American Journal of Psychiatry最新文献

{"title":"An Update on the Use of Neuromodulation Strategies in the Treatment of Schizophrenia.","authors":"Nicholas H Neufeld, Daniel M Blumberger","doi":"10.1176/appi.ajp.20250068","DOIUrl":"https://doi.org/10.1176/appi.ajp.20250068","url":null,"abstract":"<p><p>The field of neuromodulation has evolved tremendously and now includes a vast array of interventions utilizing different technologies that span electrical, magnetic, and ultrasound forms of stimulation. The evolution of interventions holds the promise of fewer adverse effects and a noninvasive approach, increasing the scale at which these interventions may be offered in hospital and community settings. While the majority of neuromodulation studies have focused on patients with mood disorders, predominantly depression, there is an unmet need for patients with schizophrenia, who are in dire need of novel therapeutic options. Advances in neuroimaging and approaches for examining individual variability and transdiagnostic symptoms may lead to more effective neuromodulation treatments in this patient population. This overview explores the modern landscape of invasive and noninvasive neuromodulation treatments for patients with schizophrenia. It begins with approaches that involve diffuse stimulation of the cortex and subcortex and then reviews more focal stimulation approaches at the cortical and subcortical levels. The authors also reflect on the relationship between our understanding of the neurobiology of schizophrenia and neuromodulation interventions.</p>","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"182 4","pages":"332-340"},"PeriodicalIF":15.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750733","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":"Targeting Schizophrenia.","authors":"Roy H Perlis","doi":"10.1176/appi.ajp.20250091","DOIUrl":"https://doi.org/10.1176/appi.ajp.20250091","url":null,"abstract":"","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"182 4","pages":"329-331"},"PeriodicalIF":15.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750425","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":"Long-Term Antipsychotic Use and the Benefit-to-Harm Balance: More on the Risk of Relapse.","authors":"Robin Emsley","doi":"10.1176/appi.ajp.20250031","DOIUrl":"https://doi.org/10.1176/appi.ajp.20250031","url":null,"abstract":"","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"182 4","pages":"316-318"},"PeriodicalIF":15.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750045","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":"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":"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}