Biological Psychiatry最新文献

{"title":"Building Resilience: The Stress Response as a Driving Force for Neuroplasticity and Adaptation.","authors":"Erno J Hermans, Talma Hendler, Raffael Kalisch","doi":"10.1016/j.biopsych.2024.10.016","DOIUrl":"https://doi.org/10.1016/j.biopsych.2024.10.016","url":null,"abstract":"<p><p>People exhibit an extraordinary capacity to adjust to stressful situations. Here, we argue that the acute stress response is a major driving force behind this adaptive process. In addition to immediately freeing energy reserves, facilitating a rapid and robust neurocognitive response, and helping to reinstate homeostasis, the stress response also critically regulates neuroplasticity. Understanding the healthy acute stress response is therefore crucial for understanding stress resilience: the maintenance or rapid recovery of mental health during and after times of adversity. Contemporary resilience research distinguishes between resilience factors (RFs) and resilience mechanisms (RMs). RFs refer to a broad array of social, psychological, or biological variables that are stable but potentially malleable and predict resilient outcomes. RMs, by contrast, refer to proximate mechanisms activated during acute stress that enable individuals to effectively navigate immediate challenges. In this paper, we review literature related to how neurotransmitter and hormonal changes during acute stress regulate the activation of RMs. We integrate literature on the timing-dependent and neuromodulator-specific regulation of neurocognition, episodic memory, and behavioral and motivational control, highlighting the distinct and often synergistic roles of catecholamines (dopamine and norepinephrine) and glucocorticoids. We conclude that stress resilience is bolstered by improved future predictions and the success-based reinforcement of effective coping strategies during acute stress. The resulting generalized memories of success, controllability, and safety constitute beneficial plasticity that lastingly improves self-control under stress. Insight into such mechanisms of resilience is critical for the development of novel interventions focused on prevention rather than treatment of stress-related disorders.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494164","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":"Convergence on CaMK4: a key modulator of autism-associated signaling pathways in neurons.","authors":"Jacqueline Kaiser, Alana Risteska, Abbey G Muller, Haoxiong Sun, Bethany Lei, Kevin Nay, Anthony R Means, Margot A Cousin, David H Drewry, Jonathan S Oakhill, Bruce E Kemp, Anthony J Hannan, Michael Berk, Mark A Febbraio, Andrew L Gundlach, Elisa L Hill-Yardin, John W Scott","doi":"10.1016/j.biopsych.2024.10.012","DOIUrl":"https://doi.org/10.1016/j.biopsych.2024.10.012","url":null,"abstract":"<p><p>Although the precise underlying cause(s) of autism spectrum disorder remain unclear, more than 1000 rare genetic variations are associated with the condition. For a large number of people living with profound autism, this genetic heterogeneity has impeded the identification of common biological targets for therapy development for core and comorbid traits that include significant impairments in social communication, and repetitive and restricted behaviors. A substantial number of genes associated with autism encode proteins involved in signal transduction and synaptic transmission that are critical for brain development and function. CAMK4 is an emerging risk gene for autism spectrum disorder that encodes the Ca²⁺-calmodulin-dependent protein kinase-4 (CaMK4) enzyme. CaMK4 is a key component of a Ca²⁺-activated signaling pathway that regulates neurodevelopment and synaptic plasticity. In this review, we discuss three genetic variants of CAMK4 found in individuals with hyperkinetic movement disorder and comorbid neurological symptoms including autism spectrum disorder that are likely pathogenic with monogenic effect. We also comment on four other genetic variations in CAMK4 that display associations with autism spectrum disorder, as well as twelve examples of autism-associated variations in other genes that impact CaMK4 signaling pathways. Finally, we highlight three environmental risk factors that impact CaMK4 signaling based on studies in preclinical models of autism and/or clinical cohorts. Overall, we review molecular, genetic, physiological, and environmental evidence that suggest defects in the CaMK4 signaling pathway may play an important role in a common autism pathogenesis network across numerous patient groups, and propose CaMK4 as a potential therapeutic target.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494165","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":"Neuroimaging meta-analyses reveal convergence of interoception, emotion, and social cognition across neurodegenerative diseases.","authors":"Jessica L Hazelton, Fábio Carneiro, Marcelo Maito, Fabian Richter, Agustina Legaz, Florencia Altschuler, Leidy Cubillos-Pinilla, Yu Chen, Colin P Doherty, Sandra Baez, Agustín Ibáñez","doi":"10.1016/j.biopsych.2024.10.013","DOIUrl":"https://doi.org/10.1016/j.biopsych.2024.10.013","url":null,"abstract":"<p><strong>Introduction: </strong>Simultaneous interoceptive, emotional, and social cognition deficits are observed across neurodegenerative diseases. Indirect evidence suggests shared neurobiological bases underlying these impairments, termed the allostatic-interoceptive network (AIN). However, no study has yet explored the convergence of these deficits in neurodegenerative diseases or examined how structural and functional changes contribute to cross-domain impairments.</p><p><strong>Methods: </strong>A PRISMA Activated Likelihood Estimate (ALE) metanalyses encompassed studies meeting inclusion criteria: interoception, emotion, or social cognition tasks; neurodegenerative diseases (behavioral variant frontotemporal dementia (bvFTD), primary progressive aphasias (PPAs) Alzheimer's disease (AD), Parkinson's Disease (PD), multiple sclerosis (MS)); and neuroimaging (structural: MRI voxel-based morphometry; functional: fMRI and FDG-PET).</p><p><strong>Results: </strong>From 20,593 studies, 170 met inclusion criteria (58 interoception, 65 emotion, and 47 social cognition) involving 7032 participants (4963 patients and 2069 healthy controls). In all participants combined, conjunction analyses revealed AIN involvement of the insula, amygdala, orbitofrontal cortex, anterior cingulate, striatum, thalamus, and hippocampus across domains. In bvFTD this conjunction was replicated across domains, with further involvement of the temporal pole, temporal fusiform cortex, and angular gyrus. A convergence of interoception and emotion in the striatum, thalamus, and hippocampus in PD and the posterior insula in PPAs was also observed. In AD and MS, disruptions in the AIN were observed during interoception, but no convergence with emotion was identified.</p><p><strong>Interpretation: </strong>Neurodegeneration induces dysfunctional AIN across atrophy, connectivity, and metabolism, more accentuated in bvFTD. Findings bolster the predictive coding theories of large-scale AIN, calling for more synergistic approaches to understanding interoception, emotion, and social cognition impairments in neurodegeneration.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494166","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":"Polyconnectomic scoring of functional connectivity patterns across eight neuropsychiatric and three neurodegenerative disorders.","authors":"Ilan Libedinsky, Koen Helwegen, Jackson Boonstra, Laura Guerrero Simón, Marius Gruber, Jonathan Repple, Tilo Kircher, Udo Dannlowski, Martijn P van den Heuvel","doi":"10.1016/j.biopsych.2024.10.007","DOIUrl":"https://doi.org/10.1016/j.biopsych.2024.10.007","url":null,"abstract":"<p><strong>Background: </strong>Neuropsychiatric and neurodegenerative disorders involve diverse changes in brain functional connectivity. As an alternative to approaches searching for specific mosaic patterns of affected connections and networks, we used polyconnectomic scoring to quantify disorder-related whole-brain connectivity signatures into interpretable, personalized scores.</p><p><strong>Methods: </strong>The polyconnectomic score (PCS) measures the extent to which an individual's functional connectivity (FC) mirrors the whole-brain circuitry characteristics of a trait. We computed PCS for eight neuropsychiatric conditions (attention-deficit/hyperactivity disorder, anxiety-related disorders, autism spectrum disorder, obsessive-compulsive disorder, bipolar disorder, major depressive disorder, schizoaffective disorder, and schizophrenia) and three neurodegenerative conditions (Alzheimer's disease, frontotemporal dementia, and Parkinson's disease) across 22 datasets with resting-state functional MRI of 10,667 individuals (5,325 patients, 5,342 controls). We further examined PCS in 26,673 individuals from the population-based UK Biobank cohort.</p><p><strong>Results: </strong>PCS was consistently higher in out-of-sample patients across six of the eight neuropsychiatric and across all three investigated neurodegenerative disorders ([min, max]: AUC = [0.55, 0.73], p_FDR = [1.8 x 10^-16, 4.5 x 10^-2]). Individuals with elevated PCS levels for neuropsychiatric conditions exhibited higher neuroticism (p_FDR < 9.7 x 10^-5), lower cognitive performance (p_FDR < 5.3 x 10^-5), and lower general wellbeing (p_FDR < 9.7 x 10^-4).</p><p><strong>Conclusions: </strong>Our findings reveal generalizable whole-brain connectivity alterations in brain disorders. PCS effectively aggregates disorder-related signatures across the entire brain into an interpretable, subject-specific metric. A toolbox is provided for PCS computation.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457148","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":"Advancing Mental Health Research Through Strategic Integration of Transdiagnostic Dimensions and Genomics.","authors":"Alysa E Doyle, Carrie E Bearden, Raquel E Gur, David H Ledbetter, Christa L Martin, Thomas H McCoy, Bogdan Pasaniuc, Roy H Perlis, Jordan W Smoller, Lea K Davis","doi":"10.1016/j.biopsych.2024.10.006","DOIUrl":"https://doi.org/10.1016/j.biopsych.2024.10.006","url":null,"abstract":"<p><p>Genome wide studies are yielding a growing catalogue of common and rare variants that confer risk for psychopathology. Yet, despite representing unprecedented progress, emerging data also indicate that the full promise of psychiatric genetics - including understanding pathophysiology and improving personalized care - will not be fully realized by targeting traditional, dichotomous diagnostic categories. The current article provides reflections on themes emerging from a 2021 NIMH sponsored conference convened to address strategies for the evolving field of psychiatric genetics. As anticipated by NIMH's Research Domain Framework, multi-level investigations of dimensional and transdiagnostic phenotypes, particularly when integrated with biobanks and big data, will be critical to advancing knowledge. The path forward will also require more diverse representation in source studies. Additionally, progress will be catalyzed by a range of converging approaches, including capitalizing on computational methods, pursuing biological insights, working within a developmental framework, and engaging healthcare systems and patient communities.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457039","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":"Adenosine 2A Receptors Link Astrocytic Alpha-1 Adrenergic Signaling to Wake-Promoting Dopamine Neurons.","authors":"Nicholas Petersen, Katharine E McCann, Mihaela A Stavarache, Lisa Y Kim, David Weinshenker, Danny G Winder","doi":"10.1016/j.biopsych.2024.09.030","DOIUrl":"https://doi.org/10.1016/j.biopsych.2024.09.030","url":null,"abstract":"<p><strong>Background: </strong>Sleep and arousal disorders are common, but the underlying physiology of wakefulness is not fully understood. The locus coeruleus promotes arousal via alpha-1 adrenergic receptor (α₁AR) driven recruitment of wake-promoting dopamine (DA) neurons in the ventral periaqueductal gray (vPAG^DA neurons). α₁AR expression is enriched on vPAG astrocytes, and chemogenetic activation of astrocytic G_q signaling promotes wakefulness. Astrocytes can release extracellular \"gliotransmitters,\" such as ATP and adenosine, but the mechanism underlying how vPAG astrocytic α₁ARs influence sleep/wake behavior and vPAG^DA neuron physiology is unknown.</p><p><strong>Methods: </strong>In this study, we utilized genetic manipulations with ex vivo calcium imaging in vPAG^DA neurons and astrocytes, patch-clamp electrophysiology, and behavioral experiments in mice to probe our hypothesis that astrocytic α₁ARs mediate noradrenergic modulation of wake-promoting vPAG^DA neurons via adenosine signaling.</p><p><strong>Results: </strong>Activation of α₁ARs with phenylephrine increased calcium transients in vPAG^DA neurons and vPAG astrocytes, and increased vPAG^DA neuron excitability ex vivo. Chemogenetic Gq-DREADD activation of vPAG astrocytes similarly increased vPAG^DA neuron calcium activity and intrinsic excitability. Conversely, shRNA knockdown of vPAG astrocytic α₁ARs reduced the excitatory effect of phenylephrine on vPAG^DA neurons and blunted arousal during the wake phase. Pharmacological blockade of adenosine 2A (A_2A) receptors precludes the α₁AR-induced increase in vPAG^DA calcium activity and excitability in brain slices, as well as the wake-promoting effects of vPAG α₁AR activation in vivo.</p><p><strong>Conclusions: </strong>We have identified a crucial role for vPAG astrocytic α₁AR receptors in sustaining arousal through heightened excitability and activity of vPAG^DA neurons mediated by local A_2A receptors.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457038","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":"Multiomics Reveals Biological Mechanisms Linking Macroscale Structural Covariance Network Dysfunction With Neuropsychiatric Symptoms Across the Alzheimer's Disease Continuum.","authors":"Jiwei Jiang, Kun Zhao, Wenyi Li, Peiyang Zheng, Shirui Jiang, Qiwei Ren, Yunyun Duan, Huiying Yu, Xiaopeng Kang, Junjie Li, Ke Hu, Tianlin Jiang, Min Zhao, Linlin Wang, Shiyi Yang, Huiying Zhang, Yaou Liu, Anxin Wang, Yong Liu, Jun Xu","doi":"10.1016/j.biopsych.2024.08.027","DOIUrl":"https://doi.org/10.1016/j.biopsych.2024.08.027","url":null,"abstract":"<p><strong>Background: </strong>The highly heterogeneity of neuropsychiatric symptoms (NPSs) hinder further exploration of their role in neurobiological mechanisms and Alzheimer's disease (AD). We aimed to delineate NPS patterns based on brain macroscale connectomics to understand the biological mechanisms of NPSs on the AD continuum.</p><p><strong>Methods: </strong>We constructed Regional Radiomics Similarity Networks (R2SN) for 550 participants (AD with NPSs [AD-NPS, n=376], AD without NPSs [AD-nNPS, n=111], and normal controls [n=63]) from CIBL study. We identified R2SN connections associated with NPSs, and then cluster distinct subtypes of AD-NPS. An independent dataset (n=189) and internal validation were performed to assess the robustness of the NPS subtypes. Subsequent multiomics analysis were performed to assess the distinct clinical phenotype and biological mechanisms in each NPS subtype.</p><p><strong>Results: </strong>AD-NPS patients were clustered into severe (n=187), moderate (n=87), and mild NPS (n=102) subtypes, each exhibiting distinct brain network dysfunction patterns. A high level of consistency in clustering NPS was internally and externally validated. Severe and moderate NPSs showed significant cognitive impairment, increased plasma p-Tau₁₈₁ levels, extensive decreased brain volume and cortical thickness, and accelerated cognitive decline. Gene set enrichment analysis (GSEA) revealed enrichment of differentially expressed genes in ion transport and synaptic transmission with variations for each NPS subtype. Genome-wide association studies (GWAS) analysis defined the specific gene loci for each subtype of AD-NPS (i.e, logical memory), aligning with clinical manifestations and progression patterns.</p><p><strong>Conclusions: </strong>This study identified and validated three distinct NPS subtypes, underscoring the role of NPSs in neurobiological mechanisms and progression of the AD continuum.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457146","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":"Sex-differential markers of psychiatric risk and treatment response based on premature aging of functional brain network dynamics and peripheral physiology.","authors":"Raluca Petrican, Sidhant Chopra, Christopher Murgatroyd, Alex Fornito","doi":"10.1016/j.biopsych.2024.10.008","DOIUrl":"https://doi.org/10.1016/j.biopsych.2024.10.008","url":null,"abstract":"<p><strong>Background: </strong>Aging is a multilevel process of gradual decline that predicts morbidity and mortality. Independent investigations have implicated senescence of brain and peripheral physiology in psychiatric risk, but it is unclear whether these effects stem from unique or shared mechanisms.</p><p><strong>Methods: </strong>To address this question, we analyzed clinical, blood chemistry and resting state functional neuroimaging data in a healthy aging cohort (N= 427; age 36-100 years) and two disorder-specific samples encompassing patients with early psychosis (100 patients, 16-35 years) and major depressive disorder (MDD) (104 patients, 20-76 years).</p><p><strong>Results: </strong>We identified sex-dependent coupling between blood chemistry markers of metabolic senescence (i.e., homeostatic dysregulation), functional brain network aging, and psychiatric risk. In females, premature aging of frontoparietal and somatomotor networks was linked to greater homeostatic dysregulation. It also predicted the severity and treatment resistance of mood symptoms (depression/anxiety [all three samples], anhedonia [MDD]) and social withdrawal/behavioral inhibition (avoidant personality disorder [healthy aging]; negative symptoms [early psychosis]). In males, premature aging of the default mode, cingulo-opercular, and visual networks was linked to reduced homeostatic dysregulation and predicted severity and treatment resistance of symptoms relevant to hostility/aggression (antisocial personality disorder [healthy aging]; mania/positive symptoms [early psychosis]), impaired thought processes (early psychosis, MDD) and somatic problems (healthy aging, MDD).</p><p><strong>Conclusions: </strong>Our findings identify sexually dimorphic relationships between brain dynamics, peripheral physiology, and risk for psychiatric illness, suggesting that the specificity of putative risk biomarkers and precision therapeutics may be improved by considering sex and other relevant personal characteristics.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457150","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":"Subscribers Page","authors":"","doi":"10.1016/S0006-3223(24)01595-6","DOIUrl":"10.1016/S0006-3223(24)01595-6","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432661","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":"Multimodal Retinal Imaging Findings in Schizophrenia Spectrum Disorders","authors":"Paulo Lizano,&nbsp;Erik Velez-Perez","doi":"10.1016/j.biopsych.2024.08.020","DOIUrl":"10.1016/j.biopsych.2024.08.020","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432668","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}