Biological Psychiatry最新文献

{"title":"Nuclear calcium signaling in D1 receptor-expressing neurons of the nucleus accumbens regulates molecular, cellular and behavioral adaptations to cocaine.","authors":"Estefani Saint-Jour, Marie-Charlotte Allichon, Andry Andrianarivelo, Enrica Montalban, Claire Martin, Lisa Huet, Nicolas Heck, Anna M Hagenston, Aisha Ravenhorst, Mélanie Marias, Nicolas Gervasi, Faustine Arrivet, Adèle Vilette, Katleen Pinchaud, Sandrine Betuing, Thomas Lissek, Jocelyne Caboche, Hilmar Bading, Peter Vanhoutte","doi":"10.1016/j.biopsych.2025.01.013","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.01.013","url":null,"abstract":"<p><strong>Background: </strong>The persistence of cocaine-evoked adaptations relies on gene regulations within the reward circuit, especially in the ventral striatum (i.e., nucleus accumbens (NAc)). Notably, activation of the extracellular signal-regulated kinase (ERK) pathway in the striatum is known to trigger a transcriptional program shaping long-term responses to cocaine. Nuclear calcium signaling has also been shown to control multiple forms of transcription-dependent neuroadaptations but the dynamics and roles of striatal nuclear calcium signaling in preclinical models of addiction remains unknown.</p><p><strong>Methods: </strong>A genetically-encoded cell-type-specific nuclear calcium probe has been developed to monitor calcium dynamics in the nuclei of striatal neurons, including in freely-moving mice. A cell-type-specific inhibitor of nuclear calcium signaling, combined with 3D imaging of neuronal morphology, immunostaining and behavior, was used to disentangle the roles of nuclear calcium in NAc medium-sized spiny neurons (MSN) expressing the dopamine D1 (D1R) or D2 (D2R) receptor on cocaine-evoked responses.</p><p><strong>Results: </strong>The D1R-mediated potentiation of calcium influx through glutamate N-methyl-D-aspartate receptors (NMDAR), which shapes cocaine effects, also drives nuclear calcium transients. Fiber photometry revealed that cocaine-treated mice display a sustained nuclear calcium increase in NAc D1R-MSN. Disrupting nuclear calcium in D1R-MSN, but not D2R-MSN, blocks cocaine-evoked morphological changes of MSN and gene expression, and blunts cocaine's rewarding effects.</p><p><strong>Conclusions: </strong>Our study unravels the dynamics and roles of cocaine-induced nuclear calcium signaling increases in D1R-MSN on molecular, cellular and behavioral adaptations to cocaine, and brings a significant breakthrough as it could contribute to the development of innovative strategies with therapeutic potential to alleviate addiction symptoms.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing brainstem glucagon-like peptide-1 control of sensory-specific-satiety in male and female rats across the estrous cycle.","authors":"Sarah V Applebey, Allison G Xiao, Erin P Harris, Caleb Levine, Drew L Belser, Caroline E Geisler, Marise B Parent, Debra A Bangasser, Richard C Crist, Benjamin C Reiner, Matthew R Hayes","doi":"10.1016/j.biopsych.2025.01.012","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.01.012","url":null,"abstract":"<p><strong>Background: </strong>Meal variety promotes overconsumption by delaying sensory-specific-satiety (SSS), the transient reduction in reward value of a recently consumed food. Despite its role in meal cessation, the neuroendocrine mechanisms underlying SSS are largely unknown.</p><p><strong>Methods: </strong>Here, we developed a preclinical model of SSS wherein rats consume more of a different food compared to the same food presented again, leading to greater caloric intake. Using pharmacological and molecular approaches targeting the brainstem, we investigated the involvement of the satiation signal, glucagon-like peptide-1 (GLP-1), in mediating SSS in male rats (n=96) and in female rats (n=85) across their estrous cycle. We also evaluated the sufficiency of the hormone estradiol to modulate GLP-1 and SSS.</p><p><strong>Results: </strong>In males, brainstem GLP-1 receptors (GLP-1Rs) were necessary for the SSS-induced decrease in same food intake, while agonizing brainstem GLP-1Rs was sufficient to attenuate overconsumption of the different food. Female rats showed SSS in an estrous cycle-dependent manner and did not consume more of the different food in diestrus-to-Proestrus and proestrus-to-Estrus. However, blockade of brainstem GLP-1R restored different food overconsumption. Furthermore, the brainstem's nucleus tractus solitarius and area postrema showed increased expression of the GLP-1 precursor, glucagon (Gcg), during diestrus-to-Proestrus and proestrus-to-Estrus, and greater Glp1r expression in proestrus-to-Estrus. Similarly, 17β-estradiol injections in males not only increased Glp1r and Gcg expression, but also reduced SSS.</p><p><strong>Conclusion: </strong>We identified a bidirectional role for brainstem GLP-1R signaling in modulating SSS; effects that are estrous cycle-dependent. Moreover, our data indicate that estradiol regulates Glp1r and Gcg expression and likely influences SSS.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcranial Direct Current Stimulation Improves Paranoia and Social Functioning in Schizophrenia: A Randomized Clinical Trial.","authors":"Linlin Fan, Sara Carrico, Yiyi Zhu, Robert A Ackerman, Amy E Pinkham","doi":"10.1016/j.biopsych.2025.01.011","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.01.011","url":null,"abstract":"<p><strong>Background: </strong>Innovative treatments for paranoia, which significantly impairs social functioning in schizophrenia (SCZ), are urgently needed. The pathophysiology of paranoia implicates the amygdala-prefrontal (PFC) circuits; thus, this study systematically investigated whether transcranial direct current stimulation (tDCS) to the ventrolateral PFC can attenuate paranoia and improve social functioning in SCZ.</p><p><strong>Methods: </strong>A double-blind, within-subjects, crossover design was used to compare active vs. sham tDCS effects in 50 participants with SCZ (ClinicalTrials.gov Identifier: NCT05746494). Participants completed two stimulation visits, each including two tDCS sessions about a week apart, with active (2mA for 20mins) and sham conditions counterbalanced across the two visits. Alongside lab-based measurements of state paranoia and its associated social cognitive biases, Ecological Momentary Assessment (EMA) was used. This involved daily evaluations of paranoia and social functioning, administered three times per day for seven days in each EMA period (EMA-baseline, EMA-active, EMA-sham).</p><p><strong>Results: </strong>For lab-based assessments, participants showed greater reductions in state paranoia and improvements in paranoia-related social cognitive biases after active stimulation compared to sham, including lower self-reported hostility and hostile attributions in ambiguous situations post-active versus post-sham. Similarly, in the EMA-active period, participants had lower daily paranoia compared to the EMA-sham period and higher social interaction motivation with better attitudes compared to baseline and the EMA-sham period.</p><p><strong>Conclusions: </strong>Extending our pilot study, the current findings further supported the efficacy of tDCS in SCZ patients in mitigating paranoia and enhancing social functioning. This work sheds light on the neuropathology of paranoia and identifies a promising avenue for future large-scale interventions.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations in Prefrontal Cortical Somatostatin Neurons in Schizophrenia: Evidence for Weaker Inhibition of Pyramidal Neuron Dendrites.","authors":"Samuel J Dienel, Kirsten L Wade, Kenneth N Fish, David A Lewis","doi":"10.1016/j.biopsych.2025.01.010","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.01.010","url":null,"abstract":"<p><strong>Background: </strong>Certain cognitive processes require inhibition provided by the somatostatin (SST) class of gamma-aminobutyric acid (GABA) neurons in the dorsolateral prefrontal cortex (DLPFC). This inhibition onto pyramidal neuron dendrites depends on both SST and GABA signaling. Although SST mRNA levels are lower in the DLPFC in schizophrenia, it is not known if SST neurons exhibit alterations in the capacity to synthesize GABA, principally via the 67-kilodalton isoform of glutamic acid decarboxylase (GAD67).</p><p><strong>Methods: </strong>GAD67 and SST mRNA levels were quantified in individual SST neurons using fluorescence in situ hybridization in DLPFC layers 2-superficial 3, where SST neurons are enriched, in schizophrenia (n=46) and unaffected comparison (n=46) individuals. Findings were compared to GAD67 and SST mRNA levels quantified by polymerase chain reaction and to final educational attainment, a proxy measure for cognitive functioning.</p><p><strong>Results: </strong>GAD67 (F_1,84=13.1, p=0.0005, Cohen's d = -0.78) and SST (F_1,84=10.1, p=0.002, Cohen's d = -0.64) mRNA levels in SST neurons were lower in schizophrenia, with no group differences in the relative density of SST neurons (F_1,84=0.21, p=0.65). A presynaptic index of dendritic inhibition, derived by summing the alterations in GAD67 and SST mRNAs, was lower in 80.4% of individuals with schizophrenia and was associated with final educational attainment (adjusted odds ratio=1.44, p=0.022).</p><p><strong>Conclusions: </strong>Deficits in both GAD67 and SST mRNAs within SST neurons indicate that these neurons have a markedly reduced ability to inhibit postsynaptic pyramidal neuron dendrites in schizophrenia. These alterations likely contribute to cognitive dysfunction in schizophrenia.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Speak and you shall predict: evidence that speech at initial cocaine abstinence is a biomarker of long-term drug use behavior.","authors":"Carla Agurto, Guillermo Cecchi, Sarah King, Elif K Eyigoz, Muhammad A Parvaz, Nelly Alia-Klein, Rita Z Goldstein","doi":"10.1016/j.biopsych.2025.01.009","DOIUrl":"10.1016/j.biopsych.2025.01.009","url":null,"abstract":"<p><strong>Background: </strong>Valid scalable biomarkers for predicting longitudinal clinical outcomes in psychiatric research are crucial for optimizing intervention and prevention efforts. Here we recorded spontaneous speech from initially abstinent individuals with cocaine use disorder (iCUD) for use in predicting drug use outcomes.</p><p><strong>Methods: </strong>At baseline, 88 iCUD provided 5-minute speech samples describing the positive consequences of quitting drug use and negative consequences of using drugs. Outcomes, including withdrawal, craving, abstinence days, and recent cocaine use, were assessed at three-month intervals up to one year (57 iCUD included in analyses). Predictive modeling compared natural language processing (NLP) techniques, specifically sentence embeddings with established inventories as targets, with models utilizing standard demographic and baseline psychometric variables.</p><p><strong>Results: </strong>At short time intervals, maximal predictive power was obtained with non-NLP models that also incorporated the same drug use measures (as the outcomes) obtained at baseline, potentially reflecting their slow rate of change, which could be estimated by linear functions. However, for longer-term predictions, speech samples alone demonstrated statistically significant results, with Spearman r ≥ 0.46 and 80% accuracy for predicting abstinence. Hence speech samples may capture non-linear dynamics over extended intervals more effectively than traditional measures. These results need to be replicated in larger and independent samples.</p><p><strong>Conclusions: </strong>Compared to the common outcome measures used in clinical trials, speech-based measures could be leveraged as better predictors of longitudinal drug use outcomes in initially abstinent iCUD, as potentially generalizable to other subgroups with cocaine addiction, and to additional substance use disorders and related comorbidity.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MAPPING THE CEREBROSPINAL FLUID PROTEOME IN BIPOLAR DISORDER.","authors":"Andreas Göteson, Jessica Holmén-Larsson, Hatice Celik, Aurimantas Pelanis, Carl M Sellgren, Timea Sparding, Erik Pålsson, Henrik Zetterberg, Kaj Blennow, Lina Jonsson, Johan Gobom, Mikael Landén","doi":"10.1016/j.biopsych.2025.01.007","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.01.007","url":null,"abstract":"<p><strong>Background: </strong>Bipolar disorder (BD) is a severe psychiatric condition with unclear etiology and no established biomarkers. Here, we aimed to characterize the cerebrospinal fluid (CSF) proteome in euthymic BD individuals to identify potential protein biomarkers.</p><p><strong>Methods: </strong>We employed nano-flow liquid chromatography coupled to high-resolution mass spectrometry to quantify over 2,000 CSF proteins in 374 individuals from two independent clinical cohorts (n=164+89 and 66+55 cases and controls, respectively). A subset of the cases was followed longitudinally and reexamined after a median of 6.5 years.</p><p><strong>Results: </strong>Differential abundance analysis revealed 41 proteins with robust case-control association in both cohorts. These included lower levels of synaptic proteins (e.g., APP, CLSTN1, NPTX2, NRXN1), axon guidance and cell adhesion molecules (e.g., NEO1, NCAM1, SEMA7A), higher levels of blood-brain-barrier integrity proteins (e.g., VTN, SERPIN3), and complement components (e.g., C1RL, C3, C5). The findings were consistently driven by the BD type 1 subtype. Comparing BD type 1 with controls increased discoverability, revealing 86 replicated associations despite a loss of statistical power. Moreover, longitudinal analyses of co-expression modules revealed dynamic changes in the CSF proteome composition that correlated with clinical outcomes, including disease severity, future manic episodes, and symptom improvement. Finally, we conducted association analyses of CSF proteins with genetic risk loci for bipolar disorder and schizophrenia.</p><p><strong>Conclusions: </strong>This study represents the first large-scale untargeted profiling of the CSF proteome in BD, unveiling potential biomarkers and providing in vivo support for altered synaptic and brain connectivity processes, impaired neurovascular integrity, and complement activation in the pathology of BD.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Descriptives and genetic correlates of eating disorder diagnostic transitions and presumed remission in the Danish registry.","authors":"Mohamed Abdulkadir, Janne Tidselbak Larsen, Loa Clausen, Christopher Hübel, Clara Albiñana, Laura M Thornton, Bjarni J Vilhjálmsson, Cynthia M Bulik, Zeynep Yilmaz, Liselotte Vogdrup Petersen","doi":"10.1016/j.biopsych.2025.01.008","DOIUrl":"10.1016/j.biopsych.2025.01.008","url":null,"abstract":"<p><strong>Objective: </strong>Eating disorders (EDs) are serious psychiatric disorders with an estimated 3.3 million healthy life-years lost worldwide yearly. Understanding the course of illness, diagnostic transitions and remission, and their associated genetic correlates could inform both ED etiology and treatment. The authors investigated occurrences of ED transitions and presumed remission and their genetic correlates as captured by polygenic scores (PGSs) in a large Danish register-based cohort.</p><p><strong>Methods: </strong>The sample was compromised of 10,565 individuals with a diagnosis of anorexia nervosa (AN), bulimia nervosa (BN), or eating disorder not otherwise specified (EDNOS) with at least two registered hospital contacts between 1995 and 2018. Based on medical records, occurrence of diagnostic transitions and periods of presumed remission were identified. Associations between 422 PGS and diagnostic transitions and presumed remission were evaluated using Cox proportional hazard models.</p><p><strong>Results: </strong>A minority of ED cases (14.1%-23.1%) experienced a diagnostic transition. Presumed remission ranged between 86.9%-89.8%. Higher (one SD increase) PGS for major depressive disorder and multisite chronic pain were positively associated with transitioning from AN to either BN or EDNOS. Higher PGS on a measure of body fat percentage and financial difficulties were positively associated with presumed remission from AN. Higher PGS for mood swings was positively associated with presumed remission from EDNOS whereas higher PGS for health rating showed the opposite.</p><p><strong>Conclusions: </strong>The authors found that most ED patients did not experience diagnostic transitions but were more likely to experience a period of presumed remission. Both diagnostic transitions and presumed remission have significant polygenic component.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Mechanisms of Persisting Disability in Schizophrenia: Imprecise Predictive Coding via Corticostriatothalamic-Cortical Loop Dysfunction","authors":"Peter F. Liddle,&nbsp;Musa B. Sami","doi":"10.1016/j.biopsych.2024.08.007","DOIUrl":"10.1016/j.biopsych.2024.08.007","url":null,"abstract":"<div><div>Persisting symptoms and disability remain a problem for an appreciable proportion of people with schizophrenia despite treatment with antipsychotic medication. Improving outcomes requires an understanding of the nature and mechanisms of the pathological processes underlying persistence. Classical features of schizophrenia, which include disorganization and impoverishment of mental activity, are well-recognized early clinical features that predict poor long-term outcome. Substantial evidence indicates that these features reflect imprecise predictive coding. Predictive coding provides an overarching framework for understanding efficient functioning of the nervous system. Imprecise predictive coding also has the potential to precipitate acute psychosis characterized by reality distortion (delusions and hallucinations) at times of stress. On the other hand, substantial evidence indicates that persistent reality distortion itself gives rise to poor occupational and social function in the long term. Furthermore, abuse of psychotomimetic drugs, which exacerbate reality distortion, contributes to poor long-term outcome in schizophrenia. Neural circuits involved in modulating volitional acts are well understood to be implicated in addiction. Plastic changes in these circuits may account for the association between psychotomimetic drug abuse and poor outcomes in schizophrenia. We propose a mechanistic model according to which unbalanced inputs to the corpus striatum disturb the precision of subcortical modulation of cortical activity supporting volitional action. This model accounts for the evidence that early classical symptoms predict poor outcome, while in some circumstances, persistent reality distortion also predicts poor outcome. This model has implications for the development of novel treatments that address the risk of persisting symptoms and disabilities in schizophrenia.</div></div>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"97 2","pages":"Pages 109-116"},"PeriodicalIF":9.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Robust Brain Correlates of Cognitive Performance in Psychosis and Its Prodrome","authors":"Heather Burrell Ward ,&nbsp;Adam Beermann ,&nbsp;Jing Xie ,&nbsp;Gulcan Yildiz ,&nbsp;Karlos Manzanarez Felix ,&nbsp;Jean Addington ,&nbsp;Carrie E. Bearden ,&nbsp;Kristin Cadenhead ,&nbsp;Tyrone D. Cannon ,&nbsp;Barbara Cornblatt ,&nbsp;Matcheri Keshavan ,&nbsp;Daniel Mathalon ,&nbsp;Diana O. Perkins ,&nbsp;Larry Seidman ,&nbsp;William S. Stone ,&nbsp;Ming T. Tsuang ,&nbsp;Elaine F. Walker ,&nbsp;Scott Woods ,&nbsp;Michael J. Coleman ,&nbsp;Sylvain Bouix ,&nbsp;Roscoe O. Brady Jr.","doi":"10.1016/j.biopsych.2024.07.012","DOIUrl":"10.1016/j.biopsych.2024.07.012","url":null,"abstract":"<div><h3>Background</h3><div>Neurocognitive impairment is a well-known phenomenon in schizophrenia that begins prior to psychosis onset. Connectome-wide association studies have inconsistently linked cognitive performance to resting-state functional magnetic resonance imaging. We hypothesized that a carefully selected cognitive instrument and refined population would allow identification of reliable brain-behavior associations with connectome-wide association studies. To test this hypothesis, we first identified brain-cognition correlations via a connectome-wide association study in early psychosis. We then asked, in an independent dataset, if these brain-cognition relationships would generalize to individuals who develop psychosis in the future.</div></div><div><h3>Methods</h3><div>The Seidman Auditory Continuous Performance Task (ACPT) effectively differentiates healthy participants from those with psychosis. Our connectome-wide association study used the HCP-EP (Human Connectome Project for Early Psychosis) (<em>n</em> = 183) to identify links between connectivity and ACPT performance. We then analyzed data from the NAPLS2 (North American Prodrome Longitudinal Study 2) (<em>n</em> = 345), a multisite prospective study of individuals at risk for psychosis. We tested the connectome-wide association study–identified cognition-connectivity relationship in both individuals at risk for psychosis and control participants.</div></div><div><h3>Results</h3><div>Our connectome-wide association study in early-course psychosis identified robust associations between better ACPT performance and higher prefrontal-somatomotor connectivity (<em>p</em> &lt; .005). Prefrontal-somatomotor connectivity was also related to ACPT performance in at-risk individuals who would develop psychosis (<em>n</em> = 17). This finding was not observed in nonconverters (<em>n</em> = 196) or control participants (<em>n</em> = 132).</div></div><div><h3>Conclusions</h3><div>This connectome-wide association study identified reproducible links between connectivity and cognition in separate samples of individuals with psychosis and at-risk individuals who would later develop psychosis. A carefully selected task and population improves the ability of connectome-wide association studies to identify reliable brain-phenotype relationships.</div></div>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"97 2","pages":"Pages 139-147"},"PeriodicalIF":9.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain Network Localization of Gray Matter Atrophy and Neurocognitive and Social Cognitive Dysfunction in Schizophrenia","authors":"Yan Cheng ,&nbsp;Huanhuan Cai ,&nbsp;Siyu Liu ,&nbsp;Yang Yang,&nbsp;Shan Pan,&nbsp;Yongqi Zhang,&nbsp;Fan Mo,&nbsp;Yongqiang Yu,&nbsp;Jiajia Zhu","doi":"10.1016/j.biopsych.2024.07.021","DOIUrl":"10.1016/j.biopsych.2024.07.021","url":null,"abstract":"<div><h3>Background</h3><div>Numerous studies have established the presence of gray matter atrophy and brain activation abnormalities during neurocognitive and social cognitive tasks in schizophrenia. Despite a growing consensus that diseases localize better to distributed brain networks than individual anatomical regions, relatively few studies have examined brain network localization of gray matter atrophy and neurocognitive and social cognitive dysfunction in schizophrenia.</div></div><div><h3>Methods</h3><div>To address this gap, we initially identified brain locations of structural and functional abnormalities in schizophrenia from 301 published neuroimaging studies with 8712 individuals with schizophrenia and 9275 healthy control participants. By applying novel functional connectivity network mapping to large-scale resting-state functional magnetic resonance imaging datasets, we mapped these affected brain locations to 3 brain abnormality networks of schizophrenia.</div></div><div><h3>Results</h3><div>The gray matter atrophy network of schizophrenia comprised a broadly distributed set of brain areas predominantly implicating the ventral attention, somatomotor, and default networks. The neurocognitive dysfunction network was also composed of widespread brain areas primarily involving the frontoparietal and default networks. By contrast, the social cognitive dysfunction network consisted of circumscribed brain regions mainly implicating the default, subcortical, and visual networks.</div></div><div><h3>Conclusions</h3><div>Our findings suggest shared and unique brain network substrates of gray matter atrophy and neurocognitive and social cognitive dysfunction in schizophrenia, which may not only refine the understanding of disease neuropathology from a network perspective but may also contribute to more targeted and effective treatments for impairments in different cognitive domains in schizophrenia.</div></div>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"97 2","pages":"Pages 148-156"},"PeriodicalIF":9.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}