Biological Psychiatry最新文献

{"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}

{"title":"Editorial Board Page","authors":"","doi":"10.1016/S0006-3223(24)01594-4","DOIUrl":"10.1016/S0006-3223(24)01594-4","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":"142434039","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":"Tracing the Trajectory: Polyunsaturated Fatty Acids and Early Adult Psychosis","authors":"Ying He,&nbsp;Linlin Zhao,&nbsp;Xiaogang Chen","doi":"10.1016/j.biopsych.2024.08.014","DOIUrl":"10.1016/j.biopsych.2024.08.014","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":"142432667","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":"Guide for Authors","authors":"","doi":"10.1016/S0006-3223(24)01598-1","DOIUrl":"10.1016/S0006-3223(24)01598-1","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":"142432665","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":"GABAergic Interneuron Dysfunction in Neurodevelopmental Disorders: A New Role for the Transcription Factor MEF2C in Regulating Parvalbumin Interneuron Survival and Function","authors":"Jyoti Gupta","doi":"10.1016/j.biopsych.2024.09.001","DOIUrl":"10.1016/j.biopsych.2024.09.001","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":"142432669","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":"Noninvasive modulation of subcallosal cingulate and depression with focused ultrasonic waves.","authors":"Thomas S Riis, Daniel A Feldman, Sarah S Kwon, Lily C Vonesh, Vincent Koppelmans, Jefferson R Brown, Daniela Solzbacher, Jan Kubanek, Brian J Mickey","doi":"10.1016/j.biopsych.2024.09.029","DOIUrl":"https://doi.org/10.1016/j.biopsych.2024.09.029","url":null,"abstract":"<p><strong>Background: </strong>Severe forms of depression have been linked to excessive subcallosal cingulate (SCC) activity. Stimulation of SCC with surgically implanted electrodes can alleviate depression, but current noninvasive techniques cannot directly and selectively modulate deep targets. We developed a new noninvasive neuromodulation approach that can deliver low-intensity focused ultrasonic waves to the SCC.</p><p><strong>Methods: </strong>Twenty-two subjects with treatment-resistant depression participated in a randomized, double-blind, sham-controlled study. Ultrasonic stimulation was delivered to bilateral SCC during concurrent functional MRI to quantify target engagement. Mood state was measured with the Sadness subscale of the Positive and Negative Affect Schedule before and after 40 minutes of real or sham SCC stimulation. Change in depression severity was measured with the 6-item Hamilton Depression Rating Scale (HDRS- 6) at 24 hours and 7 days.</p><p><strong>Results: </strong>Functional MRI demonstrated a target-specific decrease in SCC activity during stimulation (p=0.028, n=16). In 7 of 16 participants, SCC neuromodulation was detectable at the individual-subject level with a single 10-minute scan (p<0.05, small-volume-correction). Mood and depression scores improved more with real than with sham stimulation. In the per-protocol sample (n=19), real stimulation was superior to sham for HDRS-6 at 24 hours and for Sadness (both p<0.05, d>1). Non-significant trends were found in the intent-to-treat sample.</p><p><strong>Conclusions: </strong>This small pilot study indicates that ultrasonic stimulation modulates SCC activity and can rapidly reduce depressive symptoms. The capability to noninvasively and selectively target deep brain areas creates new possibilities for future development of circuit-directed therapeutics, and for the dissection of deep-brain circuit function in humans.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457147","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}