{"title":"Angiotensin receptor blockade modulates resting state functional connectivity in the memory network rather than fear network – implications for posttraumatic stress disorder","authors":"Lorika Shkreli , Caroline Nettekoven , Sirius Boessenkool , Marieke Martens , Nicola Filippini , Liliana Capitão , Phil Cowen , Andrea Reinecke","doi":"10.1016/j.psychres.2025.116458","DOIUrl":"10.1016/j.psychres.2025.116458","url":null,"abstract":"<div><div>Population-based studies have shown that the intake of Angiotensin-II receptor blockers (ARBs), commonly used to treat high blood pressure, is associated with reduced post-traumatic stress disorder (PTSD) symptoms. However, the underlying neural mechanisms remain unclear. While PTSD development is characterized by maladaptive processing within brain networks associated with fear processing and memory formation during trauma exposure, there is increasing evidence that such aberrations manifest in altered resting state functional connectivity (rsFC) of brain regions in these networks.</div><div>In this double-blind placebo-controlled study in 45 healthy volunteers with high trait-anxiety, we investigated whether the ARB losartan would affect rsFC in prominent seeds of the fear and memory network, counteracting effects seen in PTSD.</div><div>Seed selection was informed by established rsFC aberrations seen in PTSD and consisted of the hippocampus and the parahippocampal gyrus (memory network), as well the amygdala and insula (fear network).</div><div>Our results showed that a single dose of the ARB losartan decreased rsFC in the memory network from modulatory structures in the frontal cortex: losartan decreased rsFC (i) between the hippocampus and the inferior frontal gyrus involved in threat processing and memory intrusion development, and (ii) between the parahippocampal gyrus and the dorsolateral prefrontal cortex involved in top-down control. There were no drug effects on the fear network seeds. These findings may imply that ARB preserves adaptive memory function during trauma.</div></div>","PeriodicalId":20819,"journal":{"name":"Psychiatry Research","volume":"348 ","pages":"Article 116458"},"PeriodicalIF":4.2,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wei Zhang , Weiwen Wang , Yongjie Zhou , Jiesi Wang
{"title":"A comparative study of blood and hippocampal D-serine change patterns in drug-naïve patients and animal models of depression","authors":"Wei Zhang , Weiwen Wang , Yongjie Zhou , Jiesi Wang","doi":"10.1016/j.psychres.2025.116453","DOIUrl":"10.1016/j.psychres.2025.116453","url":null,"abstract":"<div><div>The dysfunction of the N-methyl-<span>d</span>-aspartate receptor (NMDAR) has been implicated in depression, and D‑serine, an endogenous co-agonist of NMDAR, plays a critical role in its function. However, the pattern and relationship of alterations in central and peripheral D‑serine concentrations in depression remain unclear. In this study, we conducted two parallel cross-sectional studies to investigate D‑serine alterations in depression. In the clinical study, we recruited drug-naïve patients with major depressive disorder (MDD) and age and sex-matched healthy controls to assess peripheral D‑serine levels in serum. In the preclinical study, a chronic social defeat stress (CSDS) mouse model of depression was used to measure both peripheral and hippocampal D‑serine levels, given the hippocampus's key role in depression. Our results revealed significantly higher levels of D‑serine and the D‑serine/L‑serine ratio in the serum of MDD patients compared to controls, while L‑serine levels showed no significant differences. Similarly, in the CSDS mouse model, serum D‑serine levels were also increased. However, hippocampal D‑serine and L‑serine levels were decreased in depressed mice compared to controls, with no significant correlation observed between blood and hippocampal D‑serine levels. These findings suggest a potential pattern of D‑serine concentrations between peripheral blood and the hippocampus in depression. However, the clinical implications of contrasting changes in D‑serine in the peripheral and central systems, as well as the underlying mechanisms, require further investigation.</div></div>","PeriodicalId":20819,"journal":{"name":"Psychiatry Research","volume":"348 ","pages":"Article 116453"},"PeriodicalIF":4.2,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Takeshi Shimada , Shoko Ito , Ayumi Yamanushi , Ami Koizumi , Masayoshi Kobayashi
{"title":"Effect of aerobic exercise versus cognitive remediation versus a combination of both on cognition among patients with schizophrenia: A three-arm, randomized controlled study","authors":"Takeshi Shimada , Shoko Ito , Ayumi Yamanushi , Ami Koizumi , Masayoshi Kobayashi","doi":"10.1016/j.psychres.2025.116454","DOIUrl":"10.1016/j.psychres.2025.116454","url":null,"abstract":"<div><div>Aerobic exercise (AE) and cognitive remediation (CR) have both shown promising effects on cognition in schizophrenia. However, the efficacy of combining these interventions has not been thoroughly evaluated. We conducted a randomized controlled trial to test the 3-month effects of AE, CR, and their combination on cognition and functioning in patients with schizophrenia. A total of 59 patients were randomized into three groups: AE alone (<em>n</em> = 19), CR alone (<em>n</em> = 19), or a combination of both (<em>n</em> = 21). The intervention consisted of a combination of individual and group AEs and a computer-assisted CR. The overall retention rate was 91.53 %. The primary outcome was the change in cognition from baseline, assessed using the Brief Assessment of Cognition in Schizophrenia (BACS). Significant improvements from baseline to post-treatment were observed in the combined AE and CR group compared to the AE alone group for verbal memory, executive function, and the composite score on the BACS. Similarly, greater improvements were found in the combined AE and CR group than in the CR group alone in verbal memory, working memory, attention, executive function, and the composite BACS score, with effect sizes ranging from moderate to large. No significant differences were found in functional level changes from baseline to post-treatment in the pairwise comparisons between groups, as assessed using the modified Global Assessment of Functioning for social functioning Scale. Our results indicate that patients with schizophrenia in the combined AE and CR group achieved greater cognitive improvement than those in the AE or CR alone group.</div></div>","PeriodicalId":20819,"journal":{"name":"Psychiatry Research","volume":"348 ","pages":"Article 116454"},"PeriodicalIF":4.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Federico Pacheco Sudar , Samar Samy Zekerallah , Michael Paulzen , Klaus Mathiak , Arnim Johannes Gaebler
{"title":"Unraveling antipsychotic induced weight gain in schizophrenia – A proof-of-concept study exploring the impact of the cumulative historical occupancy of different receptors by antipsychotics","authors":"Federico Pacheco Sudar , Samar Samy Zekerallah , Michael Paulzen , Klaus Mathiak , Arnim Johannes Gaebler","doi":"10.1016/j.psychres.2025.116452","DOIUrl":"10.1016/j.psychres.2025.116452","url":null,"abstract":"<div><div>Obesity is a common complication in schizophrenia contributing to increased mortality rates. We present a proof-of-concept study displaying a new method to investigate the impact of antipsychotic drugs (APs) on obesity in terms of their cumulative historical receptor occupancy (CHRO) in 150 selected from 174 patients with schizophrenia. Based on a thorough medication history, we estimated CHRO of serotonin 5-HT<sub>2C</sub>, histamine H<sub>1</sub>, dopamine D<sub>2</sub> and muscarinic M<sub>3</sub> receptors and studied their relationship with different metabolic outcome variables utilizing stepwise regression analysis and structural equation modelling (SEM).</div><div>Stepwise regression analysis revealed a significant positive relationship of Body Mass Index (BMI) with H<sub>1<img></sub>CHRO, but a negative relationship with M<sub>3<img></sub>CHRO. Moreover, H<sub>1<img></sub>CHRO was associated with increased triglyceride concentration, while 5-HT<sub>2C<img></sub>CHRO was associated with increased waist circumference and blood pressure. SEM, while confirming the diverging effects of H<sub>1</sub>-/5-HT<sub>2C</sub>- and M<sub>3<img></sub>CHRO on obesity, suggested that their effect on other metabolic variables was indirect, i.e. mediated by obesity.</div><div>Our results suggest that the metabolic side effects of antipsychotics can be described by their cumulative historical receptor occupancy with unique contributions of the different receptors. In particular, M<sub>3</sub> receptor antagonism seems to exert a protective effect, confirming findings from rodent M<sub>3</sub> receptor knock out models.</div><div>These findings may provide a framework for estimating the metabolic burden of future APs, guiding the development of drugs with more favorable metabolic profiles.</div></div>","PeriodicalId":20819,"journal":{"name":"Psychiatry Research","volume":"348 ","pages":"Article 116452"},"PeriodicalIF":4.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zoe Bridges-Curry , Jessica N. Coleman , Patrick S. Calhoun , VA Mid-Atlantic MIRECC Workgroup
{"title":"Trauma exposure typologies as predictors of PTSD and functional impairment among male and female veterans","authors":"Zoe Bridges-Curry , Jessica N. Coleman , Patrick S. Calhoun , VA Mid-Atlantic MIRECC Workgroup","doi":"10.1016/j.psychres.2025.116450","DOIUrl":"10.1016/j.psychres.2025.116450","url":null,"abstract":"<div><div>Individuals exposed to multiple trauma types (i.e., polyvictimization) are at increased risk for poor mental health outcomes. However, despite high rates of exposure to traumatic events among veterans, few studies have examined typologies of lifetime trauma exposure or tested long-term impacts of these patterns of exposure in this population. The present study used latent profile analysis (LPA) to identify typologies of trauma among male and female post-9/11 veterans (<em>N</em> = 774) and test these typologies as predictors of posttraumatic stress disorder (PTSD) symptoms and functional impairment at 10-year follow-up. Three subgroups were identified among male veterans, including low exposure, combat exposure, and polyvictimization. Three subgroups were also identified among female veterans, including moderate exposure, intimate partner violence, and polyvictimization. Relative to low exposure, polyvictimization but not combat exposure predicted elevated PTSD symptoms at follow-up for male veterans. These findings call attention to the long-term deleterious impacts of polyvictimization among male veterans and highlight the unique experiences of female veterans, including disproportionate rates of exposure to interpersonal and sexual violence across the lifespan.</div></div>","PeriodicalId":20819,"journal":{"name":"Psychiatry Research","volume":"348 ","pages":"Article 116450"},"PeriodicalIF":4.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anuradhi Jayasinghe , Kate Filia , Anna L. Wrobel , George Karambelas , Linda K. Byrne , Glenn Melvin , Caroline Gao , Tracy Garvin , Amity Watson , Melissa Hasty , Craig Macneil , Lesley Berk , Michael Berk , Sue Cotton
{"title":"The role of schemas in the experience of distress, burden, and wellbeing in parents and siblings of people with serious mental health difficulties","authors":"Anuradhi Jayasinghe , Kate Filia , Anna L. Wrobel , George Karambelas , Linda K. Byrne , Glenn Melvin , Caroline Gao , Tracy Garvin , Amity Watson , Melissa Hasty , Craig Macneil , Lesley Berk , Michael Berk , Sue Cotton","doi":"10.1016/j.psychres.2025.116448","DOIUrl":"10.1016/j.psychres.2025.116448","url":null,"abstract":"<div><h3>Background</h3><div>Caregivers of people with serious mental health difficulties (SMHD), such as schizophrenia or bipolar disorder, face various psychological challenges. It is unclear if the mechanisms underlying these challenges differ between different groups of caregivers. This study examined whether the relationship between maladaptive schemas and distress, burden, and reduced wellbeing differed between parents and siblings of people with SMHD.</div></div><div><h3>Methods</h3><div>70 parents and 40 siblings completed an online survey that included measures of schemas (Young Schema Questionnaire–Short Form), depressive symptoms (Patient Health Questionnaire-9), anxiety symptoms (Generalised Anxiety Disorder Assessment-7), burden (Experience of Caregiving Inventory), and wellbeing (Ryff Scales of Psychological Wellbeing). Multivariate linear regression models with interaction effects were tested for each outcome of interest.</div></div><div><h3>Results</h3><div>Compared to parents, siblings reported significantly higher scores in each schema domain, greater distress and burden, and reduced wellbeing. Univariate analyses revealed that Disconnection (β=0.52 [0.17, 0.91], <em>t</em>(100)=2.90, <em>p</em>=.005) and the interaction between Caregiver Group and Disconnection (β=-1.17 [-2.27, -0.13], <em>t</em>(100) =-2.49, <em>p</em>=.014) significantly predicted depressive symptoms. Schema domains predicted anxiety symptoms, burden, and wellbeing; there were no significant interaction effects in these models.</div></div><div><h3>Conclusion</h3><div>Siblings seem to experience greater psychological challenges than parents. Maladaptive schemas were linked to greater psychological challenges in both groups and the relationship between schemas and distress, burden, and wellbeing was similar in parents and siblings. Further research is needed to determine if there are group differences at the individual schema level.</div></div>","PeriodicalId":20819,"journal":{"name":"Psychiatry Research","volume":"348 ","pages":"Article 116448"},"PeriodicalIF":4.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lynn E DeLisi, Brian Dean, Brita Elvevåg, Diane Carol Gooding, Dolores Malaspina, Sibylle Schwab, Antonio Vita
{"title":"The interference of politics in science march 2025: An editorial to the readers of Psychiatry Research.","authors":"Lynn E DeLisi, Brian Dean, Brita Elvevåg, Diane Carol Gooding, Dolores Malaspina, Sibylle Schwab, Antonio Vita","doi":"10.1016/j.psychres.2025.116449","DOIUrl":"https://doi.org/10.1016/j.psychres.2025.116449","url":null,"abstract":"","PeriodicalId":20819,"journal":{"name":"Psychiatry Research","volume":" ","pages":"116449"},"PeriodicalIF":4.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Enhancing effects of exercise and neurofeedback: A systematic review and meta-analysis of computer game-based interventions for pediatric ADHD","authors":"Takehiko Hamada , Masaki Seki , Eishu Nango , Taro Shibata , Shinya Imai , Toshio Miyata","doi":"10.1016/j.psychres.2025.116447","DOIUrl":"10.1016/j.psychres.2025.116447","url":null,"abstract":"<div><h3>Objective</h3><div>While numerous reviews examine digital interventions, including computer game-based, evidence regarding their effectiveness for ADHD symptoms remains mixed. Focusing on computer game-based interventions, this study aims to identify specific intervention features and trial-related factors that influence outcomes in pediatric ADHD symptoms through a systematic review and meta-analysis of randomized controlled trials.</div></div><div><h3>Methods</h3><div>Comprehensive literature searches were conducted in Web of Science, PubMed and PsycINFO. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.</div></div><div><h3>Results</h3><div>Seventeen studies were included. Beyond common game characteristics, some interventions incorporated additional elements—such as neurofeedback, physical exercise via virtual reality (VR) and social components—allowing subgroup analyses. The neurofeedback subgroup showed the largest effect size (standardized mean difference (SMD)=-0.51, 95 % confidence interval (CI) [-0.88, -0.15], heterogeneity index (I<sup>2</sup>)=45.85 %, <em>p</em> < 0.05, very low certainty of evidence), followed by the physical exercise/VR subgroup (SMD=-0.40, 95 %CI [-0.76, -0.04], I<sup>2</sup>=0.00 %, <em>p</em> < 0.05, very low certainty of evidence). Other subgroups, including those with social components or without additional elements, did not show significant effect sizes. The physical exercise/VR subgroup demonstrated small-to-medium effect sizes in both inattention and hyperactivity/impulsivity subscales, whereas the neurofeedback subgroup showed similar effects only in inattention. Trial-level factors, including participant demographics and intervention duration, showed no significant relationship with SMD in meta-regression.</div></div><div><h3>Conclusion</h3><div>Although inconclusive, synergizing with game dynamics, neurofeedback and physical exercise/VR may enhance effectiveness of computer game-based interventions in addressing pediatric ADHD symptoms. Particularly, interventions with physical exercise/VR have potential to address both inattention and hyperactivity/impulsivity.</div></div>","PeriodicalId":20819,"journal":{"name":"Psychiatry Research","volume":"348 ","pages":"Article 116447"},"PeriodicalIF":4.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jeremy Weleff , Alejandra Pulido-Saavedra , Ardavan Mohammad Aghaei , Kevin Ing , Miranda Arakelian , Rodrigo Fontenele , Neil Nero , Brian S Barnett , Akhil Anand , Anahita Bassir Nia , Gustavo A Angarita
{"title":"The therapeutic effects of psychedelics for opioid use disorder: A systematic review of clinical studies","authors":"Jeremy Weleff , Alejandra Pulido-Saavedra , Ardavan Mohammad Aghaei , Kevin Ing , Miranda Arakelian , Rodrigo Fontenele , Neil Nero , Brian S Barnett , Akhil Anand , Anahita Bassir Nia , Gustavo A Angarita","doi":"10.1016/j.psychres.2025.116446","DOIUrl":"10.1016/j.psychres.2025.116446","url":null,"abstract":"<div><div>Opioid-related overdose deaths have reached record high levels, and novel treatments for opioid use disorder (OUD) are needed. The three United States Food and Drug Administration (FDA)-approved medications for OUD function primarily at the mu-opioid receptor. While these remain the gold-standard treatment for OUD, they have shortcomings and treatment options separate from the opioid receptor system deserve attention. Preclinical, clinical, and naturalistic studies of psychedelics have shown some evidence that they may reduce opioid and other substance use. Here, we present the results of a systematic review of clinical studies investigating the therapeutic applications of psychedelics for OUD to describe the current state of the literature and guide future clinical study design in this area. Findings indicate few studies completed using serotonergic psychedelics, with most investigating ibogaine or ketamine. In addition, findings are limited by many studies of weak design focused on opioid withdrawal, and few double-blind or placebo-controlled trials with considerable methodological heterogeneity making comparisons difficult across compounds. Most studies were found to have a high risk of bias mostly related to lack of randomization, blinding, and blinding of assessment outcomes. We outline these limitations and steps towards improving the quality of future studies of psychedelics for OUD.</div></div>","PeriodicalId":20819,"journal":{"name":"Psychiatry Research","volume":"348 ","pages":"Article 116446"},"PeriodicalIF":4.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kim E. Goldstein , Robert H. Pietrzak , Sana Aladin , Sabrina Ng , Chi C. Chan , M. Mercedes Perez-Rodriguez , Keith M. Shafritz , René S. Kahn , Margaret M. McClure , Philip R. Szeszko , Erin A. Hazlett
{"title":"Neuro- and social-cognition in schizotypal personality disorder and schizophrenia: A spectrum of severity","authors":"Kim E. Goldstein , Robert H. Pietrzak , Sana Aladin , Sabrina Ng , Chi C. Chan , M. Mercedes Perez-Rodriguez , Keith M. Shafritz , René S. Kahn , Margaret M. McClure , Philip R. Szeszko , Erin A. Hazlett","doi":"10.1016/j.psychres.2025.116445","DOIUrl":"10.1016/j.psychres.2025.116445","url":null,"abstract":"<div><div>Despite the significant number of impairments shared by diagnostic groups on the schizophrenia-phenotypic-spectrum, no work has directly compared neuro- and social-cognition of individuals with schizotypal personality disorder (SPD) with that of schizophrenia. This is the first study to compare social-cognition and neuro-cognition across schizophrenia-spectrum-diagnostic groups and explore associations (1) between neuro- and social-cognition in these groups and (2) between change-over-time (nine-month follow-up) in cognition and negative-symptom-severity. This study identified 127 age- and gender-matched healthy controls (HC; <em>N</em> = 49), antipsychotic-naïve individuals with SPD (<em>N</em> = 32), and patients with recent onset schizophrenia (within eight years of illness-onset; <em>N</em> = 46). Detailed profiles of clinical symptoms and cognition were obtained using gold-standard measures (e.g., NIH MATRICS Battery). Schizophrenia patients exhibited global cognitive impairment; SPD patients only exhibited impairment in social-emotional cognition compared with HC (Cohen <em>d</em> = 0.51) but still performed better than the schizophrenia group <em>F</em>[2, 124]=15.18, <em>p</em> < 0.001, Cohen <em>d</em> = 0.61. Multivariable linear regression revealed that social-cognition was associated with neuro-cognition, β=0.49, <em>p</em> < 0.001. In the combined patient group, a greater increase in social-cognition over time was associated with greater reduction in negative symptoms, (<em>B</em> = –0.12, SE=0.09, <em>p</em> = 0.038). Distinct profiles emerged: generalized cognitive impairment in schizophrenia and higher-order social-cognition impairment in SPD. Furthermore, change in social-cognition over time is associated with a change in negative symptoms. Results suggest that social-cognition is impaired across the schizophrenia-spectrum, and detailed examination of social-cognitive treatments should be considered, particularly for individuals with SPD, as they receive minimal attention in research studies.</div></div>","PeriodicalId":20819,"journal":{"name":"Psychiatry Research","volume":"348 ","pages":"Article 116445"},"PeriodicalIF":4.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}