Journal of psychiatric research最新文献

{"title":"Intolerance of uncertainty as a factor in hoarding treatment","authors":"Michael G. Wheaton ,&nbsp;Rachel Van Boxtel ,&nbsp;Carolyn I. Rodriguez","doi":"10.1016/j.jpsychires.2025.12.044","DOIUrl":"10.1016/j.jpsychires.2025.12.044","url":null,"abstract":"<div><h3>Purpose</h3><div>Hoarding disorder (HD) involves difficulty discarding clutter. Existing treatments for HD (including cognitive-behavioral therapy [CBT]) yield only partial symptom reduction. Identifying factors that contribute to hoarding may inform potential treatment mechanisms. One such factor is intolerance of uncertainty (IU), the tendency to maladaptively respond to the unknown via fear, discomfort, and avoidance. While IU has been linked to hoarding symptoms, its role in treatment outcomes remains understudied.</div></div><div><h3>Methods</h3><div>41 adults with HD completed the Buried in Treasures (BIT+) Workshop (a 16-session manualized skills group using CBT principles, with 10 additional supervised in-home uncluttering practice). IU and HD symptom severity were assessed pre- and post-treatment.</div></div><div><h3>Results</h3><div>Pre-treatment IU did not significantly predict improvement in hoarding symptoms (β = .15, p = .31). However, IU significantly decreased following treatment (t = 2.23, p = .017). Smaller reductions in IU significantly predicted worse hoarding symptom outcomes, accounting for baseline severity (β = .41, <em>p</em> &lt; .01).</div></div><div><h3>Conclusions</h3><div>Results suggest that high initial levels of IU may not prevent patients from benefiting from hoarding treatment via the BIT+, but that reduction in IU accounts for a significant increment in hoarding treatment gains. Given the room for improvement evident in HD treatments, future research might consider augmenting existing treatment with IU-specific interventions to boost treatment efficacy.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"194 ","pages":"Pages 116-122"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863317","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":"Association between pulse width and clinical response to electroconvulsive therapy","authors":"Richard Braithwaite ,&nbsp;Ana Jelovac","doi":"10.1016/j.jpsychires.2026.01.010","DOIUrl":"10.1016/j.jpsychires.2026.01.010","url":null,"abstract":"<div><h3>Background</h3><div>The default pulse width setting on a commonly used electroconvulsive therapy (ECT) device, 0.5 ms (ms), is untested against the proven effectiveness of conventional 1.0–1.5 ms brief pulse widths.</div></div><div><h3>Methods</h3><div>We examined the association between pulse width and clinical response using registry data from 87 centres in the United Kingdom and Republic of Ireland in patients (<em>N</em> = 1956) receiving consecutive acute courses of ECT ending during 2023 for any clinical indication. The outcome was clinical response, defined as an end-of-treatment Clinical Global Impression‒Improvement score of 1 or 2.</div></div><div><h3>Results</h3><div>Mean age was 61.6 years (SD, 16.3), 66.3 % were female, 84.2 % were treated for depressive episode, and 86.5 % received bilateral ECT. In a multivariable logistic regression analysis of all diagnostic categories, 0.5 ms (adjusted odds ratio 0.64; 95 % CI, 0.50–0.82; <em>p</em> &lt; .001) and 0.25–0.3 ms (adjusted odds ratio 0.56; 95 % CI, 0.38–0.82; <em>p</em> = .003) pulse widths were associated with significantly lower odds of response compared to 1.0 ms. Predicted probabilities of response were 73.4 % (95 % CI, 69.4 %–77.3 %) for 1.0 ms, 64.1 % (95 % CI, 61.4 %–66.8 %) for 0.5 ms, and 61.0 % (95 % CI, 53.8 %–68.3 %) for 0.25–0.3 ms. A subgroup analysis of unipolar or bipolar depressive episodes likewise showed significantly reduced odds of response with both 0.5 ms and 0.25–0.3 ms.</div></div><div><h3>Conclusion</h3><div>This study demonstrated a previously unreported association between 0.5 ms pulse width and reduced ECT response. Unless cognitive sparing is paramount in an individual case, 1.0 ms ECT should be used as standard.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"194 ","pages":"Pages 331-338"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978076","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":"Can exercise reduce the risk of suicidal ideation and behaviors in youth at school? A 12-month cluster randomized control trial","authors":"André O. Werneck ,&nbsp;Xinhe Tian ,&nbsp;Weicong Lu ,&nbsp;Danping Li ,&nbsp;Tao Liu ,&nbsp;Shiyun Wu ,&nbsp;Xiaoyue Li ,&nbsp;Runhua Wang ,&nbsp;Yanling Gao ,&nbsp;Xian Li ,&nbsp;Jinyong Chen ,&nbsp;Davy Vancampfort ,&nbsp;Marco Solmi ,&nbsp;Nicholas Fabiano ,&nbsp;Felipe Schuch ,&nbsp;Paul L. Plener ,&nbsp;Roger S. McIntyre ,&nbsp;Kwok-Fai So ,&nbsp;Brendon Stubbs ,&nbsp;Kangguang Lin","doi":"10.1016/j.jpsychires.2025.12.025","DOIUrl":"10.1016/j.jpsychires.2025.12.025","url":null,"abstract":"<div><div>Our aim was to investigate the effect of an aerobic exercise intervention on risk of suicidal ideation, behaviors and nonsuicidal self-injury among adolescents. This analysis included secondary outcomes of a randomized controlled trial investigating a 12-month aerobic exercise intervention. The intervention consisted of six months of supervised exercise delivered in a school setting, followed by six months of unsupervised exercise. There were three-four sessions of supervised moderate-intensity activities (60–80 % maximum heart rate) lasting 30 min each, with an additional of 10 min of warm-up and cool-down over the initial period. Different clusters of students were randomized into either exercise or a psychoeducation control group. Risk of suicidal ideation and nonsuicidal self-injury were assessed using the Inventory of Statements About Self-Injury, and suicidal behavior was assessed using the Columbia-Suicide Severity Rating Scale. The outcomes were analyzed using intention to treat analyses. Trial registration (<span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> register, NCT04816617). The final sample was composed of 628 adolescents (13.0 ± 0.4 years, 43.3 % girls). In the adjusted models, there was no intervention effect on nonsuicidal self-injury for the whole sample or according to baseline subclinical levels of depressive symptoms. The exercise group presented a 49 % lower incidence of nonsuicidal self-injury incidence in participants with low baseline levels of physical activity (IRR: 0.49; 95 %CI: 0.25–0.97). There was no effect of the intervention on risk of suicidal ideation and suicidal behavior. A 12-month aerobic exercise intervention was associated with lower incidence of nonsuicidal self-injury in participants with low baseline levels of physical activity. The exercise intervention had no effect on the risk suicidal ideation and suicidal behavior.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"194 ","pages":"Pages 71-78"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834140","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":"Stimulant and non-stimulant ADHD medication prescriptions for homeless veteran service users with mental illness","authors":"Katherine A. Koh ,&nbsp;Dorota Szymkowiak ,&nbsp;Jack Tsai","doi":"10.1016/j.jpsychires.2026.01.017","DOIUrl":"10.1016/j.jpsychires.2026.01.017","url":null,"abstract":"<div><h3>Objective</h3><div>Prescribing of ADHD medications has not been examined in the US homeless population. This study examined frequency of prescriptions for stimulant and non-stimulant ADHD medications, as well as risky and potentially inappropriate prescribing (RPIP) of stimulants, in three groups of veterans with mental illness.</div></div><div><h3>Methods</h3><div>Using 2021–2022 national VA administrative data, we compared frequency of stimulant and non-stimulant ADHD medication prescriptions using logistic regression between homeless veterans (n = 105,062), veterans in the Department of Housing and Urban Development-VA Supportive Housing (HUD-VASH; n = 33,884), and independently housed (IH) veterans (n = 1,875,083). We also compared indicators of RPIP of stimulants using chi-square tests between the three groups.</div></div><div><h3>Results</h3><div>Adjusted for sociodemographic, clinical, and health care utilization characteristics, homeless veterans were less likely to be prescribed stimulants (adjusted odds ratio (aOR) = 0.80, 99 % CI = 0.76–0.85) relative to IH veterans and more likely to be prescribed non-stimulants (aOR = 1.12, CI = 1.06–1.18). However, among veterans prescribed stimulants, homeless veterans had more indicators of RPIP, including being prescribed stimulants in the presence of a psychotic disorder (7.9 % vs. 6.4 % for HUD-VASH vs. 2.2 % for IH, p &lt; .001).</div></div><div><h3>Conclusion</h3><div>Homeless veterans with mental illness were less likely to be prescribed stimulants and more likely to be prescribed non-stimulant ADHD medications relative to IH veterans with mental illness. However, RPIP of stimulant prescriptions was more common for homeless and HUD-VASH veterans relative to IH veterans.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"194 ","pages":"Pages 287-293"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978217","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":"Autonomic dysfunctions in psychotic disorders, interaction with antipsychotic intervention and treatment resistance: a comprehensive systematic review and meta-analysis","authors":"Federica Iannotta ,&nbsp;Felice Iasevoli ,&nbsp;Claudio Caiazza ,&nbsp;Michele Fornaro ,&nbsp;Maria Nolano ,&nbsp;Andrea de Bartolomeis","doi":"10.1016/j.jpsychires.2025.12.041","DOIUrl":"10.1016/j.jpsychires.2025.12.041","url":null,"abstract":"<div><h3>Background</h3><div>Autonomic nervous system (ANS) dysfunctions have been increasingly implicated as a feature of psychoses’ pathophysiology. The specificity of these alterations and the role of antipsychotic medication remain controversial.</div></div><div><h3>Methods</h3><div>We conducted a systematic review and meta-analysis, following a predetermined protocol (PROSPERO/CRD42024510812) to assess heart-rate variability (HRV), electrodermal activity (EDA), and peripheral biomarkers in psychotic disorders. We searched PubMed and EMBASE from inception until July 2024. We conducted random-effects meta-analyses and assessed heterogeneity, publication bias, and risk of bias.</div></div><div><h3>Results</h3><div>Patients with psychosis showed a significant reduction in HRV compared to healthy controls, especially in indices reflecting parasympathetic activity. This result was evident in both treated and untreated patients and was also observed in the comparison between patients with psychosis and affective disorders. Among all antipsychotics, clozapine was associated with the greatest reduction in HRV. EDA and peripheral markers, i.e., alpha amylase and catecholamines, did not show significant differences between patients with psychosis and healthy controls. However, the skin conductance level (SCL) showed a trend to decrease after the introduction of antipsychotics.</div></div><div><h3>Conclusions</h3><div>These results suggest that ANS dysregulations may be a core feature of psychosis, only partially dependent on pharmacological treatment, suggesting a potential primary dysregulation within the Central Autonomic Network. Disruptions in neurotransmitter systems, particularly acetylcholine, may contribute. Autonomic profiling could refine psychiatric diagnosis, helping with tailored interventions. Longitudinal studies are needed to explore their potential in predicting treatment response.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"194 ","pages":"Pages 123-135"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878531","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":"Astrocyte-mediated hippocampal damage in the pathogenesis of dysexecutive syndrome following COVID-19: A narrative review","authors":"Antonino Messina ,&nbsp;Fabrizio Bella ,&nbsp;Giuliana Maccarone ,&nbsp;Gabriele Avincola ,&nbsp;Maria Salvina Signorelli","doi":"10.1016/j.jpsychires.2026.01.007","DOIUrl":"10.1016/j.jpsychires.2026.01.007","url":null,"abstract":"<div><div>SARS-CoV-2 infection has been implicated in hippocampal damage, contributing to the pathogenesis of dysexecutive syndrome observed in post-COVID-19 patients. Given the growing prevalence of long-COVID worldwide, understanding how SARS-CoV-2 affects hippocampal structure and function has become an urgent scientific and clinical priority. The hippocampus—crucial for memory, emotional regulation, and executive functioning—is especially susceptible to viral-driven neuroinflammatory cascades. SARS-CoV-2 triggers astrocyte and microglia activation, disrupts blood–brain barrier integrity, and induces cytokine-mediated neurotoxicity, ultimately impairing neuroplasticity and neurogenesis. These mechanisms converge to produce cognitive and affective disturbances—most notably fatigue, apathy, low mood, and executive dysfunction—that typify dysexecutive syndrome in long-COVID.</div><div>This review synthesizes current evidence from clinical and experimental studies, integrating findings on viral neurotropism, hippocampal hypometabolism, and astrocyte-mediated neurodegeneration. Distinctions between depressive symptoms driven by neuroinflammation and classical depressive disorders are clarified to improve diagnostic accuracy and guide personalized treatment. Emerging data on the neuroprotective role of COVID-19 vaccination—particularly its capacity to modulate microglial activation and support hippocampal neurogenesis—are also examined. Overall, the findings underscore the need for targeted therapeutic strategies aimed at modulating neuroinflammation and supporting hippocampal plasticity, including cognitive rehabilitation approaches.</div><div>Longitudinal studies are essential to elucidate the enduring impact of SARS-CoV-2 on hippocampal function and to inform effective clinical interventions.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"194 ","pages":"Pages 164-173"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912068","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 adding cognitive behavioral therapy to quetiapine on suicide risk, depressive symptoms, and coping style in adult patients with mood disorders","authors":"Ke Wang,&nbsp;Shan Cai,&nbsp;Xin-Rong Duanmu,&nbsp;Chen-Yu Ma,&nbsp;Rui Yan,&nbsp;Yan-Rui Cui,&nbsp;Lin Zhou,&nbsp;Liu-Liu Xu","doi":"10.1016/j.jpsychires.2026.01.005","DOIUrl":"10.1016/j.jpsychires.2026.01.005","url":null,"abstract":"<div><h3>Objective</h3><div>Quetiapine is an atypical antipsychotic with a broad spectrum of use including anti-anxiety and mood stabilizing properties and has proved effective in mood disorders, such as major depressive disorder and bipolar depression. An integration of cognitive behavioral therapy (CBT) with pharmacological treatment has shown to outperform drugs alone in reducing suicide risk for patients with mood disorders. In this study, we investigated the effect of adding cognitive behavioral therapy (CBT) to quetiapine on suicide risk, depressive symptoms, and coping style in adult patients with mood disorders.</div></div><div><h3>Methods</h3><div>One hundred and thirty-seven patients were randomized to QUE group (n = 70) and QUE + CBT group (n = 67). The primary outcome was suicide risk assessed by the Nurses’ Global Assessment of Suicide Risk (NGASR) scale. The secondary outcomes were depressive symptoms assessed by the 24-item Hamilton Depression Rating Scale (HDRS-24) and coping style assessed by the Simplified Coping Style Questionnaire (SCSQ).</div></div><div><h3>Results</h3><div>The QUE + CBT group showed a significantly lower percentage with high suicide risk in the modified intention-to-treat population than the QUE group after 12-week intervention (χ² = 5.50; p = 0.02). The analysis of covariance (ANCOVA) controlling for baseline scores indicated a significantly main effect of treatment in scores of NGASR [F(1, 135) = 25.30, p &lt; 0.01, partial η² = 0.16], HDRS-24 [F(1, 135) = 27.00, p &lt; 0.01, partial η² = 0.17], positive coping [F(1, 135) = 10.00, p &lt; 0.01, partial η² = 0.07] and negative coping of SCSQ [F(1, 135) = 26.70, p &lt; 0.01, partial η² = 0.17], suggesting that lower scores of NGASR and HDRS-24, a higher positive coping score, and a lower negative coping score in the QUE + CBT group than in the QUE group after 12-week intervention.</div></div><div><h3>Conclusion</h3><div>These results suggest that adding CBT to quetiapine could decrease suicide risk, improve depressive symptoms, and enhance coping style for adult patients with mood disorders.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"194 ","pages":"Pages 145-150"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912053","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":"Implicit social animations lead to distinct changes of dopaminergic, corticostriatal and thalamocortical functional connectivity in schizophrenia and bipolar disorder","authors":"Ricardo Martins ,&nbsp;João Valente Duarte ,&nbsp;Nuno Madeira ,&nbsp;António Macedo ,&nbsp;Miguel Castelo-Branco","doi":"10.1016/j.jpsychires.2026.01.016","DOIUrl":"10.1016/j.jpsychires.2026.01.016","url":null,"abstract":"<div><h3>Objective</h3><div>Theory of mind (ToM) is a central pillar of social cognition and crucial for effective social interactions. Impairment in ToM is a major predictor of global functioning in schizophrenia (SCZ) and bipolar disorder (BPD). Based on the hypothesis that subcortical and reward circuit functional connectivity is distinct in SCZ and BPD and can be better revealed using ToM task-based approaches, we tested whether functional connectivity patterns of cortico-subcortical networks are a discriminative feature of these disorders.</div></div><div><h3>Methods</h3><div>We conducted a cross-sectional study (n = 60) to investigate the modulation of task-induced functional connectivity in SCZ (n = 20), BPD (n = 20), and healthy controls (n = 20) during implicit ToM processing with a visual paradigm leading to the interpretation of social meaning based on simple geometric figures with implied social content. Functional connectivity was estimated using generalized psychophysiological analysis of functional magnetic resonance imaging data.</div></div><div><h3>Results</h3><div>We found unique connectivity patterns in SCZ and BPD within subcortical loops. The SCZ group exhibited specifically disrupted connectivity in corticostriatal and thalamocortical pathways involving ToM and the mesolimbic pathways. A single common pattern of aberrant connectivity in BPD and SCZ occurred between the VTA and dorsal striatum, suggesting increased midbrain-striatal (actor-critic) connectivity in both disorders.</div></div><div><h3>Conclusions</h3><div>The unique patterns of altered connectivity in SCZ (imbalance between striatothalamic and thalamocortical connectivity), and BPD, while sharing a common pattern of increase between VTA and dorsal striatum, may represent candidate biomarkers of pathophysiological significance, or as biological targets for validating differential therapeutic neuromodulation.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"194 ","pages":"Pages 303-311"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978074","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":"A translational neuroscience & computational evaluation of a D1R partial agonist for schizophrenia (TRANSCENDS): Rationale and study design of a brain-based clinical trial","authors":"Clara Fonteneau ,&nbsp;Zailyn Tamayo ,&nbsp;Ally Price ,&nbsp;Lining Pan ,&nbsp;Yvette Afriyie-Agyemang ,&nbsp;Shriya Agrawal ,&nbsp;Audrey Butler ,&nbsp;Courtney Cail ,&nbsp;Monica Calkins ,&nbsp;Ananthsrinivas Rao Chakilam ,&nbsp;Kimberlee Forselius-Bielen ,&nbsp;Geena Fram ,&nbsp;Allea Frazier ,&nbsp;Roberto Gil ,&nbsp;Preetika Govil ,&nbsp;David L. Gray ,&nbsp;Jack Grinband ,&nbsp;Ruben C. Gur ,&nbsp;Natalka K. Haubold ,&nbsp;Zachary Heffernan ,&nbsp;John H. Krystal","doi":"10.1016/j.jpsychires.2025.12.020","DOIUrl":"10.1016/j.jpsychires.2025.12.020","url":null,"abstract":"<div><div>Despite decades of research, cognitive impairment remains a critical untreated symptom for many patients with schizophrenia. One way to accelerate the development of pro-cognitive therapies for schizophrenia is to evaluate compounds using biomarker approaches tailored to relevant neural mechanisms. While D1/D5 receptor (D1R/D5R) agonism has been extensively studied in neuroscience, its therapeutic potential for cognitive impairment in schizophrenia remains untapped. The Translational Neuroscience &amp; Computational Evaluation of a D1R Partial Agonist for Schizophrenia (TRANSCENDS) clinical trial tests this mechanism using a ‘target engagement’ approach. Multiple, double-blind doses of a D1/D5R partial agonist were administered in advance of a functional neuroimaging (fMRI) session that deployed a cognitive paradigm explicitly designed to capture a translational micro-circuit mechanism underlying spatial working memory in patients with schizophrenia. Specifically, this study will assess whether the D1R/D5R partial agonist CVL-562 induces a dose-dependent engagement of spatial working memory circuits in schizophrenia using fMRI. This design, and the use of spatial working memory neural circuits as a dependent measure, was selected on the basis of a translational and computational understanding of prefrontal micro-circuitry and a mechanistic understanding of the role of D1R/D5Rs in schizophrenia. To enhance data integration and scalability, TRANSCENDS employs an automated informatics framework for seamless neuroimaging data sharing and electronic clinical data capture. This ensures high-standards for regulatory compliance, data quality, and data sharing across sites, improving aspects of current clinical trial data management. We share the study design and approach with the goal of advancing future pro-cognitive drug development and strategies for developing mechanistically-driven biomarkers in psychiatry.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"194 ","pages":"Pages 196-210"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927687","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":"Imaging transcriptomics identifies gene signatures associated with cortical thinning in schizophrenia","authors":"Ye Tu ,&nbsp;Shenrui Li ,&nbsp;Shaodi Guan ,&nbsp;Yueyang Xin ,&nbsp;Hong Tao ,&nbsp;Zhiqiang Zhou ,&nbsp;Shaofang Wang ,&nbsp;Hongwei Jiang ,&nbsp;Hui Xu","doi":"10.1016/j.jpsychires.2026.01.008","DOIUrl":"10.1016/j.jpsychires.2026.01.008","url":null,"abstract":"<div><h3>Background</h3><div>Schizophrenia, a debilitating neuropsychiatric disorder with profound socioeconomic consequences, manifests characteristic cortical thinning patterns observable through neuroimaging. While structural magnetic resonance imaging (MRI) studies consistently demonstrate these anatomical disturbances, their molecular signatures remain poorly understood.</div></div><div><h3>Methods</h3><div>We employed an integrative neuroimaging-transcriptomic approach, combining structural MRI data from 50 schizophrenia patients and 125 healthy controls with postmortem gene expression profiles from the Allen Human Brain Atlas. Spatial relationships between transcriptional patterns and cortical thickness variations were quantified using partial least squares regression. Subsequent analyses included gene ontology enrichment, cell-type deconvolution, and protein-protein interaction network.</div></div><div><h3>Results</h3><div>Schizophrenia patients demonstrated significant cortical thinning in limbic and paralimbic regions critical for emotional processing, including anterior cingulate and insular cortices. Imaging transcriptomic analyses revealed strong associations between cortical alterations and schizophrenia-risk genes <em>STON2, ANK3,</em> and <em>KCNN3</em>. Enriched biological pathways included stress-responsive signaling, calcium homeostasis, and synaptic plasticity. Cell-type analyses implicated excitatory and inhibitory neurons, together with microglia, while network analysis identified KCNB1, PTGS2, and TPT1 as central molecular hubs.</div></div><div><h3>Conclusions</h3><div>This study reveals specific molecular correlates of cortical thinning in schizophrenia, highlighting biological mechanisms that may contribute to structural abnormalities. The identified genes and pathways offer potential therapeutic targets for addressing both neuroanatomical changes and affective disturbances in schizophrenia.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"194 ","pages":"Pages 151-163"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912036","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}