning. On current evidence CBTp leads to a small improvement in functioning which, however, is not sustained. The case for beneficial effects on quality of life and distress appear, from studies to date, to be weak. Overall, the three meta-analyses performed provide only equivocal support for the non-quasi-neuroleptic hypothesis of CBTp, with its emphasis on these outcomes.
95% Confidence Intervals
Cognitive Behavioural Therapy for psychosis
Global Assessment of Functioning scale
Global Assessment Scale
Global Severity Index
Independent Living Skills Survey
Life Skills Profile
Manchester Short Assessment of Quality of Life
Multnomah Community Ability Scale
Modular System for quality of life
National Collaborating Centre for Mental Health
National Institute for Care and Health Excellence
Personal and Social Performance Scale
Psychotic Symptom Rating Scale
Quality of life, Enjoyment and Satisfaction Questionnaire
Quality of life scale
Randomised Controlled Trial
Role Functioning Scale
Social Behaviour Schedule
Social Functioning Scale
Scottish Intercollegiate Guidelines Network
Standardised mean difference
Social and Occupational Functioning Assessment Scale
Treatment as usual
World Health Organisation Quality Of Life Scale
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We would like to thank authors who kindly supplied additional data upon request.
SJ is in receipt of funding from the National Institute for Health Research Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King’s College London and JMAS Sim Fellowship form the Royal College of Physicians, Edinburgh.
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Tejinder K. Kondel
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ND - did the searches and initial analyses, contributed critically to writing drafts; KL had the idea for the meta-analysis, checked all analyses, contributed critically to initial draft, rewrites and interpretation; TK contributed critically to rewrites and clinical interpretation; PJM contributed critically to redrafts, final writing and interpretation; SJ contributed critically to redrafts and final writing and interpretation. All authors read and approved the final manuscript.
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Additional file 1:.
Randomised Controlled Trials that measured functioning as an outcome (DOCX 20 kb)
Additional file 2:
Randomised controlled trials of CBTp that measured distress as an outcome measure (DOCX 17 kb)
Additional file 3:
Randomised Controlled Trials that measured quality of life as an outcome measure (DOCX 23 kb)
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Laws, K.R., Darlington, N., Kondel, T.K. et al. Cognitive Behavioural Therapy for schizophrenia - outcomes for functioning, distress and quality of life: a meta-analysis. BMC Psychol 6 , 32 (2018). https://doi.org/10.1186/s40359-018-0243-2
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Published : 17 July 2018
DOI : https://doi.org/10.1186/s40359-018-0243-2
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- Cognitive behavioural therapy
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The ABCs of Cognitive-Behavioral Therapy for Schizophrenia
This article examines the use of cognitive-behavioral therapy for psychosis, the evidence for its use, and the implications for practicing psychiatrists given the short-comings of pharmacologic therapy.
Cognitive-behavioral therapy (CBT) in schizophrenia was originally developed to provide additional treatment for residual symptoms, drawing on the principles and intervention strategies previously developed for anxiety and depression. In the 1950s, Aaron Beck 1 had already treated a psychotic patient with a cognitive approach, but thereafter the research in this specific area lay dormant for decades. Only after cognitive therapy had been firmly established for depression and anxiety, in the 1990s, did the research into psychological treatments for psychotic conditions gather force-again, with Beck in the forefront.
Pharmacologic therapy can leave as many as 60% of psychotic patients with persistent positive and negative symptoms, even when the patients are compliant with their medication instructions. 2 Furthermore, medication compliance remains a major problem despite the introduction of modern atypical antipsychotics. Studies have shown treatment discontinuation in an estimated 74% of patients in both outpatient and inpatient settings. 3
The evidence for the efficacy of CBT in treating patients with persistent symptoms of schizophrenia has progressed from case studies, case series, and uncontrolled trials to methodologically rigorous, randomized, controlled trials that include patients from both the acute 4 and the chronic end of the schizophrenia spectrum. 5-7 Subsequent meta-analysis 8 and systematic reviews have further strengthened the evidence base.
CBT is now recognized as an effective intervention for schizophrenia in clinical guidelines developed in the United States 9 and in Europe . 10 In spite of the evidence base and absence of side effects, however, the general availability of this treatment approach within community settings is still low. 11 This article will examine the procedure of CBT for psychosis, the evidence for its use, and the implications for practicing psychiatrists.
The therapeutic techniques used for patients with schizophrenia are based on the general principles of CBT. Links are established between thoughts, feelings, and actions in a collaborative and accepting atmosphere. Agendas are set and used but are generally more flexibly developed than in traditional CBT. The duration of therapy varies according to the individual's need, generally between 12 and 20 sessions, but often with an option of ongoing booster sessions. CBT for psychosis usually proceeds through the following phases.
The assessment begins by allowing the patient to express his or her own thoughts about his experiences while the therapist listens actively. The use of rating scales-both specific and general-is encouraged to monitor progress, and the results are shared with the patient. Diagrams and written material can be most useful, especially for patients with chaotic lifestyles. The formulation of symptom causation and maintenance is also shared with the patient and evolves throughout the therapy as new information is considered.
Initially the therapist will state clearly what the therapy is about (including a safe and collaborative method of looking at causes of distress). Throughout the therapy, the use of Socratic questioning is emphasized. This involves drawing out the person's own understanding of his situation and ways of coping with it through a process of guided discovery. Attempts are made to empathize with the patient's unique perspective and feelings of distress and to show flexibility at all times. A vulnerability-stress model is used, so that the patient can understand that vulnerability is a dynamic concept that can be influenced by many factors, such as life events, coping mechanisms, or physical illness. The therapist stresses that he or she does not have all the answers but that useful explanations can be developed in cooperation. The typical nonspecific therapeutic factors of warmth, genuineness, humor, and empathy are of great value in this type of therapy, as in all other therapeutic encounters.
The ABC model, which was originally developed by Ellis and Harper, 12 can be used to give the patient a way of organizing confusing experiences . It involves slowly and thoroughly moving the patient through the various steps using Socratic questioning to clarify the links between the emotional distress the patient is experiencing and the beliefs he holds ( Table ). It includes the following steps:
- Based on a scale of 0 to 10, the patient rates the intensity of distress.
- The consequence (C) is assessed and divided into emotional and behavioral Cs.
- The patient gives his own explanation as to what activating events (As) seemed to cause C; and the therapist ensures that the factual events are not “contaminated” by judgments and interpretations.
- The therapist provides feedback to the patient to acknowledge the A-C connection.
- The therapist assesses the patient's belief, evaluations, and images and communicates to the patient that a personal meaning is lacking in the A-C model; simple examples can be provided to facilitate understanding.
- The patient's own belief (B), which is actually the cause of C, is then discussed; often, this can be rationalized, and a B such as “nobody will like me if I tell them about my voices” can be disputed and changed to “I can't demand that everyone likes me. Some people will and some won't...Maybe some friends might find it interesting.” This may lead to a change in C, ie, less sadness and isolation.
“Voices are driving me mad”
“I’ll never find the truth”
“The doctors will not tell me the truth”
“I’ll never be normal”
“Voices are in control of my life”
Emotions Sorrow Depression Loneliness Desperation
Realistic goals for therapy should be discussed early in the therapy with the patient, using the distressing consequences (C) to fuel the motivation for change. It is the therapist's job to ensure that the goals are measurable, realistic, and achievable. The goals are revisited both during and at the end of therapy.
A normalizing rationale 11,13 is helpful in decatastrophizing psychotic experiences. Education regarding the fact that many people can have unusual experiences in a range of different circumstances (stressful events, hyperventilation, torture, hunger, thirst, falling asleep, etc) reduces anxiety and the sense of isolation. By having the psychotic experiences placed on a continuum with normal experiences, the patient will often feel less alienated and stigmatized. As a consequence, the possibility of recovery seems less distant.
Critical collaborative analysis
To proceed to this stage, the therapeutic relationship must have developed a degree of trust. The therapist uses gentle Socratic questioning to help the patient appreciate potentially illogical deductions and conclusions:
- “If your voices came from the radiator, why can't anyone else hear them?” or
- “Hold on for a moment, this puzzles me. How do you explain your rape by this famous actor, since we know for a fact that he has never been to this country?”
Testing the evidence for and against maladaptive beliefs can safely be carried out without causing distress as long as the therapist remains nonjudgmental, empathic, and open-minded. An assessment is made of how the beliefs occurred-through inferences or cognitive distortions (eg, dichotomous thinking, selective inference, emotional reasoning, jumping to conclusions). Reviewing antecedents (stress, trauma, loss) that prepare the ground for psychotic change can be an eye-opening exercise for both patient and therapist. Identification of misattributions and attempts to reattribute are as productive as homework tasks.
Developing alternative explanations
It is of crucial importance to let the patient develop his own alternatives to previous maladaptive assumptions, preferably by looking for alternative explanations and coping strategies already present in the patient's mind. It can be dangerously tempting to force the therapist's readymade explanations onto the patient. The patient's own healthier explanations might just be temporarily weakened by either external factors or dysfunctional thinking patterns. If the patient is not forthcoming with alternative explanations, new ideas can be constructed in cooperation with the therapist. Certain seeds might have been sown earlier in the therapy (from leaflets and previous discussions) that can now be used as building blocks.
Tina is a 64-year-old woman who has been hearing voices for 45 years. She has been hospitalized 4 times over the years, often in connection with life events, such as her mother's death and her brother's alcoholism and violence towards her. She has never accepted a diagnosis of schizophrenia but is compliant with medication and happily agreed to CBT, explaining that she would like to talk to a “nice young man” like the therapist. Following the assessment, it was clear that the patient's main problems were lack of confidence, a tendency to isolate herself at home, and a belief that the voices had an external source (the central heating system). She was still working as a caregiver in a rest home, but after her partner's and mother's deaths 15 to 20 years previously had increasingly lost contact with friends and family. As protective factors, Tina was a healthy, likable woman with a good sense of humor. She was also very happy with her job.
Engagement was unproblematic, but the concepts of continuum and the ABC model proved to be difficult for Tina to understand. It helped when examples-such as temperature-were given to explain the concept of a continuum. To illustrate the ABC model to Tina, a book was held up and the therapist read aloud what he could see on the back of the cover, while she read the front of the cover. She subsequently understood that there could be different angles from which to view the same issue. While the therapist critically looked at her understanding, he also made extensive use of normalizing.
The patient's general functioning, mood, and self-confidence improved significantly, but she remained adamant that the voices had an external source. She had also gained a much larger social life. After a couple of relapse-prevention sessions, it was decided to stop the therapy. Tina had had 22 sessions in all, and the voices were now largely benign and seen as conversational partners that conveniently would remind her about duties such as vacuuming and writing cards to her nephews and nieces.
The general finding has been that CBT significantly improves both negative and positive symptoms in different subgroups of patients with schizophrenia. 8 The meta-analysis by Gould and associates 14 indicated a strong effect size of 0.65 for positive symptoms. In spite of initial concerns, there is no evidence that suicidality develops during CBT; quite the contrary. 15 At this stage, the factors mediating treatment success in these interventions are not clearly known and should be researched further. Compared with pharmacologic therapy, the dropout rates are remarkably low at around 12% in the randomized controlled trials. 14 This is quite an achievement considering the severely unwell patient group, and it may indeed carry an important message to service providers about service users' preferences. It must, however, be added that all studies so far have been conducted on patients receiving antipsychotic medication. The proven efficacy of CBT for schizophrenia is also cost-effective. 10
Patient predictors of response to CBT remain uncertain. Although there is some evidence that a degree of cognitive flexibility and willingness to disclose are auspicious signs, cognitive variables were not found to be related to treatment response. 16 Several of the comparison treatments (supportive counseling, befriending) have been shown to have some effect on a number of symptoms, but CBT has shown clear superiority in durability. 5
It appears that CBT equips patients with a set of tools they can use to fight back the symptoms long after the therapy has been terminated. The effect in the comparison groups is thought to be a product of nonspecific therapeutic factors and the impact of being the object of caring attention. The studies have the same methodologic limitations as most other research into psychotherapy, including suitable comparison groups, blinding, and inclusion and exclusion criteria. Recent studies have, to a large degree, dealt with these issues, and the outcome generally remains positive.
It would be wrong to believe that CBT can only be used in formal therapy settings. Many aspects of the therapy can readily be implemented in the day-to-day management of patients with schizophrenia, including the ABC model, normalization, and the search for alternative explanations. The use of these approaches does not necessarily require formal training in CBT. On the other hand, the lack of supervision and of fully accredited therapists are major obstacles in the development of a service that lives up to the standard requirements. 17 This area will undoubtedly receive further attention over the coming years, especially as patients and caregivers become more vocal about their needs and preferences.
Over the past decade, CBT has emerged as an evidence-based intervention that provides a long-needed integrative approach to schizophrenia. The emergence of CBT for schizophrenia has added new optimism to the treatment of a highly stigmatized condition and may, in the long term, contribute to a change in the way the general public views people with schizophrenia. As the news about an effective talking therapy penetrates a wider audience, schizophrenia may no longer be seen as an essentially untreatable, incomprehensible, biologic condition beyond the reach of reasoning.
All psychiatrists should therefore at least be acquainted with the basic principles of CBT for schizophrenia in order to incorporate this knowledge into the daily management of severely mentally ill patients and to be able to appropriately refer patients for specialist therapy. Although the existing evidence base for CBT in schizophrenia shares some of the same limitations that exist for other psychotherapies, research has firmly established the evidence for reduction of symptomatology, low dropout rates, and cost-effectiveness. Despite this, widespread availability of CBT for psychotic patients is currently lacking, and providing sufficient availability of this method is one of the greatest challenges facing mental health services today.
Dr Hansen is a Danish-born consultant psychiatrist working in the department of psychiatry, University of Southampton, UK. He is an accredited member of the British Association of Behavioural and Cognitive Psychotherapists and holds a medical doctorate from the University of Southampton. He reports that he has no conflicts of interest concerning the subject matter of this article.
Dr Kingdon is professor of mental health care delivery at the University of Southampton and honorary consultant psychiatrist with Hampshire Partnership Trust. He reports that he has no conflicts of interest concerning the subject matter of this article.
Dr Turkington is a senior lecturer of psychiatry at Newcastle University with a special interest in cognitive-behavioral therapy for schizophrenia. He reports that he has no conflicts of interest concerning the subject matter of this article.
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Introduction, cognitive behavior therapy, cbt techniques, cbt for schizophrenia, the evidence base for cbt in schizophrenia, cbt and functional outcome, developments in cbt for schizophrenia, mindfulness-based approaches, acceptance and commitment therapy, compassionate mind training, meta-cognitive therapy, the method of levels.
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The Evolution of Cognitive Behavior Therapy for Schizophrenia: Current Practice and Recent Developments
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Sara Tai, Douglas Turkington, The Evolution of Cognitive Behavior Therapy for Schizophrenia: Current Practice and Recent Developments, Schizophrenia Bulletin , Volume 35, Issue 5, September 2009, Pages 865–873, https://doi.org/10.1093/schbul/sbp080
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Cognitive behavior therapy (CBT) evolved from behavioral theory and developed to focus more on cognitive models that incorporated reappraisal of thinking errors and schema change strategies. This article will describe the key elements of CBT for schizophrenia and the current evidence of its efficacy and effectiveness. We conclude with a description of recent concepts that extend the theoretical basis of practice and expand the range of CBT strategies for use in schizophrenia. Mindfulness, meta-cognitive approaches, compassionate mind training, and method of levels are postulated as useful adjuncts for CBT with psychotic patients.
Cognitive behavior therapy (CBT) is an evidence-based talking therapy that attempts cognitive and behavioral change based on an individualized formulation of a client's personal history, problems, and world views. CBT as a treatment for schizophrenia can be understood within a wider framework of CBT as applied to a range of mental disorders such as anxiety, posttraumatic stress disorder (PTSD), and depression. The influences and fundamental building blocks upon which theory and practice are based are varied and far reaching, and in clinical practice, CBT sessions do not always look the same. As a result, CBT has been criticized as a set of techniques and tools. However, CBT is better understood in terms of a set of core principles that rely on a personalized conceptualization of an individual's problems to guide the application of techniques and strategies. CBT continues to evolve and develop through reciprocal relationships among theory, research, and practice.
Cognitive therapy for depression was first described in a clear manualized format by Aaron T. Beck in 1979. 1 This manual that emphasized the need to focus on conscious thinking was a direct challenge to behaviorism and thus became termed the cognitive revolution or “second wave.” The theory developed by Beck built on behavioral principles in that it not only recognized how behavior was the result of learned contingencies between stimuli and events but also emphasized clear relationships between cognition, physiology, and emotion.
Beck based his early theory upon an assumption fundamental to psychoanalytical thinking, ie, that early life experiences and social environment can contribute to the development of adult emotional problems. He stressed the salience of early life experiences in forming beliefs or schemas about the self, other people, and the world. These beliefs were then thought to lead to certain cognitive distortions and negative styles of thinking. Beck 2 postulated that through the examination of thought processes and by evaluating their accuracy, many negative emotional reactions due to inaccurate or distorted thinking could be reduced or extinguished.
The key elements of CBT as described by Beck included engaging the patient, collaboratively developing a problem list, and deciding on a clear goal for the therapy session. Once the goal had been decided on, a CBT technique would be used (eg, guided discovery and Socratic questioning [described below]) to identify distortions in thinking style. This would be followed by an agreed task (homework) for the patient to complete by themselves before the following appointment (eg, attempting to identify these distortions over the next week and trying to correct them). Regular feedback and asking the patient to provide a capsule summary (ie, personal understanding) of the session were also crucial elements. This therapy structure relied very much on collaborative working with the patient within an empirical methodology. A formulation (narrative of the person's history) was jointly generated to make sense of the emergence and maintenance of the problem at hand. This psychotherapy revolution placed the patient at the heart of the recovery process and introduced the concept of rational review of appraisal errors.
Beck used narrative formation or the development of a coherent personal story of one's experience as an explanatory framework to make hypotheses about the development, maintenance and links between different problems. There is evidence that developing such a narrative formation is a therapeutic process in itself and an essential aspect of recovery. 3
Beck specified how thoughts and beliefs can be examined for their truth by questioning. He showed the usefulness of the “Socratic questioning” technique to encourage the probing of evidence, reason, and rationale. For example, a patient who believed that he was under surveillance was asked to give a rationale for his belief. The CBT therapist used questions to explore the individual's reasoning (eg, “How do you know that is happening?,” “Can you give me an example of that?,” “What do you think causes this to happen?,” “When you think it through now, are these reasons good enough?”).
Another technique commonly employed in CBT is “reality testing” where a patient will be encouraged to actively find evidence to test the reality base of a belief or assumption; a process which is done in collaboration with the therapist. For example, a person who believes in the existence of giant moths that will eat people might be encouraged to find some evidence-based information about moths and discover that these insects tend only to live for approximately 1–2 weeks and would be unable to bite a human as they have no teeth!
“Behavioral experiments” are another method frequently utilized in CBT whereby a “scientific experiment” can be set up to test a specific prediction. For example, a person who believes that his next door neighbor is communicating threats to him by coughing might set up an experiment in which he watches a television program to test alternative predictions that there are other reasons why people cough. The CBT therapist will facilitate the patient in developing awareness (guided discovery) of how people might cough due to smoking, allergy, or a chest infection. Once the patient can see that the people on the TV are possibly coughing for other reasons the patient can, then the local environment can begin to be explored, and the reality of the patient's ideas specifically about his or her neighbor's coughing can be explored.
Some might argue that behavioral experiments look no different to exposure or behavior modification, but they clearly illustrate the way in which the underlying theory of CBT has evolved from behavior to cognitive theory. Beck et al 1 described how “For the behaviour therapist, the modification of behaviour is an end in itself; for the cognitive therapist it is a means to an end—namely cognitive change” (p119).
CBT for schizophrenia, as first described in a single case study by Beck in 1952, 4 has subsequently been developed in the last 30 years from the traditional model of CBT for depression as described above. 2 , 5 However, cognitive theory and interventions for anxiety, social phobia, PTSD, and obsessive-compulsive disorder (OCD) also find application within the practice of CBT for psychosis.
Earlier forms of CBT for schizophrenia relied primarily on behavioral strategies to affect change, with a secondary focus on the cognitive components. These earlier forms of CBT for schizophrenia focused on improving coping, 6 building social and independent living skills, and increasing compliance using behavioral strategies such as linking tablet taking to another activity. 7 Similarly, negative symptoms were targeted by providing graded activity programs. 8 These approaches have continued to be applied where deficit symptoms of schizophrenia and improving functional outcomes are the main focus of intervention. 9
For many years, it was assumed that the positive symptoms associated with schizophrenia lay outside of the realms of normal psychological functioning. Thus, the transition to incorporating more cognitive theory and techniques into practice came much later compared with CBT for nonpsychotic disorders.
Cognitive models outline how hallucinations and delusions can occur when anomalous experiences that are common to the majority of the population 10 are misattributed in a way that has extreme and threatening personal meaning. 11 , 12 These models specify the role of faulty beliefs, increased attention to threat-related stimuli, biased information processing of confirmatory evidence, and safety behaviors (ie, avoidance of specific situations) in the experience of positive symptoms. The emphasis is on distress resulting not necessarily from difficult experiences but the meaning placed on those very experiences. For example, an individual who experiences physical sensations of tingling and attributes this to job stress is likely to have a markedly different outcome to persons who believe that people at work are persecuting them and have planted microchips under their skin. Cognitive theory is based on the notion that the cognitive processes implicated in mood and anxiety disorders occur transdiagnostically. 13 Research findings support the notion that psychotic symptoms can be conceptualized with reference to normal psychological processes, whereby the content of symptoms is understandable and amenable to CBT. 14 For example, Chadwick et al 15 built on the work of Beck in OCD to demonstrate that voices could be conceptualized as intrusive thoughts.
Kingdon and Turkington 16 and Fowler et al 17 described how CBT for disorders such as anxiety and depression could be applied in schizophrenia. There were some key amendments. Stigma was addressed by identifying the negative beliefs and assumptions people held about the diagnosis and prognosis of schizophrenia and then providing evidence that some of these experiences are actually fairly common in the general population (normalizing). In addition, the therapist provided alternative explanations, such as the role of stress, that provided more optimistic and hopeful perspectives. 18 Compared with CBT for other disorders, the sessions were often shorter in length and much more flexible, and homework was simplified. The role of sleep disturbance, affect, and safety behaviors (eg, behaviors such as avoidance that maintained faulty beliefs) was identified to produce mini-formulations of positive symptom maintenance. 19 Figure 1 presents an example demonstrating how critical hallucinations, triggered by sleep deprivation, are maintained by a negative appraisal, emotions of sadness and shame, and safety behaviors including social withdrawal.
Mini-formulation of Hallucination Maintenance.
Cognitive biases are directly addressed by CBT predominantly through focusing on the content of thoughts and styles of thinking. These include the jumping to conclusions error and biases in styles of judgment found in individuals with unusual beliefs (delusions) and the biases in attributional styles and attentional processing associated with hallucinations. In CBT, it is the individual's personal meaning, understanding, and coping with symptoms that are the focus of treatment. For example, individuals are facilitated in testing out the location of the hallucinations (internal vs external), carefully examining the appearance and behavior of suspected persecutors, and attempting homework that is pertinent to their stated goals.
There is now a considerable body of evidence that illustrates the efficacy of CBT for schizophrenia. 20 Randomized controlled trials (RCTs) have shown moderate effect sizes for positive and negative symptoms at the end stages of therapy with sustained benefits over time. 21 There is evidence that these research findings are also sustained in clinical settings 22 , 23 and are cost effective. 24 Virtually, all trials have been on patients with stabilized antipsychotic medication regimes; however, case series exist showing that there is a potential benefit of CBT being offered to patients who refuse medication treatment. 25 Both hallucinations and delusions respond to CBT. 26 , 27 Not only negative symptoms respond 28 but also there is a durable effect at medium term follow-up. 23 The cognitive models relating to these presentations have all been recently described in detail. 29 Patients with substance misuse and other comorbidities are likely to be more difficult to engage and treat, but there are promising signs. 30 CBT struggles more where people have difficulty identifying that they have mental health problems, 31 delusional systems, 32 or extreme primary negative symptoms. 33 Similarly, when comorbidities accumulate, CBT effects are liable to be significantly less. Meta-analysis of Zimmermann et al 34 found that acute presentations do better than chronic. However, people in acute episodes usually improve with standard nursing care or supportive counseling. CBT would seem to be of benefit in treating psychotic prodromes of mild/moderate severity and for those who are at ultrahigh risk of conversion or with severe symptomatology. 35 , 36
On the basis of such consistent evidence over the last 10–15 years, in the UK and US, the National Institute for Clinical Excellence 37 and The Schizophrenia Patient Outcomes Research Team 38 guidelines, respectively, are recommending that CBT be offered routinely to individuals with residual symptoms of schizophrenia. More recently, further evidence is being provided that CBT is likely to be of particular benefit to individuals with recent onset of schizophrenia. 37
Despite a clear message that CBT for psychotic symptoms appears to be beneficial, questions remain. The extent to which CBT is limited to effecting change only within the peripheral features (consequences) of the disorder, such as distress and behavioral reactions that contribute symptom maintenance or target more central mechanisms and processes hypothesized to underlie the specific symptoms of schizophrenia, is unclear. It is not clear whom CBT works for and when, raising further questions as to how therapeutic change occurs. Overall, what does the impact of CBT inform us about the nature of schizophrenia itself? These questions may partially be answered by pre- and post-CBT functional neuroimaging studies that are currently under way.
The cognitive model predicts improved functioning, and empirical studies support the efficacy of CBT in this regard. CBT can improve functioning even when symptoms do not improve, which is one reason it is consistent with recovery and an important adjunct to antipsychotic medication. CBT can be seen to be complementary to dopaminergic blockade that reduces the salience of environmental cues. 39 Lieberman et al 40 argued that atypical antipsychotic medication improved neurogenesis, and this would also complement a psychotherapy targeted on the acquisition of new skills.
Ongoing research and practice of CBT have led to emerging evidence of other important factors in schizophrenia, in addition to thought content and thinking styles. These include the role of arousal, 41 emotion, 42 attachment and interpersonal issues, 43 , 44 loss and trauma, 45 self-esteem, 46 and acceptance and self-to-self relating. 47 These processes may potentially have a causal role in the development of the disorder and may contribute to the symptoms experienced in schizophrenia, the way in which these are expressed and the subsequent course of the disorder. The importance of these factors has been demonstrated in recovery approaches to psychosis, where there has been marked value in helping individuals to develop personal meaning and empowerment from their own psychotic experiences, acquire a sense of inner control and self-regulation, and enable emotional and cognitive change facilitating the attainment of goals and recovery. 48 Appreciation of the heterogeneity and complexity of processes operating in schizophrenia beg a broader approach to treatment that incorporates evolving cognitive theory and practice.
Cognitive schema theory underlying CBT has thus evolved over the years, changing the way in which mental disorders are understood. This occurred in part due to criticisms of earlier theory underlying CBT having been developed on the basis of clinical caveats with no scientifically tested model of concepts such as “schemas.” This caused difficulties in relating clinical findings to the work of cognitive scientists who had developed theories of how the mind worked that were based on experimental observations and data. A common problem in CBT was in accounting for the gap that commonly occurs between logical reasoning and strong emotion (eg, persons can “know” rationally that they are not being followed by the mafia, but simultaneously they still “feel” that they are being followed and continue to be distressed). Cognitive science has developed our understanding of how people develop beliefs and emotions on the basis of 2 types of “knowledge.” Propositional knowledge is a kind of “rational knowledge”—based on referentially specific information (eg, facts and figures). The other is implicational knowledge that is the more abstract “knowing with the heart”—based on integrated information drawn through the senses (eg, sight, smell, taste, etc) that is involved in creating more elaborate schematic models of the self. 49
Thus, there has been a shifting away from linear formulations of how irrational thoughts directly lead to maladaptive behaviors and negative emotions to an increased understanding of the complex interacting and self-regulating relationships between thoughts, behavior, feelings, and physical sensations. 49 Practical application of theory within cognitive behavioral therapies has advocated a shift from predominantly challenging the content of negative thoughts and schemas to instead altering a person's relationship to both thoughts and feelings. In this sense, it is not necessarily the thought that is problematic but the way in which an individual thinks about their thoughts! For example, someone who responds to distressing intrusive thoughts by worrying and trying to suppress the intrusions increases his anxiety and attentional focus on these unwanted experiences. He is likely to suffer an exacerbation of the intrusions and greater distress and emotional disorder compared with someone who does not ruminate and distracts himself by listening to music.
There is a growing trend in CBT to focus less on changing faulty thinking and employ additional therapeutic methods to emphasize working with different components of schema, interpersonal relationships, emotional regulation, information processing (ie, attentional biases), and ways of relating to the self. Control is highlighted as having central importance within mental disorder. Interpersonal control can be regarded a developmental factor, loss of control is a consequence, and mental control is an important maintenance process. Control in other forms is also evident, such as the reduced interpersonal control often reported during therapy (collaborative or client-centered styles of therapy) and control of one's life as a goal or outcome for most people. 50 This evolution in thinking and practice has lead to what has been increasingly referred to as the “third wave” after Hayes used it to describe acceptance and commitment therapy (ACT), a mindfulness-based therapy. 51
The last 5–10 years has witnessed a general burgeoning of therapeutic approaches that push beyond original cognitive theory and extend to include an eclectic combination of theories and philosophical influences. Examples of third-wave approaches include mindfulness, meta-cognitive therapy (MCT), compassionate mind training (CMT), and the method of levels (MOL). The extent to which these approaches can be considered third wave is debatable as this suggests something “new” to CBT. These more recent CBTs have made some theoretical departures from traditional cognitive and behavioral theory, but the practical application of these approaches echoes the field. These more recent approaches are still in their infancy but have potential to influence the application of CBT for schizophrenia. Each approach will be described briefly.
Mindfulness approaches (ie, mindfulness-based stress reduction 52 and mindfulness-based cognitive therapy [MBCT]) 53 , 54 have been used for a range of disorders and have a good developing evidence base. 55 All involve training of the mind to disengage from unhelpful and automated patterns of thinking (“meta-cognition” is the term used to describe thinking about one's thinking). Each mindfulness-based approach is somewhat distinct with its own individual theoretical orientation and techniques. The commonality is an element of contemplation—the directing of attention or concentration, influenced by Eastern traditions of meditation such as Buddhism. Approaches might also involve the teaching of behaviors of kindness, compassion and generosity, the advocacy of empathic strategies (ie, being nonjudgmental and giving and resonating with another's suffering), and cognitive strategies of developing a mind set—a sense of self-betterment and personal transformation through openness or receptiveness. Instead of becoming preoccupied with difficult experiences (eg, hallucinations, unwanted memories, or thoughts), individuals are encouraged to focus attention on their experiences in order to develop different ways of relating to these thoughts and feelings, no matter how unpleasant they are. Attention to meta-cognitive processes is not new to traditional CBT where strategies for identifying cognitive errors and maladaptive thinking styles are frequently used. However, mindfulness differs in the way it places significantly greater emphasis on different aspects of meta-cognitive components of therapy. For example, persons who experience distressing critical voices might in traditional CBT be encouraged to utilize distraction techniques or reappraise their related thoughts. In mindfulness-based approaches, the person would be encouraged to engage with the voice with an emphasis on altering the emotional experiences associated with its presence. A case example is of a man who suffered from distressing command hallucinations for more than 20 years. Whenever the voices started up, he would respond with anger, pacing the room and shouting back at them. A mindful approach taught him that his unsuccessful attempts to avoid the experience led to him interpreting the voices as taunting him purposefully, which he would ruminate about and experience anger. He trained in accepting the presence of the voices and shifting his attention to them while adopting a nonjudgemental and indifferent attitude, leading to the voices being less distressing and less intrusive.
Chadwick and colleagues have applied MBCT to working with people with psychotic symptoms with evidence that this is a feasible intervention that can be useful and beneficial for some people. 56 , 57 They have also been using mindfulness-based CBT in group format. 58
Theory behind ACT 59 draws on relational frame theory, behavior analysis, and influences from mindfulness. ACT does not encourage people to control intrapersonal activities (thoughts, feelings, etc) as in traditional CBT but teaches them to “just notice,” accept, and encompass internal events. It emphasizes identifying an individual's personal values and encouraging them to act on these. In the process of facilitating people to discover personal meaning and value within their life, ACT strives to increase psychological flexibility. Pankey and Hayes 60 provided a thorough overview of how ACT can be applied to working with people with psychosis. They advocated helping people to use strategies to cope with psychotic experiences, such as cognitive distancing (getting people to treat their beliefs as hypothetical statements as opposed to facts), acceptance, and valued action. They argue that the focus in traditional CBT on reducing specific symptoms might paradoxically make them worse. They emphasized instead intervening on a person's willingness to have symptoms and reduce attempts to act on them. Pankey and Hayes 60 also stated that the approach can be helpful with people who might have limited cognitive ability. ACT has been used with a wide range of populations and disorders although evidence of its efficacy on the basis of high-quality clinical trials with adequate scope and follow-up are limited. Hayes et al 61 provided an overview of the literature summarizing that ACT is so far proving to be applicable and acceptable across a broad range of problems of varying severity, effect sizes appearing greater for more severe problems. For psychosis, Bach and Hayes 62 demonstrated that ACT significantly reduced hallucinations and hospitalization days. These findings were replicated by Gaudiano and Herbert. 63 Application of mindfulness-based techniques, such as ACT, is more commonly being augmented into CBT as a treatment for psychosis. 64
CMT is an approach to be delivered within traditional CBT but with an additional emphasis on increasing awareness of negative self-to-self relating. It draws its theoretical links from evolutionary social ranking theory. 65 CMT specifically targets shame and self-criticism from the point of view that this can act as an internal hostile signal stimulating submissive and negative affective responses that can maintain psychiatric disorders. 47 , 66 The key principles of CMT are to facilitate individuals caring for their own well-being, becoming sensitive to and accepting of their own needs and distress, and to respond toward themselves with warmth and compassion. 67 Techniques are used such as “2-chair technique” where the “inner bully” is interviewed, giving a “voice” to a person's critical self-talk and facilitating a functional analysis of self-attacking. Many traditional CBT techniques such as Socratic questioning are also employed with the aim of reframing self-criticism changing the tone of the associated emotional experience and developing more compassionate beliefs and sensitivity to the self. Working with the patient's mental imagery (eg, altering the mental image of the inner bully) is also employed as a significant therapeutic aid in CMT. 68 These strategies are particularly important when working with psychotic symptoms. Self-criticism and negative self-to-self relating have been demonstrated to be particularly relevant, especially in instances where comorbid anxiety and affective disorder are present. 69–71 Self-attacking is a psychological vulnerability factor increasing potential for relapse. 71 , 72 Voices are believed to operate like external social relationships and might often resemble an individual's social sense of being powerless and controlled by others. 43 , 73
There is a clear theoretical basis for using CMT within CBT for psychotic symptoms and thus a promising outlook for its inclusion as a therapeutic strategy for symptoms common in schizophrenia. 44 , 74 Research establishing further the application of CMT in psychosis is underway.
MCT 75 is theoretically based on the Self-regulatory Executive Function model. 76 From this perspective, disorder is considered to occur as a result of thinking style and the way in which people control their thoughts (meta-cognition). MCT specifies that it is verbal styles of thinking (worry and rumination), the focus of attention on threat and negative information, and meta-cognitive actions of thought suppression and avoidance that lead to disorder. It is by targeting these meta-cognitive processes in treatment that MCT aims to change the way in which people experience and regulate their thoughts. In this sense, MCT is a departure from traditional CBT insofar as it focuses exclusively on the cognitive with no emphasis on behavioral features of treatment. MCT involves teaching people alternative skills to experience their thoughts utilizing techniques such as attention training and altering meta-cognitive beliefs that worrying is necessary or those thoughts cannot be controlled or are dangerous. There have been several studies evaluating the effectiveness of MCT providing emerging evidence of positive effects of MCT for people with generalized anxiety disorder, PTSD, OCD, and depression with stable effects at follow-up. 77 , 78 Further studies are required with follow-up of more than 12 months and with larger comparative RCTs. Valmaggia et al 79 recently applied an 8-session course of attentional training treatment in a single case to treat auditory hallucinations in the context of a diagnosis of schizophrenia, resulting in symptom reduction and increased perceived control and mastery of the hallucinations. This example demonstrated how someone who was distressed by repeated abusive hallucinatory voices experienced being very much at their beck and call. He felt that he had no control over them and was unable to function in social settings due to their presence. He was trained over 6 weeks to practice daily focusing his attention on different types of auditory stimuli. His ability to focus on the radio, clock, and traffic steadily improved. When he began to use this new skill he found that he had much more control over the voices and began to engage more in social activity. MCT is a promising development with the potential for application to schizophrenia.
MOL is a therapy based on the principles of perceptual control theory (PCT), 80 , 81 which provides an account of the mechanisms of change within psychotherapy. 82–84 It is a significant theoretical departure from CBT. PCT specifies that people do not seek to control their behavior but their perceptual experiences, where the goal is to make what is perceived from the environment match with “internal standards” (or goals). 85 Internal standards (conceptualized as being somewhat analogous to schemas in CBT) are organized in hierarchical control systems with higher goals (standards) at the top (eg, “to be close to people”) that set a series of lower goals at the levels below (eg, “spend time with others”). Emotional difficulties and unwanted perceptual experiences (eg, paranoid beliefs) arise as people often have multiple goals that are prone to conflict with one another—eg, “to be close to other people versus to stay safe by avoiding being to close to others.” 86 , 87
PCT postulates that the essential feature of successful change within CBT (or any other psychotherapy) is the shifting of a person's awareness to higher perceptual levels (goals) so that conflict in control systems can be reorganized. 88 In this sense, MOL does not claim to be a new therapy but capitalizes on what it considers to be the effective ingredient of therapy—the mobility of “mental (meta-cognitive) awareness.” 81 , 89
During a session of MOL, the patients choose to talk about any problem they wanted to discuss. The therapist observes shifts in their awareness, (identified through disruptions to the flow of conversation such as changes in gesture, tone of voice, or dialogue flow) and directs the patient's attention to these by asking them about associated background thoughts, images, or other perceptual experiences. This helps them to become aware of the higher goals and standards leading to their problems so that conflict can be reorganized. The redirecting of awareness is similar to the traditional CBT strategies such as Socratic questioning. However, in MOL, other traditional structures of CBT (formulations, advice, homework tasks, formal assessments, etc) are seen to be less relevant and potentially intrusive to meta-cognitive processing 81 and the linking of cognition, affect, and emotion in an “online” experiential way.
Outcome studies for MOL indicate that it is an effective and acceptable psychotherapy with benefits at end of therapy and in short-term follow-up studies. 88 , 90 , 91 These studies have been based only in community clinics, and larger controlled trials are required. However, Carey et al 88 advocate that this approach appears to be especially useful for people with unusual perceptual experiences and complex problems—particularly when engagement is difficult, people feel “stuck” and are unclear about their problems—and for people who might have difficulty with remembering past events. MOL can be considered an MCT that can be delivered in pure form or within traditional CBT. 92 This makes it ideal for application within schizophrenia, and preliminary case studies have demonstrated its utility when delivered within the traditional CBT format. 93 Research specifically applying MOL to working with psychotic symptoms is underway.
Cognitive models have much to offer in aiding our understanding of the maintenance of the core symptoms of schizophrenia. Cognitive behavioral therapies based on these models have been demonstrated to be effective and valuable treatments for a range of positive and negative symptoms. However, theoretical developments and advances in cognitive treatments of disorders such as anxiety and depression have also helped to reveal a more complex picture of the transdiagnostic processes operating in schizophrenia. It is becoming clear that it is necessary to develop a broader conceptualization and treatment approach to psychotic symptoms that encompasses the heterogeneity and multifaceted nature of the disorder. Recent developments in cognitive treatments branded as third-wave approaches illustrate the advantage of not only targeting the content of thoughts and beliefs but also developing alternative methods of changing the way in which people relate to their thoughts and feelings. Collectively, they present a positive and encouraging developing evidence base with promising results. Evidence of the applicability of such approaches to schizophrenia is apparent, and further research is required to examine the wider feasibility and potential as a treatment for psychosis. These developments should be regarded as evolving cognitive therapies as opposed to a new wave. It is important to view CBT as a range of therapies and increase our understanding of how they might be applied to specific problems and circumstances, where efficacy is best understood through multifaceted and individualized formulations of patients.
- cognitive-behavioral therapy
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Cognitive behavioral therapy for schizophrenia: an empirical review
- 1 Centre for Addiction and Mental Health, Clarke Institute of Psychiatry and Department of Psychiatry, University of Toronto, Ontario, Canada.
- PMID: 11379970
- DOI: 10.1097/00005053-200105000-00002
Early case studies and noncontrolled trial studies focusing on the treatment of delusions and hallucinations have laid the foundation for more recent developments in comprehensive cognitive behavioral therapy (CBT) interventions for schizophrenia. Seven randomized, controlled trial studies testing the efficacy of CBT for schizophrenia were identified by electronic search (MEDLINE and PsychInfo) and by personal correspondence. After a review of these studies, effect size (ES) estimates were computed to determine the statistical magnitude of clinical change in CBT and control treatment conditions. CBT has been shown to produce large clinical effects on measures of positive and negative symptoms of schizophrenia. Patients receiving routine care and adjunctive CBT have experienced additional benefits above and beyond the gains achieved with routine care and adjunctive supportive therapy. These results reveal promise for the role of CBT in the treatment of schizophrenia although additional research is required to test its efficacy, long-term durability, and impact on relapse rates and quality of life. Clinical refinements are needed also to help those who show only minimal benefit with the intervention.
- Research Support, Non-U.S. Gov't
- Antipsychotic Agents / therapeutic use
- Cognitive Behavioral Therapy / methods*
- Combined Modality Therapy
- Delusions / drug therapy
- Delusions / psychology
- Delusions / therapy
- Hallucinations / drug therapy
- Hallucinations / psychology
- Hallucinations / therapy
- Psychotherapy / methods
- Randomized Controlled Trials as Topic
- Schizophrenia / drug therapy
- Schizophrenia / therapy*
- Schizophrenic Psychology
- Treatment Outcome
- Antipsychotic Agents
- Study Protocol
- Open access
- Published: 21 November 2023
Neurophysiological explorations across the spectrum of psychosis, autism, and depression, during wakefulness and sleep: protocol of a prospective case–control transdiagnostic multimodal study (DEMETER)
- Valeria Lucarini 1 , 2 ,
- Anaëlle Alouit 3 ,
- Delphine Yeh 4 ,
- Jeanne Le Coq 2 ,
- Romane Savatte 2 ,
- Mylène Charre 2 ,
- Cécile Louveau 2 ,
- Meryem Benlaifa Houamri 2 ,
- Sylvain Penaud 4 ,
- Alexandre Gaston-Bellegarde 4 ,
- Stéphane Rio 5 ,
- Laurent Drouet 5 ,
- Maxime Elbaz 5 ,
- Jean Becchio 6 ,
- Sylvain Pourchet 6 ,
- Estelle Pruvost-Robieux 3 , 7 ,
- Angela Marchi 8 ,
- Mylène Moyal 1 , 2 ,
- Aline Lefebvre 9 ,
- Boris Chaumette 1 , 2 ,
- Martine Grice 10 ,
- Påvel G. Lindberg 3 ,
- Lucile Dupin 11 ,
- Pascale Piolino 4 ,
- Cédric Lemogne 12 ,
- Damien Léger 5 , 13 ,
- Martine Gavaret 3 , 7 ,
- Marie-Odile Krebs 1 , 2 &
- Anton Iftimovici 1 , 2
BMC Psychiatry volume 23 , Article number: 860 ( 2023 ) Cite this article
Quantitative electroencephalography (EEG) analysis offers the opportunity to study high-level cognitive processes across psychiatric disorders. In particular, EEG microstates translate the temporal dynamics of neuronal networks throughout the brain. Their alteration may reflect transdiagnostic anomalies in neurophysiological functions that are impaired in mood, psychosis, and autism spectrum disorders, such as sensorimotor integration, speech, sleep, and sense of self. The main questions this study aims to answer are as follows: 1) Are EEG microstate anomalies associated with clinical and functional prognosis, both in resting conditions and during sleep, across psychiatric disorders? 2) Are EEG microstate anomalies associated with differences in sensorimotor integration, speech, sense of self, and sleep? 3) Can the dynamic of EEG microstates be modulated by a non-drug intervention such as light hypnosis?
This prospective cohort will include a population of adolescents and young adults, aged 15 to 30 years old, with ultra-high-risk of psychosis (UHR), first-episode psychosis (FEP), schizophrenia (SCZ), autism spectrum disorder (ASD), and major depressive disorder (MDD), as well as healthy controls (CTRL) ( N = 21 × 6), who will be assessed at baseline and after one year of follow-up. Participants will undergo deep phenotyping based on psychopathology, neuropsychological assessments, 64-channel EEG recordings, and biological sampling at the two timepoints. At baseline, the EEG recording will also be coupled to a sensorimotor task and a recording of the characteristics of their speech (prosody and turn-taking), a one-night polysomnography, a self-reference effect task in virtual reality (only in UHR, FEP, and CTRL). An interventional ancillary study will involve only healthy controls, in order to assess whether light hypnosis can modify the EEG microstate architecture in a direction opposite to what is seen in disease.
This transdiagnostic longitudinal case–control study will provide a multimodal neurophysiological assessment of clinical dimensions (sensorimotor integration, speech, sleep, and sense of self) that are disrupted across mood, psychosis, and autism spectrum disorders. It will further test the relevance of EEG microstates as dimensional functional biomarkers.
ClinicalTrials.gov Identifier NCT06045897.
In light of the genetic and neuroanatomical continuum among psychiatric illnesses [ 1 , 2 ], transdiagnostic neurophysiological approaches have demonstrated shared neurofunctional abnormalities between schizophrenia, mood, and autism spectrum disorders [ 3 , 4 ]. High-level cognitive processes have long been shown to rely on synchronized neuronal oscillations, resulting from a balance between excitatory and inhibitory populations of neurons, which can be directly measured by electroencephalography (EEG). This balance is maintained by a network of GABAergic interneurons that regulate the activity of superficial pyramidal cells [ 5 ]. The topographically precise inhibitory activity of interneurons also allows for spatial sensory coding, which is key to a variety of memory processes [ 6 ]. Disruption in these systems may therefore explain a range of cognitive symptoms seen across the spectrum of psychiatric disorders. Moreover, the timing of the disruption may explain the neurodevelopmental continuum between autism spectrum on the one hand, and psychotic and mood disorders on the other. For instance, glutamatergic NMDA receptors, which regulate interneuron activity, can be affected by genetic mutations disrupting the function of subunits expressed either in early development or later on, leading respectively to neurodevelopmental phenotypes, such as ASD, or to schizophrenia spectrum-disorders [ 7 ]. In addition, interneurons are crucial to prefrontal maturation during adolescence and early adulthood [ 8 ], a timeframe when most psychiatric disorders occur [ 9 ]. EEG quantitative approaches therefore appear as accessible and promising tools to investigate the pathophysiology of psychiatric disorders, from autism to schizophrenia spectrum disorders.
Beyond frequential or oscillatory activities, EEG analyses now allow to study the temporal dynamics of neuronal networks throughout the brain [ 10 ]. At rest, brain activities alternate very rapidly, every 80 ms or so, between states of unstable equilibrium, called microstates, and characterized by a particular polarization of the entire cerebral electrical potential field. EEG coupled with functional MRI has suggested that these microstates may correspond to particular modes of spatial organization of information processing [ 11 ]. For instance, microstate classes have been associated with various functioning profiles: verbal (class A), visual (class B), self-oriented/self-referential processing (class C), cognition (class D), and interoception and sensorimotor processing (class E) [ 12 ]. Moreover the same microstate structures have been described from waking rest to deep sleep, confirming that they may reflect a robust large-scale resting-state network architecture, similar to the resting-state connectivity seen in fMRI that is also preserved in sleep [ 13 ]. Disruption in these microstate systems has been described across the spectrum of psychiatric disorders, in schizophrenia [ 14 ], autism spectrum disorder [ 15 ], or depression [ 16 ], but also in neurological disorders such as epilepsy [ 17 ]. Thus, preliminary results from our group suggested that a certain pattern of microstates could be associated with specific stages of disease progression in psychosis, but also translated a shared dimension on the schizophrenia-autism continuum [ 18 ]. They may therefore contribute to understanding the range of transdiagnostic endophenotypes shared between neuropsychiatric diseases, such as anomalies in sleep, sensorimotor integration, speech, and sense of self. Moreover, since microstates can be modulated under hypnotic conditions [ 19 ], and medical hypnosis has been associated with improved attentional and executive control over self-referential processes [ 20 ], EEG microstates may also provide a proxy for psychotherapeutic response. Thus, the effectiveness of hypnosis has been suggested in psychiatric disorders associated with overactivation of the default mode, such as depression [ 21 ].
Sleep disturbances are strongly linked to the pathophysiology of most neuropsychiatric disorders and may explain many of the cardiovascular, pneumologic, and neurologic comorbidities of psychiatric disorders [ 22 ]. Various mechanistic models have been described in bipolar disorder and depression, including circadian rhythm anomalies, internal desynchronization, or anomalies of sleep architecture [ 23 , 24 ]. Sleep dysregulation is also highly prevalent in autism spectrum disorders, leading to severe distress and impact on quality of life [ 25 ], while in the early stages of psychosis, there is a high prevalence of insomnia, nightmare disorder, sleep-related hallucinations, excessive sleepiness disorders or restless leg syndromes [ 26 ]. Moreover, having a sleep disorder exacerbates psychotic and mood symptoms among patients with psychosis [ 26 ]. From a neurophysiological perspective, the most replicated macroscopic EEG anomaly across the spectrum of psychosis, mood disorders, and autism, is the decrease in density of sleep spindles [ 27 , 28 , 29 ], which are determinant for cognitive processes such as memory consolidation [ 30 ]. However, more quantitative EEG analyses remain to be done to further explore brain connectivity during sleep.
- Sensorimotor integration
Sensorimotor abnormalities are a cross-cutting neuropsychiatric dimension [ 31 , 32 , 33 ], which can be robustly analyzed with quantitative EEG [ 34 ]. Motor deficits linked to alterations in cortical excitability/inhibition modulation of motor areas have been identified in various neurodevelopmental pathologies such as schizophrenia or autism [ 35 , 36 ], and in particular during adaptation to a probabilistic context [ 37 ].
Specifically, autism spectrum disorders have been shown to exhibit anormal context-sensitive processing mechanisms, sensorimotor gating deficits, as well as repetitive motor movements and atypical integration of sensory stimuli [ 38 , 39 , 40 ]. Recent behavioral and imaging studies investigating tactile processing in autism, suggested no difference in light touch detection and texture, but increased sensitivity in vibration [ 41 , 42 , 43 ]. Moreover, decreased connectivity in finger somatosensory areas and slower perceptual processing speed were shown [ 44 , 45 ]. Although sensory perturbations are well known, literature on sensory integration prior to motor movement is lacking. In schizophrenia, and more generally in psychotic disorders, it is still unclear how sensorimotor mechanisms are impaired. It has been hypothesized that a general disruption may cause a functional disintegration between sensory and cognitive processes [ 32 , 46 ], yet, further investigations are needed in order to shed light on precise sensorimotor integration. Only a handful of studies showed tactile perception accuracy deficits [ 47 , 48 , 49 ], and abnormal sensory predictions in a self- and non-self-elicited sensation discrimination task [ 50 ]. This indicates a failure of normal inhibitory regulation of sensory, motor, and attentional mechanisms, common in several neurodevelopmental disorders.
Another accessible neurophysiological function that reflects thought processing and also results from a complex integration of sensorimotor signals is represented by speech, considered in its quantitative dimensions, which has also been correlated with EEG microstate patterns [ 51 ]. Given that communication difficulties are key features of autistic and psychotic disorders [ 52 ], computational methods have recently been introduced to objectively quantify linguistic anomalies in the psychosis spectrum and to identify subtle and early linguistic peculiarities in UHR individuals [ 53 ]. Recent studies have shown that analyses in the semantic and syntactic areas could predict psychotic transition [ 54 ], but the predictive role of other linguistic domains, such as phonetics, has so far been poorly investigated. A main aspect of phonetic research is prosody, the tone of voice with which words are pronounced, crucial for communication [ 55 ]. Researchers from both the phonetic and psychiatric fields have invested significant effort into trying to precisely characterize the prosodic profile of patients with schizophrenia, generally finding reduced pitch variability and increased pause duration [ 56 ]. However, among the limitations of the existing research, are a weak generalizability of the results to languages other than English, a lack of comparisons with other clinical groups and scant attention devoted to voice quality [ 56 ]. Besides, prosodic cues have scarcely been explored in individuals with high risk of psychosis and more research is needed to clarify the potential predictive role of these features [ 57 , 58 ].
Alongside traditional approaches investigating communicative behavior in psychosis focusing only on the voice of the patient, it is also necessary to investigate what happens at the interactional level [ 59 ]. Turn-taking analysis specifically explores dialogical interactional behaviors. Turn-taking is the organization of the conversation into alternating speaking turns between different interlocutors and its main goal is to assure that no more than one person is speaking at any time. Another goal is to avoid long silent gaps between the end of one speaking turn and the beginning of the next one [ 60 ]. Turn-taking analysis has rarely been applied to individuals with psychosis and at-risk mental states so far [ 61 , 62 , 63 ].
It appears that in this group turn-taking patterns involving increased mutual silence are prevalent. Interestingly, voice atypicalities have also been quantified in individuals with autism spectrum disorders, both in childhood and adulthood [ 64 ]. Moreover, recent studies have found an increased number of silent gaps as compared to controls in the early stages of dialogues [ 65 , 66 ]. Of note, there is evidence suggesting that there are shared social cognition deficits between autism and schizophrenia spectrum disorders [ 67 ]. From this perspective, there is additional motivation for comparing prosodic and turn-taking patterns in individuals with ASD and along the psychosis spectrum.
Crucially, the possible link between prosodic and turn-taking variables and their neurophysiological substrate in microstates has never been studied in patients with these profiles.
Self-reference effect and disorders of the self
Neurophysiological measures may also shed light on the individual’s phenomenological experience, such as self-consciousness [ 68 ], and its alteration in patients with psychotic disorders [ 69 ]. The sense of self is multifaceted and can be examined through two main prisms: firstly, as knowledge about “Me”, object of a reflexive construct of the self-concept, stored in long-term memory (narrative self) [ 70 ], and secondly as an “I” subject of the pre-reflexive and embodied subjective experience in the here and now (minimal self) [ 71 ]. Self-disorders constitute a core feature of the schizophrenia spectrum, markers of vulnerability to psychosis and predictors of psychotic conversion in patients at ultra-high risk or who had a first episode of psychosis. One of the possible prisms for studying these self-disorders is based on the evaluation of the self-reference effect on memory, according to which processing information closely related to the self is the most effective strategy for remembering new material [ 72 ]. Indeed, the self is intimately linked to memory and acts as a processing bias that determines how and what information is encoded and retrieved [ 73 , 74 ], particularly in episodic memory, which refers to the memory of the past experiences of the self and contributes to one’s feeling of identity and temporal continuity. However, minimal or narrative self-disorders appear associated to an altered or even lack of self-reference effect on memory [ 75 , 76 ]. Studying the self-reference effect in early psychosis could therefore contribute to characterizing the extent and course of self-disorders in prodromal (ultra-high risk) and early (first episode of psychosis) stages of schizophrenia. An innovative task has been designed using immersive virtual reality to evaluate the self-reference effect on episodic memory via a naturalistic approach, relying on the encoding of multisensory daily life events rather than simplistic lists of words or objects.
Objectives of the DEMETER study
Building on our preliminary results, the DEMETER project (“Détermination Des Microétats EEG associés Aux Troubles Psychiques Dans Les États à Risque”—EEG Microstates Across At-Risk Mental States) is a prospective observational study that aims to characterize the EEG microstate signature with regard to underlying neurophysiological functions, including sensorimotor integration, speech, sleep, and sense of self, across a population of adolescents and young adults, with ultra-high-risk of psychosis (UHR), first-episode psychosis (FEP), schizophrenia (SCZ), autism spectrum disorder (ASD), and major depressive disorder (MDD), compared with healthy controls (CTRL) ( N = 21 × 6), between two timepoints one year apart.
Participants will undergo deep phenotyping based on psychopathology and neuropsychological assessments at baseline and after one year of follow-up, high-resolution EEG (64 electrodes) with a resting period and a sensorimotor task, a recording of the characteristics of their speech (prosody and turn-taking), a one-night polysomnography, and biological sampling for multi-omic analyses, and a self-reference effect task in virtual reality (the latter only in UHR, FEP, and CTRL).
The main questions it aims to answer are as follows. 1) Are EEG microstate anomalies associated with specific disorders, and clinical and functional prognosis, both in resting conditions and during sleep ? 2) Are EEG microstate anomalies associated with differences in sensorimotor integration, speech, and sense of self ? 3) An interventional ancillary study will involve only healthy controls, in order to assess whether light hypnosis conditions can modify the EEG microstate architecture in a direction opposite to what is seen in disease.
All participants will be included at the Clinical Research Centre (CRC), University Hospital Group Paris Psychiatry and Neurosciences (GHU). Inclusion criteria are: an age between 15 and 30 years old; French as the maternal language or spoken in the context of bilingualism; a DSM-5 diagnosis of schizophrenia or major depressive disorder or autism spectrum disorder; a diagnosis of ultra-high-risk of psychosis or first-episode psychosis based on the Comprehensive Assessment of at risk mental state (CAARMS) translated in its French version [ 77 ]; and healthy control subjects recruited from the general population. Exclusion criteria are: suicidal risk; severe or non-stabilized somatic and neurological disorders; epilepsy; head trauma; IQ below 70; presence of other psychiatric disorders (bipolar disorder, obsessive–compulsive disorder, or substance use disorders, except for tobacco or cannabis, tolerated up to 5 joints/day); for healthy control subjects, a family history of psychosis is an exclusion criterion. Pregnant or breast-feeding women will not be included.
Participants will be screened among the population of patients seen at an early psychosis outpatient clinic (Centre d’évaluation des jeunes adultes et adolescents—CJAAD, GHU). Healthy controls will be reached through the healthy volunteers database of the CRC. Participant assessment will be as follows (Fig. 1 , Table 1 ). 1) During the pre-inclusion visit, participants will be informed of all the details of the protocol, orally and in writing, and eligibility criteria will be verified. Then a two-week reflection period will be observed, before the signature of a written consent at the baseline inclusion. 2) The baseline visit will consist of a first visit of three half-day sessions including medical, psychopathological and neuropsychological assessments, biological sampling (described below), and speech recording. In the following two months, participants will undergo one night of polysomnography (everyone) and two half-day sessions for the sensorimotor task (everyone) followed by light hypnosis (only controls), and the self-reference effect task in virtual reality (only controls, UHR, and FEP). 3) The follow-up visit will consist of a second psychopathological and neuropsychological assessment, biological sampling, and shorter EEG recording (5–10 min).
Protocol design. MDD: major depressive disorder. UHR: ultra-high-risk of psychosis. FEP: first-episode psychosis. SCZ: schizophrenia. ASD: autism spectrum disorder. CTRL: healthy controls
Healthy controls will receive a compensation of 120€, and participants with a psychiatric disorder will receive a financial compensation of 60€, as they will benefit to an access to more personalized care. This protocol has been approved by the ethics committee (Comité de protection des personnes) Ouest II (approval number: 2021-A01919-32).
Clinical, psychopathological and neuropsychological assessment
A clinical assessment will include anamnestic data collection (socio-demographic characteristics, treatment history, medical history, psychiatric history); a clinical examination with a physical examination, a psychiatric examination, the CAARMS, the positive and negative syndrome scale (PANSS), the Montgomery–Åsberg Depression Rating Scale (MADRS), Social and Occupational Functioning Assessment Scale (SOFAS), and neurological soft signs [ 78 ]. The neuropsychological assessment will include intellectual functioning (WAIS-IV), executive functioning (fluences, attentional capacities, episodic and working memory), and social cognition.
Each participant will undergo a semi-structured interview with an experimenter. Interviews will focus on interests and passions, to elicit as free and spontaneous dialogues as possible. Topics related to the participants’ clinical symptomatology will not be approached, unless participants explicitly wish to do so. The recordings will not have a fixed duration, but an attempt will be made to obtain at least 15–20 min of dialogue. Both speakers will wear head-set AKG-C544L microphones, connected via AKG MPA VL phantom adaptors to a Zoom H4n Pro Handy recorder. Speech will be recorded at a sampling rating of 44,000 Hz (16-bit). The distance between the mouth and the microphone will be kept at 2 cm to ensure consistent levels of vocal loudness. Moreover, the two speakers will be placed as far as possible, to prevent crosstalk (i.e. speech of one interactant caught by the other interactant’s microphone). Finally, the recordings will be carried out in a quiet room to limit environmental noise. This is consistent with previous analyses on acoustic patterns in psychiatry [ 79 ]. The.wav files obtained will be annotated using Praat software and subsequently analyzed with Praat [ 80 ] and R. Prosodic features will be extracted using the Prosogram tool (a set of Praat scripts, open-source) [ 81 ] and voice quality features will be computed with a modified version of scripts from the Prosogram tool [ 82 ]. Turn-taking variables will be quantified with combined Praat and R scripts [ 62 , 66 , 83 ]. This task has been designed and will be supervised by an expert in Phonetics and by a psychiatrist trained in linguistic data extraction and analysis (MGr and VL).
Sensorimotor integration task
Sensorimotor integration is investigated using a visuo-tactile task. On each trial, the participant, seated in front of a screen, has a visual instruction: a point to the right or left of the screen. The task consists of pressing one of the two buttons positioned on each side of the body with the index finger of the corresponding hand according to the visual instruction. A vibrotactile stimulator (small bone conduction speakers wired to an Arduino electronic card modulated by an amplifier) is applied to the first dorsal interosseous muscle of both hands. 400 msec before the visual instruction, one of the two hands receives a tactile cue (vibration) on one hand for 100 msec. The tactile cue can be congruent or incongruent with the visual cue, both indicating or not the same hand. Depending on the block, the tactile cue can be more or less reliably coupled with the visual stimulus. In reliable blocks, 90% of the trials present the vibration and visual instruction congruently (indicating the same hand). In non-reliable blocks, only 50% of the trials are congruent, and in this case, the tactile cue is not reliable. Two blocks with 70% congruent cases are carried out intermediately. Finally, a baseline block which does not contain any tactile cues is presented at the beginning and the end of the task. The order of the 90% and 50% blocks is randomized. The tactile and visual stimuli are generated with a MATLAB script. Each block consists of 100 trials, in total 500 trials. EEG data is recorded throughout the task, using a 64-channel EEG cap (from Biosemi). The setup is coupled to an eye tracker in order to control that the participant is fixing the cross at the center of the screen during each block. At the end of the task, a five minute eyes closed resting-state EEG will also be recorded. In order to examine attentional modulation, measurement of alpha power band (in Hz) is computed. Cortical excitability and inhibition are analyzed with mu and theta bands (in Hz), and integration of sensory information as somatosensory evoked potentials (SEPs), where amplitudes (in µV) and latencies (in msec) are extracted. The adaptation of the reaction time (in msec) to the button press according to the probabilistic context of congruency is examined. Analysis is conducted with Python scripts with dedicated libraries such as MNE-Python [ 84 ]. This task has been designed and will be supervised by researchers trained in neurophysiology recording and analysis (AA, LD).
After the sensorimotor integration task, healthy controls will undergo a light hypnosis task coupled with two control tasks, in addition to the eyes-closed resting-state already recorded. First, participants will be asked to listen to a neutral text (a refrigerator manual) read by the investigator, with the instruction to listen attentively in order to be able to answer specific questions regarding the content of text. Second, participants will do a mental calculation test. Third, participants will undergo the light hypnosis task. Light hypnosis is based on Ericksonian hypnosis without inducing a trance state, and has been developed by the Collège International des Techniques par Activation de la Conscience (CITAC; Jean Becchio, Sylvain Pourchet) as part of the Paris-Saclay university training in clinical hypnosis. Participants will be asked to focus on any type of preoccupation they may have, and then to picture the first step towards resolving this preoccupation. They will then be asked to provide resources or qualities they have. The light hypnosis session will then start by asking the participant to assume a comfortable and at the same time tonic position, sitting straight, the back lifted from the chair. They will be asked to close their eyes, while being informed that they can open them at any time if needed. They will then be asked to picture their objective, and the first step toward its solution. Then, they will be asked to picture themselves in a situation where they learnt to do something. Proprioceptive, sensory (each of the five senses), and metaphorical suggestions based on their resources will be provided in order to guide the participant in this exercise. This task has been designed and will be performed by two psychiatrists trained in clinical hypnosis (AI, CLo).
Self-reference effect task in virtual reality
Virtual reality immersion will be achieved using the HTC VIVE Pro Eye (Taoyuan City, Taiwan: HTC corporation) virtual reality headset. The self-reference effect task will consist in a walk through a virtual city, where participants will encounter a total of 32 multisensory daily life events that aim to be incidentally encoded in episodic memory. Participants will embody a virtual avatar and navigate twice through two distinct parts of the city. Prior to each navigation, avatar embodiment will be induced using a visuomotor stimulation in front of a virtual mirror, asking participants to move their different body parts while looking at them directly or in the mirror. To manipulate the minimal self-reference, one navigation will be associated with a synchronous avatar to induce a high sense of embodiment, and therefore a stronger sense of minimal self. The other navigation will be associated with an asynchronous avatar with a 700 ms-delay between participants’ real performed movements and the seen movements of the avatar, to induce a low sense of embodiment, and thus a weaker sense of minimal self. To manipulate the narrative self-reference, in each navigation path, half of the events will be associated to the participants themselves (Self), and the other to someone else (Other). The association will be induced by asking participants to take a picture of each event and rate its personal significance for either Self or Other. All conditions will be counterbalanced.
Following each navigation, participants will be submitted to self-reported questionnaires assessing their sense of embodiment (Embodiment Questionnaire) [ 85 ], sense of presence (Igroup Presence Questionnaire) [ 86 ], cybersickness (Simulator Sickness Questionnaire) [ 87 ], and current emotional state (Mood Visual Analogue Scale) [ 88 ].
Finally, participants will undergo two episodic memory tests: a free recall task and a recognition task. The free recall will be based on a verbal interview of 20 min, during which participants will be asked to recall all the events that they remember encountering in the virtual city. The recognition test will be programmed using the Python module Neuropsydia [ 89 ] and consists of displaying on a computer screen all 32 encountered events mixed with 16 lures which were not encountered in a random order, and asking participants whether they encountered this event in the virtual city. For both memory tests, participants will be asked to provide systematically and the most precisely possible, for each recalled event: description of the event, spatiotemporal situation, source, referent for the personal significance rating, perceptive and phenomenological details, degree of reliving or familiarity of the event. This task has been designed by Delphine Yeh under the supervision of Pascale Piolino, and derived from Sylvain Penaud’s protocol for the procedures linked to the minimal self-reference [ 90 ]. The virtual environment has been developed by Alexandre Gaston-Bellegarde using Unity.
An overnight polysomnography with 19 EEG channels and ventilatory polygraphy will be recorded for all participants within the first two months of inclusion, at the sleep medicine department of Hôtel-Dieu hospital, in Paris (Centre du Sommeil et de la Vigilance). Trained sleep technicians will set-up the head-sets in the evening and supervise the recording during the night. The recordings will be analyzed by trained sleep specialists (SR, LD).
Microstate analysis will be performed on eyes-closed resting-state, during the sensorimotor integration task, and during sleep. A minimal preprocessing will be done with the MNE EEG software on Python, which includes a bandpass filter between 0.5 and 40 Hz, rereferencing to the mean, and visual and automatic correction for artifacts using independent component analysis (ICA). Each recording will be visually reanalyzed by clinical neurophysiologists to check for any residual artifact. Microstate analysis will be done using the Pycrostates package [ 91 ]. Global field power (GFP) will be determined for each participant. Only EEG topographies at GFP peaks will be retained to determine microstates’ topographies, through a modified K-means clustering. For each subject the same number of GFP peaks will be extracted and concatenated into a single data set for clustering. A combined score will be used to compute the optimal number of clusters. The resulting clusters will be backfitted to each individual maps. Temporal smoothing will be used to ensure that periods of inter-peak noise, of low GFP, did not interrupt the sequences of quasi-stable segments. For each subject, three parameters will be computed for each microstate class: frequency of occurrence (“occurrence”), temporal coverage (“coverage”) and mean duration. Occurrence is the average number of times a given microstate occurs per second. Coverage (in %) is the percentage of total analysis time spent in a given microstate. Mean duration (in ms) is the average time during which a given microstate was present in an uninterrupted manner (after temporal smoothing).
Peripheral blood samples will be collected for genetic, epigenetic, proteomic, and metabolomic studies.
Statistical power estimates
We considered a minimum expected effect size around 0.5, based on pairwise comparisons of EEG microstate parameters (mean duration, time coverage, occurrence) between chronic schizophrenia and relatives of subjects with schizophrenia [ 14 ]. Accepting an alpha risk of 0.05 and 95% power, we estimate the necessary number of subjects to be included in each of the 6 groups at 15 (calculated in R with the pwr.anova.test function) (Fig. 2 ). Given the risk of overestimating the minimum effect size associated with publications based on small cohorts, we estimate that a number of 21 subjects significantly increases the chances of obtaining a power greater than 95%. This represents a total of 126 subjects.
Statistical analysis design
For all neurophysiological variables, the investigators will apply a repeated measures ANOVA, and use the following contrasts:
“UHR, FEP, SCZ, ASD, MDD” vs. “Healthy subjects”, in order to test the variables as markers of general psychopathology;
“UHR, FEP, SCZ” vs. “ASD, MDD”, in order to test the variables as specific markers of psychosis; equivalently, their specificity in MDD and ASD will be tested);
“UHR” vs. “FEP" vs. “SCZ”, in order to test the variables as markers of state;
Finally, in a dimensional approach, the functional correlates of microstates will be studied across wakefulness and sleep, and during speech, regardless of diagnosis.
The Research Domain Criteria (RDoC) strategy has led to a paradigmatic change in psychiatric research, promoting the integration of dimensional constructs beyond current nosographic boundaries. In this context, sensorimotor integration, speech, sleep–wake rhythms, and sense of self appear as relevant phenotypes to understand transdiagnostic functional impairments that lead to a high burden at the individual level [ 92 , 93 ]. In a multimodal approach, the use of neurophysiological tools such as high-density EEG, polysomnography, or audio recorders offer an accessible means to study these dimensions at a very good temporal resolution. Hypnosis or virtual reality tools further give the opportunity to non-invasively modulate and test perceptions in relation with these neurophysiological assessments. Moreover, applying quantitative EEG analyses in this framework, such as microstates, may shed light on the connectivity networks underlying thought processing and provide clinically-relevant biomarkers of state that could be easily implemented in daily practice.
This protocol describes a transdiagnostic longitudinal case–control study that includes a multimodal neurophysiological assessment of sensorimotor integration, speech, sleep, and sense of self, in patients with major depressive disorder, ultra-high-risk of psychosis, first-episode psychosis, schizophrenia, and autism spectrum disorders, compared to healthy controls, in a population of adolescents and young adults aged 15 to 30 years old. Preliminary retrospective analyses from our group, with routine clinical low-resolution EEG recordings, have suggested that a variation in EEG microstates class D may be a marker of stage across psychotic disorders, as it decreases from UHR to FEP and schizophrenia. However, these changes were not specific to psychosis, and they appeared to reflect a shared dimension on the schizophrenia-autism spectrum. We also suggested that a microstate ratio imbalance between class C and class D may perhaps be more specific to schizophrenia, although it did not appear that EEG microstates were sufficient to differentiate between different groups of diseases [ 18 ]. Building on this preliminary data, we propose this prospective study with higher resolution EEG recordings to test whether anomalies in the EEG microstate architecture may be associated with diagnosis, clinical and functional prognosis, both in resting conditions and during sleep, across psychiatric disorders. We postulate that we may find EEG microstate anomalies associated with differences in sensorimotor integration, speech, sense of self, and sleep, and that the dynamic of EEG microstates may be modulated by a non-drug intervention such as light hypnosis, as a proof-of-concept of potential usefulness in psychotherapeutic approaches.
We further hypothesize that the attentional component of somatosensory integration in preparation for a motor response is modulated through visuo-tactile stimuli in healthy subjects, and is altered in patients with psychotic disorders, probably with abnormal inhibition mechanism responses. Specifically, we expect that primary sensory cortex activity, measured as alpha and beta oscillations, influences motor cortex excitability and would be desynchronized in psychosis. We also anticipate an impaired connectivity among the primary sensorimotor network, as well as altered synchrony states in an attentional context. Finally, at rest, we expect these anomalies to be associated with a C/D microstate imbalance and with microstate class E anomalies (postulated to be correlated with interoception and sensorimotor processing).
We also expect to find differences in prosodic and turn-taking patterns between patients and healthy controls. In particular, we predict all patients to display reduced pitch variability, reduced speech output and increased pause duration. Moreover, we expect patients’ voices to overlap more with the interlocutor’s. We also hypothesize that linguistic cues could be markers of the stage, with increasing levels of atypicality from UHR to SCZ. Finally, we speculate that patients with ASD and participants along the schizophrenia spectrum will present similar prosodic and turn-taking patterns.
FInally, we postulate a reduced self-reference effect on memory performance in UHR and FEP individuals, due to patients’ self disturbances. Specifically, we expect a preserved narrative self-reference effect but no minimal self-reference effect in UHR and FEP individuals, since minimal self disturbances are already present in early stages of psychosis whereas narrative disturbances of the self are less marked, as opposed to controls who are expected to exhibit both minimal and narrative self-reference effects.
This study will address several methodological challenges. Its transdiagnostic design will allow us to test the specificity of any relevant observed association. At the data collection level, the pipeline that integrates the sensorimotor task with the high-density EEG recording will follow stringent quality checks so that the EEG recordings are interpretable with regard to the underlying task. The one-night polysomnography recordings will require to anticipate all the risks associated with prolonged recordings, such as electrodes that come off during sleep due to participant movement. This implies time-consuming regular check-ups during the night from trained technicians. In order to allow reproducible results, the ancillary light hypnosis protocol will require the use of a simple standardized strategy from the two clinicians trained in hypnosis. Regarding the linguistic data collection, high-quality double-channel audio recordings are crucial to allow precise and reliable analyses with the Praat software. Regarding the self-reference effect, the innovative task using immersive virtual reality will enable to study this effect in a naturalistic and standardized context, which will capture the richness of episodic memory and its links with the self in everyday life better than the simplistic lists of words or objects that are traditionally used in self-reference effect studies. Moreover, the task will integrate both minimal and narrative self-reference, which will enable to examine under the same design the respective but also joint contributions of both facets of the self to the self-reference effect in patients with self-disorders.
In conclusion, this multimodal, transdiagnostic neurophysiological approach will help pave the way for personalized medicine through in-depth endophenotyping of sleep, speech, sensorimotor integration and self-perception, four dimensions that overlap in the spectrum of psychiatric disorders.
Availability of data and materials
Anonymized data will be stored at GHU Paris Psychiatrie et Neurosciences, and will be made available upon reasonable request to the authors.
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We thank the team of the Délégation à la Recherche Clinique et à l’Innovation (DRCI) of GHU Paris Psychiatrie et Neurosciences for providing administrative and legal support to build this protocol, with special thanks to Bernadette Lemercier, Thujin Yoharajah, Khaoussou Sylla, Didier André, and Kahina Belkhir Hadid. We thank the Centre de Recherche Clinique (CRC) of GHU Paris Psychiatrie et Neurosciences for providing the material support of subject inclusions. Figures were done with Biorender ( https://www.biorender.com/ ).
This study is funded by the DEMETER Starting Grant, GHU Paris Psychiatrie et Neurosciences (principal investigator: Anton Iftimovici). Valeria Lucarini was supported by the doctoral grant ‘Young Talents in Psychiatry 2021’ from the Fondation FondaMental—Fondation Bettencourt-Schueller. Anaëlle Alouit was also financed by the French government’s “Investissements d’Avenir” programme (ANR-18-RHUS-0014 PsyCARE).
Authors and affiliations.
Université Paris Cité, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Team “Pathophysiology of psychiatric disorders”, GDR 3557-Institut de Psychiatrie, 102-108 Rue de la Santé, Paris, 75014, France
Valeria Lucarini, Mylène Moyal, Boris Chaumette, Marie-Odile Krebs & Anton Iftimovici
GHU Paris Psychiatrie et Neurosciences, Pôle Hospitalo-Universitaire d’évaluation, Prévention, et Innovation Thérapeutique (PEPIT), Paris, France
Valeria Lucarini, Jeanne Le Coq, Romane Savatte, Mylène Charre, Cécile Louveau, Meryem Benlaifa Houamri, Mylène Moyal, Boris Chaumette, Marie-Odile Krebs & Anton Iftimovici
Université Paris Cité, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Team “Stroke: from prognostic determinants and translational research to personalized interventions”, Paris, 75014, France
Anaëlle Alouit, Estelle Pruvost-Robieux, Påvel G. Lindberg & Martine Gavaret
Laboratoire Mémoire, Cerveau et Cognition, UR7536, Université Paris Cité, Boulogne-Billancourt, F-92100, France
Delphine Yeh, Sylvain Penaud, Alexandre Gaston-Bellegarde & Pascale Piolino
Centre du Sommeil et de la Vigilance, AP-HP, Hôtel-Dieu, Paris, France
Stéphane Rio, Laurent Drouet, Maxime Elbaz & Damien Léger
Collège International de Thérapies d’orientation de l’Attention et de la Conscience (CITAC), Paris, France
Jean Becchio & Sylvain Pourchet
Service de Neurophysiologie Clinique, GHU Paris Psychiatrie et Neurosciences, Paris, France
Estelle Pruvost-Robieux & Martine Gavaret
Epileptology and Cerebral Rhythmology, APHM, Timone Hospital, Marseille, France
Department of Child and Adolescent Psychiatry, Fondation Vallee, UNIACT Neurospin CEA - INSERM UMR 1129, Universite Paris Saclay, Gentilly, France
IfL-Phonetics, University of Cologne, Cologne, Germany
INCC UMR 8002, CNRS, Université Paris Cité, Paris, F-75006, France
Inserm, INRAE, Center for Research in Epidemiology and StatisticS (CRESS), Service de Psychiatrie de l’adulte, AP-HP, Hôpital Hôtel-Dieu, Université Paris Cité and Université Sorbonne Paris Nord, Paris, France
VIFASOM, ERC 7330, Université Paris Cité, Paris, France
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This project is the fruit of a collaborative effort, including: project funding and overall coordination (AI), speech study design (VL, MGr), sensorimotor integration study design (AA), self-reference effect in virtual reality study design (DY, PP, SP, AGB), sleep study design (AI), polysomnography set-up and analysis (SR, LD, ME, DL), hypnosis study design (AI, CLo, JB, SP), participant screening, inclusion and clinical assessment (AI, VL, MC, MBH, MOK), neuropsychological assessment (JLC and RS), EEG preprocessing and analysis protocols (AI, EPR, AM, MM, AL, MGa), biological assessment (BC). AI, VL, AA, and DY drafted the initial manuscript. All authors read and approved the final manuscript.
Correspondence to Anton Iftimovici .
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This study was approved by the ethics committee “Comité de protection des personnes” Ouest II (Approval Number: 2021-A01919-32), and is registered on ClinicalTrials.gov (ID: NCT06045897).
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Lucarini, V., Alouit, A., Yeh, D. et al. Neurophysiological explorations across the spectrum of psychosis, autism, and depression, during wakefulness and sleep: protocol of a prospective case–control transdiagnostic multimodal study (DEMETER). BMC Psychiatry 23 , 860 (2023). https://doi.org/10.1186/s12888-023-05347-x
Received : 31 October 2023
Accepted : 03 November 2023
Published : 21 November 2023
DOI : https://doi.org/10.1186/s12888-023-05347-x
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The Efficacy of Cognitive Behavioral Therapy: A Review of Meta-analyses
Cognitive behavioral therapy (CBT) refers to a popular therapeutic approach that has been applied to a variety of problems. The goal of this review was to provide a comprehensive survey of meta-analyses examining the efficacy of CBT. We identified 269 meta-analytic studies and reviewed of those a representative sample of 106 meta-analyses examining CBT for the following problems: substance use disorder, schizophrenia and other psychotic disorders, depression and dysthymia, bipolar disorder, anxiety disorders, somatoform disorders, eating disorders, insomnia, personality disorders, anger and aggression, criminal behaviors, general stress, distress due to general medical conditions, chronic pain and fatigue, distress related to pregnancy complications and female hormonal conditions. Additional meta-analytic reviews examined the efficacy of CBT for various problems in children and elderly adults. The strongest support exists for CBT of anxiety disorders, somatoform disorders, bulimia, anger control problems, and general stress. Eleven studies compared response rates between CBT and other treatments or control conditions. CBT showed higher response rates than the comparison conditions in 7 of these reviews and only one review reported that CBT had lower response rates than comparison treatments. In general, the evidence-base of CBT is very strong. However, additional research is needed to examine the efficacy of CBT for randomized-controlled studies. Moreover, except for children and elderly populations, no meta-analytic studies of CBT have been reported on specific subgroups, such as ethnic minorities and low income samples.
Cognitive-behavioral therapy (CBT) refers to a class of interventions that share the basic premise that mental disorders and psychological distress are maintained by cognitive factors. The core premise of this treatment approach, as pioneered by Beck (1970) and Ellis (1962) , holds that maladaptive cognitions contribute to the maintenance of emotional distress and behavioral problems. According to Beck’s model, these maladaptive cognitions include general beliefs, or schemas, about the world, the self, and the future, giving rise to specific and automatic thoughts in particular situations. The basic model posits that therapeutic strategies to change these maladaptive cognitions lead to changes in emotional distress and problematic behaviors.
Since these early formulations, a number of disorder-specific CBT protocols have been developed that specifically address various cognitive and behavioral maintenance factors of the various disorders. Although these disorder-specific treatment protocols show considerable differences in some of the specific treatment techniques, they all share the same core model and the general approach to treatment.
Consistent with the medical model of psychiatry, the overall goal of treatment is symptom reduction, improvement in functioning, and remission of the disorder. In order to achieve this goal, the patient becomes an active participant in a collaborative problem-solving process to test and challenge the validity of maladaptive cognitions and to modify maladaptive behavioral patterns. Thus, modern CBT refers to a family of interventions that combine a variety of cognitive, behavioral, and emotion-focused techniques (e.g., Hofmann, 2011 ; Hofmann, Asmundson, & Beck, in press ). Although these strategies greatly emphasize cognitive factors, physiological, emotional, and behavioral components are also recognized for the role that they play in the maintenance of the disorder.
A recent review of meta-analyses of CBT identified 16 quantitative reviews that included 332 clinical trials covering 16 different disorders or populations ( Butler, Chapman, Forman, & Beck, 2006 ). To our knowledge, this was the first review of meta-analytic studies examining the efficacy of CBT for a number of psychological disorders. This article has since become one of the most influential reviews of CBT. However, the search strategy was restrictive, because only one meta-analysis was selected for each disorder. Furthermore, the search only covered the period up to 2004, but many reviews have been published since then. In fact, the majority of studies (84%) was published after 2004. The goal of our review was to provide a comprehensive survey of all contemporary meta-analyses examining the evidence base for the efficacy of CBT to date. The meta-analyses included in the present review were all judged to be methodologically sound.
Search Strategy and Study Selection
To obtain the articles for this review, we searched PubMed, PsychInfo, and Cochrane library databases using the following key words: meta-analysis AND cognitive behav*, meta-analysis AND cognitive therapy, quantitative review AND cognitive behav*, quantitative review AND cognitive therapy . This initial search yielded 1,163 hits, of which 355 were duplicates and had to be excluded. The remaining 808 non-duplicate articles were further examined to determine if they met specific inclusionary criteria for the purposes of this review. All included studies had to be quantitative reviews (i.e., meta-analyses) of CBT. In order to limit this review to contemporary studies, only articles published since 2000 were included. The final sample included in this review consisted of 269 meta-analyses ( Figure 1 ). Out of those, we described a representative sample of 106 meta-analytic studies. The complete reference list for the final sample of included meta-analyses can be obtained by accessing the webpage www.bostonanxiety.org/cbtreview.html . As already noted, the majority (84%) of these studies was published after 2004, the most recent year covered by the meta-analysis by Butler and colleagues (2006) . The number of meta-analytic reviews per year is depicted in Figure 2 .
Flow diagram showing effects of inclusionary and exclusionary criteria on final sample selection.
Number of meta-analyses published by year since 2000. Note that the number of studies corresponding to 2011 only covered studies until September of that year.
Categorization of Meta-analyses
The 269 meta-analyses were categorized into groups to provide the most meaningful and extensive examination of the efficacy of CBT across a range of problem areas and study populations. The major groupings were the following: substance use disorder, schizophrenia and other psychotic disorders, depression and dysthymia, bipolar disorder, anxiety disorders, somatoform disorders, eating disorders, insomnia, personality disorders, anger and aggression, criminal behaviors, general stress, distress due to general medical conditions, chronic pain and fatigue, pregnancy complications and female hormonal conditions. In addition, some meta-analyses specifically examined CBT for disorders in children and elderly adults. For each disorder and population grouping, data were described qualitatively, considering the findings of all meta-analyses within that group. The 269 meta-analyses included a wide variety of studies that employed different methodologies and effect size estimates. Therefore, we used the designation small , medium , and large for the magnitude of effect sizes in our review of the 106 representative meta-analyses ( Cohen, 1988 ). In addition, we provide reported response rates, a widely accepted and common metric in psychiatry, from a subsample of 11 studies that examined the efficacy of CBT in randomized controlled trials.
Addiction and Substance Use Disoder
There was evidence for the efficacy of CBT for cannabis dependence, with evidence for higher efficacy of multi-session CBT versus single session or other briefer interventions, and a lower drop out rate compared to control conditions ( Dutra et al., 2008 ). However, the effect size of CBT was small as compared to other psychosocial interventions (e.g. contingency management, relapse prevention, and motivational approaches) for substance dependence, and agonist treatments showed a greater effect size than CBT in certain drug dependencies, such as opioid and alcohol dependence ( Powers, Vedel, & Emmelkamp, 2008 ).
Treatments for smoking cessation found that coping skills, which were partially based on CBT techniques, were highly effective in reducing relapse in a community sample of nicotine quitters ( Song, Huttunen-Lenz, & Holland, 2010 ), and another meta-analysis noted superiority of CBT (either alone or in combination with nicotine replacement therapy) over nicotine replacement therapy alone (Garcia-Vera & Sanz, 2006). Furthermore, there was evidence for superior performance of behavioral approaches in the treatment of problematic gambling as compared to control treatments ( Oakley-Browne et al., 2000 ). One meta-analysis ( Leung & Cottler, 2009 ) reported larger effect sizes of CBT when this treatment was grouped with other non-pharmacological treatments (such as brief interventions) as compared to pharmacological agents (e.g. naltrexone, carbamazepine, and topiramate), but CBT was not more efficacious than these other briefer, less expensive approaches.
Schizophrenia and Other Psychotic Disorders
Meta-analyses examining the efficacy of psychological treatments for schizophrenia revealed a beneficial effect of CBT on positive symptoms (i.e., delusions and/or hallucinations) of schizophrenia (e.g., Gould et al., 2001 ; Rector & Beck, 2001 ). There was also evidence (e.g., Zimmerman et al., 2005 ) that CBT is a particularly promising adjunct to pharmacotherapy for schizophrenia patients who suffer from an acute episode of psychosis rather than a more chronic condition.
CBT appeared to have little effect on relapse or hospital admission compared to other interventions, such as early intervention services or family intervention (e.g., Bird et al., 2010 ; Álvarez-Jiménez et al., 2011 ). However, CBT had a beneficial effect on secondary outcomes. For example, a more recent meta-analysis by Wykes and colleagues (2008) examined controlled trials of CBT for schizophrenia and confirmed findings from previous meta-analyses (e.g., Gould et al., 2001 ; Rector & Beck, 2001 ), suggesting that CBT had a small to medium effect size as compared to control conditions on both positive and negative symptoms. In addition, this meta-analysis revealed medium effect sizes for improvements in secondary outcomes that were not the direct targets of treatment, including general functioning, mood, and social anxiety.
Depression and Dysthymia
CBT for depression was more effective than control conditions such as waiting list or no treatment, with a medium effect size ( van Straten, Geraedts, Verdonck-de Leeuw, Andersson, & Cuijpers, 2010 ; Beltman, Oude Voshaar, & Speckens, 2010 ). However, studies that compared CBT to other active treatments, such as psychodynamic treatment, problem-solving therapy, and interpersonal psychotherapy, found mixed results. Specifically, meta-analyses found CBT to be equally effective in comparison to other psychological treatments (e.g., Beltman, Oude Voshaar, & Speckens, 2010 ; Cuijpers, Smit, Bohlmeijer, Hollon, & Andersson, 2010 ; Pfeiffer, Heisler, Piette, Rogers, & Valenstein, 2011). Other studies, however, found favorable results for CBT (e.g. Di Giulio, 2010 ; Jorm, Morgan, & Hetrick, 2008 ; Tolin, 2010 ). For example, Jorm and colleagues (2008) found CBT to be superior to relaxation techniques at post-treatment. Additionally, Tolin (2010) showed CBT to be superior to psychodynamic therapy at both post-treatment and at six months follow-up, although this occurred when depression and anxiety symptoms were examined together.
Compared to pharmacological approaches, CBT and medication treatments had similar effects on chronic depressive symptoms, with effect sizes in the medium-large range ( Vos, Haby, Barendregt, Kruijshaar, Corry, & Andrews, 2004 ). Other studies indicated that pharmacotherapy could be a useful addition to CBT; specifically, combination therapy of CBT with pharmacotherapy was more effective in comparison to CBT alone ( Chan, 2006 ).
Meta-analyses examining the efficacy of CBT for bipolar disorder revealed small to medium overall effect sizes of CBT at post-treatment, with effects typically diminishing slightly at follow-up. These findings emerged from examinations of both manic and depressive symptoms associated with bipolar disorder (e.g., Gregory, 2010a , 2010b ). There is little evidence that CBT as a stand-alone treatment (rather than as an adjunct to pharmacotherapy) is effective for the treatment of bipolar disorder.
In addition to examining CBT for attenuating symptoms of bipolar disorder, some meta-analyses focused on the efficacy of CBT for preventing relapse in bipolar patients. One study ( Beynon et al., 2008 ) examined the efficacy of CBT for preventing relapse and found it to be somewhat effective when comparing CBT vs. treatment as usual. Overall, CBT for bipolar disorder was an effective method of preventing or delaying relapses (e.g., Lam, Burbeck, Wright, & Pilling, 2009 ; Cakir & Ozerdem, 2010 ). Furthermore, the efficacy of CBT at preventing relapse did not seem to be influenced by the number of previous manic or depressive episodes.
In general, CBT is a reliable first-line approach for treatment of this class of disorders ( Hofmann & Smits, 2008 ), with support for significant positive effects of CBT on secondary symptoms such as sleep dysfunction and anxiety sensitivity ( Ghahramanlou, 2003 ). Further, internet-delivered or guided self-help CBT showed some promise in immediate symptom relief as compared to no treatment, but the long-term maintenance with this modality of CBT remains unclear ( Öst, 2008 ; Coull & Morris, 2011 ).
CBT for social anxiety disorder evidenced a medium to large effect size at immediate post-treatment as compared to control or waitlist treatments, with significant maintenance and even improvement of gains at follow-up ( Gil, Carrillo, & Meca, 2001 ). Further, exposure, cognitive restructuring, social skills training and both group/individual formats were equally efficacious ( Powers, Sigmarsson, & Emmelkamp, 2008 ), with superior performance over psychopharmacology in the long term ( Fedoroff & Taylor, 2001 ). Similarly, interoceptive exposure for treatment of panic disorder was moderately effective and superior to control/pill placebo treatments and applied relaxation ( Haby, Donnelly, Corry, & Vos, 2006 ; Furukawa, Watanabe, & Churchill, 2007 ). For panic disorder without agoraphobia, combination treatment of CBT and applied relaxation was equal in efficacy to use of either therapy approach alone, and use of either or both were superior to use of medications ( Mitte, 2005 ).
Various CBT techniques for specific phobia (systematic desensitization, exposure, cognitive therapy) were as effective as applied relaxation and applied tension, producing effect sizes in the large range, with long-term maintenance of gains ( Ruhmland & Margraf, 2001 ). For generalized anxiety disorder, CBT was superior as compared to control or pill placebo conditions, and equally efficacious as relaxation therapy, supportive therapy, or psychopharmacology, but less efficacious in comparison to attention placebos and in those with more severe generalized anxiety disorder symptoms.
CBT for post-traumatic stress disorder was equal in efficacy to eye movement desensitization and reprocessing ( Bisson et al., 2007 ), with both being superior to treatment as usual, waitlist, or other treatments (such as supportive counseling) for post-traumatic stress disorder ( Bisson & Andrew, 2008 ). However, it is questionable whether the eye-movement technique is an active treatment ingredient.
Clinical trials also revealed a large effect size for CBT and/or exposure response prevention for obsessive compulsive disorder, with evidence suggesting that a combination of in vivo and imaginal exposures outperformed the use of only in vivo exposures ( Ruhmland & Margraf, 2001 ). Furthermore, CBT was found to be similarly efficacious than clomipramine and selective reuptake inhibitors ( Eddy, Dutra, Bradley, & Westen, 2004 ).
Within the somatoform disorders category of DSM-IV, meta-analyses primarily examined the efficacy of psychological interventions for hypochondriasis and body dysmorphic disorder. One meta-analysis found a large mean effect size for CBT, which outperformed other psychological treatments (i.e., psychoeducation, explanatory therapy, cognitive therapy, exposure and response prevention, and behavioral stress management), with effect sizes in the large range, as well as pharmacotherapy treatments (paroxetine, fluoxetine, fluvoxamine, and nefazodone), which also evidenced large effect sizes ( Taylor, Asmundson, & Coons, 2005 ). The mean effect size for control conditions (e.g., wait-list control) was small. These results were partially supported by other evidence, as a more recent meta-analysis found superior outcomes of CBT for hypochondriasis compared to waiting list control, usual medical care or placebo at twelve-month follow-up ( Thomson & Page, 2007 ). However, this meta-analysis also found no differences between CBT and waiting list/placebo at post-treatment.
Meta-analyses comparing the efficacy of CBT to control treatments found that CBT was superior in significantly reducing body dysmorphic disorder symptoms ( Ipser, Sander, & Stein, 2009 ). In comparing relative efficacy of CBT versus pharmacotherapy, effect sizes were large on body dysmorphic disorder severity measures for CBT, and ranged from medium to large for pharmacotherapy ( Williams, Hadjistavropoulos, & Sharpe, 2006 ). In addition, another meta-analysis found that CBT for body image disturbances was effective, with effect sizes ranging from medium to large ( Jarry & Ip, 2005 ).
For bulimia nervosa, meta-analyses compared the efficacy of CBT to control treatments and found effect sizes in the medium range ( Thompson-Brenner, 2002 ). However, the effect of behavior therapy was greater than that of CBT, with the average effect size for behavior therapy in the large range (Thompson-Brenner, 2003). Another meta-analysis comparing CBT with control treatments found remission response rates to be higher for CBT, with a medium relative risk ratio ( Hay, Bacaltchuk, Stefano, & Kashyap, 2009 ). When comparing CBT to other psychotherapies, specifically, interpersonal therapy, dialectical behavioral therapy, hypno-behavioral therapy, supportive psychotherapy, behavioral weight loss treatment, and self-monitoring, CBT fared significantly better in remission response rates for bulimia nervosa, with a large relative risk ratio ( Hay et al., 2009 ).
For binge eating disorder, a recent meta-analysis found that psychotherapy and structured self-help yielded large effect sizes, when compared to pharmacotherapy, which yielded medium effect sizes ( Vocks et al., 2010 ). Although this study did not parse out the efficacy of CBT specifically, a majority of the included trials for psychotherapy involved CBT (19 out of 23 trials). Furthermore, a review and meta-analysis by Reas and Grilo (2008) suggested that combination treatment of psychotherapy and medications did not enhance binge-eating outcomes, but may have enhanced weight loss outcomes.
CBT for insomnia (CBT-I) has long been shown to be more efficacious than control treatments. A recent meta-analysis examined its efficacy on both subjective and objective sleep parameters in comparison to a control group for individuals with primary insomnia ( Okajima, Komada, & Inoue, 2011 ). Effect sizes for the efficacy of CBT-I versus control at the end of treatment on subjective sleep measures, which included sleep onset latency, total sleep time, wake after sleep onset, total wake time, time in bed, early morning awakening, and sleep efficiency, ranged from minimal (total sleep time) to large (early morning awakening) ( Okajima et al., 2011 ). For objective measures using a polysomnogram or actigraphic evaluation, effect sizes ranged from small (total sleep time) to large (total wake time) ( Okajima et al., 2011 ). These findings were consistent with results from another meta-analysis, which examined the relative efficacy of behavioral interventions for insomnia including CBT, relaxation, and only behavioral techniques ( Irwin, Cole, & Nicassio, 2006 ). This study reported effect sizes ranging from −.75 to 1.47 for CBT, −.60 to .53 for relaxation techniques, and −.82 to .91 for only behavioral techniques on subjective sleep outcomes.
There was one meta-analysis that examined the relative efficacy of CBT versus psychodynamic therapy for the treatment of personality disorders ( Leichsenring & Leibing, 2003 ). The findings indicated a larger overall effect size for psychodynamic therapy compared to CBT. This was consistent with observer-rated measures, which showed a similar pattern of effect sizes: stronger for psychodynamic therapy than for CBT (although this effect size was also large). Self-report measures, however, indicated larger effect sizes for CBT than for psychodynamic therapy.
Another meta-analysis compared the efficacy of eleven different psychological therapies, including CBT, for antisocial personality disorder ( Gibbon et al., 2010 ). Results suggested that compared to control treatment, CBT plus standard maintenance was more efficacious in terms of leaving the study early and cocaine use for outpatients with antisocial personality disorder and comorbid cocaine dependence. However, CBT plus treatment as usual was not better than a control condition for these antisocial personality disorder patients with regard to levels of recent verbal or physical aggression. The relative efficacy of psychological treatments for borderline personality disorder, in particular, was also examined, which yielded no differences between dialectical behavioral therapy and treatment as usual in individuals meeting criteria for borderline personality disorder at six months, or in hospital admissions in the previous three months (Binks et al., 2009).
Anger and Aggression
Two meta-analytic reviews focused on anger control problems and aggression ( Del Vecchio & O’Leary, 2004 ; Saini, 2009 ). The findings from these meta-analyses suggested that CBT is moderately effective at reducing anger problems. Findings from these reviews also suggested that CBT may be most effective for patients with issues regarding anger expression.
CBT produced medium effect sizes as compared to other psychosocial treatments and control conditions across the two reviews that conducted quantitative analyses. A meta-analysis on the effectiveness of anger treatments for specific anger problems ( Del Vecchio & O’Leary, 2004 ) included only studies in which subjects met clinically significant levels of anger on standardized anger measurements prior to treatment. This meta-analysis examined the effects of CBT, cognitive therapy, relaxation, and ‘other’ (e.g., social skills training, process group counseling) on various anger problems including driving anger, anger suppression, and anger expression difficulties.
Four separate meta-analytic studies supported the efficacy of CBT for criminal offenders ( Illescas, Sanchez-Meca, & Genovés, 2001 ; Lösel & Schmucker, 2005 ; Pearson, Lipton, Cleland, & Yee, 2002 ; Wilson, Bouffard, Mackenzie, 2005 ). Out of several theoretical orientations and types of psychological interventions for criminal activity, behavior therapy and CBT appeared to be the superior interventions in reducing recidivism rates, both with medium mean effect sizes ( Illescas, Sanchez-Meca, & Genovés, 2001 ). Effect sizes for other interventions ranged from small to medium ( Illescas et al., 2001 ). Another study demonstrated consistent findings with a small weighted mean effect size of behavior therapy or CBT for reducing recidivism ( Pearson, Lipton, Cleland, & Yee, 2002 ). Similarly, Wilson and colleagues (2005) found an overall small-to-medium mean effect size for CBT programs for convicted offenders.
For sexual offenders in particular, physical treatments, such as surgical castration and hormonal treatment, were demonstrated to have greater efficacy in reducing sexual recidivism in comparison to CBT, with large significant odds ratios for both of these alternative interventions ( Lösel & Schmucker, 2005 ). Of the various psychological interventions for sexual offenders, however, classical behavioral and CBT approaches indicated the strongest efficacy, with odds ratios in the medium to large range ( Lösel & Schmucker, 2005 ) as compared to insight-oriented and therapeutic community interventions.
A study of CBT for domestic violence indicated no differences between CBT and the Duluth model (which is based on a feminist psycho-educational approach) for treating domestically violent males ( Babcock, Green, & Robie, 2004 ). The aggregated data from experimental and quasi-experimental studies showed that CBT had an overall small effect size, and the Duluth model had an overall slightly larger, but still small effect size ( Babcock et al., 2004 ).
Four meta-analyses examined occupational stress and the majority of their results were quite similar: CBT interventions were more effective in comparison to other intervention types such as organization focused therapies, especially when CBT focused on psycho-social outcomes in employees ( Kim, 2007 ; Richardson & Rothstein, 2008 ; van der Klink, Blonk, Schene, & van Dijk, 2001 ). For example, Richardson and Rothstein (2008) found CBT alone to be more effective in comparison to CBT combined with additional psychological components. These studies found a large effect size for overall CBT interventions, large effect size for single-mode CBT interventions, and small effect size for CBT interventions with four or more components. In contrast, Marine and colleagues (2006) chose not to compare CBT with other interventions, such as relaxation techniques for psychological stress, because most interventions comprised both elements and could not be evaluated separately. With respect to stress in parents of children with developmental disabilities, positive effects were found for CBT, but the effect size was relatively small ( Singer, Ethridge, & Aldana, 2007 ). In contrast to the results of Richardson and Rothstein (2008) , this meta-analysis found multiple component interventions which combined CBT, behavioral parent training and in some cases other forms of support services, to have a higher and large effect size in comparison to CBT alone ( Singer, Ethridge, & Aldana, 2007 ).
Distress Due to General Medical Conditions
Limited well-controlled studies existed in the study of non-ulcer dyspepsia, multiple sclerosis, physical disability following traumatic injury, non-epileptic seizures, post-concussion syndrome, chronic obstructive pulmonary disease, hypertension, Type II diabetes, and burning mouth syndrome (e.g. Soo et al., 2004 ; Thomas, Thomas, Hillier, Galvin, & Baker, 2006 ; Baker, Brooks, Goodfellow, Bodde, & Aldenkamp, 2007 ; Ismail, Winkley, & Rabe-Hesketh, 2004 ). However, cancer was studied more rigorously and with more robust methodological attention, indicating small to medium effect sizes of individual CBT as compared to patient education only in gynecological and head/neck cancers ( Zimmerman & Heinrichs, 2006 ; Luckett, Britton, Clover, & Rankin, 2011 ), on secondary outcomes such as quality of life, psychological distress (i.e., depression and anxiety), and pain. Further, CBT was shown to be equally effective as exercise interventions in treating cancer-related fatigue ( Kangas, Bovbjerg, & Montgomery, 2008 ).
Small to medium effect sizes were observed in treatment of secondary symptoms (anxiety and stress) experienced by individuals who were HIV positive, with particular efficacy (particularly for stress management) in reducing anger symptoms as compared to supportive therapy ( Crepaz et al., 2008 ), but not for outcomes such as low cell count, medication adherence, or when used with marginalized populations such as ethnic minorities and women ( Crepaz et al., 2008 ; Rueda et al., 2006 ).
CBT was shown to be superior in the treatment of secondary symptoms of spinal cord injury as compared to controls in assertiveness skills, coping, depression and quality of life ( Dorstyn, Mathias, & Denson, 2011 ), better than placebo or diet/exercise alone ( Shaw, O’Rourke, Del Mar, & Kenardy, 2005 ), but equal to yoga/education in depressive symptoms ( Martinez-Devesa, Perera, Theodoulou, & Waddell, 2010 ). CBT was only slightly more effective than usual care or waitlist condition in the treatment of irritable bowel syndrome, with peppermint oil having greater efficacy in providing relief in this particular disorder ( Enck, Junne, Klosterhalfen, Zipfel, & Martens, 2010 ).
Chronic Pain and Fatigue
Meta-analyses examining the efficacy of psychosocial treatments for chronic pain have investigated chronic low back pain, fibromyalgia, rheumatoid arthritis, chronic fatigue syndrome, chronic musculoskeletal pain, and non-specific chest pain. These reviews have examined the effect of a range on treatments on chronic pain, including relaxation techniques, mindfulness-based techniques, acceptance-based techniques, biofeedback, psycho-education, and behavioral and cognitive-behavioral treatments. Results of these meta-analyses revealed varying effect sizes for these treatments depending on the type of chronic pain targeted; however, CBT treatments for chronic pain were consistently in the small to medium effect size range.
Similar results were found in a meta-analysis examining psychological treatments for fibromyalgia ( Glombiewski et al., 2010 ). This meta-analysis revealed that CBT was superior to other psychological treatments for decreasing pain intensity. Pre-post analyses revealed a medium effect size for CBT as compared to a small effect size for all other psychological treatments combined (excluding CBT). CBT treatments for chronic fatigue syndrome were moderately effective (e.g., Malouff et al., 2008 ; Price et al., 2008 ). Malouff and colleagues (2008) conducted a meta-analysis revealing a medium effect size in post-treatment fatigue for participants receiving CBT versus those in control conditions.
Pregnancy Complications and Female Hormonal Conditions
One meta-analysis found CBT to be more effective in comparison to control conditions for perinatal depression ( Sockol, Epperson, & Barber, 2011 ), and another meta-analysis found beneficial effects of CBT for postnatal depression, but these results need to be interpreted with caution because it is difficult to causally link depression with pregnancy and hormonal changes in these studies ( Dennis, & Hodnett, 2007 ). Further, Bledsoe and Grote (2006) found greater decreases in depression for women experiencing non-psychotic major depression in pregnancy and postnatal periods treated with combination treatment in comparison to antidepressant medication alone, which was itself more effective in comparison to CBT alone. The effect size for postnatal treatments was large in comparison to the small to medium effects of prenatal treatments, but when pharmacological treatments were excluded, the effect size for postnatal treatments decreased to the medium range.
For the treatment of premenstrual syndrome, Busse and colleagues (2009) found that CBT significantly reduced depressive and anxiety symptoms associated with this syndrome, as indicated by a medium effect size. Once again, these results need to be interpreted carefully due to the small number of well-controlled studies on which these reviews were based.
CBT for Special Populations
Within internalizing symptoms, there was support for the preferential use of CBT approaches in treatment of anxiety disorders in children and adolescents, with effect sizes in the large range ( Santacruz et al., 2002 ; James, Soler, & Weatherall, 2005 ). Further, CBT treatment for obsessive compulsive disorder as compared to alternative approaches (no treatment, other psychosocial treatments and medications such as clomipramine and fluvoxamine) resulted in significantly better outcomes ( Phillips, 2003 ; Guggisberg, 2005 ). The data supporting CBT for depression was less strong, but still in the medium effect size range across meta-analyses, with maintenance in 6-month follow-up periods ( Santacruz et al., 2002 ). In addition, CBT seemed to work equally well as other psychotherapies (i.e. interpersonal therapy and family systems therapy), but was regarded as superior to selective reuptake inhibitors due to reduced chance of side effects and greater cost effectiveness ( Haby, Tonge, Littlefield, Carter & Vos, 2004 ). The studies on efficacy of CBT for addressing suicidal behaviors were scarce ( Robinson, Hetrick, & Martin, 2011 ), and warrant further investigation.
The picture was more mixed for other disorders, with CBT showing equal efficacy in reducing disruptive classroom behaviors and aggressive/antisocial behaviors, as other psychosocial treatments, better efficacy as compared to no treatment or treatment as usual, and less efficacy than pharmacological approaches ( Lösel & Beelmann, 2003 ; Özabaci, 2011 ). Similarly, CBT for attention deficit hyperactivity disorder showed some efficacy, but was not superior to medications ( Van der Oord, Prins, Oosterlaan, & Emmelkamp, 2008 ). The efficacy of behavioral techniques (e.g. motivational enhancement and behavioral contingencies) was small to medium for the treatment of adolescent smoking and substance use as compared to no treatment, but not more so than other psychotherapies. In addition, there was a medium to large effect size of CBT over waitlist across meta-analyses examining chronic headache pain. Finally, the data on efficacy for CBT in juvenile sex offenders, childhood sexual abuse survivors, childhood obesity, fecal incontinence, and juvenile diabetes was limited, showing preliminary support for CBT as compared to no treatment, but equal efficacy to other psychosocial approaches ( Walker, McGovern, Poey, & Otis, 2005 ; Macdonald, Higgins, & Ramchandani, 2006 ).
With respect to mood disorders, with depression as the most commonly examined disorder, nearly all meta-analyses showed that CBT was more effective than waiting list control conditions, but equally effective in comparison to other active treatment methods, such as reminiscence, (an intervention that uses recall of past events, feelings and thoughts to facilitate pleasure, quality of life or adaptation to the present; Peng, Huang, Chen, & Lu, 2009 ), psychodynamic therapy, and interpersonal therapy ( Krishna et al., 2011 ; Wilson, Mottram, & Vassilas, 2008 ). Pinquart and colleagues (2007) , however, found a large effect size for CBT, whereas the effect sizes for the other active treatment conditions were in the medium-large range. When long-term outcomes were examined, results of one meta-analysis indicated that treatment gains of CBT for depression were maintained at 11-months follow-up ( Krishna et al., 2011 ), but long-term follow-up data remained scarce in the other meta-analyses. In a meta-analysis assessing the additive effects of CBT and pharmacological approaches, Peng and colleagues (2009) found that CBT was more effective in comparison to placebo, but CBT as an adjunct to antidepressant medication did not increase the effectiveness of antidepressants in this population.
For anxiety disorders in the elderly, CBT (alone or augmented with relaxation training) did not enhance outcomes beyond relaxation training alone ( Thorp et al., 2009 ), although many of these studies were uncontrolled. In contrast to the findings by Thorp and colleagues (2009) , Hendriks and colleagues (2008) found that anxiety symptoms were significantly decreased following CBT than after either a waiting-list control condition or other treatment methods. Additionally, CBT significantly alleviated accompanying symptoms of worry and depression when compared to waiting-list control or an active control condition.
Response Rates of Randomized Controlled Studies
The meta-analytic studies that provided response rates are listed in Table 1 . The response rates of CBT varied between 38% for treating obsessive compulsive disorder ( Eddy et al., 2004 ) and 82% for treating body dysmorphic disorder ( Ipser et al, 2009 ). In contrast, the response rates of the waitlist groups ranged from 2% for the treatment of bulimia nervosa (Thompson-Brenner, 2003) to 14% for generalized anxiety disorder ( Hunot et al., 2007 ). CBT also demonstrated higher response rates in comparison to treatment as usual in treatment of generalized anxiety disorder and chronic fatigue ( Price et al., 2008 ), and higher or equal response rates as compared to other therapies or psychopharmacological interventions in most studies. CBT only produced a lower response rate than psychodynamic therapy for the personality disorders (47% vs. 59%; Leichsenring & Leibing, 2003 ).
Pooled meta-analytic response rates for CBT versus other conditions across disorders.
Note . The table shows response rate percentages for CBT (from highest to lowest) compared to each comparison condition for every meta-analaytic study reporting such data across disorder groups; -: no data reported; >: higher efficacy; <: lower efficacy; =: equal efficacy. MED = Medication/ pharmacological approaches; OT = Other therapies (consisting of relaxation therapy, supportive therapy, or psychodynamic therapy); PBO = placebo/control treatments; TAU= Treatment as usual; WL= Waitlist treatment; BDD: Body dysmorphic disorder; PD: Panic disorder without agoraphobia; GAD = Generalized anxiety disorder; OCD = Obsessive-compulsive disorder.
CBT is arguably the most widely studied form of psychotherapy. We identified 269 meta-analytic reviews that examined CBT for a variety of problems, including substance use disorder, schizophrenia and other psychotic disorders, depression and dysthymia, bipolar disorder, anxiety disorders, somatoform disorders, eating disorders, insomnia, personality disorders, anger and aggression, criminal behaviors, general stress, distress due to general medical conditions, chronic pain and fatigue, distress related to pregnancy complications and female hormonal conditions. Additional meta-analytic reviews examined the efficacy of CBT for various problems in children and elderly adults. The vast majority of studies (84%) was published after 2004, which was the last year of coverage of the review by Butler and colleagues (2006) , making the present study the most comprehensive and contemporary review of meta-analytic studies of CBT to date.
For the treatment of addiction and substance use disorder , the effect sizes of CBT ranged from small to medium, depending on the type of the substance of abuse. CBT was highly effective for treating cannabis and nicotine dependence, but less effective for treating opioid and alcohol dependence. For treating schizophrenia and other psychotic disorders , the empirical literature suggested appreciable efficacy of CBT particularly for positive symptoms and secondary outcomes in the psychotic disorders, but lesser efficacy than other treatments (e.g. family intervention or psychopharmacology) for chronic symptoms or relapse prevention.
The meta-analytic literature on the efficacy of CBT for depression and dysthymia was mixed with some studies suggesting strong evidence and others reporting weak support. Some authors have suggested that the strong effects in some studies may be an overestimation due to a publication bias ( Cuijpers, et al., 2010 ). Similarly, the efficacy of CBT for bipolar disorder was small to medium in the short-term in comparison to treatment as usual. However, there was limited evidence for the superiority of CBT alone over pharmacological approaches; for the treatment of depressive symptoms in bipolar disorder, the use of CBT was well supported. However, the long-term superiority compared to other treatments is still uncertain.
The efficacy of CBT for anxiety disorders was consistently strong, despite some notable heterogeneity in the specific anxiety pathology, comparison conditions, follow-up data, and severity level. Large effect sizes were reported for the treatment of obsessive compulsive disorder, and at least medium effect sizes for social anxiety disorder, panic disorder, and post-traumatic stress disorder. Medium to large CBT treatment effects were reported for somatoform disorders , such as hypochondriasis and body dysmorphic disorder. However, more studies using larger trials and greater sample sizes are needed to draw more conclusive findings with regard to CBT’s relative efficacy in comparison to other active treatments.
For the treatment of bulimia , CBT was considerably more effective than other forms of psychotherapies, but less is known for other eating disorders. Similarly, CBT demonstrated superior efficacy as compared to other interventions for treating insomnia when examining sleep quality, total sleep time, waking time, and sleep efficiency outcomes. However, although there were small effects of CBT for sleep problems among older adults (aged 60+), these effects may not be long lasting ( Montgomery & Dennis, 2009 ).
For personality disorders , there was some evidence for superior efficacy of CBT as compared to other psychosocial treatments for the personality disorders. However, the studies showed considerable variation in measurement methods, comorbid disorders, and demographic variables. CBT also produced medium to large effect sizes for treating anger and aggression (e.g., Saini, 2009 ), although a greater number of well-controlled studies are needed to more adequately parse out the specific efficacy of CBT compared to the psychosocial treatments for anger on the whole. Similarly, more studies are needed before any firm conclusions can be drawn about the efficacy of this treatment for criminal behaviors .
As a stress management intervention, CBT was more effective that other treatments, such as organization-focused therapies. However, more research on the long-term effects of CBT for occupational stress is needed. Furthermore, there are open questions about the relative efficacy of CBT versus pharmacological approaches to stress management. Similarly, several common concerns recurred across meta-analytic examinations of CBT for chronic medical conditions , chronic fatigue and chronic pain , namely: (1) a scarcity of studies and small sample sizes; (2) poor methodological design of studies that are included in meta-analyses; and (3) grouping of CBT with a host of other psychotherapies (such as psychodynamic therapy, hypnotherapy, mindfulness, relaxation, and supportive counseling), which made it difficult to parse out whether there are any superior effects of CBT in the majority of medical conditions examined.
There was preliminary evidence for CBT for treating distress related to pregnancy complications and female hormonal conditions . However, more research is needed due to a scarcity of follow-up data and low quality studies. This appeared to be a highly promising area for CBT given that the alternative – pharmacological treatments – can be associated with serious risks of adverse effects for pregnant women and breastfeeding mothers.
In our review of meta-analyses, CBT tailored to children showed robust support for treating internalizing disorders, with benefits outweighing pharmacological approaches in mood and anxiety symptoms. The evidence was more mixed for externalizing disorders, chronic pain, or problems following abuse. Moreover, there remains a need for a greater number of high-quality trials in demographically diverse samples. Similarly, CBT was moderately efficacious for the treatment of emotional symptoms in the elderly , but no conclusions about long-term outcomes of CBT or combination therapies consisting of CBT, and medication could be made.
Finally, our review identified 11 studies that compared response rates between CBT and other treatments or control conditions. In 7 of these reviews, CBT showed higher response rates than the comparison conditions, and in only one review ( Leichsenring & Leibig, 2003 ), which was conducted by authors with a psychodynamic orientation, reported that CBT had lower response rates than comparison treatments.
In sum, our review of meta-analytic studies examining the efficacy of CBT demonstrated that this treatment has been used for a wide range of psychological problems. In general, the evidence-base of CBT is very strong, and especially for treating anxiety disorders. However, despite the enormous literature base, there is still a clear need for high-quality studies examining the efficacy of CBT. Furthermore, the efficacy of CBT is questionable for some problems, which suggests that further improvements in CBT strategies are still needed. In addition, many of the meta-analytic studies included studies with small sample sizes or inadequate control groups. Moreover, except for children and elderly populations, no meta-analytic studies of CBT have been reported on particular subgroups, such as ethnic minorities and low income samples.
Despite these weaknesses in some areas, it is clear that the evidence-base of CBT is enormous. Given the high cost-effectiveness of the intervention, it is surprising that many countries, including many developed nations, have not yet adopted CBT as the first-line intervention for mental disorders. A notable exception is the Improving Access to Psychological Therapies initiative by the National Health Commissioning in the United Kingdom ( Rachman & Wilson, 2008 ). We believe that it is time that others follow suit.
The authors would like to acknowledge the following research assistants who provided crucial and much-appreciated assistance with background literature reviews, initial identification of articles, and obtained articles for use by the authors: Dan Brager, Rachel Kaufmann, Rebecca Grossman, and Brian Hall.
Dr. Hofmann is a paid consultant of Merck Pharmaceutical (Schering-Plough) for work unrelated to this study. This study was partially supported by NIMH grants MH-078308 and MH-081116 awarded to Dr. Hofmann and MH-73937.
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What to Know About Pregnancy and Women With Schizophrenia
Info for soon-to-be mothers with schizophrenia and schizoaffective disorder..
Posted November 24, 2023 | Reviewed by Davia Sills
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- Mothers with schizophrenia or schizoaffective disorder may experience more pregnancy complications.
- Postpartum relapses may happen if treatment is discontinued during pregnancy.
- The pregnancy rates of women with a psychotic disorder have tripled in recent past decades.
- Reproductive health education and earlier treatment must happen to increase the chances of a fulfilling life.
It used to be that people with schizophrenia were not thought capable of living fulfilling lives, including raising children and starting families. But it appears this isn’t the case in recent times, with birthrates for women with schizophrenia tripling in the last few decades.
If you’re a woman who suffers from this disorder or if you are thinking about starting a family with one, what do you need to know?
Mothers living with schizophrenia disorders are more likely to be single mothers, relying on child welfare programs. Due to the cognitive impairments of the disorder and its instability, many women may be isolated from a social network that would, in turn, help the individual live and care for her child and family. Women with schizophrenia or schizoaffective disorder may be more reliant on governmental aid rather than the familial aid that would naturally come from a social support system.
Psychotic mothers are more likely to run into birth complications. There are health complications that may arise while treating the mental health condition itself. Mothers may seek to discontinue treatment for their psychotic disorder, such as withdrawing from antipsychotics , fearing harm to the newborn. Although antipsychotics aren’t necessarily a risk to a newborn baby, many women fear the lasting effects of the drugs on their children. If treatment is discontinued during pregnancy , mothers may be more at risk of experiencing postpartum psychosis . Psychotic mothers are also more likely to run into obstetric problems.
When researchers studied this demographic to assess the truth of these trends, 197 women with schizophrenia and schizoaffective disorder in Spain were used to test whether the trends of the reproductive outcomes were still true.
They found out that 39.1 percent of mothers with schizophrenia were single and were living with a “first-degree” family member (24.6 percent). Most (53.7 percent) of the women were receiving federal aid, and 81.1 percent of the mothers had an obstetric complication. Those who developed their disorder earlier in age were more likely to be single, and the researchers believe that it is due to the poorer prognosis, thus reducing quality of life earlier. Only about a quarter of the mothers experienced a planned pregnancy. Notably, the study showed that women with schizoaffective disorder versus schizophrenia were more likely to be mothers, even though the sample included 147 mothers with schizophrenia and 45 with schizoaffective disorder.
The study showed results against the trends as well, revealing only 2.2 percent required increased psychiatric care during pregnancy, and 9.9 percent required it postpartum. About 66.3 percent of the mothers received adequate social and family care, and 47.9 percent were cooperatively caring for their children with spouses.
The statistics only reveal the need for more proactive reproductive planning programs to prevent obstetric problems and unwanted pregnancies. The trend of able mothers having their own kids is only an upward one, however, and it is an indicator that advancements and early treatment for these conditions only improve the chances that people living with schizophrenia and schizoaffective disorder can live a fulfilling life.
Safont, G., Garriga, M., González-Rodríguez, A., Amoretti, S., Simón, O., Solè, E., ... & Bernardo, M. (2023). Maternity in women with schizophrenia and schizoaffective disorder. Spanish Journal of Psychiatry and Mental Health .
Sarah An Myers is a writer with a Master of Arts in psychology and behavioral neuroscience from the University of Missouri-St. Louis. She researches novel computational and therapeutic methods for treating and diagnosing mental disorders.
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