Biological Psychiatry最新文献

{"title":"Towards understanding and halting legacies of trauma.","authors":"William Wesley Taylor, Laura Korobkova, Nabeel Bhinderwala, Brian George Dias","doi":"10.1016/j.biopsych.2025.02.010","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.02.010","url":null,"abstract":"<p><p>Echoes of natural and anthropogenic stressors not only reverberate within the physiology, biology, and neurobiology of the generation directly exposed to them but also within the biology of future generations. With the intent of understanding this phenomenon, significant efforts have sought to establish how exposure to psychosocial stress, chemicals, over- and under-nutrition, and chemosensory experiences exert multi-generational influences. From these studies, we are gaining new appreciation for how negative environmental events experienced by one generation impact future generations. This review first outlines the need to operationally define dimensions of negative environmental events in the laboratory and the routes via which the impact of such events are felt through generations. Next, it discusses molecular processes that cause the effects of negative environmental events to be initiated in the exposed generation and then perpetuated across generations. Finally, we discuss how legacies of flourishing can be engineered to halt or reverse multi-generational influences of negative environmental events. In summary, this review synthesizes our current understanding of the concept, causes and consequences of multi-generational echoes of stress and looks to opportunities to halt them.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432297","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":"Global diversity in bipolar disorder: the role of cultural and social differences with a view to genomics.","authors":"Janice M Fullerton, Markos Tesfaye","doi":"10.1016/j.biopsych.2025.02.008","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.02.008","url":null,"abstract":"<p><p>As global gene discovery efforts turn away from a historic Eurocentric focus and advance towards embracing more diverse populations, consideration of sociocultural aspects of bipolar disorder become critical to their success. Diversity can be leveraged to accelerate gene discovery, via different patterns of linkage disequilibrium that lead to greater resolution of mapping association signals, and convergence of genes and pathways implicated within and across diverse ancestral groups improving our understanding of the molecular underpinnings of disease. However it is not just the differences in linkage disequilibrium structure and allele frequency that drive differences in genomic signals between populations. This review focuses on the role of social, cultural and societal factors on bipolar disorder, and their potential impact on disease prevalence, clinical course and outcome, and disease burden. Social, cultural, and geographical differences in expression of symptoms, and frequency of clinical subtypes in bipolar disorder present both opportunities and challenges to the field. In this era of global multi-ancestry research, resources that facilitate the collection and harmonization of data from culturally and ancestrally-diverse population groups will enhance our ability to gain true biological understanding. Such resources are essential to disambiguate the genetic and environmental components of disease risk, as well as inform effective lifestyle interventions to improve outcome for global citizens living with bipolar disorder.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432292","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 drug discovery drought in bipolar disorder: barriers and solutions.","authors":"Jee Hyun Kim, Ken Walder, Bruna Panizzutti, Lana J Williams, Michael Berk","doi":"10.1016/j.biopsych.2025.02.006","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.02.006","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424928","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":"Prediction of treatment outcome in bipolar disorder - when can we expect clinical relevance?","authors":"Katie Scott, Anouar Khayachi, Martin Alda, Abraham Nunes","doi":"10.1016/j.biopsych.2025.02.005","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.02.005","url":null,"abstract":"<p><p>Long-term pharmacological treatment is the cornerstone of the management of bipolar disorder (BD). Clinicians typically select mood stabilizing medications from among several options through trial-and-error. This process could be optimized by using robust predictors of treatment response. We review clinical features and biological markers studied in relation to outcome of long-term treatment of BD. To date, the literature focused mostly on lithium and to a lesser extent on anticonvulsants valproate and lamotrigine. The most promising results show association of lithium response with certain clinical features (episodic clinical course and absence of rapid cycling, low rates of comorbid conditions, family history of bipolar disorder and lithium response) as well as low polygenic risk for schizophrenia and major depression. The clinical application of these findings remains limited, however, due to heterogeneity of the illness as well as unanswered questions about specificity of the effects of different medications.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424927","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 PROMISE OF INVESTIGATING NEURAL VARIABILITY IN PSYCHIATRIC DISORDERS.","authors":"Konstantinos Tsikonofilos, Arvind Kumar, Konstantinos Ampatzis, Douglas D Garrett, Kristoffer N T Månsson","doi":"10.1016/j.biopsych.2025.02.004","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.02.004","url":null,"abstract":"<p><p>The synergy of psychiatry and neuroscience has recently sought to identify biomarkers that can diagnose mental health disorders, predict their progression, and forecast treatment efficacy. However, biomarkers have achieved limited success to date, potentially due to a narrow focus on specific aspects of brain signals. This highlights a critical need for methodologies that can fully exploit the potential of neuroscience to transform psychiatric practice. In recent years, there is emerging evidence of the ubiquity and importance of moment-to-moment neural variability for brain function. Single-neuron recordings and computational models have demonstrated the significance of variability even at the microscopic level. Concurrently, studies involving healthy humans using neuroimaging recording techniques have strongly indicated that neural variability, once dismissed as undesirable noise, is an important substrate for cognition. Given the cognitive disruption in several psychiatric disorders, neural variability is a promising biomarker in this context and careful consideration of design choices is necessary to advance the field. This review provides an overview of the significance and substrates of neural variability across different recording modalities and spatial scales. We also review the existing evidence supporting its relevance in the study of psychiatric disorders. Finally, we advocate for future research to investigate neural variability within disorder-relevant, task-based paradigms and longitudinal designs. Supported by computational models of brain activity, this framework holds the potential for advancing precision psychiatry in a powerful and experimentally feasible manner.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424929","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":"Transcriptional and neurochemical signatures of cerebral blood flow alterations in schizophrenia and individuals at clinical high-risk for psychosis.","authors":"Samuel R Knight, Leyla Abbasova, Yashar Zeighami, Justine Y Hansen, Daniel Martins, Fernando Zelaya, Ottavia Dipasquale, Thomas Liu, David Shin, Matthijs Bossong, Matilda Azis, Mathilde Antoniades, Oliver D Howes, Ilaria Bonoldi, Alice Egerton, Paul Allen, Owen O'Daly, Philip McGuire, Gemma Modinos","doi":"10.1016/j.biopsych.2025.01.028","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.01.028","url":null,"abstract":"<p><strong>Background: </strong>The brain integrates multiple scales of description, from the level of cells and molecules to large-scale networks and behaviour. Understanding relationships across these scales may be fundamental to advancing understanding of brain function in health and disease. Recent neuroimaging research has shown that functional brain alterations that are associated with schizophrenia spectrum disorders (SSD) are already present in young adults at clinical high-risk for psychosis (CHR-P), yet the cellular and molecular determinants of these alterations remain unclear.</p><p><strong>Methods: </strong>Here, we used regional cerebral blood flow (rCBF) data from 425 individuals (122 SSD compared to 116 HCs, and 129 CHR-P compared to 58 HCs) and applied a novel pipeline to integrate brain-wide rCBF case-control maps with publicly available transcriptomic data (17,205 gene maps) and neurotransmitter atlases (19 maps) from 1074 healthy volunteers.</p><p><strong>Results: </strong>We identified significant correlations between astrocyte, oligodendrocyte precursor cell, and vascular leptomeningeal cell gene modules for both SSD and CHR-P rCBF phenotypes, and additionally microglia and oligodendrocytes in CHR-P. Receptor distribution significantly predicted case-control rCBF differences, with dominance analysis highlighting dopamine (D₁, D₂, DAT), acetylcholine (VAChT, M₁), GABA_A, and NMDA receptors as key predictors for SSD (R²_adj=.58, P_FDR<.05) and CHR-P (R²_adj=.6, P_FDR<.05) rCBF phenotypes. These associations were primarily localised in subcortical regions and implicate cell-types involved in stress response and inflammation, alongside specific neuroreceptor systems, in shared and distinct rCBF phenotypes in psychosis.</p><p><strong>Conclusions: </strong>Our findings underscore the value of integrating multi-scale data as a promising hypothesis-generating approach towards decoding biological pathways involved in neuroimaging-based psychosis phenotypes, potentially guiding novel interventions.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381653","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":"Epigenetic control of an auxiliary subunit of voltage-gated sodium channels regulates the strength of drug-cue associations and relapse-like cocaine seeking.","authors":"Daniel J Wood, Evgeny Tsvetkov, Susana Comte-Walters, Colin L Welsh, Michelle Bloyd, Timothy G Wood, Rose Marie Akiki, Ethan M Anderson, Rachel D Penrod, Lalima K Madan, Lauren E Ball, Makoto Taniguchi, Christopher W Cowan","doi":"10.1016/j.biopsych.2025.01.027","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.01.027","url":null,"abstract":"<p><strong>Background: </strong>Repeated use of illicit drugs produces long-lasting and prepotent drug-cue associations that increase vulnerability for relapse in individuals with a substance use disorder. Epigenetic factors, like histone deacetylase 5 (HDAC5), play a key role in regulating the formation of drug-cue associations, but the underlying mechanisms remain unclear.</p><p><strong>Methods: </strong>We used a combination of molecular biology, cultured cells, tandem mass spectrometry, deacetylase activity measurements, co-immunoprecipitation, and molecular dynamics simulations to assess HDAC5 structure-activity relationships. In male and female Long-Evans rats, we used viral-mediated expression of HDAC5 mutants in nucleus accumbens (NAc) to test effects on cocaine intravenous self-administration (SA) and cue-reinstated cocaine seeking. We also used in silico analysis of single-nucleus RNA sequencing data, quantitative RT-PCR, viral-mediated expression of Scn4b shRNA, patch-clamp electrophysiology, and rat cocaine or sucrose SA to assess Scn4b's effects on NAc intrinsic excitability and cued reward seeking.</p><p><strong>Results: </strong>We discovered that two conserved cysteines located near HDAC5's catalytic domain were required for its intrinsic deacetylase activity, and that HDAC5's deacetylase activity was required in NAc medium spiny neurons to limit relapse-like cue-reinstated cocaine seeking. Moreover, we found that HDAC5 limited cocaine, but not sucrose, seeking behavior by reducing NAc MSN intrinsic excitability through the deacetylase-dependent repression of Scn4b, which codes for an auxiliary subunit of voltage-gated sodium channels.</p><p><strong>Conclusions: </strong>Our findings suggest that HDAC5's control of NAc Scn4b expression governs the formation of cocaine-cue, but not sucrose-cue, associations through modulation of NAc MSN intrinsic excitability and drug-induced NAc plasticity mechanisms.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381650","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":"A critical role of philanthropic support in paving the way to precision medicine for bipolar disorder.","authors":"Daniel L Pham, Emily G Baxi, Kelsey M Barcomb, Veronica C Beck, Katherine E Burdick, Mark A Frye, Eric J Nestler, Cara M Altimus","doi":"10.1016/j.biopsych.2025.02.002","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.02.002","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373516","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":"Empirical classification of neuropsychiatric symptoms and association of classes with diagnostic progression and cognitive decline in MCI and AD populations.","authors":"Jong-Il Park, Seonjoo Lee, Benjamin Huber, Davangere P Devanand, Hyun Kim, Terry E Goldberg","doi":"10.1016/j.biopsych.2025.01.026","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.01.026","url":null,"abstract":"<p><strong>Background: </strong>To identify classes of cognitively impaired older individuals based on their neuropsychiatric symptoms(NPS) and to investigate the contribution of NPS class to cognitive decline and Alzheimer's disease(AD) risk in mild cognitive impairment(MCI).</p><p><strong>Methods: </strong>Our study included 1,472 participants(age range 55-91) from the Alzheimer's Disease Neuroimaging Initiative(ADNI) who were diagnosed with MCI or mild AD and had a complete neuropsychiatric Inventory at their baseline visit. We employed latent class analysis to categorize groups by NPS patterns. Linear mixed models of repeated measures(LMMRMs) were used to compare changes in cognitive performance across 5years as a function of NPS class. Subsequently, the Cox proportional hazards model was employed in individuals with MCI to assess whether rate of conversion to AD differed across the NPS groups.</p><p><strong>Results: </strong>We identified three latent classes of NPS: No NPS (n=799, 51.7%), Apathy/Affective (n=572, 39.8%), Complex (n=108, 8.5%) NPS. In longitudinal analyses we observed interactions between class and time, indicating accelerated cognitive decline in memory and executive function in the Apathy/Affective class. In MCI, hazard ratios for conversion to AD were 1.39(95% CI: 1.10-1.76) for the Apathy/Affective class and 2.03(95% CI: 1.33-3.10) for the Complex class compared to the No NPS group after adjusting for age, sex, education, global cognition, and ApoE4 positivity.</p><p><strong>Conclusions: </strong>Among cognitively impaired elderly, empirically derived clusters of NPS profiles were associated with cognitive decline and risk of conversion from MCI to AD. Such NPS classes may reflect specific neurobiological mechanisms within or related to AD-related neurodegeneration. Further studies with biological markers are needed to clarify these neurobiological mechanisms.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373574","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":"Targeting GABA Polarity During Cortical Development Improves Circuit and Sensory Deficits in Fragile X Mice","authors":"Ragunathan Padmashri,&nbsp;Anna Dunaevsky","doi":"10.1016/j.biopsych.2024.12.006","DOIUrl":"10.1016/j.biopsych.2024.12.006","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"97 5","pages":"Pages 420-421"},"PeriodicalIF":9.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143178800","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}