{"title":"Activating β2-adrenergic receptor is a potential cross-disease therapeutic strategy for Alzheimer’s disease, obesity and type 2 diabetes","authors":"Ruonan Zhou , Mengli Luo , Jiaxin Lv , Wenbin Shang","doi":"10.1016/j.euroneuro.2025.11.006","DOIUrl":"10.1016/j.euroneuro.2025.11.006","url":null,"abstract":"","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"102 ","pages":"Pages 12-13"},"PeriodicalIF":6.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145571098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Persistent mortality gap in schizophrenia: current challenges and future directions","authors":"Joe Kwun-Nam Chan, Wing-Chung Chang","doi":"10.1016/j.euroneuro.2025.11.001","DOIUrl":"10.1016/j.euroneuro.2025.11.001","url":null,"abstract":"","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"102 ","pages":"Pages 1-2"},"PeriodicalIF":6.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145571097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nini de Boer , Zara Vučko , Derek IJ. Koster , Marte van der Horst , Michael Davidson , Wiepke Cahn , Jurjen J. Luykx
{"title":"The effect of switching antipsychotics to aripiprazole versus paliperidone on weight/cardiometabolic parameters: 18-month follow-up findings from the European Long-acting Antipsychotics in Schizophrenia Trial (EULAST)","authors":"Nini de Boer , Zara Vučko , Derek IJ. Koster , Marte van der Horst , Michael Davidson , Wiepke Cahn , Jurjen J. Luykx","doi":"10.1016/j.euroneuro.2025.11.014","DOIUrl":"10.1016/j.euroneuro.2025.11.014","url":null,"abstract":"<div><div>Antipsychotic-induced weight gain (AiWG) is a common, burdensome adverse effect. Switching to antipsychotics with lower metabolic risks, such as aripiprazole, is recommended, but long-term data is limited. Long-acting injectables (LAIs) may offer metabolic benefits over oral formulations, yet evidence is inconsistent. We compared long-term effects of switching to aripiprazole versus paliperidone on bodyweight, considering administration route and smoking. To that end, we analyzed data from 241 participants (mean age = 31.0; 32 % female) in the European Long-acting Antipsychotics in Schizophrenia Trial (EULAST), a multicentre, open-label, randomized trial. Participants received aripiprazole (<em>n</em> = 119) or paliperidone (<em>n</em> = 122), orally or as LAIs. Bodyweight was assessed over 18 months. Secondary outcomes included changes in BMI and cardiometabolic parameters. Both groups showed progressive weight gain: over 18 months, body weight increased by 4.7 kgs (95 % CI 3.0–6.5). Weight gain was 4.5 kgs with aripiprazole (95 % CI 2.1–7.0) and 4.9 kgs with paliperidone (95 % CI 2.3–7.4). Clinically significant weight gain (≥5 %) occurred in 41.1 % and 58.7 % of users, respectively (NNH = 5; <em>p</em> = 0.06). Weight gain was more pronounced among participants receiving LAIs (difference of 5.57 kgs; 95 % CI: 0.8–10.4; <em>p</em> = 0.02). Smoking was associated with greater weight gain (+2.3 kgs; 95 % CI: 0.9–3.6; <em>p</em> = 0.001). In conclusion, switching to aripiprazole or paliperidone did not prevent AiWG and LAIs showed no metabolic advantage relative to oral counterparts. The association between smoking and increased weight gain suggests smoking may represent a modifiable risk factor, warranting further investigation of smoking cessation as a potential intervention in AiWG management.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"102 ","pages":"Pages 49-57"},"PeriodicalIF":6.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mikkel Højlund , Helin Y. Kafali , Begüm Kırmızı , Paolo Fusar-Poli , Christoph U. Correll , Samuele Cortese , Michel Sabé , Jess Fiedorowicz , Gayatri Saraf , Josephine Zein , Michael Berk , Muhammad I. Husain , Joshua D. Rosenblat , Ruby Rubaiyat , Kim Corace , Stanley Wong , Simon Hatcher , Mark Kaluzienski , Lakshmi N. Yatham , Andrea Cipriani , Marco Solmi
{"title":"Efficacy, all-cause discontinuation, and safety of serotonergic psychedelics and MDMA to treat mental disorders: A living systematic review with meta-analysis","authors":"Mikkel Højlund , Helin Y. Kafali , Begüm Kırmızı , Paolo Fusar-Poli , Christoph U. Correll , Samuele Cortese , Michel Sabé , Jess Fiedorowicz , Gayatri Saraf , Josephine Zein , Michael Berk , Muhammad I. Husain , Joshua D. Rosenblat , Ruby Rubaiyat , Kim Corace , Stanley Wong , Simon Hatcher , Mark Kaluzienski , Lakshmi N. Yatham , Andrea Cipriani , Marco Solmi","doi":"10.1016/j.euroneuro.2025.09.011","DOIUrl":"10.1016/j.euroneuro.2025.09.011","url":null,"abstract":"<div><div>Serotonergic psychedelics and 3,4-methylendioxtmethamphetamine (MDMA) are promising treatments for mental disorders with a continuously evolving evidence base. We searched Pubmed/Scopus/clinical trial registries up to 08july2025 for double-blind randomized controlled trials (RCTs) testing MDMA or serotonergic psychedelics in patients with mental disorders. Primary outcomes were change in disease-specific symptoms and all-cause discontinuation. Standardized mean differences (SMD) and relative risk (RR) were estimated using random-effects meta-analysis. Risk of bias (RoB) was assessed with Cochrane’s RoB-tool version 2 and certainty of evidence with GRADE. The review is maintained as living systematic review (<span><span>https://ebipsyche-database.org/</span><svg><path></path></svg></span>). We included 30 RCTs (1480 participants; female=45.8 %; with psychological support=83.3 %; high RoB=83.3 %). In post-traumatic stress disorder (PTSD), MDMA reduced PTSD symptoms compared to any control (<em>k</em> = 11; SMD=-0.85 [-1.09; -0.60]; I<sup>2</sup>=0 %; GRADE=low). In major depressive disorder (MDD), psilocybin/ayahuasca/LSD reduced depressive symptoms (<em>k</em> = 8; SMD=-0.62 [-0.97; -0.28]; I<sup>2</sup>=55 %; GRADE=very low). In anxiety disorders, both MDMA and serotonergic psychedelics reduced anxiety symptoms (SMD<sub>MDMA</sub>=-1.18 [-2.04; -0.32]; I<sup>2</sup>=0 %; <em>k</em> = 2; GRADE=low and SMD<sub>serotonergic</sub>=-0.88 [-1.70; -0.06]; I<sup>2</sup>=54 %;<em>k</em> = 5; GRADE=very low). In alcohol use disorder, neither psilocybin nor LSD reduced abstinence rates (<em>k</em> = 6; RR=1.42 [0.89; 2.26]; I<sup>2</sup>=7 %; GRADE=very low). In attention-deficit hyperactivity disorder (ADHD), LSD did not reduce ADHD symptoms (<em>k</em> = 1; SMD=0.22 [-0.32; 0.76]; GRADE=very low). Moderate certainty in evidence was only found for MDMA on PTSD symptoms when compared to placebo. MDMA/serotonergic psychedelics were not associated with higher risk of all-cause discontinuation (RR<sub>MDMA</sub>=0.74 [0.32; 1.72]; RR<sub>serotonergic</sub>=0.81 [0.56; 1.15]). Overall, MDMA/serotonergic psychedelics are promising for the treatment of PTSD, MDD, and anxiety disorders with moderate to large effect sizes. Pragmatic trials, long-term, head-to-head trials exploring the role of psychological support, aiming to identify predictors of response, and accounting for expectancy and functional unblinding are needed. Studies addressing these limitations will likely be required for regulatory approval of psychedelic drugs.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"101 ","pages":"Pages 41-55"},"PeriodicalIF":6.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145475443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Commentary on the article \"Efficacy of pharmacogenetic-guided antidepressant treatment on functional outcomes and quality of life in adults with anxiety and affective disorders: A systematic review and meta-analysis\"","authors":"Yuxuan Gao, Weili Wang, Jiapeng Leng","doi":"10.1016/j.euroneuro.2025.10.004","DOIUrl":"10.1016/j.euroneuro.2025.10.004","url":null,"abstract":"","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"101 ","pages":"Pages 20-21"},"PeriodicalIF":6.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145388258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mandy Meijer , Marieke Klein , Doretta Caramaschi , Shaunna L. Clark , Marta Cosin-Tomas , Nastassja Koen , Xueling Lu , Rosa H. Mulder , Stefan W. Röder , Yining Zhang , Lea Zilich , Mariona Bustamente , Michael Deuschle , Janine F. Felix , Juan Ramos González , Regina Gražulevičiene , Fabian Streit , John Wright , Angel Carracedo , Charlotte A.M. Cecil , Edwin J.C.G. van den Oord
{"title":"Cell type-specific methylome-wide association studies of childhood ADHD symptoms","authors":"Mandy Meijer , Marieke Klein , Doretta Caramaschi , Shaunna L. Clark , Marta Cosin-Tomas , Nastassja Koen , Xueling Lu , Rosa H. Mulder , Stefan W. Röder , Yining Zhang , Lea Zilich , Mariona Bustamente , Michael Deuschle , Janine F. Felix , Juan Ramos González , Regina Gražulevičiene , Fabian Streit , John Wright , Angel Carracedo , Charlotte A.M. Cecil , Edwin J.C.G. van den Oord","doi":"10.1016/j.euroneuro.2025.09.010","DOIUrl":"10.1016/j.euroneuro.2025.09.010","url":null,"abstract":"<div><div>Studying DNA methylation (DNAm) can provide insights into gene-regulatory mechanisms underlying attention-deficit/hyperactivity disorder (ADHD). While most DNAm studies were performed in bulk tissue, this study used statistical deconvolution to identify cell type-specific DNAm profiles, from five major blood cell types, associated with childhood ADHD symptoms. We performed meta-analyses of methylome-wide association studies (MWAS) for ADHD symptoms (age<sub>range</sub>=4–16 years) in peripheral blood collected during childhood and in cord blood. The investigated cohorts included seven array-based methylation datasets assaying up to 450 K CpGs from the Pregnancy And Childhood Epigenetics Consortium (N=2 934 peripheral blood; N=2 546 cord blood) and a sequencing-based methylation dataset assaying nearly all 28 million CpGs in blood from the Great Smoky Mountain Study (GSMS; N=583). The meta-analyses resulted in methylome-wide significant (FDR<0.05) ADHD associations in CD8T cells (<em>RPL31P11</em> and <em>KCNJ5)</em> for peripheral blood, and, in cord blood, in monocytes (<em>PDE6B</em>), CD8T cells (<em>KCNA3</em> and <em>HAND2</em>), and NK cells (<em>KIFC1</em>). Notably, several significant sites detected in peripheral blood (<em>RPL31P11</em> and <em>KCNJ5</em>) were also detected in cord blood. Furthermore, extended MWAS of all sites available for GSMS detected 69 and 17 additional CpGs in monocytes and granulocytes, respectively. In this first cell type-specific MWAS for ADHD, we identified DNAm associations for ADHD symptoms; some associations were seen in both peripheral blood and cord blood, suggesting potential susceptibility markers for increased ADHD risk. These findings show that cell type-specific analyses and sequencing-based approaches can increase insights into the epigenetic patterns associated with ADHD symptoms in childhood.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"101 ","pages":"Pages 7-17"},"PeriodicalIF":6.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Toward rigorous control conditions in trials of digital therapeutics","authors":"Nathan T.M. Huneke , Blanca Bolea-Alamañac","doi":"10.1016/j.euroneuro.2025.09.013","DOIUrl":"10.1016/j.euroneuro.2025.09.013","url":null,"abstract":"","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"101 ","pages":"Pages 1-2"},"PeriodicalIF":6.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A call for more robust and interpretable models in predicting treatment-resistant depression","authors":"Souichi Oka , Kota Takemura , Yoshiyasu Takefuji","doi":"10.1016/j.euroneuro.2025.09.012","DOIUrl":"10.1016/j.euroneuro.2025.09.012","url":null,"abstract":"","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"101 ","pages":"Pages 18-19"},"PeriodicalIF":6.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145388349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ting-Hui Liu , Jheng-Yan Wu , Po-Yu Huang , Wan-Lin Cheng , Chih-Cheng Lai
{"title":"Response to the letter regarding “Risk of manic switch and suicidal outcomes in bipolar depression treated with esketamine”","authors":"Ting-Hui Liu , Jheng-Yan Wu , Po-Yu Huang , Wan-Lin Cheng , Chih-Cheng Lai","doi":"10.1016/j.euroneuro.2025.10.001","DOIUrl":"10.1016/j.euroneuro.2025.10.001","url":null,"abstract":"","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"101 ","pages":"Page 5"},"PeriodicalIF":6.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}