The American journal of psychiatry最新文献

{"title":"Association Between Age-Dependent DNA Methylation Changes at <i>FKBP5</i> Enhancer Sites and Increased Cortical Gene Expression in Schizophrenia.","authors":"Katrina Z Edmond, Dominic Kaul, Natan Yusupov, Maik Ködel, Susann Sauer, Anna S Fröhlich, James Kentro, Ran Tao, Joel E Kleinman, Daniel R Weinberger, Thomas M Hyde, Darina Czamara, Elisabeth B Binder, Natalie Matosin","doi":"10.1176/appi.ajp.20250473","DOIUrl":"https://doi.org/10.1176/appi.ajp.20250473","url":null,"abstract":"<p><strong>Objective: </strong>An increasingly compelling body of literature indicates that the glucocorticoid receptor cochaperone FK506-binding protein 51 (FKBP51; encoded by <i>FKBP5</i>) is a promising target for psychiatric therapeutics. Increased mRNA expression of <i>FKBP5</i> in postmortem brains with psychiatric diagnoses and with aging have been reported previously. The epigenetic mechanisms underlying these effects in the human brain remain largely unknown.</p><p><strong>Methods: </strong>The authors analyzed previously generated DNA methylation (DNAm) array, single-nucleotide polymorphism genotyping, and bulk RNA-, single-nucleus RNA-, and single-nucleus assay for transposase-accessible chromatin (snATAC)-sequencing data to examine <i>FKBP5</i> DNAm patterns in postmortem human brain samples from the dorsolateral prefrontal cortex and orbitofrontal cortex of individuals who lived with a major psychiatric disorder (schizophrenia, major depressive disorder, or bipolar disorder) across two independent cohorts (N=378 cases and N=209 controls).</p><p><strong>Results: </strong>Several cytosine-phosphate-guanine dinucleotides (CpGs) were identified across the proximal enhancer of the <i>FKBP5</i> locus where DNAm was negatively correlated with gene expression, with validation across both cohorts. Data from single-nucleus analyses supported the relevance of these associations across all major cell types. In this functional region, as well as additional sites, associations were observed with age, rs1360780 genotype (CC versus CT/TT), and psychiatric diagnosis. Notably, individuals with schizophrenia exhibited significantly lower DNAm levels in the proximal enhancer region that showed additional converging effects of age and genotype, specifically in glucocorticoid response element-associated CpG sites.</p><p><strong>Conclusions: </strong>This evidence supports the association of aging and psychiatric diagnosis with changes in <i>FKBP5</i> DNAm in functionally relevant regulatory elements of the human frontal cortex. This suggests that related changes in <i>FKBP5</i> mRNA levels may be mediated by these epigenetic mechanisms.</p>","PeriodicalId":520786,"journal":{"name":"The American journal of psychiatry","volume":" ","pages":"appiajp20250473"},"PeriodicalIF":14.7,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820970","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":"Youth Autistic Traits and Brain Activation States During Socioemotional Processing.","authors":"Carolyn Lasch, Andrew T Goldberg, Deanna M Barch, Natasha Marrus, M Catalina Camacho, Chad M Sylvester","doi":"10.1176/appi.ajp.20251035","DOIUrl":"10.1176/appi.ajp.20251035","url":null,"abstract":"<p><strong>Objective: </strong>Different aspects of social-emotional processing are linked to unique whole-brain patterns of neural activity termed \"activation states.\" Autistic traits in youths include impairments in socioemotional processing that vary depending on age and comorbidity. Characterizing differences in activation states associated with these impairments may explain why youths with high autistic traits process socioemotional information differently than peers.</p><p><strong>Methods: </strong>This study examined the frequency of three previously identified activation states in 545 youths (ages 5-15 years, 39% female, 54% White, 68% non-Hispanic) from the Healthy Brain Network study as they watched a socially engaging movie. Regressions examined associations between autistic traits (measured by the Social Responsiveness Scale, 2nd ed.) and overall time spent in activation states, and whether these associations varied with age or co-occurring attention deficit hyperactivity disorder (ADHD) and anxiety symptoms (measured by the Strengths and Weaknesses Assessment of ADHD and Normal Behavior and the Screen for Child Anxiety Related Disorders).</p><p><strong>Results: </strong>At younger ages (<9 years), children with more autistic traits spent more time in an activation state associated with increased activation in somatomotor and visual networks. At older ages (>14 years), children with more autistic traits spent more time in an activation state characterized by greater default mode and ventral attention network activation. Across all ages, children with more ADHD symptoms spent less time in an activation state associated with greater cingulo-opercular network activation.</p><p><strong>Conclusions: </strong>Autistic traits are associated with differences in brain activation during socioemotional processing that vary with age and co-occurring mental health symptoms. Youths with more autistic traits may experience an altered developmental trajectory of social-emotional processing compared to peers with fewer autistic traits. Results inform personalized interventions and progress monitoring for youths with social impairments.</p>","PeriodicalId":520786,"journal":{"name":"The American journal of psychiatry","volume":" ","pages":"appiajp20251035"},"PeriodicalIF":14.7,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148715224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychiatry's Duty to Model Respectful Disagreement: Response to McDeavitt and Kaliebe.","authors":"Aaron S Breslow, Arjee Restar, Elizabeth Cavic, Jonathan E Alpert, Benjamin Lê Cook","doi":"10.1176/appi.ajp.20260411","DOIUrl":"https://doi.org/10.1176/appi.ajp.20260411","url":null,"abstract":"","PeriodicalId":520786,"journal":{"name":"The American journal of psychiatry","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148674974","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":"Pediatric Gender Medicine: Psychiatry's Duty to Model Respectful Disagreement.","authors":"Kathleen McDeavitt, Kristopher Kaliebe","doi":"10.1176/appi.ajp.20260075","DOIUrl":"https://doi.org/10.1176/appi.ajp.20260075","url":null,"abstract":"","PeriodicalId":520786,"journal":{"name":"The American journal of psychiatry","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148674951","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":"Subtypes of Somatostatin and Other Interneurons Are Real, Whether We Believe in Them or Not.","authors":"Laramie Duncan","doi":"10.1176/appi.ajp.20260532","DOIUrl":"https://doi.org/10.1176/appi.ajp.20260532","url":null,"abstract":"","PeriodicalId":520786,"journal":{"name":"The American journal of psychiatry","volume":"183 8","pages":"520-522"},"PeriodicalIF":14.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148650468","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":"Cognitive, Electrophysiological, and Behavioral Presentation of First-Episode Psychosis With or Without Cannabis Exposure.","authors":"Deepak Cyril D'Souza, Jose Cortes-Briones, Justin Raj, Suhas Ganesh, K L Vidya, Sai Krishna Tikka, Umesh Shreekantiah, Nirmal Singh, Pratima Murthy, Juan Urrutia-Gandolfo, Daya Ram, Priyamvada Sharma, Vinod K Sinha, Nishant Goyal","doi":"10.1176/appi.ajp.20250726","DOIUrl":"10.1176/appi.ajp.20250726","url":null,"abstract":"<p><strong>Objective: </strong>Cannabis use is a known risk factor for psychosis, but it remains unclear whether cannabis-associated psychosis (CAP) differs meaningfully from non-cannabis-associated psychosis (NCAP) in clinical presentation, biology, or illness course. The objective of this study was to characterize the presentation and course of first-episode psychosis with and without cannabis exposure.</p><p><strong>Methods: </strong>In this prospective study, males hospitalized for new-onset psychosis with confirmed cannabis exposure (CAP; N=66) were compared with those without cannabis exposure (NCAP; N=53). Participants were assessed at admission and after 4 weeks of standardized inpatient treatment, using cognitive tests (CogState Schizophrenia Battery, Hopkins Verbal Learning Test), electroencephalography (EEG), and symptom scales (Positive and Negative Syndrome Scale [PANSS], Calgary Depression Rating Scale [CDRS], Young Mania Rating Scale [YMRS]).</p><p><strong>Results: </strong>Cognitive test performance significantly improved in the CAP group but not in the NCAP group, despite the absence of group differences at the time of admission. At admission, relative to the NCAP group, the CAP group had significantly higher power spectral density exponent in the EEG, a proxy index of cortical excitatory/inhibitory (E/I) balance. CAP participants presented with lower PANSS negative and total scores but greater depressive (CDRS) and manic (YMRS) symptoms at admission. Psychosis symptoms improved with treatment in both groups, but the CAP group experienced greater improvement in mood symptoms. Follow-up data were available for 16 CAP participants; 10 were rehospitalized for psychosis exacerbation after resuming cannabis use, whereas relapse was rare among those who remained abstinent.</p><p><strong>Conclusions: </strong>Relative to the NCAP group, the CAP group exhibited better cognitive function, lower cortical E/I balance, lesser negative symptoms, and greater mood symptoms. Cannabis resumption was associated with relapse, highlighting its role in illness recurrence. Together, these results raise the possibility that cannabis-associated psychosis is a distinct subtype of first-episode psychosis. Given the increasing rates of psychosis related to cannabis, further studies are needed to examine its long-term trajectory and refine treatment approaches.</p>","PeriodicalId":520786,"journal":{"name":"The American journal of psychiatry","volume":" ","pages":"552-561"},"PeriodicalIF":14.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148153142","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":"Doxycycline and the Parasite × Genotype × Stress Model of Schizophrenia.","authors":"Javier I Borráz-León, Markus J Rantala","doi":"10.1176/appi.ajp.20251284","DOIUrl":"10.1176/appi.ajp.20251284","url":null,"abstract":"","PeriodicalId":520786,"journal":{"name":"The American journal of psychiatry","volume":" ","pages":"593-594"},"PeriodicalIF":14.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147937327","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":"Doxycycline and Schizophrenia: Response to Letters.","authors":"Ian Kelleher, Ulla Lång, Johanna Metsälä, Colm Healy","doi":"10.1176/appi.ajp.20260263","DOIUrl":"10.1176/appi.ajp.20260263","url":null,"abstract":"","PeriodicalId":520786,"journal":{"name":"The American journal of psychiatry","volume":" ","pages":"595-596"},"PeriodicalIF":14.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147937328","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":"Doxycycline Use, Developmental Vulnerability, Patterns of Care, and Antibiotic Selection.","authors":"Apurva Parikh, Geoffrey Russell","doi":"10.1176/appi.ajp.20260100","DOIUrl":"10.1176/appi.ajp.20260100","url":null,"abstract":"","PeriodicalId":520786,"journal":{"name":"The American journal of psychiatry","volume":" ","pages":"594-595"},"PeriodicalIF":14.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147937337","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":"Highlights From the Residents' Journal: June 2026.","authors":"","doi":"10.1176/appi.ajp.26183009","DOIUrl":"https://doi.org/10.1176/appi.ajp.26183009","url":null,"abstract":"","PeriodicalId":520786,"journal":{"name":"The American journal of psychiatry","volume":"183 8","pages":"597"},"PeriodicalIF":14.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148650450","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}