Biological psychiatry global open science最新文献

{"title":"Transdiagnostic Symptom Domains Have Distinct Patterns of Association With Head Motion During Multimodal Imaging in Children","authors":"Kavari Hercules ,&nbsp;Zhiyuan Liu ,&nbsp;Eleni Christofilea ,&nbsp;Jia Wei ,&nbsp;Gladys Venegas ,&nbsp;Olivia Ciocca ,&nbsp;Alice Dyer ,&nbsp;Goeun Lee ,&nbsp;Sasha Santini-Bishop ,&nbsp;Heather Shappell ,&nbsp;Dylan G. Gee ,&nbsp;Denis G. Sukhodolsky ,&nbsp;Karim Ibrahim","doi":"10.1016/j.bpsgos.2025.100506","DOIUrl":"10.1016/j.bpsgos.2025.100506","url":null,"abstract":"<div><h3>Background</h3><div>It is unclear how transdiagnostic symptoms including attention, disruptive behavior, and internalizing problems are linked to in-scanner motion in children across structural and functional magnetic resonance imaging (fMRI). In the current study, we examined whether transdiagnostic symptoms of attention, disruptive behavior, and internalizing problems were associated with scanner motion in children during multimodal imaging.</div></div><div><h3>Methods</h3><div>In 9045 children ages 9 to 10 years in the ABCD (Adolescent Brain Cognitive Development) Study, logistic regression and linear mixed-effects models were used to examine associations between motion and behavior. Motion was indexed using ABCD Study quality control (QC) metrics and mean framewise displacement for T1- and T2-weighted structural, resting-state, and diffusion MRI; stop-signal task; monetary incentive delay task; and emotional n-back task. The Child Behavior Checklist was used as a continuous measure of symptom severity.</div></div><div><h3>Results</h3><div>Greater severity of attention and disruptive behavior problems was associated with a lower likelihood of passing motion QC across imaging modalities, while increased internalizing severity was associated with a higher likelihood of passing. There was also an interaction between sex and attention-related problems in passing QC for T2-weighted and diffusion MRI scans. Increased attention and disruptive behavior problems were associated with increased mean motion, whereas increased internalizing problems were associated with decreased mean motion. Greater severity of attention problems was associated with worse performance across the fMRI tasks.</div></div><div><h3>Conclusions</h3><div>These findings have implications for advancing the development of computational and behavioral approaches for mitigating motion effects in youths, enhancing accessibility of imaging protocols and representativeness influences across child psychiatric disorders, and identifying brain-based biomarkers.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 4","pages":"Article 100506"},"PeriodicalIF":4.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169374","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":"Antidepressant Effects of Nitrous Oxide in Major Depressive Disorder: A Phase 2b Randomized Clinical Trial","authors":"Paul S. Myles ,&nbsp;Jayashri Kulkarni ,&nbsp;Jessica Kasza ,&nbsp;Sophie Wallace ,&nbsp;Carolyn Deng ,&nbsp;Alisa Turbić ,&nbsp;Verna Aykanat ,&nbsp;Charles R. Conway ,&nbsp;Frank Brown ,&nbsp;Royce Lee ,&nbsp;Robert D. Gibbons ,&nbsp;Peter Nagele","doi":"10.1016/j.bpsgos.2025.100504","DOIUrl":"10.1016/j.bpsgos.2025.100504","url":null,"abstract":"<div><h3>Background</h3><div>Nitrous oxide (“laughing gas”) is an NMDA receptor antagonist. In the current study, our aim was to investigate the efficacy, safety, and likely optimal dose of nitrous oxide in adults with major depressive disorder (MDD).</div></div><div><h3>Methods</h3><div>In this phase 2b randomized, double-blind trial, 81 patients with MDD were allocated on a 1:1 basis to receive nitrous oxide or oxygen/air (control); the nitrous group was further randomized to either 50% or 25% inspired nitrous oxide. All participants received four 1-hour-long treatment sessions at 1-week intervals and were followed for an additional 4 weeks. The primary outcome was the change in the 21-item Hamilton Depression Rating Scale (HAM-D) over the 4 treatment sessions. Secondary outcomes included remission (HAM-D ≤7 points), the Computerized Adaptive Test-Depression Inventory (CAT-DI) and Computerized Adaptive Test-Suicide Scale (CAT-SS).</div></div><div><h3>Results</h3><div>The mean averaged change in HAM-D scores over the 4 weeks of treatment was lower with nitrous oxide than with control (−1.9 [95% CI, −3.9 to 0.0], <em>p</em> = .051). In the first week, 15 of 39 (38%) in the nitrous oxide group and 5 of 39 (13%) in the control group were remitted (<em>p</em> = .031). The mean averaged change in CAT-DI scores was −7.7 (95% CI, −14.1 to −1.4), <em>p</em> = .017; the mean averaged change in CAT-SS scores was −8.3 (95% CI, −14.4 to −2.1), <em>p</em> = .008, both favoring nitrous oxide.</div></div><div><h3>Conclusions</h3><div>In this study, we confirmed that nitrous oxide has likely beneficial antidepressant effects in people with MDD.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 4","pages":"Article 100504"},"PeriodicalIF":4.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144154372","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":"Peripheral MicroRNA Signatures in Adolescent Depression","authors":"Alice Morgunova ,&nbsp;Nicholas O’Toole ,&nbsp;Fatme Abboud ,&nbsp;Saché Coury ,&nbsp;Gary Gang Chen ,&nbsp;Maxime Teixeira ,&nbsp;Eamon Fitzgerald ,&nbsp;Gustavo Turecki ,&nbsp;Anthony J. Gifuni ,&nbsp;Ian H. Gotlib ,&nbsp;Corina Nagy ,&nbsp;Michael J. Meaney ,&nbsp;Tiffany C. Ho ,&nbsp;Cecilia Flores","doi":"10.1016/j.bpsgos.2025.100505","DOIUrl":"10.1016/j.bpsgos.2025.100505","url":null,"abstract":"<div><h3>Background</h3><div>Adolescent depression is linked to enduring maladaptive outcomes, chronic severity of symptoms, and poor treatment response. Identifying epigenetic signatures of adolescent depression is urgently needed to improve early prevention and intervention strategies. MicroRNAs (miRNAs) are epigenetic regulators of adolescent neurodevelopmental processes, but their role as markers and mediators of adolescent depression is unknown.</div></div><div><h3>Methods</h3><div>Here, we examined miRNA profiles from dried blood spot samples of male and female adolescents with clinical depression and psychiatrically healthy male and female adolescents (<em>N</em> = 62). We processed and sequenced these samples using a small RNA protocol tailored for miRNA identification.</div></div><div><h3>Results</h3><div>We identified 9 differentially expressed (DE) miRNAs (adjusted <em>p</em> value &lt; .05), all of which were upregulated in adolescents with depression. At future follow-ups post blood collection, expression of miR-3613-5p, mir-30c-2, and miR-942-5p were positively associated with depression severity but not anxiety, suggesting a stronger link to persistent depression symptoms. Expression of miR-32-5p inversely correlated with hippocampal volume, highlighting a potential neurobiological basis. Common predicted gene targets of the DE miRNAs are involved in neurodevelopment, cognitive processing, and depressive disorders.</div></div><div><h3>Conclusions</h3><div>These findings lay the groundwork for identifying adolescent peripheral miRNA markers that reflect neurodevelopmental pathways that shape lifelong psychopathology risk.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 4","pages":"Article 100505"},"PeriodicalIF":4.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169370","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":"High Baseline Plasma Anthranilic Acid Predicts Remission Upon Acute-Series Ketamine Infusion for Treatment-Resistant Depression","authors":"Stephen A. Murata ,&nbsp;Zachary B. Madaj ,&nbsp;Colt D. Capan ,&nbsp;Ryan D. Sheldon ,&nbsp;Rif S. El-Mallakh ,&nbsp;Sagar V. Parikh ,&nbsp;William V. Bobo ,&nbsp;Fernando S. Goes ,&nbsp;Owen M. Wolkowitz ,&nbsp;Jennifer L. Vande Voort ,&nbsp;Louis J. Nykamp ,&nbsp;Balwinder Singh ,&nbsp;Gustavo C. Medeiros ,&nbsp;Erik B. Nelson ,&nbsp;Michael E. Thase ,&nbsp;Gregory F. Oxenkrug ,&nbsp;Mark A. Frye ,&nbsp;John F. Greden ,&nbsp;Eric D. Achtyes ,&nbsp;Lena C. Brundin","doi":"10.1016/j.bpsgos.2025.100503","DOIUrl":"10.1016/j.bpsgos.2025.100503","url":null,"abstract":"<div><h3>Background</h3><div>Treatment-resistant depression (TRD) remains a challenge, but intravenous racemic ketamine offers rapid antidepressant effects. Reliable biomarkers are needed. In this study, we examined kynurenine pathway metabolites and inflammatory cytokines as predictors of ketamine response.</div></div><div><h3>Methods</h3><div>The Bio-K study was a multicenter, open-label trial of 74 patients with TRD who received 3 ketamine infusions over 11 days. Remission (Montgomery–Åsberg Depression Rating Scale [MADRS] score ≤9) was assessed 24 hours post infusion 3, with a subset of study participants continuing weekly infusions. Plasma biomarkers (9 kynurenines, 14 cytokines) were measured at baseline and post infusion. Mixed-effects models and logistic regression analyses were used, adjusting for sex, age, body mass index, benzodiazepine use, and baseline MADRS scores. Second-generation <em>p</em> values were used to determine significance.</div></div><div><h3>Results</h3><div>Of the 74 participants, 52% (<em>n</em> = 38) achieved remission. Higher baseline anthranilic acid (AA) levels predicted remission (β = −0.93, <em>p</em> = .02). Composite ratios, including AA:intercellular adhesion molecule-1 (ICAM-1) (β = −1.15, <em>p</em> = .002) and AA:tryptophan (TRP) (β = −0.98, <em>p</em> = .007), significantly improved predictive accuracy (area under the receiver operating characteristic curve = 0.75 vs. 0.64, <em>p</em> = .03). The findings were independent of demographic and clinical covariates.</div></div><div><h3>Conclusions</h3><div>Elevated AA levels and AA-based biomarker ratios predicted ketamine remission in patients with TRD, supporting biomarker-driven personalized treatment. These findings highlight immunometabolic mechanisms in ketamine response.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 4","pages":"Article 100503"},"PeriodicalIF":4.0,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138986","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":"Antidepressant Switching as a Proxy Phenotype for Drug Nonresponse: Investigating Clinical, Demographic, and Genetic Characteristics","authors":"Chris Wai Hang Lo ,&nbsp;Alexandra C. Gillett ,&nbsp;Matthew H. Iveson ,&nbsp;Michelle Kamp ,&nbsp;Chiara Fabbri ,&nbsp;Win Lee Edwin Wong ,&nbsp;Dale Handley ,&nbsp;Oliver Pain ,&nbsp;Evangelos Vassos ,&nbsp;Naomi R. Wray ,&nbsp;Heather C. Whalley ,&nbsp;Danyang Li ,&nbsp;Allan H. Young ,&nbsp;Andrew M. McIntosh ,&nbsp;Cathryn M. Lewis","doi":"10.1016/j.bpsgos.2025.100502","DOIUrl":"10.1016/j.bpsgos.2025.100502","url":null,"abstract":"<div><h3>Background</h3><div>Selective serotonin reuptake inhibitors (SSRIs) are a first-line pharmacological therapy in major depressive disorder (MDD), but treatment response rates are low. Clinical trials lack the power to study the genetic contribution to SSRI response. Real-world evidence from electronic health records provides larger sample sizes, but novel response definitions are needed to accurately define SSRI nonresponders.</div></div><div><h3>Methods</h3><div>In the UK Biobank (UKB) (<em>N</em> = 38,813) and Generation Scotland (<em>N</em> = 1777) datasets, SSRI switching was defined using ≤90-day gap between prescriptions for an SSRI and another antidepressant in primary care. Nonswitchers were participants with ≥3 consecutive prescriptions for an SSRI. In the UKB, clinical, demographic, and polygenic score (PGS) associations with switching were determined, and the common-variant heritability was estimated.</div></div><div><h3>Results</h3><div>In the UKB, 5133 (13.2%) SSRI switchers and 33,680 nonswitchers were defined. The mean time to switch was 28 days (interquartile range, 17–49). Switching patterns were consistent across the UKB and Generation Scotland (<em>n</em> = 498 switchers). Higher annual income and educational levels (odds ratio [OR] [95% CI] for a university degree, 0.73 [0.67–0.79] compared with no qualifications) were associated with lower levels of switching. PGSs for nonremission, based on clinical studies, were associated with increased risk of switching (OR, 1.07 [1.02–1.12], <em>p</em> = .007). MDD PGSs and family history of depression were not significantly associated with switching. Using genome-wide complex trait Bayesian, the single nucleotide polymorphism–based heritability was approximately 4% (SE 0.016) on the observed scale.</div></div><div><h3>Conclusions</h3><div>This study identified SSRI switching as a proxy for nonresponse, scalable across biobanks with electronic health records, capturing demographics and genetics of treatment nonresponse, and independent of MDD genetics.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 4","pages":"Article 100502"},"PeriodicalIF":4.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144154371","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":"Grin2a Hypofunction Impairs Spatial Working Memory and Disrupts Hippocampal Network Oscillations and Excitatory-Inhibitory Balance","authors":"Hassan Hosseini ,&nbsp;Sky Evans-Martin ,&nbsp;Emma Bogomilsky ,&nbsp;Dominique L. Pritchett ,&nbsp;Kevin S. Jones","doi":"10.1016/j.bpsgos.2025.100500","DOIUrl":"10.1016/j.bpsgos.2025.100500","url":null,"abstract":"<div><h3>Background</h3><div>NMDA receptors, particularly those containing the GluN2A subunit, are critical for hippocampal-dependent learning and memory. The GluN2A subunit is encoded by the <em>GRIN2A</em> gene and is essential for maintaining cognitive function, including working memory. In this study, we explored how full or partial ablation of the mouse <em>Grin2a</em> gene impairs working memory and disrupts hippocampal network oscillations and excitatory/inhibitory (E/I) balance.</div></div><div><h3>Methods</h3><div>Male <em>Grin2a</em> mutant mice were assessed for spatial working memory deficits using the 8-arm radial maze. We utilized multielectrode arrays and whole-cell patch-clamp electrophysiology to evaluate network oscillations and synaptic inputs to pyramidal cells in ex vivo hippocampal slices. We performed an immunohistochemical analysis of hippocampal slices to evaluate changes in the abundance of GABAergic (gamma-aminobutyric acidergic) neurons.</div></div><div><h3>Results</h3><div><em>Grin2a</em> deficiency impaired spatial working memory and disrupted coupling of theta-gamma oscillations in the hippocampus. Moreover, <em>Grin2a</em> mutants expressed an overabundance of parvalbumin-expressing interneurons that integrated into hippocampal circuits and destabilized E/I input to CA1 pyramidal neurons.</div></div><div><h3>Conclusions</h3><div>This study highlights the critical role of GluN2A-containing NMDA receptors in maintaining hippocampal network synchrony. Impairments in network synchrony and E/I balance within the hippocampus may contribute to cognitive deficits observed in <em>Grin2a</em>-related disorders such as schizophrenia, epilepsy, and intellectual disability.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 4","pages":"Article 100500"},"PeriodicalIF":4.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144088832","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":"Cardiac and Electrodermal Responses to Threats: Modulation by Childhood Sexual Abuse History","authors":"Mariana Xavier ,&nbsp;Arthur V. Machado ,&nbsp;Eliane Volchan ,&nbsp;Letícia Oliveira ,&nbsp;Liana Catarina L. Portugal ,&nbsp;Gabriela G.L. Souza ,&nbsp;Fátima S. Erthal ,&nbsp;Raquel M. Gonçalves ,&nbsp;Camila M.F. Gama ,&nbsp;Rita de Cássia S. Alves ,&nbsp;Izabela Mocaiber ,&nbsp;Mirtes G. Pereira","doi":"10.1016/j.bpsgos.2025.100499","DOIUrl":"10.1016/j.bpsgos.2025.100499","url":null,"abstract":"<div><h3>Background</h3><div>Childhood sexual abuse (CSA) is associated with significant negative lifelong consequences for physical and mental health. However, the impact of CSA history on danger perception and response has been understudied. In this study, we explored how autonomic reactivity to threat<del>s</del> is influenced by the history of CSA in a nonclinical sample.</div></div><div><h3>Methods</h3><div>Participants were undergraduate students with no current diagnosis of cardiovascular disease or mental disorders. After exclusion criteria were applied, the sample consisted of 135 participants. Among these 135 participants, 48 (mean age, 20.43 years; SD, 3.07; 9 men) reported having experienced significant CSA (CSA group), and 87 (mean age, 20.89 years; SD, 4.99; 30 men) reported not having had such experiences (non-CSA group). The participants viewed trauma-unrelated threatening or neutral pictures while their skin conductance response and heart rate data were collected.</div></div><div><h3>Results</h3><div>Compared with the neutral pictures, when viewing trauma-unrelated threatening pictures, the non-CSA group presented bradycardia, which is a typical cardiac response upon exposure to negative images. In contrast, the CSA group presented a blunted cardiac response. Furthermore, we observed an overrepresentation of skin conductance nonresponders in the CSA group.</div></div><div><h3>Conclusions</h3><div>Taken together, these findings suggest that youth who are exposed to CSA seem to have blunted autonomic responsiveness to threats. This blunted responsiveness is an atypical pattern that may represent a biomarker of many unfavorable physiological and psychological outcomes.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 4","pages":"Article 100499"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929217","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 of Leukocyte Telomere Length With Trait Resilience, Adverse Childhood Experiences, and Psychological Distress Among Expecting Parents in the FinnBrain Birth Cohort","authors":"Viivi Mondolin ,&nbsp;Hasse Karlsson ,&nbsp;Laura Perasto ,&nbsp;Tiina Paunio ,&nbsp;Emma Vitikainen ,&nbsp;Dries S. Martens ,&nbsp;Linnea Karlsson ,&nbsp;Jetro J. Tuulari ,&nbsp;Eeva-Leena Kataja","doi":"10.1016/j.bpsgos.2025.100498","DOIUrl":"10.1016/j.bpsgos.2025.100498","url":null,"abstract":"<div><h3>Background</h3><div>Telomere attrition has previously been associated with mental health problems and adverse childhood experiences (ACEs). Resilience has been shown to protect against mental health problems even in the context of ACEs. In this study, we examined the associations between leukocyte telomere length (LTL), symptoms of psychological distress, ACEs, and trait resilience. We examined whether LTL mediates the negative effects of ACEs and whether trait resilience moderates the association between LTL and distress.</div></div><div><h3>Methods</h3><div>The study population was drawn from the ongoing FinnBrain Birth Cohort Study and included 342 mothers and 339 fathers who had provided blood samples and questionnaire data during pregnancy. Questionnaire data included the Connor-Davidson Resilience Scale 10, Edinburgh Postnatal Depression Scale, Symptom Checklist-90, and Trauma and Distress Scale. Data analysis included regression analysis, mixed-methods models, and statistical evaluation.</div></div><div><h3>Results</h3><div>ACEs were associated with depressive and anxiety symptoms. However, contrary to the initial hypothesis, LTL was not associated with ACEs or distress symptoms and thus did not mediate their association. Furthermore, resilience was not associated with LTL and did not moderate the possible association between LTL and distress symptoms.</div></div><div><h3>Conclusions</h3><div>We found no association between TL and ACEs, psychological distress, or trait resilience. The mild distress symptoms, limited exposure to high ACEs, and the predominantly moderate to high socioeconomic status in the sample may be relevant to interpreting these findings. Encouragingly, not all ACEs necessarily lead to telomere attrition.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 4","pages":"Article 100498"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936960","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":"Rare Copy Number Variants Reveal Critical Cell Types and Periods of Brain Development in Neurodevelopmental Disorders","authors":"Susmita Malwade ,&nbsp;Carl M. Sellgren ,&nbsp;Navneet A. Vasistha ,&nbsp;Konstantin Khodosevich","doi":"10.1016/j.bpsgos.2025.100495","DOIUrl":"10.1016/j.bpsgos.2025.100495","url":null,"abstract":"<div><h3>Background</h3><div>Multiple copy number variations (CNVs) in the human genome are associated with neurodevelopmental disorders (NDDs). Their markedly larger effect sizes and penetrance than common risk variants make them invaluable for investigating the etiology of NDDs.</div></div><div><h3>Methods</h3><div>We integrated &gt;1 million single-cell transcriptomes from multiple datasets, capturing major brain regions and the entire timeline of human brain development. We performed expression-weighted cell-type enrichment analysis of genes contained in 127 CNVs associated with NDDs to identify human brain cell types, brain regions, and periods of development most susceptible to variations in gene dosage.</div></div><div><h3>Results</h3><div>We identified 3 groups of CNVs differentially enriched in developing cell types. Two groups of CNVs were preferentially expressed during early fetal brain development. While group A could be defined as developing neuron CNVs, group B was precursor CNVs, which were highly enriched in radial glia. Group A CNVs were associated with synaptic signaling, suggesting that synaptic dysfunction observed in NDDs may originate very early during fetal brain development. Group B CNVs were related to cell cycle and suggest dysfunction in proliferation and differentiation of precursor cells. Postnatally, expression of groups A and B genes was enriched in intratelencephalic neurons that integrate cortical information.</div></div><div><h3>Conclusions</h3><div>Overall, we showed that although NDDs are only diagnosed during childhood or adolescence, the actual effect of genetic mutations on embryonic progenitor cells or early neurons may be strongest during fetal brain development, which could program the cascade for subsequent developmental changes and, together with further postnatal dysfunction, impair brain function.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 4","pages":"Article 100495"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921985","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":"Putative Mechanisms of Electroconvulsive Therapy in Treatment-Resistant Schizophrenia Examined Using Magnetic Resonance Imaging","authors":"Neelabja Roy ,&nbsp;Dhruva Ithal ,&nbsp;Urvakhsh Meherwan Mehta ,&nbsp;Rakshathi Basavaraju ,&nbsp;Rose Dawn Bharath ,&nbsp;Nicolas R. Bolo ,&nbsp;Jagadisha Thirthalli ,&nbsp;Bangalore N. Gangadhar ,&nbsp;Matcheri S. Keshavan","doi":"10.1016/j.bpsgos.2025.100494","DOIUrl":"10.1016/j.bpsgos.2025.100494","url":null,"abstract":"<div><h3>Background</h3><div>The neural mechanisms of electroconvulsive therapy (ECT) in refractory schizophrenia remain elusive. In the current study, we aimed to identify magnetic resonance imaging (MRI)–derived structural (cortical/subcortical volumes) and functional (resting-state connectivity) brain changes after ECT and their associations with clinical response.</div></div><div><h3>Methods</h3><div>We used an inductive (whole-brain, hypothesis-free) approach to examine structural and functional brain changes and their association with clinical response (positive symptom reduction) in clozapine-refractory schizophrenia (<em>n</em> = 30) after ECT (median 8 sessions). Furthermore, a deductive approach was used to compare baseline whole-brain MRI data from clozapine-refractory patients (<em>n</em> = 31) to data from clozapine responders (<em>n</em> = 23), thereby identifying regions of interest unique to clozapine-refractory schizophrenia. Changes in these regions of interest post-ECT and their association with clinical response were then examined.</div></div><div><h3>Results</h3><div>The inductive approach identified volumetric enhancement in the bilateral amygdalae (Cohen’s <em>d</em> = 0.4), which was significantly associated with clinical response (β = −0.01, <em>p</em> = .003). The deductive approach identified posterior cerebellar hyperconnectivity as being unique to clozapine-refractory schizophrenia (<em>d</em> = 1.57), which was associated with baseline positive symptoms (<em>r</em> = 0.36, <em>p</em> = .04). Following ECT, there was a significant reduction in posterior cerebellar hyperconnectivity (<em>d</em> = −0.86), and this reduction was significantly associated with clinical response (β = 0.42, <em>p</em> = .002). Increased hippocampal and frontal volumes, frontoparietal connectivity, and reduced sensorimotor connectivity were also observed but were unrelated to clinical response.</div></div><div><h3>Conclusions</h3><div>ECT may drive clinical improvement in refractory schizophrenia by increasing amygdala volumes and reducing posterior cerebellar connectivity. Randomized sham-controlled trials can confirm these findings in the future.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 4","pages":"Article 100494"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941710","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}