Psychiatry Research最新文献

{"title":"Exploring neural dynamics in self-voice processing and perception: Implications for hallucination proneness","authors":"Suvarnalata Xanthate Duggirala ,&nbsp;Hanna Honcamp ,&nbsp;Michael Schwartze ,&nbsp;Therese van Amelsvoort ,&nbsp;Ana P. Pinheiro ,&nbsp;David E.J. Linden ,&nbsp;Sonja A. Kotz","doi":"10.1016/j.psychres.2025.116461","DOIUrl":"10.1016/j.psychres.2025.116461","url":null,"abstract":"<div><div>Altered sensory feedback processing and attention control are assumed to contribute to auditory verbal hallucinations, which are experienced by the general population and patients with psychosis, implying a continuum of hallucination proneness (HP). However, the interaction of altered sensory feedback processing and attention control along this HP continuum remains unclear. We tested this interaction using electroencephalography while forty participants varying on HP, self-generated (via a button-press) and passively listened to their own voices. These voices were created by first recording each participant's neutral and angry voice and then morphing them to create final five types of voice stimuli differing in voice quality per participant (100 % neutral, 60–40 % neutral-angry, 50–50 % neutral-angry, 40–60 % neutral-angry, 100 % angry). Regardless of the voice quality, the N100 and P200 suppression effects decreased with increase in HP. This may indicate increased error awareness and attention allocation in high HP individuals for self-voice generation stemming from altered sensory feedback processing, and/or attentional control. The current findings suggest that alterations of the sensory feedback processing and/or attentional control in self-voice production are fundamental characteristics of the continuum of HP, regardless of the clinical status of voice hearers.</div></div>","PeriodicalId":20819,"journal":{"name":"Psychiatry Research","volume":"348 ","pages":"Article 116461"},"PeriodicalIF":4.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143767911","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}

{"title":"Bibliometric analysis of suicide risk assessment in children and adolescents: Trends and future directions","authors":"Christina Yeni Kustanti ,&nbsp;Rika Sarfika ,&nbsp;Ferry Efendi ,&nbsp;Khatijah Lim Abdullah ,&nbsp;Erik Adik Putra Bambang Kurniawan ,&nbsp;Nindi Eka Wijaya ,&nbsp;Wulandari Pratiwi","doi":"10.1016/j.psychres.2025.116468","DOIUrl":"10.1016/j.psychres.2025.116468","url":null,"abstract":"<div><div>Suicide risk among children and adolescents continues to rise, yet critical trends and research gaps in suicide risk assessment remain unexamined. This study aimed to analyze global research trends on suicide risk assessment in children and adolescents using Scopus-indexed literature from 1984 to 2024. VOSviewer was used to visualize keyword co-occurrence and thematic trends. Bibliometric data were extracted from abstracts, including publication volume, citation counts, and author productivity. The search strategy identified 1195 articles, with 259 meeting the inclusion criteria. Publications grew annually by 7.78 %, with contributions from 1243 unique authors and an average document age of 9.22 years. The United States was the leading contributor, followed by China, Spain, and the United Kingdom. The Journal of Affective Disorders is the one with the highest number of publications on network analysis in suicide risk assessment, followed by the Journal of Archives of Suicide Research and Psychiatry Research. Most documents were articles (236), with few reviews (15). Key research areas included suicidal ideation, psychometric evaluations, and stress markers. However, critical gaps persist, particularly in developing culturally sensitive assessment tools, integrating biological and psychosocial risk factors, and expanding research in low- and middle-income countries. Most assessment tools are developed in Western settings, limiting cross-cultural applicability. Given the role of sociocultural factors in suicidal behaviors, future research should prioritize culturally adapted assessment methods and validate self-report tools in diverse populations. Addressing these gaps is essential for improving global suicide prevention strategies.</div></div>","PeriodicalId":20819,"journal":{"name":"Psychiatry Research","volume":"348 ","pages":"Article 116468"},"PeriodicalIF":4.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726077","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":"Interpersonal difficulties and suicidal ideation in young people at clinical high-risk for psychosis and help-seeking clinical controls","authors":"Annamarie Bailey ,&nbsp;Brian W. Bauer ,&nbsp;Vijay A. Mittal ,&nbsp;Lauren M. Ellman ,&nbsp;Gregory P. Strauss ,&nbsp;Elaine F. Walker ,&nbsp;Albert R. Powers ,&nbsp;Joshua Kenney ,&nbsp;Philip R. Corlett ,&nbsp;Scott W. Woods ,&nbsp;James M. Gold ,&nbsp;Jason Schiffman ,&nbsp;James A. Waltz ,&nbsp;Steven M. Silverstein","doi":"10.1016/j.psychres.2025.116467","DOIUrl":"10.1016/j.psychres.2025.116467","url":null,"abstract":"<div><div>Young people at clinical high-risk for psychosis (CHRp) experience higher rates of suicidal ideation than same-aged peers with other mental health concerns. One reason for this may be that the relations between known risk factors for suicide (e.g., interpersonal difficulties) and experiences of suicidal ideation may differ for CHRp young people than for those with other mental health concerns. This study examined relations between interpersonal difficulties (interpersonal trauma history, global social functioning, social anhedonia severity) and presence of suicidal ideation among CHRp young people (<em>n</em> = 263) and help-seeking controls (HSC; <em>n</em> = 203) with a DSM-5 diagnosis. CHRp young people (<em>n</em> = 118; 45 %) reported significantly higher rates of suicidal ideation than HSCs (<em>n</em> = 51; 25 %). CHRp young people also reported greater interpersonal trauma, <em>t</em>(436.49) = 3.28, <em>p</em> = .001, poorer global social functioning, <em>t</em>(447.00) = -5.81, <em>p</em> &lt; .001, and greater social anhedonia severity, <em>t</em>(460.14) = 5.43, <em>p</em> &lt; .001, than HSCs. In logistic regression models, greater interpersonal trauma, <em>OR</em> = 1.20, 95 % CI [1.01, 1.42], <em>p</em> = .04, and poorer global social functioning, <em>OR</em> = 0.70, 95 % CI [0.52, 0.90], <em>p</em> = .008, but not social anhedonia, <em>OR</em> = 1.26, 95 % CI [0.94, 1.69], <em>p</em> = .11, were each associated with presence of suicidal ideation. Diagnostic group did not moderate the associations between any interpersonal difficulty and suicidal ideation (<em>OR</em>s 0.94–1.17, <em>p’</em>s 0.35-0.84). Together, findings suggest that greater rates of suicidal ideation in CHRp young people relative to HSCs may be attributable to transdiagnostic interpersonal mechanisms.</div></div>","PeriodicalId":20819,"journal":{"name":"Psychiatry Research","volume":"348 ","pages":"Article 116467"},"PeriodicalIF":4.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759661","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":"Treatment and long-term outcome of mental disorders: The grim picture from a quasi-epidemiological investigation in 54,826 subjects from 40 countries","authors":"Konstantinos N. Fountoulakis ,&nbsp;Gregory Karakatsoulis ,&nbsp;Seri Abraham ,&nbsp;Kristina Adorjan ,&nbsp;Helal Uddin Ahmed ,&nbsp;Renato D. Alarcón ,&nbsp;Kiyomi Arai ,&nbsp;Sani Salihu Auwal ,&nbsp;Michael Berk ,&nbsp;Sarah Levaj ,&nbsp;Julio Bobes ,&nbsp;Teresa Bobes-Bascaran ,&nbsp;Julie Bourgin-Duchesnay ,&nbsp;Cristina Ana Bredicean ,&nbsp;Laurynas Bukelskis ,&nbsp;Akaki Burkadze ,&nbsp;Indira Indiana Cabrera Abud ,&nbsp;Ruby Castilla-Puentes ,&nbsp;Marcelo Cetkovich ,&nbsp;Hector Colon-Rivera ,&nbsp;Daria Smirnova","doi":"10.1016/j.psychres.2025.116459","DOIUrl":"10.1016/j.psychres.2025.116459","url":null,"abstract":"<div><h3>Introduction</h3><div>This study registered rates of specific treatment options for mental disorders as well as their long-term outcome.</div></div><div><h3>Material and methods</h3><div>The history of mental disorders was used as a proxy for diagnosis. The data came from the COMET-G study (40 countries; 54,826 subjects, 64.73 % females, 35.45±13.51 years old). The analysis included descriptive statistics, Risk Ratios, <em>t</em>-tests, and ANCOVA's.</div></div><div><h3>Results</h3><div>²⁴.14 % reported a history of any mental disorder (depression &gt;12 %, non-affective psychosis and Bipolar disorder 1 % each, &gt;20 % self-injury, &gt;10 % had attempted suicide, 7.17 % illegal substance abuse). Most patients were not under any kind of treatment (59.44 %) and most were not receiving treatment as recommended (e.g. 90 % of Bipolar and 2/3 of psychotic patients). No treatment at all and psychotherapy as monotherapy were consistently related to poorer outcomes. In anxiety or depression, only antidepressant monotherapy and benzodiazepines, in Bipolar disorder only antipsychotic monotherapy in males and antidepressant monotherapy in females and in non-affective psychosis antipsychotics and psychotherapy in females only, were related to good outcomes. No treatment modality was related to a good outcome in those with a history of self-harm, suicidal attempts, or illegal substance use. Only depression and treatment with antidepressants were related to metabolic syndrome.</div></div><div><h3>Discussion</h3><div>In the community, the overwhelming majority of mental patients do not receive appropriate treatment or, even worse, no treatment at all. The outcome is unfavourable for the majority and only a few selective treatment options seem to make a difference.</div></div>","PeriodicalId":20819,"journal":{"name":"Psychiatry Research","volume":"348 ","pages":"Article 116459"},"PeriodicalIF":4.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759007","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}

{"title":"Emotional memory biases in patients with bipolar depression","authors":"Sung Hun Sim ,&nbsp;Eunhye Jeong ,&nbsp;C. Hyung Keun Park","doi":"10.1016/j.psychres.2025.116464","DOIUrl":"10.1016/j.psychres.2025.116464","url":null,"abstract":"<div><div>Emotional memory biases, defined as the tendency to remember emotionally valenced information more accurately than healthy controls (HCs), may contribute to the onset and persistence of bipolar depression (BD). However, specific investigations of these biases are limited. This study sought to examine emotional memory biases by comparing patients with BD to HCs and exploring potential differences between bipolar I depression (BD-I) and bipolar II depression (BD-II). A recognition task was designed to assess recognition memory for previously presented stimuli. Participants (14, 58, and 73 for BD-I, BD-II, and HCs, respectively) were shown words with positive or negative valence and were asked to identify whether each word had been presented earlier during a self-reference effect task, where they chose the more personally relevant word from a pair of positive and negative words. Mixed-model analyses of covariance compared the BD and HC groups, adjusting for years of education and medication use, and assessed BD subtypes, adjusting for age and medication use. Results indicated that patients with BD recognized negative words (“hits”) more accurately and were more likely to incorrectly identify non-presented negative words as presented (“false alarms”) compared to HCs, reflecting a pronounced bias toward negative stimuli. No significant differences were observed between the BD-I and BD-II subtypes. These findings suggest that emotional memory biases may be a key feature of BD, potentially contributing to the persistence of depressive episodes.</div></div>","PeriodicalId":20819,"journal":{"name":"Psychiatry Research","volume":"348 ","pages":"Article 116464"},"PeriodicalIF":4.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739846","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":"Rates of anxiety disorders, mood disorders, and substance use disorders in federally qualified health centers, 2019-2022","authors":"Jack Tsai ,&nbsp;Laura Witte ,&nbsp;Vanessa Schick","doi":"10.1016/j.psychres.2025.116457","DOIUrl":"10.1016/j.psychres.2025.116457","url":null,"abstract":"<div><div>Federally qualified health centers (FQHCs) provide comprehensive health care services to underserved communities throughout the U.S. and are an important setting to examine changes in mental health and substance use disorders during the COVID-19 pandemic. National data from 1359 unique FQHCS serving over 29 million patients from 2019–2022 were analyzed. Diagnoses of mental health and substance use disorders were based on the Uniform Data System. From 2019–2022, the number of patients seen in FQHCs increased by 661,521 patients (2.26 % increase). Across FQHCs, diagnoses of anxiety and trauma-related disorders (AXD) increased by 22.78 %, mood disorders (MD) increased by 1.64 %, drug use disorder (DUD) increased by 4.42 %, and alcohol-related disorders (AD) increased by 2.55 %. By U.S. state, the relatively largest increases in diagnoses of AXD and MD were in Delaware and Alabama. The largest increases in diagnoses of AD and DUD were in North Dakota and Alabama. FQHCs that served larger homeless patient populations showed smaller increases in diagnoses of mental health and substance use disorders than other FQHCs. In conclusion, there was a greater than 20 % increase in AXD diagnoses across FQHCs from 2019–2022, but a &lt;5 % increase in diagnoses of other individual common mental and substance use disorders. These findings highlight both the vulnerabilities and resilience of FQHCs and their patients during the COVID-19 pandemic.</div></div>","PeriodicalId":20819,"journal":{"name":"Psychiatry Research","volume":"348 ","pages":"Article 116457"},"PeriodicalIF":4.2,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704714","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":"Angiotensin receptor blockade modulates resting state functional connectivity in the memory network rather than fear network – implications for posttraumatic stress disorder","authors":"Lorika Shkreli ,&nbsp;Caroline Nettekoven ,&nbsp;Sirius Boessenkool ,&nbsp;Marieke Martens ,&nbsp;Nicola Filippini ,&nbsp;Liliana Capitão ,&nbsp;Phil Cowen ,&nbsp;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}

{"title":"A comparative study of blood and hippocampal D-serine change patterns in drug-naïve patients and animal models of depression","authors":"Wei Zhang ,&nbsp;Weiwen Wang ,&nbsp;Yongjie Zhou ,&nbsp;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}

{"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 ,&nbsp;Shoko Ito ,&nbsp;Ayumi Yamanushi ,&nbsp;Ami Koizumi ,&nbsp;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}

{"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 ,&nbsp;Samar Samy Zekerallah ,&nbsp;Michael Paulzen ,&nbsp;Klaus Mathiak ,&nbsp;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_2C, histamine H₁, dopamine D₂ and muscarinic M₃ 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_1<img>CHRO, but a negative relationship with M_3<img>CHRO. Moreover, H_1<img>CHRO was associated with increased triglyceride concentration, while 5-HT_2C<img>CHRO was associated with increased waist circumference and blood pressure. SEM, while confirming the diverging effects of H₁-/5-HT_2C- and M_3<img>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, M₃ receptor antagonism seems to exert a protective effect, confirming findings from rodent M₃ 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}