American Journal of Psychiatry最新文献

{"title":"Psychotic Disorders and Schizophrenia: Treatment, Risk, Brain Alterations, and Mechanisms.","authors":"Ned H Kalin","doi":"10.1176/appi.ajp.20250133","DOIUrl":"https://doi.org/10.1176/appi.ajp.20250133","url":null,"abstract":"","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"182 4","pages":"313-315"},"PeriodicalIF":15.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750424","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 Call to Psychiatrists: Deprescription of Unnecessary Anticholinergic Medications in Schizophrenia Must Start Now.","authors":"K N Roy Chengappa, Jessica M Gannon, Yash B Joshi","doi":"10.1176/appi.ajp.20250124","DOIUrl":"https://doi.org/10.1176/appi.ajp.20250124","url":null,"abstract":"","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"182 4","pages":"319-321"},"PeriodicalIF":15.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750722","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":"Anticholinergic Burden and Cognitive Function in Psychosis: A Systematic Review and Meta-Analysis.","authors":"Valentina Mancini, Caren Latreche, Jack B Fanshawe, Ioana Varvari, Chambrez-Zita Zauchenberger, Nova McGinn, Ana Catalan, Toby Pillinger, Philip K McGuire, Robert A McCutcheon","doi":"10.1176/appi.ajp.20240260","DOIUrl":"10.1176/appi.ajp.20240260","url":null,"abstract":"<p><strong>Objective: </strong>The authors synthesized evidence from studies quantifying the relationship between anticholinergic medication and cognitive function in psychosis, and additionally explored studies that investigated whether reducing anticholinergic medications affects cognitive function in individuals with psychosis.</p><p><strong>Methods: </strong>A database search was conducted in MEDLINE, Embase, and PsycINFO, from database inception to October 2023, for studies reporting objective cognitive assessment and quantification of anticholinergic burden using clinical scales, serological anticholinergic activity, or tapering of anticholinergic medications. Analyses were carried out in R using the <i>metafor</i> package. Random-effects meta-analysis models were employed, along with assessment of heterogeneity, study quality, and meta-regressions (age, sex, and antipsychotic dosage in chlorpromazine equivalents).</p><p><strong>Results: </strong>Of 1,337 citations retrieved, 40 met inclusion criteria, comprising 25 anticholinergic burden studies (4,620 patients), six serological anticholinergic activity studies (382 patients), and nine tapering studies (186 patients). A negative correlation was identified between anticholinergic burden and global cognition (r=-0.37, 95% CI=-0.48, -0.25), verbal learning (r=-0.28, 95% CI=-0.36, -0.21), visual learning (r=-0.17, 95% CI=-0.28, -0.06), working memory (r=-0.22, 95% CI=-0.29, -0.14), processing speed (r=-0.24, 95% CI=-0.35, -0.13), attention (r=-0.19, 95% CI=-0.29, -0.08), executive functions (r=-0.17, 95% CI=-0.27, -0.06), and social cognition (r=-0.12, 95% CI=-0.19, -0.05), and between serological anticholinergic activity and verbal learning (r=-0.26, 95% CI=-0.38, -0.14), working memory (r=-0.19, 95% CI=-0.35, -0.03), and executive functions (r=-0.16, 95% CI=-0.27, -0.04). Finally, tapering off anticholinergic medication improved the scores in verbal learning (d=0.77, 95% CI=0.44, 1.1), working memory (d=0.94, 95% CI=0.63, 1.26), and executive functions (d=0.44, 95% CI=0.26, 0.62).</p><p><strong>Conclusions: </strong>Anticholinergic burden is associated with the cognitive impairments observed in psychosis. From a clinical perspective, tapering off anticholinergic medication in patients with psychosis may improve cognition. However, randomized clinical trials are needed for an unbiased quantification of benefit.</p>","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":" ","pages":"349-359"},"PeriodicalIF":15.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497496","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":"What Do Four Decades of Research Tell Us About the Association Between Childhood Adversity and Psychosis: An Updated and Extended Multi-Level Meta-Analysis.","authors":"Lan Zhou, Iris E C Sommer, Pengyuan Yang, Lev Sikirin, Jim van Os, Richard P Bentall, Filippo Varese, Marieke J H Begemann","doi":"10.1176/appi.ajp.20240456","DOIUrl":"https://doi.org/10.1176/appi.ajp.20240456","url":null,"abstract":"<p><strong>Objective: </strong>Estimating the current association between childhood adversity and the risk of psychosis is crucial for prevention and intervention. We provided an updated synthesis of evidence from the past four decades, expanded the available data by investigating a broad array of adversity subtypes, and explored sex differences and the age of psychosis onset as relevant factors.</p><p><strong>Methods: </strong>We searched PubMed, EMBASE, PsycINFO, Web of Science, WANFANG, and CNKI, for case-control, cross-sectional and cohort studies on the association between adversity and psychotic symptoms/illness. Multi-level meta-analysis, prediction intervals calculation, and sensitivity analyses were conducted.</p><p><strong>Results: </strong>The main analysis included 183 study samples (N=349,265), with 119 case-control studies (15,186 cases; 14,879 controls), 51 cross-sectional studies (N=299,659), and 13 cohort studies (N=19,541). Significant associations between adversity and psychosis were observed across all study designs, yielding an overall odds ratio of 2.80 (95% CI=2.18, 3.60). Secondary analyses revealed that exposure to each adversity subtype increased the odds of psychosis, with the highest odds ratio (3.54 [95% CI=3.04, 4.13]) for emotional abuse, and the lowest odds ratio of (1.58 [95% CI=1.48, 1.68]) for parental antipathy. No statistically significant sex differences were observed, although the odds ratio for sexual abuse was higher for women. Onset of psychosis was earlier in adversity-exposed individuals (mean difference=-0.79 years, 95% CI=-1.47 to -0.12).</p><p><strong>Conclusions: </strong>This is the largest meta-analysis to date on the association between childhood adversity and psychosis. The results have broad clinical implications, as they highlight the need for selective prevention of exposure to early adversities and the implementation of trauma-informed therapies in the treatment of psychosis.</p>","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"182 4","pages":"360-372"},"PeriodicalIF":15.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750696","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":"When the Bow Breaks: Are We Ever Going to Prevent Childhood Adversity?","authors":"C Neill Epperson","doi":"10.1176/appi.ajp.20250121","DOIUrl":"https://doi.org/10.1176/appi.ajp.20250121","url":null,"abstract":"","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"182 4","pages":"322-325"},"PeriodicalIF":15.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750697","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":"Estimating Multimodal Structural Brain Variability in Schizophrenia Spectrum Disorders: A Worldwide ENIGMA Study.","authors":"Wolfgang Omlor, Finn Rabe, Simon Fuchs, Werner Surbeck, Giacomo Cecere, Gao-Yang Huang, Stephanie Homan, Nils Kallen, Foivos Georgiadis, Tobias Spiller, Erich Seifritz, Thomas Weickert, Jason Bruggemann, Cynthia Weickert, Steven Potkin, Ryota Hashimoto, Kang Sim, Kelly Rootes-Murdy, Yann Quide, Josselin Houenou, Nerisa Banaj, Daniela Vecchio, Fabrizio Piras, Federica Piras, Gianfranco Spalletta, Raymond Salvador, Andriana Karuk, Edith Pomarol-Clotet, Amanda Rodrigue, Godfrey Pearlson, David Glahn, David Tomecek, Filip Spaniel, Antonin Skoch, Matthias Kirschner, Stefan Kaiser, Peter Kochunov, Feng-Mei Fan, Ole A Andreassen, Lars T Westlye, Pierre Berthet, Vince D Calhoun, Fleur Howells, Anne Uhlmann, Freda Scheffler, Dan Stein, Felice Iasevoli, Murray J Cairns, Vaughan J Carr, Stanley V Catts, Maria A Di Biase, Assen Jablensky, Melissa J Green, Frans A Henskens, Paul Klauser, Carmel Loughland, Patricia T Michie, Bryan Mowry, Christos Pantelis, Paul E Rasser, Ulrich Schall, Rodney Scott, Andrew Zalesky, Andrea de Bartolomeis, Annarita Barone, Mariateresa Ciccarelli, Arturo Brunetti, Sirio Cocozza, Giuseppe Pontillo, Mario Tranfa, Annabella Di Giorgio, Sophia I Thomopoulos, Neda Jahanshad, Paul M Thompson, Theo van Erp, Jessica Turner, Philipp Homan","doi":"10.1176/appi.ajp.20230806","DOIUrl":"10.1176/appi.ajp.20230806","url":null,"abstract":"<p><strong>Objective: </strong>The clinical diversity of schizophrenia is reflected by structural brain variability. It remains unclear how this variability manifests across different gray and white matter features. In this meta- and mega-analysis, the authors investigated how brain heterogeneity in schizophrenia is distributed across multimodal structural indicators.</p><p><strong>Methods: </strong>The authors used the ENIGMA dataset of MRI-based brain measures from 22 international sites with up to 6,037 individuals for a given brain measure. Variability and mean values of cortical thickness, cortical surface area, cortical folding index, subcortical volume, and fractional anisotropy were examined in individuals with schizophrenia and healthy control subjects.</p><p><strong>Results: </strong>Individuals with schizophrenia showed greater variability in cortical thickness, cortical surface area, subcortical volume, and fractional anisotropy within the frontotemporal and subcortical network. This increased structural variability was mainly associated with psychopathological symptom domains, and the schizophrenia group frequently displayed lower mean values in the respective structural measures. Unexpectedly, folding patterns were more uniform in individuals with schizophrenia, particularly in the right caudal anterior cingulate region. The mean folding values of the right caudal anterior cingulate region did not differ between the schizophrenia and healthy control groups, and folding patterns in this region were not associated with disease-related parameters.</p><p><strong>Conclusions: </strong>In patients with schizophrenia, uniform folding patterns in the right caudal anterior cingulate region contrasted with the multimodal variability in the frontotemporal and subcortical network. While variability in the frontotemporal and subcortical network was associated with disease-related diversity, uniform folding may indicate a less flexible interplay between genetic and environmental factors during neurodevelopment.</p>","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":" ","pages":"373-388"},"PeriodicalIF":15.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497515","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":"Kynurenic Acid and Promotion of Activity-Dependent Synapse Elimination in Schizophrenia.","authors":"Funda Orhan, Susmita Malwade, Neda Khanlarkhani, Asimenia Gkogka, Angelika Langeder, Oscar Jungholm, Marja Koskuvi, Šárka Lehtonen, Lilly Schwieler, Kent Jardemark, Jari Tiihonen, Jari Koistinaho, Sophie Erhardt, Göran Engberg, Samudyata Samudyata, Carl M Sellgren","doi":"10.1176/appi.ajp.20240048","DOIUrl":"https://doi.org/10.1176/appi.ajp.20240048","url":null,"abstract":"<p><strong>Objective: </strong>Schizophrenia is a neurodevelopmental disorder characterized by an excessive loss of synapses. Kynurenic acid (KYNA), a neuroactive metabolite of tryptophan along the kynurenine pathway, can induce schizophrenia-related phenotypes in rodents, and clinical studies have revealed elevated KYNA levels in the CNS of individuals with schizophrenia. However, the factors that cause elevated KYNA levels in schizophrenia, and the mechanisms by which KYNA contributes to pathophysiology, remain largely elusive. The authors used patient-derived cellular modeling to test the hypothesis that KYNA can induce microglia-mediated synapse engulfment by reducing neuronal activity.</p><p><strong>Methods: </strong>Patient-derived induced pluripotent stem cells were used to generate 2D cultures of neurons and microglia-like cells, as well as forebrain organoids with innately developing microglia, to study how KYNA influences synaptic activity and microglial uptake of synaptic structures. To verify the experimental data in a clinical context, large-scale developmental postmortem brain tissue and genetic datasets were used to study coexpression networks for the KYNA-producing kynurenine aminotransferases (KATs) regarding enrichment for common schizophrenia genetic risk variants and functional annotations.</p><p><strong>Results: </strong>In these patient-derived experimental models, KYNA induced uptake of synaptic structures in microglia, and inhibition of the endogenous KYNA production led to a decrease in the internalization of synapses in microglia. The integrated large-scale transcriptomic and genetic datasets showed that KYNA-producing KATs enriched for genes governing synaptic activity and genetic risk variants for schizophrenia.</p><p><strong>Conclusions: </strong>Together, these results link genetic risk variants for schizophrenia to elevated production of KYNA and excessive and activity-dependent internalization of synaptic material in microglia, while implicating pharmacological inhibition of KATs as a strategy to avoid synapse loss in schizophrenia.</p>","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"182 4","pages":"389-400"},"PeriodicalIF":15.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750735","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":"Continuous Dopamine D₂ Receptor Blockade and Long-Term Outcome in First-Episode Schizophrenia.","authors":"Jari Tiihonen, Antti Tanskanen, Marco Solmi, Jose M Rubio, Christoph U Correll, John M Kane, Heidi Taipale","doi":"10.1176/appi.ajp.20240321","DOIUrl":"10.1176/appi.ajp.20240321","url":null,"abstract":"<p><strong>Objective: </strong>It is not known what proportion of patients experience relapse in first-episode schizophrenia despite continuous dopamine D₂ receptor blockade and whether breakthrough psychosis is attributable to long-term use of D₂-blocking antipsychotics. Using data from a Finnish nationwide cohort, the authors sought to test the hypothesis that the incidence of breakthrough psychosis is accelerated among previously relapse-free patients receiving continuous D₂ antagonist treatment beyond 5 years.</p><p><strong>Methods: </strong>All persons age 45 years or younger with first-episode schizophrenia were identified from the nationwide registry of inpatient care for the years 1996-2014. The primary outcome was a severe relapse leading to hospitalization among those treated continuously with long-acting injectable (LAI) antipsychotics. The secondary outcome was the incidence rate ratio (IRR) of relapse during years 2-10, using year 1 as the reference.</p><p><strong>Results: </strong>A total of 305 patients initiated ensured LAI use during the first 30 days of follow-up. Kaplan-Meier analysis showed that during the 10-year follow-up, their cumulative probability of relapse was 45% (95% CI=35-57). The annual relapse incidence per person-year decreased from 0.26 (95% CI=0.20-0.35) during the first year to 0.05 (95% CI=0.01-0.19) during the fifth year, corresponding to an IRR of 0.18 (95% CI=0.04-0.74). During years 6-10, only four relapses occurred during 128 person-years, corresponding to an IRR of 0.12 (95% CI=0.03-0.33) compared with year 1.</p><p><strong>Conclusions: </strong>About 40%-50% of patients with first-episode schizophrenia will relapse despite continuous D₂ blockade, apparently due to non-dopaminergic elements of the pathophysiology of the illness, as the results show that long-term dopamine receptor blockade is not associated with an increased risk of breakthrough psychosis.</p>","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":" ","pages":"341-348"},"PeriodicalIF":15.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447757","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":"Variability Rather Than Means? Harnessing the Adversary to Advance Precision Psychiatry.","authors":"Raquel E Gur, David R Roalf, Daniel H Wolf, Ruben C Gur","doi":"10.1176/appi.ajp.20250108","DOIUrl":"https://doi.org/10.1176/appi.ajp.20250108","url":null,"abstract":"","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"182 4","pages":"326-328"},"PeriodicalIF":15.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750485","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":"High-Potency Cannabis Use and Health: A Systematic Review of Observational and Experimental Studies.","authors":"Stephanie Lake, Conor H Murray, Brittany Henry, Liza Strong, Kendall White, Beau Kilmer, Ziva D Cooper","doi":"10.1176/appi.ajp.20240269","DOIUrl":"https://doi.org/10.1176/appi.ajp.20240269","url":null,"abstract":"<p><strong>Objective: </strong>Amid continuously rising concentrations of delta-9-tetrahydrocannabinol (THC) in cannabis (i.e., potency), high-potency cannabis is a major topic in contemporary cannabis policy discussions, yet its impact on health is not well understood. The authors conducted a systematic review of observational and experimental studies examining the relationship between high-potency cannabis use and a range of health outcomes.</p><p><strong>Methods: </strong>Records were obtained from a systematic search of five biomedical research databases. The authors developed ecologically relevant potency (percent THC) exposure-comparison categories (1%-9%, 10%-19%, 20%-30%, kief/resin [∼30%-50%], concentrates [≥60%]) and used a landmark scientific report on cannabis and cannabinoids to determine outcome eligibility. Two reviewers independently conducted article screening and selection, extraction, and quality assessment. Findings were synthesized using both quantitative (association direction, binomial test) and narrative approaches. Certainty in the evidence was determined via the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework.</p><p><strong>Results: </strong>Of 4,545 screened records, 42 were eligible. Most studies addressed outcomes in the mental health, \"problem\" cannabis use, and other substance use domains. Findings in the \"problem\" cannabis use domain were suggestive of an association with higher-potency cannabis use. Findings were less consistent in other domains but tended to favor poorer outcomes with higher-potency use. Therapeutic outcomes were limited and mixed. Overall, certainty in the evidence was \"very low.\"</p><p><strong>Conclusions: </strong>Findings within the \"problem\" cannabis use domain were suggestive of an association with high-potency use. Research is largely limited to cross-sectional studies spanning few adverse health domains, underscoring the need for prospective studies probing therapeutic, cardiorespiratory, cancer, and pre- and perinatal outcomes. Policies to curb high-potency cannabis use may be warranted while the evidence base improves.</p>","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":" ","pages":"appiajp20240269"},"PeriodicalIF":15.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708281","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}