Biological psychiatry. Cognitive neuroscience and neuroimaging最新文献

{"title":"In Vivo PET Imaging of Preynaptic Density Reveals Stress-Associated Synaptic Deficits Related to Behavioral and Molecular Alterations in Rats.","authors":"Ruth H Asch, Nira Hernandez Martin, Rolando Garcia-Milian, Krista Fowles, Ralph J DiLeone, Zhengxin Cai, Conor M Liston, Irina Esterlis","doi":"10.1016/j.bpsc.2025.09.021","DOIUrl":"https://doi.org/10.1016/j.bpsc.2025.09.021","url":null,"abstract":"<p><strong>Background: </strong>Preclinical research indicates chronic stress can induce synaptic loss in corticolimbic brain regions regulating mood and cognition. Presynaptic density can now be measured in vivo using radioligands targeting synaptic vesicle protein 2A and positron emission tomography (PET). We conducted a first in vivo PET study to investigate chronic stress-induced synaptic density changes in rats and examined correlates with behavior and protein expression.</p><p><strong>Methods: </strong>Male and female Long-Evans rats were exposed to chronic unpredictable stress (CUS; n=24/sex) and compared with controls (n=12/sex). Sucrose preference and novel object recognition (NOR) were used to assess stress-related behavioral phenotypes. PET with [¹⁸F]SynVesT-1 was used to measure synaptic density in a subset of rats (n=8-9/group/sex). Prefrontal cortex (PFC) and hippocampal proteins were quantified via LC-MS/MS (n=5/group/sex), followed by pathway analysis and linear regression to examine molecular profiles associated with CUS and correlated with synaptic density as measured by PET.</p><p><strong>Results: </strong>Synaptic density was lower in the PFC of CUS rats relative to controls (d=0.94, p=0.012) and correlated with sucrose preference (r=0.35, p=0.042). Synaptic density was also lower in hippocampus (d=0.55, p=0.017), which correlated with NOR (r=0.35 p=0.045). Differentially expressed proteins were enriched for transcriptional regulation and metabolic pathways. Proteins implicated in synaptogenesis and neurodegeneration were positively and negatively correlated, respectively, with synaptic density.</p><p><strong>Conclusions: </strong>We demonstrate that [¹⁸F]SynVesT-1 PET can be used for in vivo quantification of synaptic density in a rodent model of chronic stress. This method can, therefore, facilitate translational research investigating synaptic mechanisms in stress-related pathology and treatment response.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214694","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":"Predicting repetitive negative thinking in daily life: Insights from the brain-based graph-theoretical predictive modeling.","authors":"Martino Schettino, Rotem Dan, Chiara Parrillo, Federico Giove, Antonio Napolitano, Cristina Ottaviani, Diego A Pizzagalli","doi":"10.1016/j.bpsc.2025.09.020","DOIUrl":"https://doi.org/10.1016/j.bpsc.2025.09.020","url":null,"abstract":"<p><strong>Background: </strong>Abnormalities in the functional connectivity of large-scale brain networks, including the default mode (DMN), salience (SN), fronto-parietal (FPN), and limbic networks, have been implicated in repetitive negative thinking (RNT), a construct characterized by persistent and intrusive thoughts. However, the potential of these large-scale network abnormalities for predicting RNT in daily life remains underexplored.</p><p><strong>Methods: </strong>We leveraged the brain-based graph-theoretical predictive modeling (GPM) to predict daily-life RNT in 54 individuals. Functional MRI data were acquired during: (i) resting-state and (ii) an RNT-induced state. RNT severity and its momentary fluctuations were assessed using ecological momentary assessments (EMA).</p><p><strong>Results: </strong>The GPM identified key functional organizational properties of the DMN, FPN, and limbic networks that differentially predicted the severity and fluctuations of RNT and its specific clinical features (intrusiveness, repetitiveness, RNT-related anxiety). Specifically, the centrality of the medial prefrontal cortex (DMN) predicted EMA fluctuations of intrusiveness and severity of anxiety. Conversely, the strength and centrality of the orbitofrontal cortex (part of the limbic network) predicted EMA fluctuations of repetitiveness, and the segregation of the temporal pole (limbic network) predicted overall severity of RNT. Last, fluctuations in total RNT were predicted from the strength of the orbitofrontal cortex (limbic network) and segregation of the posterior mid-cingulate cortex (FPN). Notably, RNT was better predicted from daily-life prospective assessments than from lab-assessed clinical questionnaires.</p><p><strong>Conclusions: </strong>These findings highlight the utility of the GPM for predicting the emergence of daily-life RNT and suggest specific network-level attributes (e.g., centrality, segregation) underlying RNT and its clinical features.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214760","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":"Assessment of Glymphatic System Function in Children with Tourette Syndrome Using DTI-ALPS.","authors":"Jirui Wang, Tianyuan Lei, Xianbin Wang, Wenyan Zhang, Zhongyi Liu, Anyi Zhang, Weiwei Men, Guojun Zhang, Xu Hong, Yonghua Cui","doi":"10.1016/j.bpsc.2025.09.017","DOIUrl":"https://doi.org/10.1016/j.bpsc.2025.09.017","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to evaluate glymphatic system function in children with Tourette syndrome (TS) using diffusion tensor image analysis along the perivascular space (DTI-ALPS), and explored its potential role in TS pathophysiology.</p><p><strong>Methods: </strong>Seventy-six children with TS and eighty-two age- and sex-matched typically developing (TD) controls underwent DTI scans. Glymphatic function was quantified using the ALPS index, derived from atlas-based regions of interest in the superior corona radiata and superior longitudinal fasciculus. We examined associations between the left ALPS index (ALPS_L) and clinical measures, including tic severity (Yale Global Tic Severity Scale, YGTSS) and quality of life (Gilles de la Tourette Syndrome Quality of Life Scale, GTS-QOL). Mediation analysis assessed whether tic severity mediated the relationship between ALPS_L and GTS-QOL subscales.</p><p><strong>Results: </strong>The ALPS_L was significantly reduced in the TS group compared to the TD group (P < 0.05). The ALPS_L showed significant negative correlations with YGTSS motor tic (r = -0.850, P < 0.001), total tic (r = -0.702, P < 0.001), and global tic severity (r = -0.629, P < 0.001). It was also negatively correlated with the physical/ADL (r = -0.265, P = 0.020) and obsessive-compulsive (r = -0.380, P < 0.001) subscales of GTS-QOL. Motor tic severity partially mediated the relationship between the ALPS_L and physical/ADL scores (β = -0.037, 95% CI: [-0.060, -0.015]).</p><p><strong>Conclusions: </strong>Children with TS exhibit altered glymphatic function, associated with tic severity and impaired quality of life. These findings suggest glymphatic dysfunction may underlie TS-related neurobiological abnormalities.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208643","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":"Associations between past and current use of oral contraceptives and fear regulation.","authors":"Lisa-Marie Davignon, Alexandra Brouillard, Sean Devine, Vincent Taschereau-Dumouchel, Mathieu Roy, Marie-France Marin","doi":"10.1016/j.bpsc.2025.09.018","DOIUrl":"https://doi.org/10.1016/j.bpsc.2025.09.018","url":null,"abstract":"<p><strong>Background: </strong>Low endogenous estradiol (E2) levels can occur naturally during menstruation or through oral contraceptive (OC) use. Such low levels have been suggested as vulnerability factors for impaired fear extinction memory recall. Although hormonal contraceptives have been linked to enduring psychological outcomes, their possible long-term relevance for extinction memory remains underexplored.</p><p><strong>Methods: </strong>This study aimed to replicate findings linking OC use with altered extinction recall, and to examine potential long-term associations and neural correlates. To do so, a validated fear protocol (day 1: fear conditioning, extinction learning; day 2: extinction recall, fear renewal) was administered to 147 healthy adults. Psychophysiological (skin conductance responses; SCRs) and neural between-group differences were examined across the protocol using two types of groupings: (1) E2-based groups (men, current OC users, women in the early follicular phase, women in the pre-ovulatory phase) and (2) OC-history-based groups (men, current OC users, never OC users, past OC users).</p><p><strong>Results: </strong>During extinction recall, higher SCRs were found in current OC users relative to pre-ovulatory women (grouping 1) and to never users (grouping 2). Among current OC users, SCRs during extinction recall correlated with hippocampus, dorsal-rostral anterior cingulate cortex (ACC), and ventromedial prefrontal cortex (vmPFC) activations. Exploratory analyses revealed that past OC users who were in the early follicular phase exhibited SCRs as high as current users.</p><p><strong>Conclusion: </strong>These findings highlight impaired extinction recall in current OC users, with vmPFC, ACC and hippocampal involvement. Past OC use may carry lasting associations with fear dysregulation, particularly under low-E2 states.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208664","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":"Endocannabinoids Mediate Racial/Ethnic Discrimination Prediction of Post-Traumatic Stress Disorder Symptoms Moderated by Resting-State Functional Connectivity in Black and African American Individuals.","authors":"Emily A Albertina, Lucas Torres, Garrett Sauber, Cecilia J Hillard, Jacklynn M Fitzgerald, Terri A deRoon-Cassini, Christine L Larson","doi":"10.1016/j.bpsc.2025.09.016","DOIUrl":"https://doi.org/10.1016/j.bpsc.2025.09.016","url":null,"abstract":"<p><strong>Background: </strong>Individuals from marginalized ethnoracial groups face higher risk for posttraumatic stress disorder (PTSD) symptoms, exacerbated by experiencing racial/ethnic discrimination. Prior work separately explored the endocannabinoid (eCB) system and functional connectivity response to stress/trauma, and suggests that experiences of chronic minority stress, such as racial discrimination, contribute to eCB tone and resting state functional connectivity. We explored how circulating eCB tone, in conjunction with resting-state connectivity, contributes to increased risk for PTSD symptoms following trauma among individuals experiencing discrimination.</p><p><strong>Methods: </strong>Black/African Americans (n=74, Mage=33.81) were recruited from a Level 1 trauma center. Correlational and linear models explored whether experiences of racial/ethnic discrimination (PEDQ), eCB (AEA, 2-AG) concentrations, default mode network (DMN), or salience network (SN) functional connectivity were associated with PTSD symptoms (PCL-5). We then explored moderated mediation models where discrimination predicted PTSD symptoms with eCB concentration as a mediator and functional connectivity as a moderator.</p><p><strong>Results: </strong>Discrimination was correlated with PTSD symptoms (r=0.50), serum AEA concentration (r=0.43), and DMN connectivity (r=0.23). When including urine THC, lifetime trauma, age, and sex as covariates, AEA concentration was associated with PTSD symptoms (r=0.30) and DMN connectivity (r=0.24). AEA mediated the relationship between discrimination and PTSD symptoms, and SN connectivity moderated this mediation (B=52.46).</p><p><strong>Conclusions: </strong>Our findings highlight how racial/ethnic discrimination impacts neurobiological systems that may lead to increased vulnerability for PTSD symptoms following an injury. Future work should continue to explore biological factors associated with the social-ecological model of health as mechanisms of risk for adverse outcomes following trauma.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187996","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":"Longitudinal associations of structural and functional brain connectivity with dimensions of psychopathology in adolescence.","authors":"Lucy Vanes, Divyangana Rakesh, Tobias Banaschewski, Arun L W Bodke, Sylvane Desrivières, Herta Flor, Hugh Garavan, Penny Gowland, Antoine Grigis, Andreas Heinz, Herve Lemaitre, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Eric Artiges, Frauke Nees, Dimitri Papadopoulos Orfanos, Luise Poustka, Michael N Smolka, Sarah Hohmann, Nathalie Holz, Nilakshi Vaidya, Henrik Walter, Robert Whelan, Gunter Schumann, Gareth J Barker","doi":"10.1016/j.bpsc.2025.09.015","DOIUrl":"https://doi.org/10.1016/j.bpsc.2025.09.015","url":null,"abstract":"<p><strong>Background: </strong>Adolescence is a critical period of neurodevelopment marked by ongoing maturation of structural and functional brain connectivity. Simultaneously, this period is associated with an increase in mental health problems, spanning from subclinical symptoms to diagnosable disorders.</p><p><strong>Methods: </strong>This study investigates longitudinal associations between psychopathology dimensions and voxelwise brain measures related to connectivity across three time points (ages 14, 19, and 23) in over 1500 individuals using the IMAGEN dataset. White matter microstructure was indexed using diffusion metrics quantified along the white matter (WM) skeleton (N = 1736), while functional connectivity was captured as voxelwise degree centrality (DC) derived from resting-state functional imaging (N = 1510).</p><p><strong>Results: </strong>Development of WM microstructure was selectively linked to externalising (but not internalising) symptomatology. Here, higher externalising symptoms were associated with widespread reductions in fractional anisotropy (FA) across the WM skeleton, as well as accelerated decreases in FA in the corticospinal tract over time. In contrast, functional DC was developmentally associated with general, rather than specific, psychopathology in frontal and temporal regions. An increase in total difficulties over time was associated with developmental decrease in DC in bilateral superior frontal gyri. In addition, a positive association between total difficulties and DC in left inferior temporal gyrus was observed in younger, but not older, adolescents or young adults.</p><p><strong>Conclusions: </strong>These findings highlight the dynamic interplay between brain connectivity development and psychopathology in adolescence, with potential implications for identifying neural markers of risk and resilience during sensitive windows of development.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180767","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":"Functional network connectivity deviation is associated with transdiagnostic symptomatology.","authors":"Josina D Kist, Charlotte Fraza, Hannah S Savage, Peter C R Mulders, Janna N Vrijsen, Rose M Collard, Indira Tendolkar, Philip van Eijndhoven, Andre F Marquand","doi":"10.1016/j.bpsc.2025.09.014","DOIUrl":"https://doi.org/10.1016/j.bpsc.2025.09.014","url":null,"abstract":"<p><strong>Background: </strong>Large comorbidity and heterogeneity within psychiatric populations have prompted the use of transdiagnostic methods to account for this variability in brain-phenotype associations. Normative modelling offers a way to map individual deviations in brain functioning with respect to a large reference population. This study aims to explore brain-phenotype associations, using normative modelling to compute individual deviation scores of brain functioning, and relating them to different levels of psychopathology within a naturalistic patient sample.</p><p><strong>Methods: </strong>We applied normative modelling to estimate individual deviations in brain functional connectivity in a naturalistic sample (N=309) comprising both patients and healthy controls. We examined the association between the resulting neural deviation scores and levels of psychopathology, including traditional diagnostic categories, transdiagnostic symptom profiles, and cognition measures using sparse canonical correlation analysis (sCCA) RESULTS: We successfully estimated normative models using data from the MIND-Set study, and found significantly more extreme deviation scores in the patient as compared to the control population. We found a significant association (R_c=0.16, R² = 2.56%, p=0.021) between neural deviations scores and transdiagnostic symptom profiles, aligning with four Research Domain Criteria (RDoC) domains: negative valence, cognition, arousal/inhibition and social systems.</p><p><strong>Conclusions: </strong>With the use of normative modelling, we could detect differences in functional brain connectivity in patients as compared to controls, even in a highly heterogeneous and comorbid patient sample. Additionally, transdiagnostic approaches, like those embodied in the RDoC framework, are more accurate in uncovering shared neurobiological mechanisms than traditional diagnostic categories or cognitive measures.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152198","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":"Integrated Early Life Factors and Depression: A Multi-Level Investigation of Brain Structural, Immunometabolic, and Genetic Mechanisms.","authors":"Guangrui Yang, Hao Huang, Jingxuan Wang, Shuxiao Shi, Xuanwei Jiang, Zixuan Zhang, Meng Chen, Nannan Feng, Lan Xu, Xihao Du, Victor W Zhong","doi":"10.1016/j.bpsc.2025.09.010","DOIUrl":"https://doi.org/10.1016/j.bpsc.2025.09.010","url":null,"abstract":"<p><strong>Background: </strong>Early life factors before age 18 years significantly influence depression risk, but their differential contributions and biological mechanisms remain understudied.</p><p><strong>Methods: </strong>In this prospective UK Biobank study (N=104,035), an early life factor score (ELFS) was constructed using elastic net Cox models incorporating 15 early life factors, including perinatal conditions, childhood adversities, physical development, and social-environmental exposures. Cox models assessed associations of both individual factors and ELFS with depression. We conducted genome-wide association study (GWAS) to identify genetic variants associated with ELFS, Mendelian randomization to assess causality, and linear regression to examine associations with brain structures and blood markers. Structural equation modeling (SEM) explored biological pathways linking early life factors to depression.</p><p><strong>Results: </strong>During 14.6-year median follow-up, 4168 participants developed depression. Each 1-point increase in ELFS was associated with 49% higher depression risk, with high ELFS showing 2.8-fold increased risk compared to low ELFS. GWAS identified 46 significant SNPs associated with ELFS, mapped to 17 genes including FOXP2, with enrichment in metabolic pathways. Mendelian randomization analysis supported the causal relationship between ELFS and depression. Higher ELFS was associated with smaller volumes particularly in emotion-regulation brain regions, and with altered inflammatory markers and lipid metabolism. SEM integrating multi-level evidence revealed biological pathways linking early life factors, brain structure, immunometabolic markers, and depression.</p><p><strong>Conclusions: </strong>Early life factors collectively influence depression risk through an integrated score capturing differential factor contributions. Multiple biological pathways involving brain structure and immunometabolic markers were identified, providing insights into potential mechanisms linking early life factors to depression.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126378","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":"Sulcal Depth and Genetic Susceptibility influence initial Treatment Response in Adults with Attention-Deficit/Hyperactivity Disorder.","authors":"Jonathan Laatsch, Friederike S David, Frederike Stein, Carlo Maj, Andreas J Forstner, Simon Maier, Swantje Matthies, Esther Sobanski, Barbara Alm, Ludger Tebartz van Elst, Axel Krug, Alexandra Philipsen","doi":"10.1016/j.bpsc.2025.09.012","DOIUrl":"https://doi.org/10.1016/j.bpsc.2025.09.012","url":null,"abstract":"<p><strong>Background: </strong>As neurobiological markers gain prominence in guiding personalised treatments, sulcal depth (SD) remains an underexplored yet pivotal factor in neural processing and therapeutic efficacy. While genetic influences shape cortical architecture, their role in modulating the relationship between SD and treatment outcomes remain unclear. This study investigates whether pre-treatment SD predicts symptom alleviation in adults with Attention-Deficit/Hyperactivity Disorder (ADHD) and explores moderating effects of genetic susceptibility for ADHD and cross-disorder influences.</p><p><strong>Methods: </strong>Using structural neuroimaging data from the Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study, we examined associations between SD and treatment response following a 12-week intervention involving either group psychotherapy or clinical management with methylphenidate or placebo. Pre-treatment SD was derived from 119 T1-weighted anatomical scans and analysed using linear regression models to assess its predictive value for post-treatment symptom severity. Subsequently, we explored the moderating role of polygenic scores for ADHD and cross-disorder susceptibility. Structural analyses were performed using the threshold-free cluster enhancement approach in the Computational Anatomy Toolbox, with moderation analyses conducted in SPSS (30.0.0).</p><p><strong>Results: </strong>Results revealed that SD in parietal, temporal, and occipital regions significantly predicted symptom alleviation, linking deeper sulci with greater treatment efficacy. Moreover, genetic predisposition for ADHD and cross-disorder traits influenced these relationships, highlighting an interaction between cortical structure and genetic susceptibility in determining treatment outcomes.</p><p><strong>Conclusion: </strong>These findings highlight SD as a promising neurobiological marker of ADHD treatment response and emphasize the importance of integrating neurobiological- and genetic factors into predictive models of therapeutic efficacy in psychiatry.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126422","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":"Disrupted Brain Connectivity in Newborns Following Antenatal Opioid Exposure.","authors":"Josepheen De Asis-Cruz, Jung-Hoon Kim, Kushal Kapse, Yao Wu, Stephanie L Merhar, Carla M Bann, Jamie E Newman, Nicole Mack, Sara B DeMauro, Namasivayam Ambalavanan, Scott A Lorch, Deanne Wilson-Costello, Brenda B Poindexter, Myriam Peralta-Carcelen, Jonathan M Davis, Catherine Limperopoulos","doi":"10.1016/j.bpsc.2025.09.011","DOIUrl":"https://doi.org/10.1016/j.bpsc.2025.09.011","url":null,"abstract":"<p><strong>Background: </strong>The neural bases of adverse neurodevelopmental outcomes in antenatal opioid exposure are poorly understood. Very limited in vivo human newborn imaging studies have reported disrupted functional connectivity (FC) in limbic and reward-related brain regions, but these studies used small samples and lacked matched controls. Our objective was to compare brain FC in antenatal opioid-exposed and unexposed newborns to study the impact of opioid exposure on early brain development.</p><p><strong>Methods: </strong>Resting state functional MRI data were collected using 3T MRIs at four centers as part of the prospective, observational Outcomes of Babies with Opioid Exposure study. We used seed-based correlation analysis to estimate the FC of 93 brain regions. Voxel-wise linear regression with covariate adjustment and correction for multiple comparisons was used to determine significant between-group differences. FC differences based on opioid type were also investigated.</p><p><strong>Results: </strong>We performed 248 scans (158 opioid-exposed/90 unexposed). Canonical sensorimotor and higher-order resting state network maps in exposed newborns (mean postmenstrual age at MRI±sd:42.80±1.9wks,52M) were comparable to controls (42.82±2.2, 88; Dice indices>0.9 across seven networks). Exposed newborns showed decreased FC from seeds in bilateral pre- and left postcentral gyri, bilateral orbitofrontal regions, and cerebellum, and increased FC from seeds in peri-opercular, subcortical (e.g., amygdala, hippocampus, and putamen), and mid-to-superior occipital regions (family-wise error rate,α<0.05). Connectivity from 23/93 (24.7%) seeds differed between groups. Methadone- and buprenorphine-exposed newborns showed disrupted regional FC compared to controls, but no FC differences between them.</p><p><strong>Conclusions: </strong>In a large sample of antenatally opioid-exposed newborns, we report altered organization of brain functional networks, particularly in integrative sensorimotor-affective circuits.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126437","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}