Biological Psychiatry最新文献

{"title":"Differential Effects of Illness and Antipsychotics on Cortical Thinning in First-Episode Psychosis: A Randomized, Placebo-Controlled Magnetic Resonance Imaging Study.","authors":"Sidhant Chopra, Alexander Holmes, Ashlea Segal, Xi-Han Zhang, Shona M Francey, Brian O'Donoghue, Vanessa Cropley, Barnaby Nelson, Jessica Graham, Lara Baldwin, Hok Pan Yuen, Andrew Thompson, Kelly Allott, Mario Alvarez-Jimenez, Susy Harrigan, Avram J Holmes, Christos Pantelis, Stephen J Wood, Patrick McGorry, Alex Fornito","doi":"10.1016/j.biopsych.2026.06.028","DOIUrl":"10.1016/j.biopsych.2026.06.028","url":null,"abstract":"<p><strong>Background: </strong>Cortical gray matter loss is a common finding in magnetic resonance imaging (MRI) studies of psychosis and can progress with ongoing illness. A major unresolved question concerns whether these changes are driven by the illness or represent iatrogenic effects of antipsychotics.</p><p><strong>Methods: </strong>In a triple-blind, randomized, placebo-controlled MRI study, 62 antipsychotic-naïve people with first-episode psychosis (FEP) received a second-generation antipsychotic or placebo over 6 months (n = 35 at 12 months) alongside a healthy control group (n = 27 at baseline, n = 21 at 12 months). T1-weighted scans were collected at baseline, 3 months, and 12 months. Linear mixed-effects models fitted to >160,000 cortical loci examined illness- and antipsychotic-related thickness changes. We also examined whether cortical changes were enriched within functional networks or cytoarchitectonic classes and whether they spatially correlated with normative positron emission tomography receptor/transporter densities and transcriptomically imputed cell densities.</p><p><strong>Results: </strong>Over 12 months, the placebo group showed widespread cortical thinning compared with the control group (false discovery rate [FDR]-corrected p < .05), with the largest effects in frontal, cingulate, and occipital areas. No significant difference was detected between patients treated with antipsychotics and control participants. Thinning was not concentrated within specific functional networks, but highly differentiated koniocortical areas were relatively protected (p_spin < .05 FDR-corrected). Thinning spatially aligned with normative distributions of GABA_A/BZ, 5-HT_1B, 5-HT_2A, and H₃ receptors (0.17 <r < 0.28; p_spin < .05 FDR-corrected). No associations between thinning and symptom change were identified.</p><p><strong>Conclusions: </strong>Widespread cortical thinning occurs over the first year of FEP in people not receiving antipsychotics. No such thinning is evident in patients receiving antipsychotics. These findings suggest that cortical thinning in early psychosis is an illness-related phenomenon.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886359","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":"Therapeutic Potential of Incretin-Based Therapies for Alcohol Use Disorder : A Narrative Review of Available Clinical Evidence.","authors":"Mette Kruse Klausen, Anders Fink-Jensen","doi":"10.1016/j.biopsych.2026.07.010","DOIUrl":"10.1016/j.biopsych.2026.07.010","url":null,"abstract":"<p><p>Alcohol use disorder (AUD) remains a major global health burden, but pharmacological treatment options are limited, and there is an urgent need for novel molecular targets for the treatment of AUD. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been used for more than 2 decades to treat type 2 diabetes and subsequently overweight and obesity. Unexpected effects, including reduced alcohol intake, have been reported by patients as well as by clinicians, and these (often anecdotal) reports have been supported by a growing body of data from large registry studies; target trial emulation analyses; preclinical experiments with mice, rats, and nonhuman primates; and randomized clinical trials associating the use of GLP-1RAs with reduced alcohol consumption. This convergence has sparked growing interest in GLP-1RAs as a novel therapeutic strategy for AUD. In this narrative review, we synthesize current evidence on the effects of GLP-1RAs in individuals with AUD. To date, only 3 randomized controlled trials have examined GLP-1RAs in AUD, showing reductions in alcohol cue brain reactivity and alcohol consumption, particularly among individuals with overweight or obesity. We also report on observational data, including large registry studies, target trial emulation analyses, and real-world data, which have consistently associated GLP-1RA use with reduced alcohol consumption. Case reports and social media analyses further corroborate reductions in alcohol craving and consumption. Mechanistically, emerging evidence points to modulation of reward circuitry, incentive salience, gastric emptying, and metabolic signaling. Overall, GLP-1RAs represent a promising and mechanistically novel approach to AUD treatment, warranting confirmation in larger, long-term randomized trials.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148560924","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":"Glucagon-Like Peptide-1 Receptor Agonists as a Candidate Treatment for Opioid Use Disorder: From Rats to Humans.","authors":"Patricia Sue Grigson, Scott C Bunce, Timothy R Brick, Christopher S Freet, Jennifer E Nyland, Sarah S Kawasaki, Christopher G Brandl, Elise Shealy, Kendall Huddleston","doi":"10.1016/j.biopsych.2026.06.033","DOIUrl":"10.1016/j.biopsych.2026.06.033","url":null,"abstract":"<p><p>Despite recent progress and at least 3 medications approved for the treatment of opioid use disorder (OUD), the number of deaths due to opioid overdose remains unacceptably high. Therefore, there is a need for new treatments. To this end, glucagon-like peptide-1 receptor agonists (GLP-1RAs), dual GLP-1RA+glucose-dependent insulinotropic polypeptide (GIP) receptor agonists (e.g., tirzepatide), and triple agonists (e.g., GLP-1RA+neuropeptideY1/Y2 receptor agonists) show promise. Here, we review preclinical and clinical data. In the preclinical studies, acute administration of exendin-4 and the longer-acting liraglutide, semaglutide, tirzepatide, and other dual and triple agonists reduced opioid taking and/or opioid seeking when elicited by exposure to drug-related cues, the drug itself, or by stress. Chronic treatment with GLP-1RAs also reduced responding for opioids, but tolerance occurred with chronic administration of higher doses of GLP-1RAs. In the human studies, 1 small clinical trial found a 40% reduction in opioid craving following treatment with the GLP-1RA liraglutide. Three other clinical trials are ongoing, with 2 testing the efficacy of semaglutide and 1 testing the efficacy of tirzepatide as adjunctive treatments to buprenorphine or methadone. Pending completion of these clinical trials, recent studies used data from electronic health records, the TriNetX database, and Medicare claims and found a 40% reduction in opioid overdose and in hospital admissions for OUD in patients treated with a GLP-1RA or a GLP-1RA/GIP agonist for type 2 diabetes and/or for obesity. Thus, while additional clinical trials are needed, these data suggest that GLP-1RAs hold promise as a novel treatment for OUD in humans.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547640","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":"Potential of Neurosteroids for Precision Medicine in Psychiatry.","authors":"Tauryn L Dargan, Najah L Walton, Jamie L Maguire","doi":"10.1016/j.biopsych.2026.07.009","DOIUrl":"10.1016/j.biopsych.2026.07.009","url":null,"abstract":"<p><p>One of the most significant challenges in treating individuals suffering from psychiatric illnesses is the biological heterogeneity that exists throughout the patient population. This heterogeneity has hindered both timely diagnoses for those impacted as well as the development of new treatment options to combat these disorders. Ongoing efforts have been centered around stratifying individuals based on comprehensive phenotyping; however, biological heterogeneity remains a critical driver of psychiatric illness and poses a significant challenge in the field. Here, we review the current state of the field in biomarker development and the need for personalized medicine in psychiatry. Neurosteroid-based treatments have proven effective for the treatment of postpartum depression, but failed to gain approval for major depressive disorder, likely due to the inability to stratify patients amenable to this treatment approach. We discuss the potential of a biomarker approach to identify individuals with disruption in endogenous neurosteroid synthesis that may have transdiagnostic potential. Exciting emerging studies suggest that a biomarker indicating altered or a reduced capacity for endogenous neurosteroidogenesis would be beneficial for identifying individuals at risk for postpartum depression and could potentially predict treatment response to neurosteroid-based treatments. This review aims to provide a comprehensive report on the production of endogenous neurosteroids in the brain, the current clinical landscape for the use of neurosteroid-based therapies in psychiatry, and the potential utility of measuring neurosteroidogenesis capacity as a biomarker for the diagnosis and treatment of psychiatric illnesses.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547765","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":"Unique Environmental and Familial Influence on Amygdalar Hyperresponsivity in Posttraumatic Stress Disorder: A Discordant Monozygotic Twin Study.","authors":"Jan C Beucke, Christian Kaufmann, Hanna Siemoneit, Ruth Genth, Jessica Holfter, Lennart May, Michael B VanElzakker, Ibai Diez, Jorge Sepulcre, Scott P Orr, Roger K Pitman, Lisa M Shin","doi":"10.1016/j.biopsych.2026.07.007","DOIUrl":"10.1016/j.biopsych.2026.07.007","url":null,"abstract":"<p><strong>Background: </strong>The partially genetic nature of posttraumatic stress disorder (PTSD) has been demonstrated in both twin and recent molecular genetics studies and complicates the assessment of unique environmental influence on altered phenotypes in PTSD. Previous functional neuroimaging studies have reported heightened amygdalar responsivity in PTSD, but whether this abnormality relates to familial factors or PTSD-triggering environmental experiences is not fully understood.</p><p><strong>Methods: </strong>We examined amygdalar responsivity in combat veterans with PTSD and their combat-unexposed monozygotic co-twins (20 individuals, PTSD group n = 10), as well as in combat veterans without PTSD and their combat-unexposed co-twins (32 individuals, non-PTSD group n = 16). Within-pair comparisons were performed to isolate unique environmental influence under strict control of genetic factors. Comparisons between the unexposed co-twins of both groups were conducted to test for effects of familial vulnerability.</p><p><strong>Results: </strong>Reflecting unique environmental influence, heightened amygdalar responsivity was observed in individuals with PTSD compared with their unaffected co-twins. This was associated with the expression patterns of genes involved in brain glutamatergic synaptic transmission. Reflecting familial vulnerability, unexposed co-twins of combat veterans with PTSD showed reduced amygdalar activation compared with unexposed co-twins of combat veterans without PTSD.</p><p><strong>Conclusions: </strong>Heightened amygdalar responsivity in PTSD is best explained by an interaction of unique environmental and familial influences, which is consistent with vulnerability-stress models.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148496904","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":"Polygenic Risk for Major Depression: Diagnostic Specificity and Developmental Trajectories in an Admixed Youth Cohort","authors":"Marcelo José Abduch Adas Brañas, Lucas Toshio Ito, Marcos Signoretti Croci, Ana Beatriz Ravagnani Salto, Victoria Fogaça Doretto, Marcos Leite Santoro, Vanessa Kiyomi Ota, Luis Augusto Rohde, Giovanni Abrahão Salum, Lois W. Choi-Kain, Síntia Belangero, Euripedes Constantino Miguel, Maurício Scopel Hoffmann, Pedro Mario Pan","doi":"10.1016/j.biopsych.2026.07.006","DOIUrl":"https://doi.org/10.1016/j.biopsych.2026.07.006","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"262 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148461870","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":"Focused ultrasound blood brain barrier opening for targeted therapeutics in neurodegenerative diseases.","authors":"Negeen Halabian, Caleb Park, Lauren Omoto, Leonardo Favi Bocca, Gerardo Palacios, Kathleen Wu, Clement Hamani, Jennifer Rabin, Agessandro Abrahao, Benjamin Davidson, Nir Lipsman, Ying Meng","doi":"10.1016/j.biopsych.2026.07.008","DOIUrl":"https://doi.org/10.1016/j.biopsych.2026.07.008","url":null,"abstract":"<p><p>Therapeutic focused ultrasound (FUS) leverages the non-invasive ultrasonic waves to modify the biological tissue. When administered alongside intravenous microbubbles, low-intensity FUS enables transient, targeted disruption of the blood-brain barrier (BBB), permitting passage of systemically administered therapeutics into the central nervous system (CNS) with high spatial precision. The ability to selectively modulate BBB permeability at the disease site has the potential to substantially expand the number of therapeutics that can be utilized in treating illnesses afflicting the CNS. Herein, we review the current applications of FUS for treating neurodegenerative disorders and diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS). We discuss the research developments to date and future directions.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468797","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":"Impaired Activity-Regulated Proteostasis: A Shared Mechanism in Neurodevelopmental Disorders.","authors":"Kiran Pandey","doi":"10.1016/j.biopsych.2026.06.032","DOIUrl":"10.1016/j.biopsych.2026.06.032","url":null,"abstract":"<p><p>Proteostasis is the process by which cells control how much of each protein is made, how long it persists, and when it is removed. In neurons, proteostasis is not merely a housekeeping function, it is actively regulated by neuronal activity. When neurons fire, protein synthesis and degradation are simultaneously and transiently regulated to support synaptic plasticity. In neurodevelopmental disorders (NDDs), neurons lose this capacity to dynamically regulate their proteome in response to stimulation, disrupting synaptic plasticity and leading to cognitive impairments. This review establishes that despite diverse genetic origins, failure of activity-regulated proteostasis is a shared vulnerability across NDDs. This also explains why increasing or blocking protein synthesis or degradation alone under basal condition is insufficient to restore normal function. Our work demonstrates that restoring the coupling between neuronal activity and proteostatic response rescues both molecular and cognitive impairments in NDDs. These findings open new avenues for investigating disease biology and for developing novel therapeutic strategies.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468781","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":"GLP-1 and Alcohol-Related Behaviors: Insights From Preclinical Studies","authors":"Elisabet Jerlhag","doi":"10.1016/j.biopsych.2026.04.022","DOIUrl":"https://doi.org/10.1016/j.biopsych.2026.04.022","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"3 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148462070","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":"Reductive Stress and Dysregulated Energy Metabolism in Schizophrenia: Mechanisms and Therapeutic Targets","authors":"Onur Memetoglu,&nbsp;Fei Du,&nbsp;Virginie-Anne Chouinard,&nbsp;Dost Öngür","doi":"10.1016/j.biopsych.2025.10.008","DOIUrl":"10.1016/j.biopsych.2025.10.008","url":null,"abstract":"<div><div>Reductive stress, defined by excessive accumulation of reducing equivalents such as NADH, disrupts cellular redox balance and is emerging as a detrimental factor in schizophrenia (SZ). It is closely related to the mitochondrial defects commonly seen in SZ, which implies its importance in impaired energy metabolism. Reductive stress intersects with oxidative stress pathways and causes an underappreciated additional burden on cellular systems. The integrated stress response (ISR) is an adaptive pathway typically activated by mitochondrial oxidative phosphorylation defects and other stressors. Emerging evidence indicates that reductive stress can independently activate the ISR. These findings highlight the crucial role of reductive stress in disease pathophysiology, although the process is not fully understood. Therefore, there is a need for innovative therapeutic approaches that can address reductive stress and mitochondrial dysfunction.</div></div>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"100 2","pages":"Pages 132-139"},"PeriodicalIF":10.3,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318195","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}