American Journal of Psychiatry最新文献

{"title":"Differential Effects of Ovarian Steroids in Women With and Without Premenstrual Dysphoric Disorder: A Replication and Extension of Findings.","authors":"Shau-Ming Wei,Paul Wakim,Pedro E Martinez,Lynnette K Nieman,David R Rubinow,Peter J Schmidt","doi":"10.1176/appi.ajp.20240596","DOIUrl":"https://doi.org/10.1176/appi.ajp.20240596","url":null,"abstract":"OBJECTIVEThe authors previously demonstrated that symptoms of premenstrual dysphoric disorder (PMDD) remit during ovarian hormone suppression and recur after estradiol or progesterone is reintroduced (addback). In this study, using a substantially expanded sample, they aimed to 1) evaluate the specific contributions of estradiol and progesterone to symptom development, 2) analyze physical symptoms related to ovarian hormones, 3) identify differences between women with PMDD who experienced continued symptom remission and those who experienced symptom recurrence during hormone addback, and 4) determine whether change in hormone levels from baseline to addback is associated with PMDD symptom severity.METHODSThirty-four women with PMDD (10 from the original cohort) and 76 healthy participants (15 from the original cohort) completed a daily rating form during three hormone conditions: ovarian suppression induced by the gonadotropin-releasing hormone agonist leuprolide, leuprolide+estradiol addback, and leuprolide+progesterone addback. Affective and somatic symptom scores during the last 8 of 12 weeks of leuprolide alone were compared with scores during the first 4 weeks of estradiol addback and the first 4 weeks of progesterone addback.RESULTSFor affective symptoms (anxiety, sadness, irritability, mood swings), there were significant main effects of diagnosis and diagnosis-by-hormone interactions, reflecting a significant increase in symptom severity scores during estradiol addback and progesterone addback compared with leuprolide treatment alone. Compared to healthy comparison participants, women with PMDD had significantly higher symptom scores during each addback. With regard to physical symptoms, bloating and food cravings showed greater severity in women with PMDD regardless of hormone conditions, whereas breast pain increased in severity during estradiol addback compared with leuprolide alone and progesterone.CONCLUSIONSThe study confirmed that ovarian suppression in women with PMDD eliminated symptom cyclicity, and that symptoms emerged during ovarian steroid addback in women with PMDD but not in healthy comparison women. In PMDD, irritability and mood swings are tied more closely to progesterone than estradiol. Despite the replication of this hormone-related behavioral phenotype in PMDD, the mechanisms underlying the presumed alteration in steroid signaling require further characterization.","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"5 1","pages":"922-934"},"PeriodicalIF":17.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194540","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":"Environmental, Psychiatric, and Genetic Predictors of Alcohol Use Disorder Criterion Count: Analyses of African and European Ancestries.","authors":"Peter J Na,Joseph D Deak,Daniel F Levey,Rachel L Kember,Henry R Kranzler,Robert H Pietrzak,Joel Gelernter","doi":"10.1176/appi.ajp.20240893","DOIUrl":"https://doi.org/10.1176/appi.ajp.20240893","url":null,"abstract":"OBJECTIVEQuantifying the contribution of environmental and genetic factors to alcohol use disorder (AUD) criterion count across different ancestries may provide insight into the biopsychosocial etiology of AUD. Although polygenic risk prediction represents an important future application, its utility may be enhanced when considered in the context of environmental predictors. The authors used large African- and European-ancestry samples to examine how genetic, psychiatric, and environmental factors predict AUD criterion count.METHODSThe authors analyzed data from 11,021 individuals in the Yale-Penn Study sample: 5,843 of African ancestry (AFR) and 5,178 of European ancestry (EUR). Polygenic risk scores (PRSs) were generated from genome-wide association studies of problematic alcohol use (PAU). Generalized linear regression and relative importance analyses determined the independent and interactive effects of environmental and genetic factors on AUD criterion count.RESULTSPRSs for PAU were positively associated with AUD criterion count in both ancestries and predicted 1.9% of AUD criterion count in the EUR sample and 1.3% in the AFR sample. A combination of education, substance use in the household before age 13, annual household income, and male sex explained 73.1% of the variance in AUD criterion count in the AFR sample and 58.9% in the EUR sample. Among examined psychiatric disorders, posttraumatic stress disorder explained the most variance (10.0% in AFR, 9.4% in EUR), followed by anxiety disorders (3.4% in AFR, 6.2% in EUR) and major depressive disorder (1.3% in AFR, 2.1% in EUR). In the EUR sample, education level moderated the relationship between PRS for PAU and AUD criterion count.CONCLUSIONSIn both African and European ancestry groups, environmental factors explained the majority of the variance in AUD criterion count, but polygenic risk was also a statistically significant predictor. These findings may help inform clinical, research, and policy efforts to mitigate AUD risk.","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"11 1","pages":"appiajp20240893"},"PeriodicalIF":17.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127056","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 Case Report of Neutropenia in a Patient Treated With the Novel Antipsychotic Xanomeline/Trospium.","authors":"Michelle E Lanspa,Olivia J Hooks,Joshua R Delaney","doi":"10.1176/appi.ajp.20250214","DOIUrl":"https://doi.org/10.1176/appi.ajp.20250214","url":null,"abstract":"","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"80 1","pages":"appiajp20250214"},"PeriodicalIF":17.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127094","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":"Ketamine for Depression, but at What Cost? A Review of Ketamine's Neurotoxic Effects From Preclinical and Human Studies.","authors":"S William Li,Kristina T Kumpf,Julian Urrutia,John H Krystal,Gerard Sanacora,Samuel T Wilkinson","doi":"10.1176/appi.ajp.20250276","DOIUrl":"https://doi.org/10.1176/appi.ajp.20250276","url":null,"abstract":"This review examines ketamine's neurotoxic potential across preclinical and clinical studies. The authors synthesized data from preclinical models, then integrated findings from human clinical trials of esketamine and observational studies in recreational users. Animal studies have found that repeated or high-dose subanesthetic ketamine administration results in consistent excitotoxic neuronal damage and lasting cognitive deficits, especially in perinatal animals. Infrequently administered relatively low and moderate subanesthetic doses (<1 mg/kg approximate human intravenous equivalent) do not yield overt histopathology in rat and nonhuman primate models. In humans, observational studies in frequent high-dose (>1 g/day) ketamine users show memory and executive function impairments. In contrast, a large clinical trial found that intranasal esketamine at doses up to 84 mg, administered weekly or every other week for several years, is associated with maintained or slightly improved cognitive function in adults with major depression. Lower cognitive function (attention, processing speed) showed some potential worsening among elderly patients; the clinical significance of this is unknown. Direct comparisons of esketamine and off-label racemic ketamine at higher doses have not been done. These studies underscore the potential for neurotoxic effects when ketamine is used at doses or frequencies beyond those utilized in clinical trials, highlighting a critical need for robust longitudinal research. Clinicians are advised to exercise caution, particularly when prescribing ketamine off-label at doses significantly higher than those used in clinical trials. When deviating from this in clinical practice, strong consideration should be given to conducting repeated cognitive assessments. Funding agencies should incentivize preclinical researchers to conduct studies that further elucidate the threshold of ketamine's neurotoxicity.","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"28 1","pages":"appiajp20250276"},"PeriodicalIF":17.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025592","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":"Real-World Safety of Esketamine Nasal Spray: A Comprehensive Analysis Almost 5 Years After First Approval.","authors":"Gerard Sanacora,Muhammad Ahmed,Brianne Brown,Patricia Cabrera,Teodora Doherty,Mai Himedan,David M Kern,Lisa Lim,Oliver Lopena,Ronaldo R Naranjo,Isaac Nuamah,Amir Sarayani,Ibrahim Turkoz,Hannah E Bowrey","doi":"10.1176/appi.ajp.20240655","DOIUrl":"https://doi.org/10.1176/appi.ajp.20240655","url":null,"abstract":"OBJECTIVEThe objective of this study was to comprehensively examine the real-world safety of esketamine using 58 months of postapproval data in the United States.METHODSU.S. safety data from patient monitoring forms submitted to the esketamine Risk Evaluation and Mitigation Strategy (REMS) program and reports submitted to the Janssen U.S. Global Medical Safety (US-GMS) database were evaluated (March 5, 2019, to January 5, 2024). Patient characteristics, use and dosage patterns, adverse events of interest (actively solicited reports of sedation, dissociation, and increased blood pressure), and serious adverse events following esketamine administration were described. The incidence of suicidality and drug abuse/misuse was also evaluated.RESULTSMost patients were 26-55 years of age (64.3%) and female (61.1%). A total of 1,486,213 outpatient treatment sessions were completed by 58,483 patients who had at least one esketamine treatment session. Sedation, dissociation, and increased blood pressure were reported in 34.7%, 41.0%, and 0.9% of sessions, respectively. Serious adverse events were reported in <0.1% and 0.18% of treatment sessions in REMS and US-GMS, respectively; suicide rates were lower than background rates; and 210 incidences of all-cause abuse/misuse were reported.CONCLUSIONSAnalysis of almost 5 years of real-world use of esketamine in the United States remains consistent with the established safety profile from clinical studies and current product labeling. No new safety signals were identified.","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"72 1","pages":"appiajp20240655"},"PeriodicalIF":17.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025594","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":"Contingency Management for Stimulant Use Disorder and Association With Mortality: A Cohort Study.","authors":"Lara N Coughlin,Devin C Tomlinson,Lan Zhang,H Myra Kim,Madeline C Frost,Gabriela Khazanov,James R McKay,Dominick DePhilippis,Lewei Allison Lin","doi":"10.1176/appi.ajp.20250053","DOIUrl":"https://doi.org/10.1176/appi.ajp.20250053","url":null,"abstract":"OBJECTIVEWhile opioid overdose has begun to decrease in recent years, stimulant overdose has continued to increase and has not been adequately addressed. Unlike opioid use disorder, there are no medications approved by the U.S. Food and Drug Administration to treat stimulant use disorder (StUD). The most effective treatment is contingency management (CM), a behavioral intervention that provides tangible rewards to reinforce target behaviors, such as biochemically verified abstinence. Despite the effectiveness of CM on near-term substance use behaviors, the long-term impact on key outcomes such as mortality are unclear. The objective of this work was to examine whether patients with StUD who receive CM have a decreased risk of mortality.METHODSThis was a retrospective cohort study of patients with StUD who received or did not receive CM, using linked electronic health records and death records in the largest integrated health system in the United States, the Veterans Health Administration (VHA), from July 2018 through December 2020. The primary outcome was mortality in the year following the index CM visit. All-cause mortality data were obtained from the National Death Index and linked to electronic health record data. Adjusted hazard ratios were estimated using stratified Cox proportional hazards models.RESULTSA total of 1,481 patients with StUD who received CM were included alongside 1,481 matched control subjects. Over the 1-year follow-up period, those who received CM were 41% less likely to die (adjusted hazard ratio=0.59, 95% CI=0.36, 0.95) than those who did not receive CM.CONCLUSIONSThis study provides the first evidence that CM use in real-world health care settings is associated with reduced risk of mortality among patients with StUD.","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"24 1","pages":"appiajp20250053"},"PeriodicalIF":17.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025593","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":"Revitalizing EEG Neurofeedback Using Precision-Based Approaches.","authors":"Robin Aupperle,Evan J White,Masaya Misaki","doi":"10.1176/appi.ajp.20250657","DOIUrl":"https://doi.org/10.1176/appi.ajp.20250657","url":null,"abstract":"","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"133 1","pages":"816-818"},"PeriodicalIF":17.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959911","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":"Does Xanomeline/Trospium Have Unique Benefits for Cognitive Impairment Associated With Schizophrenia?","authors":"Rajiv Tandon","doi":"10.1176/appi.ajp.20250021","DOIUrl":"https://doi.org/10.1176/appi.ajp.20250021","url":null,"abstract":"","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"18 1","pages":"878"},"PeriodicalIF":17.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959917","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":"Future of Sensorimotor and Psychomotor Dysfunction in Mental Disorders: Emerging Tools, Methodological Challenges, and the Road Ahead.","authors":"Dusan Hirjak,Vijay A Mittal,Andreas Meyer-Lindenberg,Georg Northoff","doi":"10.1176/appi.ajp.20250533","DOIUrl":"https://doi.org/10.1176/appi.ajp.20250533","url":null,"abstract":"","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"71 1","pages":"807-812"},"PeriodicalIF":17.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960066","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":"Does Xanomeline/Trospium Have Unique Benefits for Cognitive Impairment Associated With Schizophrenia? Response to Tandon.","authors":"William P Horan,Philip D Harvey,Stephen K Brannan","doi":"10.1176/appi.ajp.20250021r","DOIUrl":"https://doi.org/10.1176/appi.ajp.20250021r","url":null,"abstract":"","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"240 2-3 1","pages":"878-879"},"PeriodicalIF":17.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960076","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}