Biological Psychiatry最新文献

{"title":"Fluoxetine and Ketamine Enhance Extinction Memory and Brain Plasticity by Triggering the p75 Neurotrophin Receptor Proteolytic Pathway.","authors":"Cassiano Ricardo Alves Faria Diniz, Ana Paula Crestani, Plinio Cabrera Casarotto, Caroline Biojone, Cecilia Cannarozzo, Frederike Winkel, Mikhail A Prozorov, Erik F Kot, Sergey A Goncharuk, Danilo Benette Marques, Leonardo Rakauskas Zacharias, Henri Autio, Madhusmita Priyadarshini Sahu, Anna Bárbara Borges-Assis, João Pereira Leite, Konstantin S Mineev, Eero Castrén, Leonardo Barbosa Moraes Resstel","doi":"10.1016/j.biopsych.2024.06.021","DOIUrl":"10.1016/j.biopsych.2024.06.021","url":null,"abstract":"<p><strong>Background: </strong>Diverse antidepressants were recently described to bind to TrkB (tyrosine kinase B) and drive a positive allosteric modulation of endogenous BDNF (brain-derived neurotrophic factor). Although neurotrophins such as BDNF can bind to p75NTR (p75 neurotrophin receptor), their precursors are the high-affinity p75NTR ligands. While part of an unrelated receptor family capable of inducing completely opposite physiological changes, TrkB and p75NTR feature a crosslike conformation dimer and carry a cholesterol-recognition amino acid consensus in the transmembrane domain. As such qualities were found to be crucial for antidepressants to bind to TrkB and drive behavioral and neuroplasticity effects, we hypothesized that their effects might also depend on p75NTR.</p><p><strong>Methods: </strong>Enzyme-linked immunosorbent assay-based binding and nuclear magnetic resonance spectroscopy were performed to assess whether antidepressants would bind to p75NTR. HEK293T cells and a variety of in vitro assays were used to investigate whether fluoxetine (FLX) or ketamine (KET) would trigger any α- and γ-secretase-dependent p75NTR proteolysis and lead to p75NTR nuclear localization. Ocular dominance shift was performed with male and female p75NTR knockout mice to study the effects of KET and FLX on brain plasticity, in addition to pharmacological interventions to verify how p75NTR signaling is important for the effects of KET and FLX in enhancing extinction memory in male wild-type mice and rats.</p><p><strong>Results: </strong>Antidepressants were found to bind to p75NTR. FLX and KET triggered the p75NTR proteolytic pathway and induced p75NTR-dependent behavioral/neuroplasticity changes.</p><p><strong>Conclusions: </strong>We hypothesize that antidepressants co-opt both BDNF/TrkB and proBDNF/p75NTR systems to induce a more efficient activity-dependent synaptic competition, thereby boosting the brain's ability for remodeling.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":"248-260"},"PeriodicalIF":9.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465994","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":"Enhancing Early Diagnosis of Bipolar Disorder in Adolescents Through Multimodal Neuroimaging.","authors":"Jinfeng Wu, Kangguang Lin, Weicong Lu, Wenjin Zou, Xiaoyue Li, Yarong Tan, Jingyu Yang, Danhao Zheng, Xiaodong Liu, Bess Yin-Hung Lam, Guiyun Xu, Kun Wang, Roger S McIntyre, Fei Wang, Kwok-Fai So, Jie Wang","doi":"10.1016/j.biopsych.2024.07.018","DOIUrl":"10.1016/j.biopsych.2024.07.018","url":null,"abstract":"<p><strong>Background: </strong>Bipolar disorder (BD), a severe neuropsychiatric condition, often appears during adolescence. Traditional diagnostic methods, which primarily rely on clinical interviews and single-modal magnetic resonance imaging (MRI) techniques, may have limitations in accuracy. This study aimed to improve adolescent BD diagnosis by integrating behavioral assessments with multimodal MRI. We hypothesized that this combination would enhance diagnostic accuracy for at-risk adolescents.</p><p><strong>Methods: </strong>A retrospective cohort of 309 participants, including patients with BD, offspring of patients with BD (with and without subthreshold symptoms), non-BD offspring with subthreshold symptoms, and healthy control participants, was analyzed. Behavioral attributes were integrated with MRI features from T1-weighted, resting-state functional MRI, and diffusion tensor imaging. Three diagnostic models were developed using GLMNET multinomial regression: a clinical diagnosis model based on behavioral attributes, an MRI-based model, and a comprehensive model integrating both datasets.</p><p><strong>Results: </strong>The comprehensive model achieved a prediction accuracy of 0.83 (95% CI, 0.72-0.92), significantly higher than the clinical (0.75) and MRI-based (0.65) models. Validation with an external cohort showed high accuracy (0.89, area under the curve = 0.95). Structural equation modeling revealed that clinical diagnosis (β = 0.487, p < .0001), parental BD history (β = -0.380, p < .0001), and global function (β = 0.578, p < .0001) significantly affected brain health, while psychiatric symptoms showed only a marginal influence (β = -0.112, p = .056).</p><p><strong>Conclusions: </strong>This study highlights the value of integrating multimodal MRI with behavioral assessments for early diagnosis in at-risk adolescents. Combining neuroimaging enables more accurate patient subgroup distinctions, facilitating timely interventions and improving health outcomes. Our findings suggest a paradigm shift in BD diagnostics, advocating for incorporating advanced imaging techniques in routine evaluations.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":"313-322"},"PeriodicalIF":9.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787180","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":"Windows of Opportunity: How Age and Sex Shape the Influence of Prenatal Depression on the Child Brain.","authors":"Kathryn Y Manning, Aliza Jaffer, Catherine Lebel","doi":"10.1016/j.biopsych.2024.07.022","DOIUrl":"10.1016/j.biopsych.2024.07.022","url":null,"abstract":"<p><p>Maternal prenatal depression can affect child brain and behavioral development. Specifically, altered limbic network structure and function is a likely mechanism through which prenatal depression impacts the life-long mental health of exposed children. While developmental trajectories are influenced by many factors that exacerbate risk or promote resiliency, the role of child age and sex in the relationship between prenatal depression and the child brain remains unclear. Here, we review studies of associations between prenatal depression and brain structure and function, with a focus on the role of age and sex in these relationships. After exposure to maternal prenatal depression, altered amygdala, hippocampal, and frontal cortical structure, as well as changes in functional and structural connectivity within the limbic network, are evident during the fetal, infant, preschool, childhood, and adolescent stages of development. Sex appears to play a key role in this relationship, with evidence of differential findings particularly in infants, with males showing smaller and females larger hippocampal and amygdala volumes following prenatal depression. Longitudinal studies in this area have only begun to emerge within the last 5 years and will be key to understanding critical windows of opportunity. Future research focused on the role of age and sex in this relationship is essential to further inform screening, policy, and interventions for children exposed to prenatal depression, interrupt the intergenerational transmission of depression, and ultimately support healthy brain development.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":"227-247"},"PeriodicalIF":9.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905799","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":"Maternal Antenatal Depression Is Associated With Metabolic Alterations That Predict Birth Outcomes and Child Neurodevelopment and Mental Health.","authors":"Polina Girchenko, Marius Lahti-Pulkkinen, Hannele Laivuori, Eero Kajantie, Katri Räikkönen","doi":"10.1016/j.biopsych.2024.07.023","DOIUrl":"10.1016/j.biopsych.2024.07.023","url":null,"abstract":"<p><strong>Background: </strong>Evidence regarding metabolic alterations associated with maternal antenatal depression (AD) is limited, and their role as potential biomarkers that improve the prediction of AD and adverse childbirth, neurodevelopmental, and mental health outcomes remains unexplored.</p><p><strong>Methods: </strong>In a cohort of 331 mother-child dyads, we studied associations between AD (a history of medical register diagnoses and/or a Center for Epidemiological Studies Depression Scale score during pregnancy ≥ 20) and 95 metabolic measures analyzed 3 times during pregnancy. We tested whether the AD-related metabolic measures increased variance explained in AD over its risk factors and in childbirth, neurodevelopmental, and mental health outcomes over AD. We replicated the findings in a cohort of 416 mother-child dyads.</p><p><strong>Results: </strong>Elastic net regression identified 15 metabolic measures that collectively explained 25% (p < .0001) of the variance in AD, including amino and fatty acids, glucose, inflammation, and lipids. These metabolic measures increased the variance explained in AD over its risk factors (32.3%, p < .0001 vs. 12.6%, p = .004) and in child gestational age (9.0%, p < .0001 vs. 0.7%, p = .34), birth weight (9.0%, p = .03 vs. 0.7%, p = .33), developmental milestones at the age of 2.3 to 5.7 years (21.0%, p = .002 vs. 11.6%, p < .001), and any mental or behavioral disorder by the age of 13.1 to 16.8 years (25.2%, p = .03 vs. 5.0%, p = .11) over AD, child sex, and age. These findings were replicated in the independent cohort.</p><p><strong>Conclusions: </strong>AD was associated with alterations in 15 metabolic measures, which collectively improved the prediction of AD over its risk factors and birth, neurodevelopmental, and mental health outcomes in children over AD. These metabolic measures may become biomarkers that can be used to identify at-risk mothers and children for personalized interventions.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":"269-278"},"PeriodicalIF":9.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911574","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":"Quantification of Glutathione and Its Associated Spontaneous Neuronal Activity in Major Depressive Disorder and Obsessive-Compulsive Disorder.","authors":"Sang Won Lee, Seungho Kim, Yongmin Chang, Hyunsil Cha, Ralph Noeske, Changho Choi, Seung Jae Lee","doi":"10.1016/j.biopsych.2024.08.018","DOIUrl":"10.1016/j.biopsych.2024.08.018","url":null,"abstract":"<p><strong>Background: </strong>Glutathione (GSH) is a crucial antioxidant in the human brain. Although proton magnetic resonance spectroscopy using the Mescher-Garwood point-resolved spectroscopy sequence is highly recommended, limited literature has measured cortical GSH using this method in major psychiatric disorders.</p><p><strong>Methods: </strong>By combining magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging, we quantified brain GSH and glutamate in the medial prefrontal cortex and precuneus and explored relationships between GSH levels and intrinsic neuronal activity as well as clinical symptoms among healthy control (HC) participants (n = 30), people with major depressive disorder (MDD) (n = 28), and people with obsessive-compulsive disorder (OCD) (n = 28).</p><p><strong>Results: </strong>GSH concentrations were lower in the medial prefrontal cortex and precuneus in both the MDD and OCD groups than in the HC group. In the HC group, positive correlations were noted between GSH and glutamate levels and between GSH and fractional amplitude of low-frequency fluctuations in both regions. However, while these correlations were absent in both patient groups, there was a weak positive correlation between glutamate and fractional amplitude of low-frequency fluctuations. Moreover, GSH levels were negatively correlated with depressive and compulsive symptoms in MDD and OCD, respectively.</p><p><strong>Conclusions: </strong>These findings suggest that reduced GSH levels and an imbalance between GSH and glutamate could increase oxidative stress and alter neurotransmitter signaling, thereby leading to disruptions in GSH-related neurochemical-neuronal coupling and psychopathologies across MDD and OCD. Understanding these mechanisms could provide valuable insights into the processes that underlie these disorders and potentially become a springboard for future directions and advancing our knowledge of their neurobiological foundations.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":"279-289"},"PeriodicalIF":9.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103999","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":"Effect of Antidepressant Treatment on 5-HT₄ Receptor Binding and Associations With Clinical Outcomes and Verbal Memory in Major Depressive Disorder.","authors":"Vibeke H Dam, Kristin Köhler-Forsberg, Brice Ozenne, Søren V Larsen, Cheng-Teng Ip, Anders Jorgensen, Dea S Stenbæk, Jacob Madsen, Claus Svarer, Martin B Jørgensen, Gitte M Knudsen, Vibe G Frokjaer","doi":"10.1016/j.biopsych.2024.08.009","DOIUrl":"10.1016/j.biopsych.2024.08.009","url":null,"abstract":"<p><strong>Background: </strong>Brain serotonin 4 receptor (5-HT₄R) levels are lower in untreated patients with major depressive disorder (MDD) and are linked to verbal memory. Here, we investigated the relationship between 5-HT₄R levels, clinical outcomes, and cognitive function in patients with MDD who initiated selective serotonin reuptake inhibitor drug treatment.</p><p><strong>Methods: </strong>Ninety patients with moderate to severe depression underwent molecular brain imaging to measure 5-HT₄R binding prior to antidepressant treatment with escitalopram. Pretreatment 5-HT₄R binding was assessed for its ability to predict treatment outcome at weeks 4, 8, or 12. In 40 patients who were rescanned 8 weeks posttreatment, change in cerebral 5-HT₄R binding was correlated with change in verbal memory and with change in depressive symptoms, as evaluated by the 6-item Hamilton Depression Rating Scale.</p><p><strong>Results: </strong>After 8 weeks of serotonergic intervention, neostriatal 5-HT₄R binding was reduced by 9%. Global change in 5-HT₄R binding from baseline was associated with verbal memory outcomes, but not with overall clinical depressive symptom outcomes. Pretreatment 5-HT₄R binding did not predict clinical recovery status at week 8 and was not associated with change in the 6-item Hamilton Depression Rating Scale scores.</p><p><strong>Conclusions: </strong>In patients with moderate to severe MDD, treatment with selective serotonin reuptake inhibitors downregulated neostriatal 5-HT₄R levels, which is consistent with the notion that the drugs increase cerebral extracellular serotonin. The less global brain 5-HT₄R levels were downregulated after selective serotonin reuptake inhibitors, the more verbal memory improved, highlighting the potential importance of 5-HT₄R as a treatment target in MDD. The findings offer insights into mechanisms that underlie antidepressant effects and point to new directions for precision medicine treatments for MDD.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":"261-268"},"PeriodicalIF":9.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054844","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":"Insomnia Subtypes Have Differentiating Deviations in Brain Structural Connectivity.","authors":"Tom Bresser, Tessa F Blanken, Siemon C de Lange, Jeanne Leerssen, Jessica C Foster-Dingley, Oti Lakbila-Kamal, Rick Wassing, Jennifer R Ramautar, Diederick Stoffers, Martijn P van den Heuvel, Eus J W Van Someren","doi":"10.1016/j.biopsych.2024.06.014","DOIUrl":"10.1016/j.biopsych.2024.06.014","url":null,"abstract":"<p><strong>Background: </strong>Insomnia disorder is the most common sleep disorder. A better understanding of insomnia-related deviations in the brain could inspire better treatment. Insufficiently recognized heterogeneity within the insomnia population could obscure detection of involved brain circuits. In the current study, we investigated whether structural brain connectivity deviations differed between recently discovered and validated insomnia subtypes.</p><p><strong>Methods: </strong>Structural and diffusion-weighted 3T magnetic resonance imaging data from 4 independent studies were harmonized. The sample consisted of 73 control participants without sleep complaints and 204 participants with insomnia who were grouped into 5 insomnia subtypes based on their fingerprint of mood and personality traits assessed with the Insomnia Type Questionnaire. Linear regression correcting for age and sex was used to evaluate group differences in structural connectivity strength, indicated by fractional anisotropy, streamline volume density, and mean diffusivity and evaluated within 3 different atlases.</p><p><strong>Results: </strong>Insomnia subtypes showed differentiating profiles of deviating structural connectivity that were concentrated in different functional networks. Permutation testing against randomly drawn heterogeneous subsamples indicated significant specificity of deviation profiles in 4 of the 5 subtypes: highly distressed, moderately distressed reward sensitive, slightly distressed low reactive, and slightly distressed high reactive. Connectivity deviation profile significance ranged from p = .001 to p = .049 for different resolutions of brain parcellation and connectivity weight.</p><p><strong>Conclusions: </strong>Our results provide an initial indication that different insomnia subtypes exhibit distinct profiles of deviations in structural brain connectivity. Subtyping insomnia may be essential for a better understanding of brain mechanisms that contribute to insomnia vulnerability.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":"302-312"},"PeriodicalIF":9.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465940","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":"Regional Structural-Functional Connectivity Coupling in Major Depressive Disorder Is Associated With Neurotransmitter and Genetic Profiles.","authors":"Tongpeng Chu, Xiaopeng Si, Haizhu Xie, Heng Ma, Yinghong Shi, Wei Yao, Dong Xing, Feng Zhao, Fanghui Dong, Qun Gai, Kaili Che, Yuting Guo, Danni Chen, Dong Ming, Ning Mao","doi":"10.1016/j.biopsych.2024.08.022","DOIUrl":"10.1016/j.biopsych.2024.08.022","url":null,"abstract":"<p><strong>Background: </strong>Abnormalities in structural-functional connectivity (SC-FC) coupling have been identified globally in patients with major depressive disorder (MDD). However, investigations have neglected the variability and hierarchical distribution of these abnormalities across different brain regions. Furthermore, the biological mechanisms that underlie regional SC-FC coupling patterns are not well understood.</p><p><strong>Methods: </strong>We enrolled 182 patients with MDD and 157 healthy control participants and quantified the intergroup differences in regional SC-FC coupling. Extreme gradient boosting (XGBoost), support vector machine, and random forest models were constructed to assess the potential of SC-FC coupling as biomarkers for MDD diagnosis and symptom prediction. Then, we examined the link between changes in regional SC-FC coupling in patients with MDD, neurotransmitter distributions, and gene expression.</p><p><strong>Results: </strong>We observed increased regional SC-FC coupling in the default mode network (t₃₃₇ = 3.233) and decreased coupling in the frontoparietal network (t₃₃₇ = -3.471) in patients with MDD compared with healthy control participants. XGBoost (area under the receiver operating characteristic curve = 0.853), support vector machine (area under the receiver operating characteristic curve = 0.832), and random forest (p < .05) models exhibited good prediction performance. The alterations in regional SC-FC coupling in patients with MDD were correlated with the distributions of 4 neurotransmitters (p < .05) and expression maps of specific genes. These enriched genes were implicated in excitatory neurons, inhibitory neurons, cellular metabolism, synapse function, and immune signaling. These findings were replicated on 2 brain atlases.</p><p><strong>Conclusions: </strong>This work enhances our understanding of MDD and paves the way for the development of additional targeted therapeutic interventions.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":"290-301"},"PeriodicalIF":9.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104000","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, Musa B Sami","doi":"10.1016/j.biopsych.2024.08.007","DOIUrl":"10.1016/j.biopsych.2024.08.007","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","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":"","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, Adam Beermann, Jing Xie, Gulcan Yildiz, Karlos Manzanarez Felix, Jean Addington, Carrie E Bearden, Kristin Cadenhead, Tyrone D Cannon, Barbara Cornblatt, Matcheri Keshavan, Daniel Mathalon, Diana O Perkins, Larry Seidman, William S Stone, Ming T Tsuang, Elaine F Walker, Scott Woods, Michael J Coleman, Sylvain Bouix, Daphne J Holt, Dost Öngür, Alan Breier, Martha E Shenton, Stephan Heckers, Mark A Halko, Kathryn E Lewandowski, Roscoe O Brady","doi":"10.1016/j.biopsych.2024.07.012","DOIUrl":"10.1016/j.biopsych.2024.07.012","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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) (n = 183) to identify links between connectivity and ACPT performance. We then analyzed data from the NAPLS2 (North American Prodrome Longitudinal Study 2) (n = 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.</p><p><strong>Results: </strong>Our connectome-wide association study in early-course psychosis identified robust associations between better ACPT performance and higher prefrontal-somatomotor connectivity (p < .005). Prefrontal-somatomotor connectivity was also related to ACPT performance in at-risk individuals who would develop psychosis (n = 17). This finding was not observed in nonconverters (n = 196) or control participants (n = 132).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","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}