Cognitive-behavioral therapy for the improvement of negative symptoms and functioning in schizophrenia: A systematic review and meta-analysis of randomized controlled trials

Yu Hong; Yiyun Chen; Yinglin Bai; Wenfei Tan

doi:10.1371/journal.pone.0324685

. 2025 May 20;20(5):e0324685. doi: 10.1371/journal.pone.0324685

Cognitive-behavioral therapy for the improvement of negative symptoms and functioning in schizophrenia: A systematic review and meta-analysis of randomized controlled trials

Yu Hong ^1,^*, Yiyun Chen ², Yinglin Bai ¹, Wenfei Tan ¹

Editor: Carlos Eduardo Thomaz,³

PMCID: PMC12091889 PMID: 40392926

Abstract

Background

Negative symptoms of schizophrenia are a range of deficits or losses in mental functioning associated with the disorder, including blunted affect, alogia, avolition, asociality, and anhedonia. These symptoms severely impact the quality of life of patients and hinder the recovery process. They significantly impair patients’ ability to live independently, maintain social relationships, and function effectively in society. However, current treatments for negative symptoms of schizophrenia are limited in efficacy and remain controversial. Cognitive-behavioral therapy (CBT) is a goal-oriented psychotherapy that aims to improve individuals’ emotional and psychological states by changing their negative thought patterns and behaviors. It helps patients identify and challenge irrational beliefs while promoting more positive behavioral changes through behavioral experiments and skills training. This study aims to conduct a meta-analysis to assess the effects of CBT on negative symptoms and function in schizophrenia.

Objectives

This study aimed to investigate the effects of cognitive behavioral therapy on negative symptoms, mental function, social skills, and social functioning in schizophrenia.

Methods

Literature was retrieved from 10 databases (PubMed, EMBASE, Cochrane Library, Web of Science, APA PsycINFO, CINAHL, MEDLINE, CNKI, Wan fang Database and SinoMed,), with the search period ranging from the inception date to 1 September 2024. Two researchers independently conducted a literature review, data extraction, and risk of bias assessment. The quality of the included studies was assessed using the Cochrane Risk of Bias tool, and the meta-analysis was conducted using RevMan 5.3. The measurement outcomes include negative symptoms of schizophrenia, overall function, social skills, and social functioning.

Result

The analysis included a total of 15 studies involving 1,311 participants. All studies used the Positive and Negative Syndrome Scale (PANSS) as the assessment tool for measuring negative symptoms of schizophrenia. The results of the meta-analysis indicated that cognitive-behavioral therapy (CBT) significantly improved negative symptoms in patients with schizophrenia compared to treatment as usual (TAU) (MD = -1.65, 95% CI = -2.10 to -1.21, p < 0.001, I² = 41%). Short-term CBT significantly improved negative symptoms in schizophrenia (MD = -2.71, 95% CI = -3.18 to -1.61, p < 0.001, I² = 48%). Medium-term CBT also significantly improved negative symptoms (MD = -1.80, 95% CI = -2.76 to -0.84, p < 0.001, I² = 29%). Long-term CBT demonstrated significant improvement in negative symptoms as well (MD = -1.70, 95% CI = -2.54 to -0.85, p < 0.001, I² = 0%). CBT significantly improved overall function in patients with schizophrenia (SMD = 0.38, 95% CI = 0.13 to 0.63, p < 0.05, I² = 0%). Additionally, CBT significantly enhanced social skills (SMD = 0.87, 95% CI = 0.58 to 1.16, p < 0.001, I² = 0%) and social functioning (SMD = 0.19, 95% CI = 0.03 to 0.36, p < 0.05, I² = 24%) in these patients.

Conclusion

The results indicate that cognitive behavioral therapy has a significant effect on improving the negative symptoms of schizophrenia and is markedly superior to Treatment as Usual (TAU). Moreover, all three sub-treatment approaches (short-term, medium-term, and long-term) can sustainably and significantly improve negative symptoms of schizophrenia. Future research should focus on developing and evaluating cognitive therapies targeting negative symptoms, providing more reliable evidence and applying these research findings to clinical practice.

Introduction

Schizophrenia is a profound and enduring mental health condition that profoundly impacts an individual’s cognition, perception, emotional responses, and actions [1]. The reach of its effects is extensive, not only deeply affecting the lives of those who live with the disorder but also significantly impacting their families and support networks [2].

Negative symptoms are an important aspect of schizophrenia, contrasting with positive symptoms such as hallucinations and delusions. They include blunted affect, alogia, avolition, asociality, and anhedonia [3,4], which can significantly impair patients’ quality of life and hinder the rehabilitation process [5,6].When treating schizophrenia, in addition to focusing on controlling positive symptoms, appropriate management and intervention for negative symptoms are also necessary.

The condition can give rise to a range of challenges, including disruptions in social interactions, hindered professional capabilities, and a diminished overall quality of life. Schizophrenia interventions encompass a comprehensive array of strategies designed to mitigate symptoms, bolster functional capabilities, and elevate the overall quality of life for those affected. Antipsychotic medications are the primary intervention for the treatment of schizophrenia. However, current evidence indicates that the efficacy of antipsychotic medications in reducing the severity of negative symptoms is highly limited, and there is a lack of robust evidence for their effectiveness in treating primary and enduring negative symptoms [7–9]. This represents a core challenge in current research on the treatment of negative symptoms, while also highlighting the insufficient evidence supporting existing interventions. In the clinical treatment of schizophrenia, we are gradually exploring ways to reduce reliance on traditional antipsychotic medications [10], instead focusing on measures of cognitive behavioral therapy to improve the condition.

In the field of schizophrenia treatment, Cognitive Behavioral Therapy (CBT) has demonstrated multidimensional intervention characteristics and has been widely applied. As a structured and goal-oriented psychotherapy, CBT has garnered significant attention in the treatment of schizophrenia in recent years [11–13], aimed at improving patients’ cognitive functions, reducing symptoms, enhancing the quality of life, and promoting the recovery of social functioning. Previous review studies have often focused on the improved effects of cognitive behavioral therapy on the positive symptoms of schizophrenia [14,15]. However, as recent studies have pointed out [16], there is still a lack of comprehensive analyses specifically addressing the improvement of negative symptoms. Xu’s study [16] has provided important insights into the efficacy of CBT in alleviating negative symptoms. Building on this foundation, our study further expands the research in this area. Specifically, we have increased the number of included studies, clearly distinguished the short-, medium-, and long-term effects of CBT, limited the control group to treatment as usual (TAU), and introduced function as an important outcome measure. To gain a deeper understanding of the efficacy of cognitive-behavioral therapy (CBT) in treating negative symptoms of schizophrenia, systematic reviews and meta-analyses are essential. They not only fill the existing research gaps but also provide more comprehensive scientific evidence to inform clinical decision-making.

Based on the above, the following research hypotheses are proposed (1) Cognitive behavioral therapy has an improving effect on the negative symptoms of schizophrenia. (2) Cognitive behavioral therapy demonstrates a superior effect compared to treatment as usual (TAU) in the management of negative symptoms in schizophrenia.

Methods

The protocol of the original review was registered in PROSPERO (number CRD: 42024579784) and published. To examine the evidence base, this meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) Statement [17]. This study is based on a meta-analysis and systematic review of published papers; hence, there is no need for an ethical statement.

Search strategy

Literature was retrieved from 11 databases (CNKI, Wan fang Database, VIP Database, CBM Database, PubMed, EMBASE, Cochrane Library, Web of Science, APA PsycINFO, CINAHL, and MEDLINE), with the search period ranging from the inception date to 1 September 2024. The following MeSH subject headings and keywords were used: (schizophrenia OR psychosis) AND (cognitive therapy OR cognitive behavioral therapy) AND (randomized controlled trial). Reference lists of relevant reviews were also hand-searched for any further relevant studies. Please see attached for details (S1).

Inclusion and exclusion criteria

Follow the PICOS principle in the “Cochrane Handbook for Systematic Reviews of Interventions” to determine the inclusion of studies [18]. (1) Population: Include patients aged 14 and above who have been diagnosed with schizophrenia, with no gender restrictions. Exclude patients with a history of alcohol or drug dependence or intellectual disability. (2) Intervention: The experimental group received cognitive behavioral therapy, regardless of frequency and duration of intervention. (3) Comparison: The control group received treatment as usual (TAU), which included waiting for treatment, supportive counseling, routine care, mental health education, educational manuals, and other therapeutic interventions. (4) Outcome: Negative Symptoms of Schizophrenia (short-term treatment, medium-term treatment, long-term treatment), overall function, social skills, and social functioning. (5) Study design: Inclusion criteria: Only randomized controlled trials were included. Only studies that used the Positive and Negative Syndrome Scale (PANSS) for measurement were included. Only studies with treatment as usual (TAU) as the control group were included. Patients diagnosed with schizophrenia. Exclusion criteria: The study was a non-randomized controlled trial. Incorrect study population, data not reported for analyses.

Data extractions

Based on the requirements of the study, two searchers independently and in a double-blind manner extracted and entered various data, including: the first author of the literature, year of publication, sample size of the experimental and control groups, gender, age of the participants, content of the intervention, intervention plan (duration, frequency, and cycle), outcome indicators, and other relevant data. We calculate the effect size by comparing the differences between the means of two independent samples. If the standard deviations (SDs) are not available, we calculate them based on the standard errors (SEs), confidence intervals (CIs), t-values, or p-values. We also attempt to obtain missing data by emailing the authors. If the authors have not reported the data in the study but have provided charts with data, we use GetData Digitizer version 2.20 software to extract the necessary data from the charts. If both unadjusted and adjusted data are presented in the paper, we use the adjusted data for our research.

Quality assessment

According to the guidelines of evidence-based medicine research, the risk of bias assessment tool from the Cochrane systematic review [19] is adopted to evaluate the quality of included studies across seven indicators: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias. In the statistical process, the quality assessment is categorized as follows: six or more indicators are considered to be at low risk of bias; three to four indicators are at moderate risk of bias; and fewer than three indicators are at high risk of bias.

Statistical analyses

Review Manager (version 5.3.5; The Cochrane Collaboration, Copenhagen, Denmark) and the Stata software (version 14; Stata Corp, TX, USA) were used for all analyses. Researchers combine data by summing the mean values and calculating the standard deviations to derive the results after intervention. For continuous data, we calculate the mean difference (MD) and standardized mean difference (SMD) along with their corresponding 95% confidence intervals (95% CI), depending on whether the outcomes are measured by the same tool. Researchers will conduct statistical tests for heterogeneity (chi-square and I-square), with the I-square statistic used to assess the degree of heterogeneity. If I² ≤ 50% and P > 0.1, a fixed-effect model will be used to pool the data; conversely, if I² > 50% and P < 0.1, a random-effects model will be employed, along with sensitivity analyses and subgroup analyses to explore the sources of heterogeneity. We have defined the subgroups for short-term treatment (closest to 3 months), medium-term treatment (closest to 6 months), and long-term treatment (closest to 1 year). We have assessed the therapeutic effects of Review Manager (version 5.3.5; The Cochrane Collaboration, Copenhagen, Denmark) and the Stata software (version 14; Stata Corp, TX, USA) were used for all analyses. Researchers combine data by summing the mean values and calculating the standard deviations to derive the results after intervention. For continuous data, we calculate the mean difference (MD) and standardized mean difference (SMD) along with their corresponding 95% confidence intervals (95% CI), depending on whether the outcomes are measured by the same tool. Researchers will conduct statistical tests for heterogeneity (chi-square and I-square), with the I-square statistic used to assess the degree of heterogeneity. If I² ≤ 50% and P > 0.1, a fixed-effect model will be used to pool the data; conversely, if I² > 50% and P < 0.1, a random-effects model will be employed, along with sensitivity analyses and subgroup analyses to explore the sources of heterogeneity. We have defined the subgroups for short-term treatment (closest to 3 months), medium-term treatment (closest to 6 months), and long-term treatment (closest to 1 year). We have assessed the therapeutic effects of cognitive behavioral therapy on the negative symptoms of schizophrenia from the perspectives of short-term, medium-term, and long-term treatments. Finally, publication bias will be assessed using the Egger test [20], and a funnel plot will be constructed using Stata 14.0 software.

On the negative symptoms of schizophrenia from the perspectives of short-term, medium-term, and long-term treatments. Finally, publication bias will be assessed using the Egger test [20], and a funnel plot will be constructed using Stata 14.0 software.

Quality of evidence

The certainty of the evidence is assessed by two researchers based on the five aspects of the Grades of Recommendation Assessment, Development, and Evaluation method (GRADE) approach: risk of bias, consistency, indirectness, imprecision, and publication bias. The certainty of the evidence is categorized into four levels (high, moderate, low, and very low) [21].

Results

Description of included studies

We conducted a thorough search of the database and identified 14504 potentially eligible studies. After reviewing for duplicates, 8794 articles were left, and then 8756 articles were excluded by reading the title and abstract carefully. Following the inclusion and exclusion criteria, 15 articles with 1311 participants were selected for this systematic review and meta-analysis by reading the full text (Fig 1).

Characteristics of the included studies

The analysis included a total of 15 studies involving 1311 participants. The intervention was cognitive-behavioral therapy (CBT), and the sample population was predominantly male. The primary assessment scale used was the Positive and Negative Syndrome Scale (PANSS). Table 1 lists the basic characteristics of the included studies.

Table 1. Characteristics of the included studies.

Study	Country/area	Design	Sample size (IG/CG)	Male proportion (IG: CG)	Mean age (IG: CG)	Experimental group	Control group	Duration/assessment time	Outcome measures
Barrowclough 2001 [22]	UK	RCT	32 (17/15)	total:92% (IG:NR,CG:NR)	total:31.1(9.69) (IG:NR,CG:NR)	CBT	TAU	18 weeks	PANSS, GAF, SFS
Barrowclough 2006 [23]	UK	RCT	113 (57/56)	total:72.6% (IG:NR,CG:NR)	total:38.83(8.6) (IG:NR,CG:NR)	CBT	TAU	Total 6 months, 18 lessons, 2 hours each	PANSS, GAF, SFS
Morrison 2014 [24]	UK	RCT	74 (37/37)	IG:45.9 CG:59.4	IG:32.95(13.11) CG:29.68(11.95)	CBT + TAU	TAU	26 treatments per week for a total of 9 months	PANSS
Rector 2003 [25]	Canada	RCT	42 (24/18)	IG:62 CG:28	IG:37.5(8.3) CG:41.2(10.9)	CBT + TAU	TAU	A total of 20 weekly treatments were administered for a total of 6 months.	PANSS
Penn 2011 [26]	USA	RCT	46 (23/23)	IG:60.9 CG:60.9	IG:23.48(3.89) CG:20.96(2.14)	CBT	TAU	36 treatments per week for a total of 12 weeks	PANSS, GAF,SSPA
Gumley 2003 [27]	UK	RCT	144 (72/72)	IG:75.0 CG:70.8	IG:35.8(9.6) CG:36.7(10.1)	CBT	TAU	Total 52 weeks, 2–3 times per week	PANSS
Müller 2020 [28]	German	RCT	25 (13/12)	IG:53.8 CG:58.3	IG:17.46(1.51) CG:17.08(1.38)	CBT + TAU	TAU	Total 9 months, 20 sessions	PANSS, GAF
Sönmez 2020 [29]	Norway	RCT	63 (32/31)	IG:53.1 CG:64.5	IG:28.6(19–51) CG:27.1(18–43)	CBT	TAU	Total 6 months, 26 treatments, 45–60 minutes per week	PANSS, GAF
Peters 2010 [30]	UK	RCT	74 (36/38)	IG:72.2 CG:52.6	IG:34(9.8) CG:39.6(10.2)	CBT	TAU	Total of 6 months, average of 16(8–28) treatments	PANSS
Tarrier 2004 [31]	UK	RCT	77 (37/40)	IG:65 CG:65	IG: 29.5 (19.7–41.3) CG: 25.9 (21.4–35.1)	CBT	TAU	A total of 3 months, with an average treatment duration of 8 hours per session	PANSS
Anthony 2018 [32]	UK	RCT	487 (242/245)	IG:73 CG:71	IG:42.2(10.7) CG:42.8(10.4)	CBT	TAU	Total 9 months, at least 1 session per week, 60 minutes each time	PANSS, PSP
Anthony(2) 2018 [33]	UK	RCT	50 (26/24)	IG:62 CG:54	IG:23.19(6.32) CG:23.21(4.97)	CBT	TAU	Total 6 months, at least 1 session per week, 60 minutes each time	PANSS
Jun Yan 2024 [34]	China	RCT	100 (50/50)	IG:100 CG:100	IG:60.42(3.26) CG:60.20(3.24)	CBT	TAU	Total 6 months, at least 2 sessions per week, 60 minutes each time	PANSS, SSFPI
Dandan Chen 2024 [35]	China	RCT	60 (30/30)	IG:56.7 CG:60	IG:35.84(6.78) CG:36.84(6.78)	CBT	TAU	Total 12 weeks, at least 3 sessions per week, 30–45 minutes each time	PANSS, SSC
Faxia Peng 2023 [36]	China	RCT	80 (40/40)	IG:NR CG:NR	IG: NR CG: NR	CBT	TAU	Total 3 months, at least 1 session per week, 30–45 minutes each time	PANSS

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Abbreviations: RCT = Randomized Controlled Trial; IG = Intervention Groups; CG = Control Group; NR = Not Reported; CBT = Cognitive Behavioral Therapy; TAU = Treatment as Usual; PANSS = Positive and Negative Symptom Scale; GAF = Global Assessment of Functioning; SFS = Social Functioning Scale; SSPA = Social Skills Performance Assessment; PSP = Personal and Social Performance Scale; SSFPI = Scale of Social Function of Psychosis Inpatients; SSC = Social Skills Checklist.

Risk of bias in the included studies

The quality of the included literature was assessed, with 9 articles classified as having a low risk of bias, 4 articles scoring 7 points, and the remaining 6 articles all classified as having a moderate risk of bias (Fig 2). A graph of the proportion of bias risk in the included studies is presented (Fig 3). Most of the included literature did not provide a detailed description of the randomization method, which affects the stability of the study.

Effect on PANSS-negative symptom

A total of 15 studies reported the effects of cognitive-behavioral therapy (CBT) on negative symptoms in schizophrenia. The experimental group included 661 participants, and the control group included 650 participants. The results showed that CBT significantly improved negative symptoms in schizophrenia and was superior to treatment as usual (TAU) (MD = -1.65, 95% CI = -2.10 to -1.21, p < 0.001, I² = 41%) (Fig 4). Four studies reported the effects of short-term CBT on negative symptoms in schizophrenia, and the results showed significant improvement in negative symptoms (MD = -2.71, 95% CI = -3.18 to -1.61, p < 0.001, I² = 48%) (Fig 5). Seven studies reported the effects of medium-term CBT on negative symptoms in schizophrenia, and the results showed significant improvement in negative symptoms (MD = -1.80, 95% CI = -2.76 to -0.84, p < 0.001, I² = 29%) (Fig 5). Eight studies reported the effects of long-term CBT on negative symptoms in schizophrenia, and the results showed significant improvement in negative symptoms (MD = -1.70, 95% CI = -2.54 to -0.85, p < 0.001, I² = 0%) (Fig 5). According to the GRADE assessment of evidence quality, the certainty of evidence for negative symptoms was rated as moderate quality, downgraded due to risk of bias (S2).

Effect on overall function

Five research studies have reported the impact of cognitive-behavioral therapy (CBT) on overall functioning in schizophrenia. The results show that CBT can significantly improve overall functioning in patients with schizophrenia and is superior to treatment as usual (TAU) (SMD = 0.38, 95% CI = 0.13 to 0.63, p < 0.05, I² = 0%) (Fig 6). According to the GRADE assessment of evidence quality, the certainty of evidence for overall functioning is rated as low quality, downgraded due to risk of bias and imprecision (S2).

Effect on social skills

Three research studies have reported the impact of cognitive-behavioral therapy (CBT) on the improvement of social skills in schizophrenia. The results show that CBT can significantly improve social skills in patients with schizophrenia and is superior to treatment as usual (TAU) (SMD = 0.87, 95% CI = 0.58 to 1.16, p < 0.001, I² = 0%) (Fig 7).According to the GRADE assessment of evidence quality, the certainty of evidence for overall functioning is rated as low quality, downgraded due to risk of bias and imprecision (S2).

Effect on social functioning

Three studies have reported the impact of cognitive-behavioral therapy (CBT) on social functioning in schizophrenia. The results show that CBT can significantly improve social functioning in patients with schizophrenia and is superior to treatment as usual (TAU) (SMD = 0.19, 95% CI = 0.03 to 0.36, p < 0.05, I² = 24%) (Fig 8). According to the GRADE assessment of evidence quality, the certainty of evidence for social functioning is rated as low quality, downgraded due to risk of bias and imprecision (S2).

Publication bias

Due to the inclusion of more than 10 studies in this research (n = 15), a publication bias test was conducted to assess the impact of cognitive therapy on improving negative symptoms [37]. The funnel plot displayed symmetry [20], indicating that the results of this study are not influenced by publication bias (S3).

Discussion

Schizophrenia is a complex and chronic mental disorder characterized by symptoms that can be broadly categorized into positive and negative symptoms [38]. Unlike the more easily identifiable positive symptoms such as hallucinations and delusions, negative symptoms manifest as blunted affect, alogia, avolition, asociality, and anhedonia [3,4]. These symptoms are often more insidious but have a profound impact on the patient’s social functioning and quality of life, and can be even more challenging to treat than positive symptoms [39]. However, current evidence suggests that antipsychotic medications have limited efficacy in reducing the severity of negative symptoms, and there is a lack of robust evidence supporting their effectiveness in treating primary and persistent negative symptoms [7–9]. This represents a core challenge in the current research on the treatment of negative symptoms and highlights the insufficient evidence supporting existing interventions. With the evolving trends in contemporary healthcare, cognitive behavioral therapy has gained increasing attention due to its safety, efficacy, minimal side effects, and high patient acceptance, and is being increasingly applied in the clinical treatment of various mental disorders [40]. Therefore, in this meta-analysis, we provide a comprehensive review of the application and efficacy of cognitive behavioral therapy in the treatment of negative symptoms in schizophrenia.

The findings of this systematic review suggest that CBT is associated with reductions in total PANSS scores, which includes improvements across positive, negative, and general psychopathology domains. Notably, the observed improvement in negative symptoms raises an important question: whether these changes reflect a direct effect on primary negative symptoms or are secondary to improvements in other symptom domains, such as positive symptoms or general functioning. This distinction is critical for understanding the mechanisms underlying the therapeutic effects of CBT in schizophrenia.

The reduction in negative symptoms observed in this review may, at least in part, be attributed to improvements in secondary negative symptoms. Secondary negative symptoms are often conceptualized as a consequence of other factors, such as the burden of positive symptoms, medication side effects, or social disengagement due to impaired functioning [3]. For instance, alleviation of positive symptoms through CBT may reduce emotional withdrawal or avolition by diminishing the distress and preoccupation associated with hallucinations or delusions [41,42]. However, it is also possible that CBT exerts a direct effect on primary negative symptoms. Primary negative symptoms are thought to arise from the core pathophysiology of schizophrenia, including deficits in neural circuits involved in motivation, reward processing, and emotional expression [43]. CBT interventions that focus on enhancing goal-directed behavior, improving emotional regulation, and challenging defeatist beliefs may directly target motivational and emotional impairments characteristic of primary negative symptoms [44]. For example, by addressing cognitive distortions and promoting adaptive coping strategies, CBT may enhance neural substrates underlying motivation and emotional processing.

This interpretation aligns with previous research suggesting that improvements in negative symptoms are often mediated by changes in other domains. Future research should aim to disentangle the direct and indirect effects of CBT on primary and secondary negative symptoms, using more specific assessment tools and study designs.

The current review cannot definitively disentangle the relative contributions of direct and indirect effects on negative symptoms. However, the observed reductions in total PANSS scores suggest that improvements in negative symptoms are likely intertwined with broader clinical and functional gains. Future studies should employ more nuanced assessments of negative symptoms, such as the use of scales that differentiate between primary and secondary negative symptoms (e.g., the Clinical Assessment Interview for Negative Symptoms [CAINS] or the Brief Negative Symptom Scale [BNSS]). Additionally, mechanistic studies using neuroimaging or biomarkers could help clarify whether CBT directly modulates the neural circuits implicated in primary negative symptoms or whether its effects are mediated by changes in other symptom domains.

In conclusion, while the findings of this review support the efficacy of CBT in reducing negative symptoms, the extent to which these improvements reflect direct effects on primary negative symptoms versus secondary effects remains unclear. This distinction has important implications for optimizing therapeutic interventions and tailoring treatments to the specific needs of individuals with schizophrenia. Future research should aim to elucidate the mechanisms underlying these improvements to inform the development of more targeted and effective interventions.

The findings of this review highlight the potential of CBT in addressing negative symptoms in schizophrenia. However, the complexity and heterogeneity of these symptoms underscore the need for further research and innovation in both assessment and treatment. Future studies should prioritize several key areas to advance our understanding and management of negative symptoms.

First, there is a critical need for more precise and nuanced assessment tools that can differentiate between primary and secondary negative symptoms. Current scales, such as the Positive and Negative Syndrome Scale (PANSS), often conflate these dimensions, limiting our ability to disentangle their underlying mechanisms [3]. The development and validation of specialized instruments, such as the Clinical Assessment Interview for Negative Symptoms (CAINS) and the Brief Negative Symptom Scale (BNSS), represent important steps forward [45,46]. These tools should be widely adopted in clinical trials to ensure that interventions are accurately targeting the intended symptom domains.

Second, future research should focus on developing and implementing personalized intervention strategies tailored to the individual needs of patients with schizophrenia. Given the heterogeneity of negative symptoms and their varying impact on functioning, a “one-size-fits-all” approach is unlikely to be effective [47]. Personalized interventions could involve the use of predictive biomarkers, clinical profiles, and patient preferences to design treatment plans that optimize outcomes. For example, patients with prominent motivational deficits might benefit more from behavioral activation therapies, while those with severe social withdrawal might respond better to social skills training or group-based interventions [48]. Advances in digital health technologies, such as mobile apps and wearable devices, could further support personalized care by providing real-time monitoring and adaptive interventions based on individual progress [49].

Third, there is a need to expand the range of targeted interventions for negative symptoms. Although CBT has shown promise in addressing these symptoms, additional approaches should be explored to address their multifaceted nature. For instance, novel psychosocial interventions, such as acceptance and commitment therapy (ACT) or mindfulness-based therapies, could help patients manage emotional blunting and improve psychological flexibility [50]. Additionally, physical exercise programs and nutritional interventions have shown potential in improving motivation and overall well-being in individuals with schizophrenia [51,52]. Combining these approaches with traditional therapies like CBT could create a more comprehensive treatment framework that addresses both the psychological and physiological aspects of negative symptoms.

Finally, future research should emphasize the importance of long-term studies to evaluate the sustained effects of interventions on negative symptoms and functional outcomes. Longitudinal designs could help identify predictors of treatment response and inform the development of maintenance strategies to prevent symptom relapse [53]. Furthermore, studies should explore the role of environmental and social factors, such as family support and community integration, in enhancing the effectiveness of interventions [54]. By addressing these factors, researchers and clinicians can develop more holistic approaches that not only reduce negative symptoms but also improve overall quality of life for individuals with schizophrenia.

In conclusion, while significant progress has been made in understanding and treating negative symptoms in schizophrenia, much work remains to be done. Future research should focus on refining assessment tools, developing personalized interventions, expanding the range of targeted therapies, and evaluating long-term outcomes. By leveraging advances in technology and adopting a patient-centered approach, we can move closer to delivering more effective and tailored interventions that address the full spectrum of this debilitating condition.

Challenges and limitations

This meta-analysis has several limitations that should be considered when interpreting the results. First, the included studies employed a variety of CBT protocols, with differences in duration, intensity, and content. Second, many of the studies had small sample sizes, which may limit the reliability of the findings and reduce the ability to detect significant effects. Larger, well-powered studies are needed to confirm these results. Third, most studies relied on the PANSS to assess negative symptoms, which does not distinguish between primary and secondary negative symptoms. As a result, it remains unclear whether the observed improvements are due to direct effects on primary symptoms or indirect effects mediated by changes in other domains, such as positive symptoms or functional capacity. Fourth, current interventions often adopt a standardized approach, which may not adequately address the individual needs of patients. Finally, the generalizability of the findings may be limited, as many studies included specific patient groups (e.g., stable outpatients). More diverse and representative samples are needed to ensure that the results apply to a broader population of individuals with schizophrenia

Conclusions

The results of this study indicate that Cognitive Behavioral Therapy (CBT) is significantly effective in improving negative symptoms in patients with schizophrenia and is markedly superior to Treatment as Usual (TAU). Moreover, CBT administered in the short term, medium term, and long term can all consistently and significantly improve negative symptoms. Additionally, CBT can also significantly enhance overall functioning, social skills, and social functioning in patients with schizophrenia. Future research should focus on developing and evaluating CBT specifically targeting negative symptoms, providing further reliable evidence and promoting the application of these research findings in clinical practice.

Supporting information

S1. Search strategy.

(DOCX)

pone.0324685.s001.docx^{(26.5KB, docx)}

S2. GRADE assessment.

(DOCX)

pone.0324685.s002.docx^{(17.5KB, docx)}

S3. Publication bias assessment: funnel plot.

(PDF)

pone.0324685.s003.pdf^{(40.6KB, pdf)}

S4. PRISMA 2020 checklist.

(PDF)

pone.0324685.s004.pdf^{(97.4KB, pdf)}

S5. Detailed data.

(XLSX)

pone.0324685.s005.xlsx^{(13.3KB, xlsx)}

S6. Data extraction information.

(XLSX)

pone.0324685.s006.xlsx^{(32.5KB, xlsx)}

S7. List of excluded studies.

(XLSX)

pone.0324685.s007.xlsx^{(1.1MB, xlsx)}

S8. Methodological quality of the trials.

(DOCX)

pone.0324685.s008.docx^{(21.2KB, docx)}

Data Availability

All relevant data are within the paper and its Supporting Information files.

Funding Statement

The author(s) received no specific funding for this work.

References

1.McGurk SR, Mueser KT. Cognitive functioning, symptoms, and work in supported employment: a review and heuristic model. Schizophr Res. 2004;70(2–3):147–73. doi: 10.1016/j.schres.2004.01.009 [DOI] [PubMed] [Google Scholar]
2.Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet (London, England). 2016;388(10053):1603–58. Epub 2016/10/14. doi: 10.1016/s0140-6736(16)31460-x PubMed ; PubMed Central PMCID: PMCPMC5388857. [DOI] [PMC free article] [PubMed] [Google Scholar]
3.Kirkpatrick B, Fenton WS, Carpenter WT Jr, Marder SR. The NIMH-MATRICS consensus statement on negative symptoms. Schizophr Bull. 2006;32(2):214–9. doi: 10.1093/schbul/sbj053 [DOI] [PMC free article] [PubMed] [Google Scholar]
4.Strauss GP, Ahmed AO, Young JW, Kirkpatrick B. Reconsidering the latent structure of negative symptoms in schizophrenia: a review of evidence supporting the 5 consensus domains. Schizophr Bull. 2019;45(4):725–9. doi: 10.1093/schbul/sby169 [DOI] [PMC free article] [PubMed] [Google Scholar]
5.García-Fernández L, Romero-Ferreiro V, Sánchez-Pastor L, Dompablo M, Martínez-Gras I, Espejo-Saavedra JM, et al. Impact of negative symptoms on functioning and quality of life in first psychotic episodes of schizophrenia. J Clin Med. 2022;11(4):983. doi: 10.3390/jcm11040983 [DOI] [PMC free article] [PubMed] [Google Scholar]
6.Novick D, Montgomery W, Cheng Y, Moneta V, Haro J. Impact of negative symptoms on quality of life in patients with schizophrenia. Value Health. 2015;18(7):A836–7. [Google Scholar]
7.Fusar-Poli P, Papanastasiou E, Stahl D, Rocchetti M, Carpenter W, Shergill S, et al. Treatments of negative symptoms in schizophrenia: meta-analysis of 168 randomized placebo-controlled trials. Schizophr Bull. 2015;41(4):892–9. doi: 10.1093/schbul/sbu170 [DOI] [PMC free article] [PubMed] [Google Scholar]
8.Krause M, Zhu Y, Huhn M, Schneider-Thoma J, Bighelli I, Nikolakopoulou A, et al. Antipsychotic drugs for patients with schizophrenia and predominant or prominent negative symptoms: a systematic review and meta-analysis. Eur Arch Psychiatry Clin Neurosci. 2018;268(7):625–39. doi: 10.1007/s00406-018-0869-3 [DOI] [PubMed] [Google Scholar]
9.Remington G, Foussias G, Fervaha G, Agid O, Takeuchi H, Lee J, et al. Treating negative symptoms in schizophrenia: an update. Curr Treat Options Psychiatry. 2016;3:133–50. doi: 10.1007/s40501-016-0075-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
10.Japanese Society of Neuropsychopharmacology. Guideline for pharmacological therapy of schizophrenia. Neuropsychopharmacol Rep. 2021;41(3):266–324. Epub 2021/08/15. doi: 10.1002/npr2.12193 PubMed ; PubMed Central PMCID: PMCPMC8411321 [DOI] [PMC free article] [PubMed] [Google Scholar]
11.Dixon LB, Dickerson F, Bellack AS, Bennett M, Dickinson D, Goldberg RW, et al. The 2009 schizophrenia PORT psychosocial treatment recommendations and summary statements. Schizophr Bull. 2010;36(1):48–70. doi: 10.1093/schbul/sbp115 [DOI] [PMC free article] [PubMed] [Google Scholar]
12.Lysaker PH, Lancaster RS, Nees MA, Davis LW. Attributional style and symptoms as predictors of social function in schizophrenia. J Rehabil Res Dev. 2004;41(2):225–32. doi: 10.1682/jrrd.2004.02.0225 [DOI] [PubMed] [Google Scholar]
13.Wykes T, Steel C, Everitt B, Tarrier N. Cognitive behavior therapy for schizophrenia: effect sizes, clinical models, and methodological rigor. Schizophr Bull. 2008;34(3):523–37. doi: 10.1093/schbul/sbm114 [DOI] [PMC free article] [PubMed] [Google Scholar]
14.Bighelli I, Huhn M, Schneider-Thoma J, Krause M, Reitmeir C, Wallis S, et al. Response rates in patients with schizophrenia and positive symptoms receiving cognitive behavioural therapy: a systematic review and single-group meta-analysis. BMC Psychiatry. 2018;18(1):380. doi: 10.1186/s12888-018-1964-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
15.Bighelli I, Salanti G, Reitmeir C, Wallis S, Barbui C, Furukawa TA, et al. Psychological interventions for positive symptoms in schizophrenia: protocol for a network meta-analysis of randomised controlled trials. BMJ Open. 2018;8(3):e019280. doi: 10.1136/bmjopen-2017-019280 [DOI] [PMC free article] [PubMed] [Google Scholar]
16.Xu F, Xu S. Cognitive-behavioral therapy for negative symptoms of schizophrenia: a systematic review and meta-analysis. Medicine (Baltimore). 2024;103(36):e39572. doi: 10.1097/MD.0000000000039572 [DOI] [PMC free article] [PubMed] [Google Scholar]
17.Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264–9, W64. doi: 10.7326/0003-4819-151-4-200908180-00135 [DOI] [PubMed] [Google Scholar]
18.O’Connor D, Green S, Higgins JP. Defining the review question and developing criteria for including studies. In Cochrane Handbook for Systematic Reviews of Interventions. 2008. pp. 81–94. [Google Scholar]
19.Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. doi: 10.1136/bmj.d5928 [DOI] [PMC free article] [PubMed] [Google Scholar]
20.Egger M, Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34. [DOI] [PMC free article] [PubMed] [Google Scholar]
21.Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schünemann HJ, et al. What is “quality of evidence” and why is it important to clinicians?. BMJ. 2008;336(7651):995–8. doi: 10.1136/bmj.39490.551019.BE [DOI] [PMC free article] [PubMed] [Google Scholar]
22.Chandler J, Cumpston M, Li T, Page MJ, Welch VJHW. Cochrane Handbook for Systematic Reviews of Interventions. 2019. [Google Scholar]
23.Barrowclough C, Haddock G, Lobban F, Jones S, Siddle R, Roberts C, et al. Group cognitive-behavioural therapy for schizophrenia. Randomised controlled trial. Br J Psychiatry. 2006;189:527–32. doi: 10.1192/bjp.bp.106.021386 [DOI] [PubMed] [Google Scholar]
24.Morrison AP, Turkington D, Pyle M, Spencer H, Brabban A, Dunn G, et al. Cognitive therapy for people with schizophrenia spectrum disorders not taking antipsychotic medication: a randomised controlled trial. Schizophrenia Res. 2014;153:S75. doi: 10.1016/s0920-9964(14)70242-7 [DOI] [PubMed] [Google Scholar]
25.Rector NA, Seeman MV, Segal ZV. Cognitive therapy for schizophrenia: a preliminary randomized controlled trial. Schizophr Res. 2003;63(1–2):1–11. doi: 10.1016/s0920-9964(02)00308-0 [DOI] [PubMed] [Google Scholar]
26.Penn DL, Uzenoff SR, Perkins D, Mueser KT, Hamer R, Waldheter E, et al. A pilot investigation of the Graduated Recovery Intervention Program (GRIP) for first episode psychosis. Schizophr Res. 2011;125(2–3):247–56. doi: 10.1016/j.schres.2010.08.006 [DOI] [PMC free article] [PubMed] [Google Scholar]
27.Gumley A, O’Grady M, McNay L, Reilly J, Power K, Norrie J. Early intervention for relapse in schizophrenia: results of a 12-month randomized controlled trial of cognitive behavioural therapy. Psychol Med. 2003;33(3):419–31. doi: 10.1017/s0033291703007323 [DOI] [PubMed] [Google Scholar]
28.Müller H, Kommescher M, Güttgemanns J, Wessels H, Walger P, Lehmkuhl G, et al. Cognitive behavioral therapy in adolescents with early-onset psychosis: a randomized controlled pilot study. Eur Child Adolesc Psychiatry. 2020;29(7):1011–22. doi: 10.1007/s00787-019-01415-4 [DOI] [PubMed] [Google Scholar]
29.Sönmez N, Romm KL, Østefjells T, Grande M, Jensen LH, Hummelen B, et al. Cognitive behavior therapy in early psychosis with a focus on depression and low self-esteem: a randomized controlled trial. Compr Psychiatry. 2020;97:152157. doi: 10.1016/j.comppsych.2019.152157 [DOI] [PubMed] [Google Scholar]
30.Peters E, Landau S, McCrone P, Cooke M, Fisher P, Steel C, et al. A randomised controlled trial of cognitive behaviour therapy for psychosis in a routine clinical service. Acta Psychiatr Scand. 2010;122(4):302–18. doi: 10.1111/j.1600-0447.2010.01572.x [DOI] [PubMed] [Google Scholar]
31.Tarrier N, Lewis S, Haddock G, Bentall R, Drake R, Kinderman P, et al. Cognitive-behavioural therapy in first-episode and early schizophrenia. 18-month follow-up of a randomised controlled trial. Br J Psychiatry. 2004;184:231–9. doi: 10.1192/bjp.184.3.231 [DOI] [PubMed] [Google Scholar]
32.Morrison AP, Pyle M, Gumley A, Schwannauer M, Turkington D, MacLennan G, et al. Cognitive behavioural therapy in clozapine-resistant schizophrenia (FOCUS): an assessor-blinded, randomised controlled trial. Lancet Psychiatry. 2018;5(8):633–43. doi: 10.1016/S2215-0366(18)30184-6 [DOI] [PMC free article] [PubMed] [Google Scholar]
33.Morrison AP, Law H, Carter L, Sellers R, Emsley R, Pyle M, et al. Antipsychotic drugs versus cognitive behavioural therapy versus a combination of both in people with psychosis: a randomised controlled pilot and feasibility study. Lancet Psychiatry. 2018;5(5):411–23. doi: 10.1016/S2215-0366(18)30096-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
34.Yan J, Liu F, Lu X. Analyzing the effects of cognitive behavioral therapy in schizophrenic patients with depressive symptoms. Psychol Month. 2024;19(10):116–8. doi: 10.19738/j.cnki.psy.2024.10.031 [DOI] [Google Scholar]
35.Chen D, Sun H. Effects of psychological care based on cognitive behavioral therapy on patients with schizophrenia. China Typical Cases Book. 2024;18(04):126–9. [Google Scholar]
36.Peng F, Zhong H, Tu W. The value of cognitive-behavioral therapy in improving adverse emotions in schizophrenia patients. Psychol Monthly. 2023;18(19):100–2. doi: 10.19738/j.cnki.psy.2023.19.029 [DOI] [Google Scholar]
37.Barrowclough C, Haddock G, Tarrier N, Lewis SW, Moring J, O’Brien R, et al. Randomized controlled trial of motivational interviewing, cognitive behavior therapy, and family intervention for patients with comorbid schizophrenia and substance use disorders. Am J Psychiatry. 2001;158(10):1706–13. doi: 10.1176/appi.ajp.158.10.1706 [DOI] [PubMed] [Google Scholar]
38.Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13(2):261–76. doi: 10.1093/schbul/13.2.261 [DOI] [PubMed] [Google Scholar]
39.Govil P, Kantrowitz JT. Negative symptoms in schizophrenia: an update on research assessment and the current and upcoming treatment landscape. CNS Drugs. 2025;39(3):243–62. doi: 10.1007/s40263-024-01151-7 [DOI] [PubMed] [Google Scholar]
40.Hassan Kariri HD, Almubaddel A. From theory to practice: revealing the real-world impact of cognitive behavioral therapy in psychological disorders through a dynamic bibliometric and survey study. Heliyon. 2024;10(18):e37763. doi: 10.1016/j.heliyon.2024.e37763 [DOI] [PMC free article] [PubMed] [Google Scholar]
41.Ventura J, Hellemann GS, Thames AD, Koellner V, Nuechterlein KH. Symptoms as mediators of the relationship between neurocognition and functional outcome in schizophrenia: a meta-analysis. Schizophr Res. 2009;113(2–3):189–99. doi: 10.1016/j.schres.2009.03.035 [DOI] [PMC free article] [PubMed] [Google Scholar]
42.Bowie CR, Gupta M, Holshausen K. Disconnected and underproductive speech in schizophrenia: unique relationships across multiple indicators of social functioning. Schizophr Res. 2011;131(1–3):152–6. doi: 10.1016/j.schres.2011.04.014 [DOI] [PubMed] [Google Scholar]
43.Millan MJ, Fone K, Steckler T, Horan WP. Negative symptoms of schizophrenia: clinical characteristics, pathophysiological substrates, experimental models and prospects for improved treatment. Eur Neuropsychopharmacol. 2014;24(5):645–92. doi: 10.1016/j.euroneuro.2014.03.008 [DOI] [PubMed] [Google Scholar]
44.Grant PM, Beck AT. Defeatist beliefs as a mediator of cognitive impairment, negative symptoms, and functioning in schizophrenia. Schizophr Bull. 2009;35(4):798–806. doi: 10.1093/schbul/sbn008 [DOI] [PMC free article] [PubMed] [Google Scholar]
45.Kring AM, Gur RE, Blanchard JJ, Horan WP, Reise SP. The Clinical Assessment Interview for Negative Symptoms (CAINS): final development and validation. Am J Psychiatry. 2013;170(2):165–72. doi: 10.1176/appi.ajp.2012.12010109 [DOI] [PMC free article] [PubMed] [Google Scholar]
46.Strauss GP, Keller WR, Buchanan RW, Gold JM, Fischer BA, McMahon RP, et al. Next-generation negative symptom assessment for clinical trials: validation of the Brief Negative Symptom Scale. Schizophr Res. 2012;142(1–3):88–92. doi: 10.1016/j.schres.2012.10.012 [DOI] [PMC free article] [PubMed] [Google Scholar]
47.Fervaha G, Foussias G, Agid O, Remington G. Motivational and neurocognitive deficits are central to the prediction of longitudinal functional outcome in schizophrenia. Acta Psychiatr Scand. 2014;130(4):290–9. doi: 10.1111/acps.12289 [DOI] [PubMed] [Google Scholar]
48.Granholm E, Holden J, Link PC, McQuaid JR. Randomized clinical trial of cognitive behavioral social skills training for schizophrenia: improvement in functioning and experiential negative symptoms. J Consult Clin Psychol. 2014;82(6):1173–85. doi: 10.1037/a0037098 [DOI] [PMC free article] [PubMed] [Google Scholar]
49.Ben-Zeev D, Brenner CJ, Begale M, Duffecy J, Mohr DC, Mueser KT. Feasibility, acceptability, and preliminary efficacy of a smartphone intervention for schizophrenia. Schizophr Bull. 2014;40(6):1244–53. doi: 10.1093/schbul/sbu033 [DOI] [PMC free article] [PubMed] [Google Scholar]
50.Khoury B, Lecomte T, Gaudiano BA, Paquin K. Mindfulness interventions for psychosis: a meta-analysis. Schizophr Res. 2013;150(1):176–84. doi: 10.1016/j.schres.2013.07.055 [DOI] [PubMed] [Google Scholar]
51.Firth J, Cotter J, Elliott R, French P, Yung AR. A systematic review and meta-analysis of exercise interventions in schizophrenia patients. Psychol Med. 2015;45(7):1343–61. doi: 10.1017/S0033291714003110 [DOI] [PubMed] [Google Scholar]
52.Vancampfort D, Firth J, Schuch FB, Rosenbaum S, Mugisha J, Hallgren M, et al. Sedentary behavior and physical activity levels in people with schizophrenia, bipolar disorder and major depressive disorder: a global systematic review and meta-analysis. World Psychiatry. 2017;16(3):308–15. doi: 10.1002/wps.20458 [DOI] [PMC free article] [PubMed] [Google Scholar]
53.Ventura J, Subotnik KL, Gitlin MJ, Gretchen-Doorly D, Ered A, Villa KF, et al. Negative symptoms and functioning during the first year after a recent onset of schizophrenia and 8 years later. Schizophr Res. 2015;161(2–3):407–13. doi: 10.1016/j.schres.2014.10.043 [DOI] [PMC free article] [PubMed] [Google Scholar]
54.Jeste DV, Wolkowitz OM, Palmer BW. Divergent trajectories of physical, cognitive, and psychosocial aging in schizophrenia. Schizophr Bull. 2011;37(3):451–5. doi: 10.1093/schbul/sbr026 [DOI] [PMC free article] [PubMed] [Google Scholar]

PLoS One. 2025 May 20;20(5):e0324685. doi: 10.1371/journal.pone.0324685.r001

Author response to Decision Letter 0

3 Sep 2024

PLoS One. doi: 10.1371/journal.pone.0324685.r002

Decision Letter 0

Carlos Thomaz

22 Feb 2025

PONE-D-24-37272Cognitive Therapy for the Improvement of Negative Symptoms in Schizophrenia: A Systematic Review and Meta-Analysis of Randomized Controlled TrialsPLOS ONE

Dear Dr. Hong,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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==============================

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Reviewer #2: Partly

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5. Review Comments to the Author

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Reviewer #1: Thank you for the opportunity to review this paper.

I will suggest changing the language in conclusion section of abstract where the line “no significant differences were observed in short term,….” Appears to indicate there was no improved from cognitive treatment and should be changed to clarify there were no differences among the 3 subsets of treatment with respect to improvement of negative symptoms.

I think it would be helpful to have a conclusion and discussion section about the future, limitations as well as what else would you have liked to know at the end of the paper.

Otherwise, it is well designed study.

Reviewer #2: This is a systematic review and meta-analysis of randomized controlled trials investigating the effect of “cognitive therapies” on the symptoms of schizophrenia. The authors report a significant reduction in symptoms across multiple domains when compared to treatment as usual. Demonstrating the therapeutic effect of psychosocial interventions in schizophrenia is important, not only because they are effective in the treatment of various symptom domains, but also because they are not associated with the side effect burden of antipsychotic medications. he evidence is limited, as the authors put it, by the lack of targeted interventions and the absence of long-term studies, which are strongly needed.

I believe the current manuscript must undergo the following major revisions in order to be accepted for publication.

Major Points:

1. Although the title specifies “negative symptoms” as the outcome under investigation, the results also include positive symptoms, depressive symptoms, and functioning. I suggest that the authors address this issue by maintaining their focus solely on negative symptoms and functioning. This is because the effect of the interventions under investigation on positive symptoms has been reported elsewhere and is not the focus of this project, unless the authors intend to explore the relationship between reductions in positive symptoms and negative symptoms. In that case, the authors should demonstrate that the reduction in negative symptoms is strongly correlated with positive symptom reduction. This point is related to subsequent comments (No. 4 and 5).

2. A recently published systematic review and meta-analysis has investigated the response to cognitive behavioral therapy (CBT) for negative symptoms in patients with schizophrenia:

o Xu F, Xu S. Cognitive-behavioral therapy for negative symptoms of schizophrenia: A systematic review and meta-analysis. Medicine (Baltimore). 2024;103(36):e39572. doi:10.1097/MD.0000000000039572

That study restricted its search to CBT and included nonrandomized trials, whereas this systematic review included both CBT and cognitive remediation therapy (CRT). CRT has been investigated in an older systematic review and meta-analysis of randomized trials:

o Cella M, Preti A, Edwards C, Dow T, Wykes T. Cognitive remediation for negative symptoms of schizophrenia: A network meta-analysis. Clin Psychol Rev. 2017;52:43-51. doi:10.1016/j.cpr.2016.11.009

Both of these systematic reviews concluded that CBT and CRT are effective in reducing the burden of negative symptoms, notwithstanding the limitations of the included studies. However, the present systematic review grouped CBT and CRT together under one category of intervention and analyzed them jointly. I suggest dedicating a portion of the introduction to justifying this methodology. Specifically, why should a systematic review combine both CBT and CRT interventions when the techniques and primary focuses of these therapies are markedly different? Sharing the label “cognitive” does not warrant this combination. As the authors know, CBT targets automatic thoughts and biases that influence emotions and behavior. It involves the use of thought records and behavioral activation, aiming to reduce distress and disability associated with psychotic symptoms. CRT, on the other hand, is a training-based intervention that aims to improve cognitive processes such as attention, memory, executive function, social cognition, or metacognition to overcome cognitive deficits.

In addition to the previous point (No. 1), I believe this issue is a major concern in the current manuscript. The authors might want to either restrict their investigation solely to CRT (since a recently published meta-analysis already covers CBT) or provide a convincing rationale for grouping both CBT and CRT in a single meta-analysis.

Minor Points:

2. In the introduction, the authors state that negative symptoms encompass “psychomotor retardation and attention deficits.” This is not accurate. The latest conceptualization of the negative domain of schizophrenia encompasses five domains to better distinguish it from psychomotor symptoms and, especially, cognitive domains. Please refer to:

o Kirkpatrick B, Fenton WS, Carpenter WT Jr, Marder SR. The NIMH-MATRICS consensus statement on negative symptoms. Schizophr Bull. 2006;32(2):214-219. doi:10.1093/schbul/sbj053

o Strauss GP, Ahmed AO, Young JW, Kirkpatrick B. Reconsidering the Latent Structure of Negative Symptoms in Schizophrenia: A Review of Evidence Supporting the 5 Consensus Domains. Schizophr Bull. 2019;45(4):725-729. doi:10.1093/schbul/sby169

3. In the introduction, the authors explain that antipsychotic treatment is not “without potential side effects.” However, this is not why they have limited use in targeting negative symptoms. The actual reason is that antipsychotic medications have very limited efficacy in reducing negative symptom severity and lack established evidence for treating primary and enduring negative symptoms. This is precisely the problem facing therapeutic research for negative symptoms, that is, the lack of evidence for available interventions. Kindly refer to:

o Fusar-Poli P, Papanastasiou E, Stahl D, et al. Treatments of Negative Symptoms in Schizophrenia: Meta-Analysis of 168 Randomized Placebo-Controlled Trials [published correction appears in Schizophr Bull. 2022 May 7;48(3):721. doi: 10.1093/schbul/sbz071.]. Schizophr Bull. 2015;41(4):892-899. doi:10.1093/schbul/sbu170

o Krause M, Zhu Y, Huhn M, et al. Antipsychotic drugs for patients with schizophrenia and predominant or prominent negative symptoms: a systematic review and meta-analysis. Eur Arch Psychiatry Clin Neurosci. 2018;268(7):625-639. doi:10.1007/s00406-018-0869-3

o Remington G, Foussias G, Fervaha G, et al. Treating Negative Symptoms in Schizophrenia: an Update. Curr Treat Options Psychiatry. 2016;3:133-150. doi:10.1007/s40501-016-0075-8

4. In the results, the authors state that “The subgroup differences (P = 0.68).” I am not sure what this means. The subgroup analysis indicates that the reduction in negative symptoms is not consistently significant across time. In the abstract and discussion, the authors argue that this lack of effect across time is “due to the lack of cognitive therapy specifically targeting negative symptoms.” This is merely a conjecture. The results, in my view, suggest that CBT and CRT do not effectively improve primary and enduring negative symptoms, which are the main targets of negative symptom treatment in schizophrenia. This needs to be mentioned as a possible interpretation of the results. After all, secondary negative symptoms in schizophrenia also respond to antipsychotic medications. Please see:

o Correll CU, Schooler NR. Negative Symptoms in Schizophrenia: A Review and Clinical Guide for Recognition, Assessment, and Treatment. Neuropsychiatr Dis Treat. 2020;16:519-534. Published 2020 Feb 21. doi:10.2147/NDT.S225643

5. Also related to the previous point is the finding in this systematic review that total PANSS scores tend to decrease with CBT or CRT, which further raises the possibility that improvement in negative symptoms is linked to improvement in other domains—that is, the effect may primarily be on secondary negative symptoms. This issue needs to be discussed in detail. Unfortunately, due to this problem, the results do not advance the field of negative symptom therapeutics, except for the finding that there is no significant difference across short- and long-term comparisons, which, in my view, indicates a lack of benefit.

**********

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Reviewer #1: No

Reviewer #2: No

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Attachment

Submitted filename: Reviewer Report_20Feb2025.pdf

pone.0324685.s009.pdf^{(152KB, pdf)}

PLoS One. 2025 May 20;20(5):e0324685. doi: 10.1371/journal.pone.0324685.r003

Author response to Decision Letter 0

20 Mar 2025

Dear Editors and Reviewers:

Thank you for your letter and for the reviewers' comments concerning our manuscript entitled “Cognitive Therapy for the Improvement of Negative Symptoms in Schizophrenia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials” (Manuscript ID: PONE-D-24-37272). Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our research. We have studied comments carefully and have made correction which we hope to meet with approval. Revised portion are marked in red (with track and highlighted changes) in the paper. The main corrections in the paper and the responses to the reviewer’s comments are as follows. Please don’t hesitate to contact us in case there are any problems regarding this manuscript.

Reviewer #1

To begin with, we thank the reviewer for the effort and time put into the review of the manuscript, special thanks to you for your good comments and warm work earnestly.

In terms of content the following;

Comment 1:

Reply 1:

Thank you for your valuable feedback. We appreciate your suggestion to clarify the language in the conclusion section of the abstract. Based on your comment, we have revised the sentence to more accurately reflect that there were no significant differences among the three subsets of treatment (short-term, medium-term, and long-term) with respect to the improvement of negative symptoms, rather than implying a lack of improvement from cognitive therapy.

The revised text now reads:

"The results indicate that cognitive behavioral therapy has a significant effect on improving the negative symptoms of schizophrenia and is markedly superior to Treatment as Usual (TAU). Moreover, all three sub-treatment approaches (short-term, medium-term, and long-term) can sustainably and significantly improve negative symptoms of schizophrenia. Future research should focus on developing and evaluating cognitive therapies targeting negative symptoms, providing more reliable evidence and applying these research findings to clinical practice."

We believe this revision addresses your concern and improves the clarity of our findings. Thank you again for your thoughtful review.

Changes in the text: (Abstract: see marked manuscript Page 4, line 77-83)

Comment 2:

I think it would be helpful to have a conclusion and discussion section about the future, limitations as well as what else would you have liked to know at the end of the paper.

Reply 2: Thank you very much for your valuable suggestions. We have added discussions on future research directions, limitations of the study, and areas for further exploration in the discussion section. These additions aim to provide readers with a more comprehensive perspective and guide future research. We greatly appreciate your contribution to enhancing the quality of our paper!

Changes in the text: (Discussion: see marked manuscript Page 14-16 line 381-494)

Comment 3: Otherwise, it is well designed study.

Reply 3: Thank you very much for your valuable comments. We truly appreciate your recognition that “it is well designed study.” Your feedback is highly important to us, and we will continue to refine our work based on your suggestions.

Thank you again for taking the time to review our manuscript. We look forward to further opportunities for discussion and improvement.

Reviewer #2

To begin with, we thank the reviewer for the effort and time put into the review of the manuscript, special thanks to you for your good comments and warm work earnestly.

General comments:

This is a systematic review and meta-analysis of randomized controlled trials investigating the effect of “cognitive therapies” on the symptoms of schizophrenia. The authors report a significant reduction in symptoms across multiple domains when compared to treatment as usual. Demonstrating the therapeutic effect of psychosocial interventions in schizophrenia is important, not only because they are effective in the treatment of various symptom domains, but also because they are not associated with the side effect burden of antipsychotic medications. he evidence is limited, as the authors put it, by the lack of targeted interventions and the absence of long-term studies, which are strongly needed.

Reply:

Thank you for your thoughtful and constructive feedback on our systematic review and meta-analysis. We greatly appreciate your recognition of the importance of demonstrating the therapeutic effects of psychosocial interventions, such as cognitive therapies, in the treatment of schizophrenia. We agree that these interventions not only show efficacy across multiple symptom domains but also offer a valuable alternative to antipsychotic medications by avoiding their associated side effect burden.

We also acknowledge your observation regarding the limitations of the current evidence, particularly the lack of targeted interventions and the absence of long-term studies. These points are indeed critical, and we have highlighted them in the discussion section of our manuscript. We fully agree that future research should prioritize the development of targeted cognitive therapies for specific symptom domains, as well as conduct long-term studies to better understand the sustained effects of these interventions.

Thank you again for your insightful comments, which have helped us strengthen the interpretation of our findings and underscore the need for further research in this area.

Comment 1:

Although the title specifies “negative symptoms” as the outcome under investigation, the results also include positive symptoms, depressive symptoms, and functioning. I suggest that the authors address this issue by maintaining their focus solely on negative symptoms and functioning. This is because the effect of the interventions under investigation on positive symptoms has been reported elsewhere and is not the focus of this project, unless the authors intend to explore the relationship between reductions in positive symptoms and negative symptoms. In that case, the authors should demonstrate that the reduction in negative symptoms is strongly correlated with positive symptom reduction. This point is related to subsequent comments (No. 4 and 5).

Reply1:

Thank you for your careful review and valuable feedback on our manuscript. We fully understand your suggestions regarding the title and the focus of our research. Indeed, while our study initially aimed to investigate the effects of cognitive therapy on negative symptoms, we also included data on positive symptoms, depressive symptoms, and functional improvement during the analysis. We agree with your perspective that the impact on positive symptoms has been extensively reported in other studies and is not the primary focus of this project.

Following your advice, we will adjust the focus of the paper to concentrate on the outcomes related to negative symptoms of schizophrenia, ensuring better alignment with the title and research objectives. We greatly appreciate this important comment, which will help us better focus on the research theme and enhance the clarity of the manuscript. If you have any further suggestions regarding the revised content, we would be more than happy to make additional improvements.

Changes in the text: (Result: see marked manuscript Page 9-11, line 248-356)

Comment 2:

A recently published systematic review and meta-analysis has investigated the response to cognitive behavioral therapy (CBT) for negative symptoms in patients with schizophrenia:

o Xu F, Xu S. Cognitive-behavioral therapy for negative symptoms of schizophrenia: A systematic review and meta-analysis. Medicine (Baltimore). 2024;103(36):e39572. doi:10.1097/MD.0000000000039572

o Cella M, Preti A, Edwards C, Dow T, Wykes T. Cognitive remediation for negative symptoms of schizophrenia: A network meta-analysis. Clin Psychol Rev. 2017;52:43-51. doi:10.1016/j.cpr.2016.11.009

Reply2:

Thank you for your valuable comments and suggestions. In response to your concerns regarding our combination of Cognitive Behavioral Therapy (CBT) and Cognitive Remediation Therapy (CRT) in the analysis, we have carefully reconsidered our approach. We acknowledge that, although both therapies share the label “cognitive,” they have distinct techniques and primary focuses, as you correctly pointed out. CBT targets automatic thoughts and biases, using thought records and behavioral activation to reduce distress and disability associated with psychotic symptoms. In contrast, CRT is a training-based intervention aimed at improving cognitive processes such as attention, memory, executive function, social cognition, or metacognition to address cognitive deficits. Given these differences, we agree that combining these interventions in a single meta-analysis may not be appropriate. Therefore, we have revised our systematic review to focus exclusively on CBT for the treatment of negative symptoms in schizophrenia. To ensure the accuracy and relevance of our findings, we have re-conducted the database search, limiting the intervention to CBT only. Specifically, we have excluded Cognitive Remediation Therapy (CRT) and restricted our investigation to Cognitive Behavioral Therapy (CBT) alone. Additionally, we have limited our analysis to Randomized Controlled Trials (RCTs) and included only studies with a control group receiving TAU (Treatment as Usual). The revised manuscript now specifically examines the efficacy of CBT for negative symptoms in schizophrenia, providing a clearer evaluation of its impact compared to TAU.

Thank you again for your valuable feedback. We believe that these changes have enhanced the rigor and clarity of our study.

Changes in the text: (Title: Cognitive-behavioral therapy for the improvement of negative symptoms and functioning in schizophrenia: a systematic review and meta-analysis of randomized controlled trials. Result: Result: see marked manuscript Page 9-11, line 248-356.)

Comment 3:

In the introduction, the authors state that negative symptoms encompass “psychomotor retardation and attention deficits.” This is not accurate. The latest conceptualization of the negative domain of schizophrenia encompasses five domains to better distinguish it from psychomotor symptoms and, especially, cognitive domains. Please refer to:

o Kirkpatrick B, Fenton WS, Carpenter WT Jr, Marder SR. The NIMH-MATRICS consensus statement on negative symptoms. Schizophr Bull. 2006;32(2):214-219. doi:10.1093/schbul/sbj053

Reply3

We thank you for your careful review and valuable comments on our manuscript and the relevant literature provided. We fully agree with your comments and have made the corresponding revisions in the revised version.In the introduction section, we initially defined "negative symptoms" as "psychomotor retardation and attention deficits," which is indeed inaccurate. Based on the studies by Kirkpatrick et al. (2006) and Strauss et al. (2019), negative symptoms should encompass five core domains: blunted affect, alogia, avolition, asociality, and anhedonia. These domains aim to better distinguish negative symptoms from psychomotor symptoms and cognitive impairments.

In the revised manuscript, we have updated the introduction to clearly outline the five core domains of negative symptoms and have cited the aforementioned studies to support this perspective. We believe this revision will enhance the accuracy and scientific rigor of our work.

Once again, we sincerely appreciate your valuable input and look forward to your further feedback.

Changes in the text: They include blunted affect, alogia, avolition, asociality, and anhedonia, which can significantly impair patients' quality of life and hinder the rehabilitation process. (Introduction: see marked manuscript Page 5, line 95-97)

Comment 4:

In the introduction, the authors explain that antipsychotic treatment is not “without potential side effects.” However, this is not why they have limited use in targeting negative symptoms. The actual reason is that antipsychotic medications have very limited efficacy in reducing negative symptom severity and lack established evidence for treating primary and enduring negative symptoms. This is precisely the problem facing therapeutic research for negative symptoms, that is, the lack of evidence for available interventions. Kindly refer to:

o Remington G, Foussias G, Fervaha G, et al. Treating Negative Symptoms in Schizophrenia: an Update. Curr Treat Options Psychiatry. 2016;3:133-150. doi:10.1007/s40501-016-0075-8

Reply4:

Thank you for your insightful comments, the provided references, and for highlighting the need to clarify the limitations of antipsychotic medications in targeting negative symptoms. We agree that the limited efficacy of antipsychotics in reducing the severity of negative symptoms, particularly primary and enduring ones, is a critical issue. This indeed represents a significant challenge in schizophrenia treatment research. In response to your feedback, we have revised the introduction and incorporated citations to the relevant literature you provided to better reflect this point. We believe these changes provide a more accurate and comprehensive discussion of the challenges in treating negative symptoms and the limitations of current interventions. Once again, we sincerely appreciate your valuable input, which has significantly improved the quality of our manuscript.

Changes i

Attachment

Submitted filename: Response to Reviews.docx

pone.0324685.s011.docx^{(28.2KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0324685.r004

Decision Letter 1

Carlos Thomaz

22 Apr 2025

PONE-D-24-37272R1Cognitive-behavioral therapy for the improvement of negative symptoms and functioning in schizophrenia: a systematic review and meta-analysis of randomized controlled trialsPLOS ONE

Dear Dr. Hong,

==============================

Most of the points raised by both reviewers have been properly addressed in this new version of the paper submitted. However, there are still some points pending that would require careful attention and revision in order to address all remaining relevant issues already raised in previous revisions.==============================

Please submit your revised manuscript by Jun 06 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

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We look forward to receiving your revised manuscript.

Kind regards,

Carlos Eduardo Thomaz, Ph.D.

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Reviewer #1: Thank you for the opportunity to review this interesting paper and taking into account the previous comments and making changes accordingly.

Reviewer #2: I would like to thank the authors for their major revision of the manuscript and for considering my suggestion to restrict their systematic review and meta-analysis to CBT and focus on negative symptoms. This has significantly strengthened the manuscript and the conclusions drawn from their analysis. The authors have addressed all the issues raised in the previous round of review and now provide a more robust discussion that situates their results within the literature on negative symptom treatment in schizophrenia. I have a few comments I believe the authors should consider:

1) The authors continue to refer to “cognitive abilities” as constituting negative symptoms. This is incorrect, as I explained in detail in my previous review. I suggest this be revised in both the abstract and the introduction.

2) In the introduction, the authors state that “there is a notable absence of systematic reviews and meta-analyses that specifically address the improvement of negative symptoms.” This is also incorrect. As I pointed out in my earlier review, there is a recent systematic review and meta-analysis that addressed this same question:

Xu, Feifei, and Sheng Xu. “Cognitive-behavioral therapy for negative symptoms of schizophrenia: A systematic review and meta-analysis.” Medicine 103, no. 36 (2024): e39572. doi:10.1097/MD.0000000000039572.

I suggest the authors explicitly justify the contribution of their study in light of this prior work. One possible approach is to highlight the aspects uniquely addressed in the current review, such as the differentiation of short-, medium-, and long-term effects, as well as the inclusion of functioning as an outcome.

3) The authors report a mean difference in the abstract, but should clarify that this pertains to the PANSS Negative Symptom subscale.

Thank you again for the opportunity to re-review this valuable manuscript.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .

Reviewer #1: No

Reviewer #2: Yes: Mohammed A. Alarabi

**********

PLoS One. 2025 May 20;20(5):e0324685. doi: 10.1371/journal.pone.0324685.r005

Author response to Decision Letter 1

24 Apr 2025

Dear Editors and Reviewers:

Thank you for your letter and for the reviewers' comments concerning our manuscript entitled “Cognitive-behavioral therapy for the improvement of negative symptoms and functioning in schizophrenia: a systematic review and meta-analysis of randomized controlled trials” (Manuscript ID: PONE-D-24-37272R1). Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our research. We have studied comments carefully and have made correction which we hope to meet with approval. Revised portion are marked in red (with track and highlighted changes) in the paper. The main corrections in the paper and the responses to the reviewer’s comments are as follows. Please don’t hesitate to contact us in case there are any problems regarding this manuscript.

Reviewer #1

Comment 1:

Thank you for the opportunity to review this interesting paper and taking into account the previous comments and making changes accordingly.

Reply 1:

Thank you very much for your positive feedback and for acknowledging the changes we have made. Your constructive comments have been invaluable in enhancing the quality of our manuscript. We truly appreciate your time and effort in reviewing our work.

Reviewer #2

To begin with, we thank the reviewer for the effort and time put into the review of the manuscript, special thanks to you for your good comments and warm work earnestly.

General comments:

I would like to thank the authors for their major revision of the manuscript and for considering my suggestion to restrict their systematic review and meta-analysis to CBT and focus on negative symptoms. This has significantly strengthened the manuscript and the conclusions drawn from their analysis. The authors have addressed all the issues raised in the previous round of review and now provide a more robust discussion that situates their results within the literature on negative symptom treatment in schizophrenia. I have a few comments I believe the authors should consider:

Reply:

Thank you very much for your positive and constructive feedback on our revised manuscript. We are pleased that you found the changes we made to be significant improvements, particularly in focusing the systematic review and meta-analysis on CBT and negative symptoms. Your suggestion has indeed strengthened the manuscript and helped us draw more robust conclusions.

We have carefully considered your additional comments and have addressed them in the latest revision of our manuscript. We believe these changes further enhance the clarity and relevance of our discussion within the context of negative symptom treatment in schizophrenia.

Thank you once again for your valuable insights and for taking the time to review our work. We truly appreciate your support and guidance.

Comment 1:

The authors continue to refer to “cognitive abilities” as constituting negative symptoms. This is incorrect, as I explained in detail in my previous review. I suggest this be revised in both the abstract and the introduction.

Reply1:

Thank you for your continued attention to detail and for bringing this important point to our attention once again. We have carefully reviewed the sections of our manuscript where we previously referred to “cognitive abilities” as constituting negative symptoms and have made the necessary revisions to correct this inaccuracy.

We have updated both the abstract and the introduction to accurately reflect the distinction between cognitive abilities and negative symptoms, ensuring that our terminology is precise and consistent with the established definitions in the literature. We appreciate your guidance on this matter and believe that these changes have further improved the accuracy and clarity of our manuscript.

Thank you once again for your valuable feedback.

Changes in the text: Negative symptoms of schizophrenia are a range of deficits or losses in mental functioning associated with the disorder, including blunted affect, alogia, avolition, asociality, and anhedonia. (Abstract: see marked manuscript Page 1-2 line 23-35)

Comment 2:

In the introduction, the authors state that “there is a notable absence of systematic reviews and meta-analyses that specifically address the improvement of negative symptoms.” This is also incorrect. As I pointed out in my earlier review, there is a recent systematic review and meta-analysis that addressed this same question:

Reply2:

Thank you very much for your detailed and constructive feedback. We appreciate your patience and the effort you have put into helping us improve our manuscript.

We have carefully reviewed the introduction and have revised the statement to accurately reflect the existing literature. We now explicitly acknowledge the recent systematic review and meta-analysis by Xu and Xu (2024) and have provided a clear justification for the unique contributions of our study.

In our revised introduction, we have highlighted the specific aspects that differentiate our review from the prior work, such as the detailed differentiation of short-, medium-, and long-term effects, as well as the inclusion of functioning as an outcome. We believe these aspects provide valuable additional insights and contribute to the broader understanding of cognitive-behavioral therapy for negative symptoms in schizophrenia.

We have also added a citation to the Xu and Xu (2024) study to ensure proper acknowledgment of their work. We hope these revisions address your concerns and provide a clearer context for our study.

Thank you once again for bringing this important point to our attention and for providing the reference. Your feedback has been invaluable in enhancing the accuracy and relevance of our manuscript.

Changes in the text: (Introduction: see marked manuscript Page 6, line 148-159)

Comment 3:

The authors report a mean difference in the abstract, but should clarify that this pertains to the PANSS Negative Symptom subscale.

Reply3:

Thank you for your careful review and for pointing out the need for clarification in the abstract. We have revised the abstract to explicitly state that the reported mean difference pertains to the PANSS Negative Symptom subscale. This change ensures that our findings are clearly understood and accurately represented.

We appreciate your attention to detail and your suggestions for improving the clarity of our manuscript.

Changes in the text: The analysis included a total of 15 studies involving 1,311 participants. All studies used the Positive and Negative Syndrome Scale (PANSS) as the assessment tool for measuring negative symptoms of schizophrenia. (Abstract: see marked manuscript Page 4, line 68-70)

We sincerely appreciate the efforts of both the editors and reviewers for their valuable feedback and guidance throughout the process. Your expertise has been instrumental in improving our manuscript.

Best wishes,

Yu Hong

Guangzhou Huali College

Attachment

Submitted filename: Response_to_Reviews_auresp_2.docx

pone.0324685.s012.docx^{(18.8KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0324685.r006

Decision Letter 2

Carlos Thomaz

29 Apr 2025

Cognitive-behavioral therapy for the improvement of negative symptoms and functioning in schizophrenia: a systematic review and meta-analysis of randomized controlled trials

PONE-D-24-37272R2

Dear Dr. Hong,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Carlos Eduardo Thomaz, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

All comments have been properly addressed. Congratulations!

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #2: Yes

**********

6. Review Comments to the Author

Reviewer #2: I would like to thank the authors for their consideration of my comments and their revision of this manuscript. This work is an important addition to the literature on the value of psychosocial interventions for patients with schizophrenia.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .

Reviewer #2: Yes: Mohammed A. Alarabi

**********

PLoS One. doi: 10.1371/journal.pone.0324685.r007

Acceptance letter

Carlos Thomaz

PONE-D-24-37272R2

PLOS ONE

Dear Dr. Hong,

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team.

At this stage, our production department will prepare your paper for publication. This includes ensuring the following:

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on behalf of

Prof. Carlos Eduardo Thomaz

Academic Editor

PLOS ONE

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

S1. Search strategy.

(DOCX)

pone.0324685.s001.docx^{(26.5KB, docx)}

S2. GRADE assessment.

(DOCX)

pone.0324685.s002.docx^{(17.5KB, docx)}

S3. Publication bias assessment: funnel plot.

(PDF)

pone.0324685.s003.pdf^{(40.6KB, pdf)}

S4. PRISMA 2020 checklist.

(PDF)

pone.0324685.s004.pdf^{(97.4KB, pdf)}

S5. Detailed data.

(XLSX)

pone.0324685.s005.xlsx^{(13.3KB, xlsx)}

S6. Data extraction information.

(XLSX)

pone.0324685.s006.xlsx^{(32.5KB, xlsx)}

S7. List of excluded studies.

(XLSX)

pone.0324685.s007.xlsx^{(1.1MB, xlsx)}

S8. Methodological quality of the trials.

(DOCX)

pone.0324685.s008.docx^{(21.2KB, docx)}

Attachment

Submitted filename: Reviewer Report_20Feb2025.pdf

pone.0324685.s009.pdf^{(152KB, pdf)}

Attachment

Submitted filename: Response to Reviews.docx

pone.0324685.s011.docx^{(28.2KB, docx)}

Attachment

Submitted filename: Response_to_Reviews_auresp_2.docx

pone.0324685.s012.docx^{(18.8KB, docx)}

Data Availability Statement

All relevant data are within the paper and its Supporting Information files.

[pone.0324685.ref001] 1.McGurk SR, Mueser KT. Cognitive functioning, symptoms, and work in supported employment: a review and heuristic model. Schizophr Res. 2004;70(2–3):147–73. doi: 10.1016/j.schres.2004.01.009 [DOI] [PubMed] [Google Scholar]

[pone.0324685.ref002] 2.Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet (London, England). 2016;388(10053):1603–58. Epub 2016/10/14. doi: 10.1016/s0140-6736(16)31460-x PubMed ; PubMed Central PMCID: PMCPMC5388857. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref003] 3.Kirkpatrick B, Fenton WS, Carpenter WT Jr, Marder SR. The NIMH-MATRICS consensus statement on negative symptoms. Schizophr Bull. 2006;32(2):214–9. doi: 10.1093/schbul/sbj053 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref004] 4.Strauss GP, Ahmed AO, Young JW, Kirkpatrick B. Reconsidering the latent structure of negative symptoms in schizophrenia: a review of evidence supporting the 5 consensus domains. Schizophr Bull. 2019;45(4):725–9. doi: 10.1093/schbul/sby169 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref005] 5.García-Fernández L, Romero-Ferreiro V, Sánchez-Pastor L, Dompablo M, Martínez-Gras I, Espejo-Saavedra JM, et al. Impact of negative symptoms on functioning and quality of life in first psychotic episodes of schizophrenia. J Clin Med. 2022;11(4):983. doi: 10.3390/jcm11040983 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref006] 6.Novick D, Montgomery W, Cheng Y, Moneta V, Haro J. Impact of negative symptoms on quality of life in patients with schizophrenia. Value Health. 2015;18(7):A836–7. [Google Scholar]

[pone.0324685.ref007] 7.Fusar-Poli P, Papanastasiou E, Stahl D, Rocchetti M, Carpenter W, Shergill S, et al. Treatments of negative symptoms in schizophrenia: meta-analysis of 168 randomized placebo-controlled trials. Schizophr Bull. 2015;41(4):892–9. doi: 10.1093/schbul/sbu170 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref008] 8.Krause M, Zhu Y, Huhn M, Schneider-Thoma J, Bighelli I, Nikolakopoulou A, et al. Antipsychotic drugs for patients with schizophrenia and predominant or prominent negative symptoms: a systematic review and meta-analysis. Eur Arch Psychiatry Clin Neurosci. 2018;268(7):625–39. doi: 10.1007/s00406-018-0869-3 [DOI] [PubMed] [Google Scholar]

[pone.0324685.ref009] 9.Remington G, Foussias G, Fervaha G, Agid O, Takeuchi H, Lee J, et al. Treating negative symptoms in schizophrenia: an update. Curr Treat Options Psychiatry. 2016;3:133–50. doi: 10.1007/s40501-016-0075-8 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref010] 10.Japanese Society of Neuropsychopharmacology. Guideline for pharmacological therapy of schizophrenia. Neuropsychopharmacol Rep. 2021;41(3):266–324. Epub 2021/08/15. doi: 10.1002/npr2.12193 PubMed ; PubMed Central PMCID: PMCPMC8411321 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref011] 11.Dixon LB, Dickerson F, Bellack AS, Bennett M, Dickinson D, Goldberg RW, et al. The 2009 schizophrenia PORT psychosocial treatment recommendations and summary statements. Schizophr Bull. 2010;36(1):48–70. doi: 10.1093/schbul/sbp115 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref012] 12.Lysaker PH, Lancaster RS, Nees MA, Davis LW. Attributional style and symptoms as predictors of social function in schizophrenia. J Rehabil Res Dev. 2004;41(2):225–32. doi: 10.1682/jrrd.2004.02.0225 [DOI] [PubMed] [Google Scholar]

[pone.0324685.ref013] 13.Wykes T, Steel C, Everitt B, Tarrier N. Cognitive behavior therapy for schizophrenia: effect sizes, clinical models, and methodological rigor. Schizophr Bull. 2008;34(3):523–37. doi: 10.1093/schbul/sbm114 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref014] 14.Bighelli I, Huhn M, Schneider-Thoma J, Krause M, Reitmeir C, Wallis S, et al. Response rates in patients with schizophrenia and positive symptoms receiving cognitive behavioural therapy: a systematic review and single-group meta-analysis. BMC Psychiatry. 2018;18(1):380. doi: 10.1186/s12888-018-1964-8 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref015] 15.Bighelli I, Salanti G, Reitmeir C, Wallis S, Barbui C, Furukawa TA, et al. Psychological interventions for positive symptoms in schizophrenia: protocol for a network meta-analysis of randomised controlled trials. BMJ Open. 2018;8(3):e019280. doi: 10.1136/bmjopen-2017-019280 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref016] 16.Xu F, Xu S. Cognitive-behavioral therapy for negative symptoms of schizophrenia: a systematic review and meta-analysis. Medicine (Baltimore). 2024;103(36):e39572. doi: 10.1097/MD.0000000000039572 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref017] 17.Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264–9, W64. doi: 10.7326/0003-4819-151-4-200908180-00135 [DOI] [PubMed] [Google Scholar]

[pone.0324685.ref018] 18.O’Connor D, Green S, Higgins JP. Defining the review question and developing criteria for including studies. In Cochrane Handbook for Systematic Reviews of Interventions. 2008. pp. 81–94. [Google Scholar]

[pone.0324685.ref019] 19.Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. doi: 10.1136/bmj.d5928 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref020] 20.Egger M, Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref021] 21.Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schünemann HJ, et al. What is “quality of evidence” and why is it important to clinicians?. BMJ. 2008;336(7651):995–8. doi: 10.1136/bmj.39490.551019.BE [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref022] 22.Chandler J, Cumpston M, Li T, Page MJ, Welch VJHW. Cochrane Handbook for Systematic Reviews of Interventions. 2019. [Google Scholar]

[pone.0324685.ref023] 23.Barrowclough C, Haddock G, Lobban F, Jones S, Siddle R, Roberts C, et al. Group cognitive-behavioural therapy for schizophrenia. Randomised controlled trial. Br J Psychiatry. 2006;189:527–32. doi: 10.1192/bjp.bp.106.021386 [DOI] [PubMed] [Google Scholar]

[pone.0324685.ref024] 24.Morrison AP, Turkington D, Pyle M, Spencer H, Brabban A, Dunn G, et al. Cognitive therapy for people with schizophrenia spectrum disorders not taking antipsychotic medication: a randomised controlled trial. Schizophrenia Res. 2014;153:S75. doi: 10.1016/s0920-9964(14)70242-7 [DOI] [PubMed] [Google Scholar]

[pone.0324685.ref025] 25.Rector NA, Seeman MV, Segal ZV. Cognitive therapy for schizophrenia: a preliminary randomized controlled trial. Schizophr Res. 2003;63(1–2):1–11. doi: 10.1016/s0920-9964(02)00308-0 [DOI] [PubMed] [Google Scholar]

[pone.0324685.ref026] 26.Penn DL, Uzenoff SR, Perkins D, Mueser KT, Hamer R, Waldheter E, et al. A pilot investigation of the Graduated Recovery Intervention Program (GRIP) for first episode psychosis. Schizophr Res. 2011;125(2–3):247–56. doi: 10.1016/j.schres.2010.08.006 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref027] 27.Gumley A, O’Grady M, McNay L, Reilly J, Power K, Norrie J. Early intervention for relapse in schizophrenia: results of a 12-month randomized controlled trial of cognitive behavioural therapy. Psychol Med. 2003;33(3):419–31. doi: 10.1017/s0033291703007323 [DOI] [PubMed] [Google Scholar]

[pone.0324685.ref028] 28.Müller H, Kommescher M, Güttgemanns J, Wessels H, Walger P, Lehmkuhl G, et al. Cognitive behavioral therapy in adolescents with early-onset psychosis: a randomized controlled pilot study. Eur Child Adolesc Psychiatry. 2020;29(7):1011–22. doi: 10.1007/s00787-019-01415-4 [DOI] [PubMed] [Google Scholar]

[pone.0324685.ref029] 29.Sönmez N, Romm KL, Østefjells T, Grande M, Jensen LH, Hummelen B, et al. Cognitive behavior therapy in early psychosis with a focus on depression and low self-esteem: a randomized controlled trial. Compr Psychiatry. 2020;97:152157. doi: 10.1016/j.comppsych.2019.152157 [DOI] [PubMed] [Google Scholar]

[pone.0324685.ref030] 30.Peters E, Landau S, McCrone P, Cooke M, Fisher P, Steel C, et al. A randomised controlled trial of cognitive behaviour therapy for psychosis in a routine clinical service. Acta Psychiatr Scand. 2010;122(4):302–18. doi: 10.1111/j.1600-0447.2010.01572.x [DOI] [PubMed] [Google Scholar]

[pone.0324685.ref031] 31.Tarrier N, Lewis S, Haddock G, Bentall R, Drake R, Kinderman P, et al. Cognitive-behavioural therapy in first-episode and early schizophrenia. 18-month follow-up of a randomised controlled trial. Br J Psychiatry. 2004;184:231–9. doi: 10.1192/bjp.184.3.231 [DOI] [PubMed] [Google Scholar]

[pone.0324685.ref032] 32.Morrison AP, Pyle M, Gumley A, Schwannauer M, Turkington D, MacLennan G, et al. Cognitive behavioural therapy in clozapine-resistant schizophrenia (FOCUS): an assessor-blinded, randomised controlled trial. Lancet Psychiatry. 2018;5(8):633–43. doi: 10.1016/S2215-0366(18)30184-6 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref033] 33.Morrison AP, Law H, Carter L, Sellers R, Emsley R, Pyle M, et al. Antipsychotic drugs versus cognitive behavioural therapy versus a combination of both in people with psychosis: a randomised controlled pilot and feasibility study. Lancet Psychiatry. 2018;5(5):411–23. doi: 10.1016/S2215-0366(18)30096-8 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref034] 34.Yan J, Liu F, Lu X. Analyzing the effects of cognitive behavioral therapy in schizophrenic patients with depressive symptoms. Psychol Month. 2024;19(10):116–8. doi: 10.19738/j.cnki.psy.2024.10.031 [DOI] [Google Scholar]

[pone.0324685.ref035] 35.Chen D, Sun H. Effects of psychological care based on cognitive behavioral therapy on patients with schizophrenia. China Typical Cases Book. 2024;18(04):126–9. [Google Scholar]

[pone.0324685.ref036] 36.Peng F, Zhong H, Tu W. The value of cognitive-behavioral therapy in improving adverse emotions in schizophrenia patients. Psychol Monthly. 2023;18(19):100–2. doi: 10.19738/j.cnki.psy.2023.19.029 [DOI] [Google Scholar]

[pone.0324685.ref037] 37.Barrowclough C, Haddock G, Tarrier N, Lewis SW, Moring J, O’Brien R, et al. Randomized controlled trial of motivational interviewing, cognitive behavior therapy, and family intervention for patients with comorbid schizophrenia and substance use disorders. Am J Psychiatry. 2001;158(10):1706–13. doi: 10.1176/appi.ajp.158.10.1706 [DOI] [PubMed] [Google Scholar]

[pone.0324685.ref038] 38.Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13(2):261–76. doi: 10.1093/schbul/13.2.261 [DOI] [PubMed] [Google Scholar]

[pone.0324685.ref039] 39.Govil P, Kantrowitz JT. Negative symptoms in schizophrenia: an update on research assessment and the current and upcoming treatment landscape. CNS Drugs. 2025;39(3):243–62. doi: 10.1007/s40263-024-01151-7 [DOI] [PubMed] [Google Scholar]

[pone.0324685.ref040] 40.Hassan Kariri HD, Almubaddel A. From theory to practice: revealing the real-world impact of cognitive behavioral therapy in psychological disorders through a dynamic bibliometric and survey study. Heliyon. 2024;10(18):e37763. doi: 10.1016/j.heliyon.2024.e37763 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref041] 41.Ventura J, Hellemann GS, Thames AD, Koellner V, Nuechterlein KH. Symptoms as mediators of the relationship between neurocognition and functional outcome in schizophrenia: a meta-analysis. Schizophr Res. 2009;113(2–3):189–99. doi: 10.1016/j.schres.2009.03.035 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref042] 42.Bowie CR, Gupta M, Holshausen K. Disconnected and underproductive speech in schizophrenia: unique relationships across multiple indicators of social functioning. Schizophr Res. 2011;131(1–3):152–6. doi: 10.1016/j.schres.2011.04.014 [DOI] [PubMed] [Google Scholar]

[pone.0324685.ref043] 43.Millan MJ, Fone K, Steckler T, Horan WP. Negative symptoms of schizophrenia: clinical characteristics, pathophysiological substrates, experimental models and prospects for improved treatment. Eur Neuropsychopharmacol. 2014;24(5):645–92. doi: 10.1016/j.euroneuro.2014.03.008 [DOI] [PubMed] [Google Scholar]

[pone.0324685.ref044] 44.Grant PM, Beck AT. Defeatist beliefs as a mediator of cognitive impairment, negative symptoms, and functioning in schizophrenia. Schizophr Bull. 2009;35(4):798–806. doi: 10.1093/schbul/sbn008 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref045] 45.Kring AM, Gur RE, Blanchard JJ, Horan WP, Reise SP. The Clinical Assessment Interview for Negative Symptoms (CAINS): final development and validation. Am J Psychiatry. 2013;170(2):165–72. doi: 10.1176/appi.ajp.2012.12010109 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref046] 46.Strauss GP, Keller WR, Buchanan RW, Gold JM, Fischer BA, McMahon RP, et al. Next-generation negative symptom assessment for clinical trials: validation of the Brief Negative Symptom Scale. Schizophr Res. 2012;142(1–3):88–92. doi: 10.1016/j.schres.2012.10.012 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref047] 47.Fervaha G, Foussias G, Agid O, Remington G. Motivational and neurocognitive deficits are central to the prediction of longitudinal functional outcome in schizophrenia. Acta Psychiatr Scand. 2014;130(4):290–9. doi: 10.1111/acps.12289 [DOI] [PubMed] [Google Scholar]

[pone.0324685.ref048] 48.Granholm E, Holden J, Link PC, McQuaid JR. Randomized clinical trial of cognitive behavioral social skills training for schizophrenia: improvement in functioning and experiential negative symptoms. J Consult Clin Psychol. 2014;82(6):1173–85. doi: 10.1037/a0037098 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref049] 49.Ben-Zeev D, Brenner CJ, Begale M, Duffecy J, Mohr DC, Mueser KT. Feasibility, acceptability, and preliminary efficacy of a smartphone intervention for schizophrenia. Schizophr Bull. 2014;40(6):1244–53. doi: 10.1093/schbul/sbu033 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref050] 50.Khoury B, Lecomte T, Gaudiano BA, Paquin K. Mindfulness interventions for psychosis: a meta-analysis. Schizophr Res. 2013;150(1):176–84. doi: 10.1016/j.schres.2013.07.055 [DOI] [PubMed] [Google Scholar]

[pone.0324685.ref051] 51.Firth J, Cotter J, Elliott R, French P, Yung AR. A systematic review and meta-analysis of exercise interventions in schizophrenia patients. Psychol Med. 2015;45(7):1343–61. doi: 10.1017/S0033291714003110 [DOI] [PubMed] [Google Scholar]

[pone.0324685.ref052] 52.Vancampfort D, Firth J, Schuch FB, Rosenbaum S, Mugisha J, Hallgren M, et al. Sedentary behavior and physical activity levels in people with schizophrenia, bipolar disorder and major depressive disorder: a global systematic review and meta-analysis. World Psychiatry. 2017;16(3):308–15. doi: 10.1002/wps.20458 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref053] 53.Ventura J, Subotnik KL, Gitlin MJ, Gretchen-Doorly D, Ered A, Villa KF, et al. Negative symptoms and functioning during the first year after a recent onset of schizophrenia and 8 years later. Schizophr Res. 2015;161(2–3):407–13. doi: 10.1016/j.schres.2014.10.043 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0324685.ref054] 54.Jeste DV, Wolkowitz OM, Palmer BW. Divergent trajectories of physical, cognitive, and psychosocial aging in schizophrenia. Schizophr Bull. 2011;37(3):451–5. doi: 10.1093/schbul/sbr026 [DOI] [PMC free article] [PubMed] [Google Scholar]

PERMALINK

Cognitive-behavioral therapy for the improvement of negative symptoms and functioning in schizophrenia: A systematic review and meta-analysis of randomized controlled trials

Yu Hong

Yiyun Chen

Yinglin Bai

Wenfei Tan

Roles

Abstract

Background

Objectives

Methods

Result

Conclusion

Introduction

Methods

Search strategy

Inclusion and exclusion criteria

Data extractions

Quality assessment

Statistical analyses

Quality of evidence

Results

Description of included studies

Fig 1. PRISMA follow diagram of the study selection process.

Characteristics of the included studies

Table 1. Characteristics of the included studies.

Risk of bias in the included studies

Fig 2. Summary of risk of bias for included studies.

Fig 3. Bias risk proportion graph for included studies.

Effect on PANSS-negative symptom

Fig 4. Forest plot of the effect of CBT on negative symptoms of schizophrenia.

Fig 5. Forest plot of the short- to medium- to long-term effects of CBT on negative symptoms in schizophrenia.

Effect on overall function

Fig 6. Forest plot of the effect of CBT on overall functioning in schizophrenia.

Effect on social skills

Fig 7. Forest plot of the effects of CBT on social skills in schizophrenia.

Effect on social functioning

Fig 8. Forest plot of the effects of CBT on social functioning in schizophrenia.

Publication bias

Discussion

Challenges and limitations

Conclusions

Supporting information

Data Availability

Funding Statement

References

Author response to Decision Letter 0

Decision Letter 0

Carlos Thomaz

Roles

Author response to Decision Letter 0

Decision Letter 1

Carlos Thomaz

Roles

Author response to Decision Letter 1

Decision Letter 2

Carlos Thomaz

Roles

Acceptance letter

Carlos Thomaz

Roles

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

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