Biological psychiatry. Cognitive neuroscience and neuroimaging最新文献

{"title":"Effects of COMT suppression in a randomized trial on the neural correlates of inhibitory processing among people with Alcohol Use Disorder.","authors":"Drew E Winters, Joseph P Schacht","doi":"10.1016/j.bpsc.2025.06.003","DOIUrl":"https://doi.org/10.1016/j.bpsc.2025.06.003","url":null,"abstract":"<p><strong>Background: </strong>Dysregulation of inhibitory control is a core feature of Alcohol Use Disorder (AUD), and is mediated, in part, by catechol-O-methyltransferase (COMT) regulation of cortical dopaminergic neurotransmission. Tolcapone, a brain-penetrant COMT inhibitor, potentiates evoked dopamine release, and may improve inhibitory control in AUD.</p><p><strong>Methods: </strong>Non-treatment-seeking participants with AUD (n=64) were randomized to tolcapone (titrated to 200 mg t.i.d.) or placebo for 8 days and completed an fMRI stop-signal task on study Days 1 (prior to medication ingestion) and 7. Brain areas in which activation for the contrast of successful vs. unsuccessful stop trials (SS>SE) differed between medication groups on Day 7 relative to Day 1 were identified. Activation of these areas, and their functional connectivity with other areas, was tested for association with changes in drinking during the medication period and with stop-signal reaction time, a behavioral index of inhibitory control.</p><p><strong>Results: </strong>The tolcapone group demonstrated greater SS>SE activation in the right dorsolateral prefrontal cortex and inferior frontal gyrus (iFG). In the tolcapone group, greater activation of both areas was associated with improved inhibitory control, and greater iFG activation was associated with reduced drinking. Increased connectivity between iFG and right anterior insula was associated with reduced drinking, and between iFG and anterior cingulate cortex with improved inhibitory control.</p><p><strong>Conclusions: </strong>Tolcapone increased activation of cortical areas implicated in inhibitory control. The associations between increased iFG activation and connectivity, improved inhibitory control, and reduced drinking suggest that pharmacological interventions that increase cortical dopamine may rescue dysregulated inhibitory control among people with AUD.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormal association between neural activity and genetic expressions of impulsivity in attention deficit hyperactivity disorder: an Adolescent Brain Cognitive Development study.","authors":"Soohyun Jeon, Jae-Eon Kang, Jundong Hwang, Vince D Calhoun, Jong-Hwan Lee","doi":"10.1016/j.bpsc.2025.06.002","DOIUrl":"https://doi.org/10.1016/j.bpsc.2025.06.002","url":null,"abstract":"<p><strong>Background: </strong>Impulsivity in highly heritable attention deficit hyperactivity disorder (ADHD) has been studied using neural activity via fMRI or genetic data, but rarely with multivariate methods linking both. We investigated coupled neural activity and gene expression signatures, using parallel independent component analysis (pICA) and Adolescent Brain Cognitive Development data.</p><p><strong>Methods: </strong>Children with ADHD (n = 394; 63% males) and healthy controls (n = 1,000; 47% males) of European ancestry were included. The subjects were randomly divided into 80% discovery and 20% replication datasets with demographic stratification. We analyzed neural activity and gene expressions from the discovery datasets using pICA and extracted paired independent components (pICs). The loading coefficients of the pICs were utilized to predict behavioral and cognitive data for stop signal task (SST) in replication datasets.</p><p><strong>Results: </strong>We identified three pICs estimated from gene expression in the cortex, cerebellum, and nucleus accumbens. Significant neural activity was mainly localized to the orbital/inferior/middle frontal gyri, rectal gyrus, precuneus, inferior temporal gyrus, inferior parietal lobule, and cerebellum. Significant gene components were associated with immunoglobulin, taste receptor, and immunity-related terms and were overlapped with ADHD-related genes. The extracted fMRI-/Gene-ICs were significantly correlated with mean reaction time, stop signal reaction time of SST, and behavioral inhibition with a large boost in sensitivity when both the paired fMRI-/Gene-ICs and their interaction were used in a multimodal regression analysis.</p><p><strong>Conclusion: </strong>We reported biologically plausible pairs of neural activity and gene sets using pICA, which were significantly associated with ADHD impulsivity-related behavioral and cognitive data.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurite Density and Kurtosis in the Gray Matter of People with Early Schizophrenia.","authors":"Peter C Van Dyken, Ali R Khan, Lena Palaniyappan","doi":"10.1016/j.bpsc.2025.06.001","DOIUrl":"https://doi.org/10.1016/j.bpsc.2025.06.001","url":null,"abstract":"<p><strong>Background: </strong>Classical models of diffusion weighted imaging, especially diffusion tensor imaging, are unsuited for application to the cortical gray matter, given the regions high microstructural complexity. As such, most neuroimaging studies thus far have focused on gross structural effects of schizophrenia, such as cortical thickness differences. More recently developed models, such as the neurite orientation dispersion and density imaging (NODDI) model and diffusion kurtosis imaging (DKI), incorporate higher resolution data and may provide more sensitive descriptions of schizophrenia pathology with more specific interpretations.</p><p><strong>Methods: </strong>We applied the NODDI and DKI models to the cortical gray matter of people with early schizophrenia (n=54) and healthy controls (n=51) from the Human Connectome Project - Early Psychosis dataset. Comparisons between groups were made using region-of-interest and clustering approaches. The effect sizes of these approaches were compared to those of cortical thickness differences. We also investigated the relationship between these parameters and lifetime antipsychotic usage.</p><p><strong>Results: </strong>Cortical thickness differences were most prominent between groups in terms of global effect size and spatial extent. We also observed a diffuse, right-hemisphere dominant increase in mean kurtosis and isotropic diffusion fraction throughout the gray matter, not fully explained by partial volume effects. Additionally, a lower neurite density index (NDI) correlated with greater lifetime antipsychotic usage.</p><p><strong>Conclusions: </strong>Increases in mean kurtosis and isotropic diffusion fraction are both markers of schizophrenia, consistent with inflammation models of the gray matter in schizophrenia. NDI reduction, reflecting intraneurite pathology, becomes prominent only in those with greater disease burden.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebello-Thalamo-Cortical Dysconnectivity in Schizophrenia Spectrum Disorders: A Resting-State fMRI Meta-Analysis.","authors":"Orsolya Lányi, Daniel Zahemszky, Alexander Schulze Wenning, Marie Anne Engh, Zsolt Molnár, András Attila Horváth, Péter Hegyi, Gábor Csukly","doi":"10.1016/j.bpsc.2025.05.017","DOIUrl":"https://doi.org/10.1016/j.bpsc.2025.05.017","url":null,"abstract":"<p><strong>Background: </strong>Cerebello-thalamo-cortical (CTC) network dysfunctions are well-documented in schizophrenia spectrum disorders (SSD) and preclinical states. However, small samples and methodological heterogeneity often limit individual neuroimaging studies. To overcome these challenges, we conducted a coordinate-based meta-analysis to characterize CTC alterations across illness stages and examine associations with symptom dimensions.</p><p><strong>Methods: </strong>Our meta-analysis was preregistered and followed the PRISMA guideline and the recommendations of the Cochrane Handbook. A systematic search was conducted in three databases in September 2023. Included articles used seed-based resting-state fMRI in patients with schizophrenia-spectrum disorders, first-episode psychosis, clinical high-risk for psychosis, and healthy control groups. Seeds were defined in the thalamus and the cerebellum. Two coordinate-based meta-analytic methods, Activation Likelihood Estimation and Seed-based D Mapping were used. Risk of bias was evaluated per the OHBM recommendations.</p><p><strong>Results: </strong>Thalamic hypoconnectivity in the prefrontal cortex, limbic lobe, thalamus and the cerebellum, and hyperconnectivity in the somato-motor and visual association areas was found in SSD (29 studies, 2768 patients). Dysconnectivity was linked to disease progression and symptoms. Cerebellar analysis indicated hypoconnectivity in the prefrontal cortex, cerebellum, and thalamus, with hyperconnectivity in the motor cortex, somatosensory cortex, and orbitofrontal cortex (19 studies, 1159 patients). Cerebellar clusters did not survive multiple comparison correction.</p><p><strong>Conclusions: </strong>Our findings provide robust meta-analytic evidence of cerebello-thalamo-cortical dysconnectivity in SSD, suggesting this network captures a core neurobiological feature of psychotic disorders. Consistent patterns of altered CTC connectivity underscore the importance of future clinical investigations of this network as a potential target for therapeutic interventions.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Auditory and Visual Thalamocortical Connectivity Alterations in Unmedicated People with Schizophrenia: An Individualized Sensory Thalamic Localization and Resting-State Functional Connectivity Study.","authors":"John C Williams, Philip N Tubiolo, Roberto B Gil, Zu Jie Zheng, Eilon B Silver-Frankel, Natalka K Haubold, Sameera K Abeykoon, Dathy T Pham, Najate Ojeil, Kelly Bobchin, Mark Slifstein, Jodi J Weinstein, Greg Perlman, Guillermo Horga, Anissa Abi-Dargham, Jared X Van Snellenberg","doi":"10.1016/j.bpsc.2025.05.016","DOIUrl":"10.1016/j.bpsc.2025.05.016","url":null,"abstract":"<p><strong>Background: </strong>Converging evidence from clinical neuroimaging and animal models has strongly implicated dysfunction of thalamocortical circuits in the pathophysiology of schizophrenia. Preclinical models of genetic risk for schizophrenia have shown reduced synaptic transmission from auditory thalamus to primary auditory cortex, which may represent a correlate of auditory disturbances such as hallucinations. Human neuroimaging studies, however, have found a generalized increase in resting state functional connectivity (RSFC) between whole thalamus and sensorimotor cortex in people with schizophrenia (PSZ). We aimed to more directly translate preclinical findings by specifically localizing auditory and visual thalamic nuclei in unmedicated PSZ and measuring RSFC to primary sensory cortices.</p><p><strong>Methods: </strong>In this case-control study, 82 unmedicated PSZ and 55 matched healthy controls (HC) completed RSFC functional magnetic resonance imaging (fMRI). Auditory and visual thalamic nuclei were localized for 55 unmedicated PSZ and 46 HC who additionally completed a sensory thalamic nuclei localizer fMRI task (N = 101). Using localized nuclei as RSFC seeds we assessed group differences in auditory and visual thalamocortical connectivity and associations with positive symptom severity.</p><p><strong>Results: </strong>Auditory thalamocortical connectivity was not significantly different between PSZ and HC, but hyperconnectivity was associated with greater positive symptom severity in bilateral superior temporal gyrus. Visual thalamocortical connectivity was significantly greater in PSZ relative to HC in secondary and higher-order visual cortex, but not predictive of positive symptom severity.</p><p><strong>Conclusion: </strong>These results indicate that visual thalamocortical hyperconnectivity is a generalized marker of schizophrenia, while hyperconnectivity in auditory thalamocortical circuits relates more specifically to positive symptom severity.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Neural Spectrum of Disturbed Emotion.","authors":"Maurizio Sicorello","doi":"10.1016/j.bpsc.2025.05.014","DOIUrl":"https://doi.org/10.1016/j.bpsc.2025.05.014","url":null,"abstract":"","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Face Processing in School-Aged Preterm Children: Assessing Neural Sensitivity to Facial Identity and Expression Using Frequency-Tagging EEG.","authors":"Tiffany Tang, Matthijs Moerkerke, Nicky Daniels, Stephanie Van der Donck, Jean Steyaert, Gunnar Naulaers, Kaat Alaerts, Els Ortibus, Bart Boets","doi":"10.1016/j.bpsc.2025.05.015","DOIUrl":"https://doi.org/10.1016/j.bpsc.2025.05.015","url":null,"abstract":"<p><strong>Background: </strong>Preterm (PT) birth is associated with important social vulnerabilities that can have long-term implications and may result in psychopathology (e.g., autism spectrum disorder). A recurring \"preterm behavioral phenotype\" has been described, although these difficulties may often be subtle and subclinical. As face processing is crucial for social interactions and several studies reported impaired face processing performance in PT populations, we hypothesize that face processing difficulties may contribute to or be a part of these social difficulties. Here, we investigate the neural sensitivity for crucial socio-communicative facial cues in school-aged PT children.</p><p><strong>Methods: </strong>Thirty-nine 8-to-12-year-old PT children born between 24 and 32 weeks of gestation and thirty-eight term-born matched controls performed a series of innovative facial identity and expression discrimination frequency-tagging electroencephalography paradigms. More specifically, we evaluated the neural sensitivity to implicitly and automatically discriminate a different facial identity among a stream of identical faces, as well as an expressive face (fearful and happy, in separate sequences) among a stream of neutral faces.</p><p><strong>Results: </strong>We found intact implicit facial identity and expression processing in both groups. Unexpectedly, PT participants showed a significantly greater neural sensitivity towards these subtle socio-communicative facial cues. Correlations with neonatal measures such as gestational age and birth weight showed that this greater neural sensitivity is uniformly present among the PT group.</p><p><strong>Conclusion: </strong>Evidence suggests that impaired neural sensitivity for facial cues may not be the primary cause for behavioral face processing and social difficulties often encountered in PT children.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Granularity of emotions in brain and behavior and resilience to childhood violence exposure.","authors":"David G Weissman, Shafi Rubbani, Stephanie N DeCross, Steven W Kasparek, Katie A McLaughlin","doi":"10.1016/j.bpsc.2025.05.012","DOIUrl":"https://doi.org/10.1016/j.bpsc.2025.05.012","url":null,"abstract":"<p><strong>Background: </strong>This study identified behavioral and neural indices of the specificity of emotion representations in adolescents' brains and assessed their association with resilience to childhood violence exposure.</p><p><strong>Methods: </strong>Eighty 13-18-year-old adolescents with variable exposure to violence viewed emotion-eliciting videos and rated how angry, disgusted, sad, scared, and upset they felt. Sixty-nine participants viewed the same videos in the MRI scanner, once while labelling their emotions and once while counting the number of people.</p><p><strong>Results: </strong>Emotion labelling (vs. counting) led to greater BOLD activation in medial and ventrolateral prefrontal cortex. Based on RSA, if two stimuli elicited more similar patterns of activation within those brain regions, those stimuli had more similar emotion ratings, suggesting that encoding of emotion categories within these brain regions is reflected in their activation patterns. Moreover, emotion differentiation measured behaviorally and the mean neural dissimilarity across all stimulus pairs for each participant each moderated the association between violence exposure and psychopathology, such that the association between violence exposure and psychopathology was weaker in those with greater emotion differentiation and neural dissimilarity.</p><p><strong>Conclusions: </strong>The granularity of emotions reflected in adolescents' brains and behavior contribute to resilience and therefore may serve as a target for preventative interventions.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computationally-informed insights into anhedonia and treatment by k-opioid receptor antagonism.","authors":"Bilal A Bari, Andrew D Krystal, Diego A Pizzagalli, Samuel J Gershman","doi":"10.1016/j.bpsc.2025.05.011","DOIUrl":"https://doi.org/10.1016/j.bpsc.2025.05.011","url":null,"abstract":"<p><strong>Background: </strong>Anhedonia, the loss of pleasure, is prevalent and impairing. Parsing its computational basis promises to explain its transdiagnostic character. One manifestation of anhedonia-reward insensitivity-may be linked to limited memory. Further, the need to economize on limited memory engenders a perseverative bias towards frequently chosen actions. Anhedonia may also be linked with deviations from optimal perseveration for a given memory capacity, a pattern that causes inefficiency because it results in less reward for the same memory cost.</p><p><strong>Methods: </strong>To test these hypotheses, we apply a theory of optimal decision-making under memory constraints that decomposes behavior into a memory component and an efficiency component. We apply this theory to behavior on the Probabilistic Reward Task, a reward learning paradigm validated in anhedonia, and perform secondary analysis of a randomized controlled trial testing κ-opioid receptor (KOR) antagonism for anhedonia (N=24 KOR; N=31 placebo), as well as analyses of three other datasets (N=100, 66, 24 respectively). We fit a resource-bounded reinforcement-learning model to behavior.</p><p><strong>Results: </strong>Across clinical and nonclinical populations, anhedonia is associated with deficits in efficiency but not memory. The reinforcement learning models demonstrate that deficits in efficiency arise from the inability to perseverate optimally. KOR antagonism, which likely elevates tonic dopamine, increases both memory and efficiency, and the model demonstrates that this arises from increased reward sensitivity and perseveration.</p><p><strong>Conclusions: </strong>KOR antagonism therefore has distinct cognitive effects, only one related to anhedonia. These findings have potential implications for the applications of KOR antagonists.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Penetrance of neurodevelopmental copy number variants is associated with variations in cortical morphology.","authors":"Ana I Silva, Ida E Sønderby, George Kirov, Abdel Abdellaoui, Ingrid Agartz, David Ames, Nicola J Armstrong, Eric Artiges, Tobias Banaschewski, Anne S Bassett, Carrie E Bearden, John Blangero, Rune Boen, Dorret I Boomsma, Robin Bülow, Nancy J Butcher, Vince Calhoun, Linda E Campbell, Eva W C Chow, Simone Ciufolini, Michael C Craig, Benedicto Crespo-Farroco, Adam C Cunningham, Shareefa Dalvie, Eileen Daly, Paola Dazzan, Eco J C de Geus, Greig I de Zubicaray, Joanne L Doherty, Gary Donohoe, Mark Drakesmith, Thomas Espeseth, Vincent Frouin, Hugh Garavan, David C Glahn, Naomi J Goodrich-Hunsaker, Penny A Gowland, Hans J Grabe, Antoine Grigis, Maria Gudbrandsen, Boris A Gutman, Jan Haavik, Asta K Håberg, Jeremy Hall, Andreas Heinz, Sarah Hohmann, Jouke-Jan Hottenga, Sébastien Jacquemont, Neda Jahanshad, Rachel K Jonas, Derek K Jones, Erik G Jönsson, Sanne Koops, Kuldeep Kumar, Stephanie Le Hellard, Herve Lemaitre, Jingyu Liu, Astri J Lundervold, Jean-Luc Martinot, Karen A Mather, Donna M McDonald-McGinn, Katie L McMahon, Allan F McRae, Sarah E Medland, Clara A Moreau, Kieran C Murphy, Declan Murphy, Robin M Murray, Frauke Nees, Michael J Owen, Marie-Laure Paillère Martinot, Diimitri Papadopoulos Orfanos, Tomas Paus, Luise Poustka, Tiago Reis Marques, David R Roalf, Perminder S Sachdev, Freda Scheffler, J Eric Schmitt, Gunter Schumann, Vidar M Steen, Dan J Stein, Lachlan T Strike, Alexander Teumer, Anbupalam Thalamuthu, Sophia I Thomopoulos, Diana Tordesillas-Gutiérrez, Julian N Trollor, Anne Uhlmann, Ariana Vajdi, Dennis van 't Ent, Therese van Amelsvoort, Marianne B M van den Bree, Dennis van der Meer, Javier Vázquez-Bourgon, Julio E Villalón-Reina, Uwe Völker, Henry Völzke, Jacob A S Vorstman, Lars T Westlye, Nigel Williams, Katharina Wittfeld, Margaret J Wright, Paul M Thompson, Ole A Andreassen, David E J Linden","doi":"10.1016/j.bpsc.2025.05.010","DOIUrl":"https://doi.org/10.1016/j.bpsc.2025.05.010","url":null,"abstract":"<p><strong>Background: </strong>Copy number variants (CNVs) increase risk for neurodevelopmental conditions. The neurobiological mechanisms linking these high-risk genetic variants to clinical phenotypes are largely unknown. An important question is whether brain abnormalities in individuals carrying CNVs are associated with their degree of penetrance.</p><p><strong>Methods: </strong>We investigated if increased CNV-penetrance for schizophrenia and other developmental disorders was associated with variations in cortical and subcortical morphology. We pooled T1-weighted brain magnetic resonance imaging and genetic data from 22 cohorts from the ENIGMA-CNV consortium. In the main analyses, we included 9,268 individuals (aged 7 to 90 years, 54% females), from which we identified 398 carriers of 36 neurodevelopmental CNVs at 20 distinct loci. A secondary analysis was performed including additional neuroimaging data from the ENIGMA-22q consortium, including 274 carriers of the 22q11.2 deletion and 291 non-carriers. CNV-penetrance was estimated through penetrance scores that were previously generated from large cohorts of patients and controls. These scores represent the probability risk to develop either schizophrenia or other developmental disorders (including developmental delay, autism spectrum disorder and congenital malformations).</p><p><strong>Results: </strong>For both schizophrenia and developmental disorders, increased penetrance scores were associated with lower surface area in the cerebral cortex and lower intracranial volume. For both conditions, associations between CNV-penetrance scores and cortical surface area were strongest in regions of the occipital lobes, specifically in the cuneus and lingual gyrus.</p><p><strong>Conclusions: </strong>Our findings link global and regional cortical morphometric features with CNV-penetrance, providing new insights into neurobiological mechanisms of genetic risk for schizophrenia and other developmental disorders.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}