Presence or absence of recent stress preceding emergence of depressive symptoms may play a distinctive role in determining underlying etiological processes, explaining part of the significant heterogeneity characteristic of depression. Separately studying genetic associations of depressive symptoms appearing following, or independently of stress may help disentangle the genetic background of distinct depression subtypes in a general population sample. We included UK Biobank data (application number 1602) of nearly 120,000 subjects, and conducted three separate genome-wide analyses focusing on current depressive symptoms in three groups based on level of stress exposure in the past two years and analysed results from the aspect of neurobiological relationships between genetic variation and brain function. GWAS results were evaluated on SNP and gene-set levels. Heritability estimation revealed 10.4 %, 8.8 % and 5.1 % heritability in major-stress, minor-stress and no-stress groups, respectively. In the no-stress group 22, in the minor-stress group 22, and in the major-stress group 14 SNPs with suggestive significance were identified, with notable differences in the specific genes and processes implicated in the three groups. In the no-stress group marked association with long non-coding and micro-RNA emerged whereas in the major-stress group results implicate involvement of circadian genes and immunological pathways. Our findings reveal marked differences in the genetic underpinnings of depressive symptoms following exposure to different levels of recent stress, arguing that etiological heterogeneity of depression should be considered in both research and clinical applications, and pave the way of distinguishing between subtypes of depression based on the etiological contribution of stress.
{"title":"Three shades of gloom: investigating the genetic background of current depressive symptoms associated with different severity of current stress exposure in a general population","authors":"Berta Erdelyi-Hamza , Dora Torok , Nora Eszlari , Gyorgy Bagdy , Gabriella Juhasz , Xenia Gonda","doi":"10.1016/j.euroneuro.2025.11.005","DOIUrl":"10.1016/j.euroneuro.2025.11.005","url":null,"abstract":"<div><div>Presence or absence of recent stress preceding emergence of depressive symptoms may play a distinctive role in determining underlying etiological processes, explaining part of the significant heterogeneity characteristic of depression. Separately studying genetic associations of depressive symptoms appearing following, or independently of stress may help disentangle the genetic background of distinct depression subtypes in a general population sample. We included UK Biobank data (application number 1602) of nearly 120,000 subjects, and conducted three separate genome-wide analyses focusing on current depressive symptoms in three groups based on level of stress exposure in the past two years and analysed results from the aspect of neurobiological relationships between genetic variation and brain function. GWAS results were evaluated on SNP and gene-set levels. Heritability estimation revealed 10.4 %, 8.8 % and 5.1 % heritability in major-stress, minor-stress and no-stress groups, respectively. In the no-stress group 22, in the minor-stress group 22, and in the major-stress group 14 SNPs with suggestive significance were identified, with notable differences in the specific genes and processes implicated in the three groups. In the no-stress group marked association with long non-coding and micro-RNA emerged whereas in the major-stress group results implicate involvement of circadian genes and immunological pathways. Our findings reveal marked differences in the genetic underpinnings of depressive symptoms following exposure to different levels of recent stress, arguing that etiological heterogeneity of depression should be considered in both research and clinical applications, and pave the way of distinguishing between subtypes of depression based on the etiological contribution of stress.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"102 ","pages":"Pages 17-25"},"PeriodicalIF":6.7,"publicationDate":"2025-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596284","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":"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":"2025-11-22","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}
Pub Date : 2025-11-22DOI: 10.1016/j.euroneuro.2025.11.003
Natalia E. Fares-Otero , Monika Budde , Jonathan Laatsch , Mathias Harrer , Teuntje Pelgrim , Alexandra Philipsen , Urs Heilbronner , Eduard Vieta , Roos van Westrhenen , PSY-PGx Consortium
{"title":"Reply to the commentary on “Efficacy of pharmacogenetic (PGx)-guided antidepressant treatment on functional outcomes and quality of life in adults with anxiety and affective disorders: A systematic review and meta-analysis”","authors":"Natalia E. Fares-Otero , Monika Budde , Jonathan Laatsch , Mathias Harrer , Teuntje Pelgrim , Alexandra Philipsen , Urs Heilbronner , Eduard Vieta , Roos van Westrhenen , PSY-PGx Consortium","doi":"10.1016/j.euroneuro.2025.11.003","DOIUrl":"10.1016/j.euroneuro.2025.11.003","url":null,"abstract":"","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"102 ","pages":"Pages 14-16"},"PeriodicalIF":6.7,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145586545","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}
Pub Date : 2025-11-21DOI: 10.1016/j.euroneuro.2025.10.006
Ryan Sai Ting Chu , Crystal Nok Yiu Yau , Chris Chit Sze Fung , Vivian Shi Cheng Fung , Janet Hiu Ching Lei , Gabbie Hou Sem Wong , Sherry Kit Wa Chan , Edwin Ho-Ming Lee , Christy Lai-Ming Hui , Eric Yu-Hai Chen , Wing-Chung Chang
Evidence has underscored clinical significance of subjective quality of life (SQoL) as a key therapeutic goal for early psychosis. However, the patterns, predictors and outcomes of SQoL trajectories over long-term follow-up in early psychosis have not been explored. We conducted a 12-year follow-up of the randomized-controlled-trial on extended early intervention for first-episode psychosis with an aim to identify distinct trajectories of the SQoL, their baseline predictors and relationships with 12-year outcomes. Premorbid adjustment, illness characteristics, symptom severity, functioning, and treatment profiles were assessed. Latent growth mixture modeling was employed to derive SQoL trajectories based on 36-Item Short Form Health Survey (SF-36) mental-health component summary scores over 12-year follow-up. Participants who completed SF-36 at three or more time points, including baseline, and 1-, 2-, 3- and 12-year follow-up, were included in the analysis, resulting in 144 patients. Our results identified three distinct trajectories, including high-stable class (36.8 %, n = 53), moderate-improving class (40.3 %, n = 58) and low-stable class (22.9 %, n = 33). Patients in high-stable class had less severe depressive symptoms at baseline than those in moderate-improving class, and less severe positive, negative and depressive symptoms at baseline compared to patients in low-stable class. Additionally, patients with high-stable trajectory exhibited higher rate of personal recovery and lower depressive symptom severity at 12-year follow-up relative to patients with low-stable trajectory. In conclusion, approximately one-fourths of patients displayed consistently poor SQoL over 12 years. Depressive symptoms represent a major determinant of SQoL trajectories, indicating the need to optimize treatment for depression in early psychosis to enhance SQoL outcome.
{"title":"Patterns, predictors and outcomes of trajectories for subjective quality of life in patients with early psychosis: 12-year follow-up of the randomized controlled trial on extended early intervention","authors":"Ryan Sai Ting Chu , Crystal Nok Yiu Yau , Chris Chit Sze Fung , Vivian Shi Cheng Fung , Janet Hiu Ching Lei , Gabbie Hou Sem Wong , Sherry Kit Wa Chan , Edwin Ho-Ming Lee , Christy Lai-Ming Hui , Eric Yu-Hai Chen , Wing-Chung Chang","doi":"10.1016/j.euroneuro.2025.10.006","DOIUrl":"10.1016/j.euroneuro.2025.10.006","url":null,"abstract":"<div><div>Evidence has underscored clinical significance of subjective quality of life (SQoL) as a key therapeutic goal for early psychosis. However, the patterns, predictors and outcomes of SQoL trajectories over long-term follow-up in early psychosis have not been explored. We conducted a 12-year follow-up of the randomized-controlled-trial on extended early intervention for first-episode psychosis with an aim to identify distinct trajectories of the SQoL, their baseline predictors and relationships with 12-year outcomes. Premorbid adjustment, illness characteristics, symptom severity, functioning, and treatment profiles were assessed. Latent growth mixture modeling was employed to derive SQoL trajectories based on 36-Item Short Form Health Survey (SF-36) mental-health component summary scores over 12-year follow-up. Participants who completed SF-36 at three or more time points, including baseline, and 1-, 2-, 3- and 12-year follow-up, were included in the analysis, resulting in 144 patients. Our results identified three distinct trajectories, including high-stable class (36.8 %, <em>n</em> = 53), moderate-improving class (40.3 %, <em>n</em> = 58) and low-stable class (22.9 %, <em>n</em> = 33). Patients in high-stable class had less severe depressive symptoms at baseline than those in moderate-improving class, and less severe positive, negative and depressive symptoms at baseline compared to patients in low-stable class. Additionally, patients with high-stable trajectory exhibited higher rate of personal recovery and lower depressive symptom severity at 12-year follow-up relative to patients with low-stable trajectory. In conclusion, approximately one-fourths of patients displayed consistently poor SQoL over 12 years. Depressive symptoms represent a major determinant of SQoL trajectories, indicating the need to optimize treatment for depression in early psychosis to enhance SQoL outcome.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"102 ","pages":"Pages 3-11"},"PeriodicalIF":6.7,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145571096","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}
Pub Date : 2025-11-21DOI: 10.1016/j.euroneuro.2025.11.001
Joe Kwun-Nam Chan, Wing-Chung Chang
{"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":"2025-11-21","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}
Pub Date : 2025-11-07DOI: 10.1016/j.euroneuro.2025.09.011
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
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 (https://ebipsyche-database.org/). 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 (k = 11; SMD=-0.85 [-1.09; -0.60]; I2=0 %; GRADE=low). In major depressive disorder (MDD), psilocybin/ayahuasca/LSD reduced depressive symptoms (k = 8; SMD=-0.62 [-0.97; -0.28]; I2=55 %; GRADE=very low). In anxiety disorders, both MDMA and serotonergic psychedelics reduced anxiety symptoms (SMDMDMA=-1.18 [-2.04; -0.32]; I2=0 %; k = 2; GRADE=low and SMDserotonergic=-0.88 [-1.70; -0.06]; I2=54 %;k = 5; GRADE=very low). In alcohol use disorder, neither psilocybin nor LSD reduced abstinence rates (k = 6; RR=1.42 [0.89; 2.26]; I2=7 %; GRADE=very low). In attention-deficit hyperactivity disorder (ADHD), LSD did not reduce ADHD symptoms (k = 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 (RRMDMA=0.74 [0.32; 1.72]; RRserotonergic=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.
{"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":"2025-11-07","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}
Pub Date : 2025-11-06DOI: 10.1016/j.euroneuro.2025.10.005
Andrea de Bartolomeis , Michele Fornaro , Elena Scopetta , Claudio Ricci , Antonella Irano , Giuseppe De Simone , Stefano Comai , Felice Iasevoli , Claudio Caiazza
The kynurenine pathway (KP) has emerged as a key mediator of inflammation and synaptic plasticity, which play a significant role in the pathophysiology of chronic stress (CS). CS, in turn, is a major environmental factor in the development of psychiatric disorders. Despite growing evidence linking the KP to psychiatric disorders, the mechanisms underlying its alterations under CS remain poorly understood. To address this gap, we conducted the first comprehensive meta-analysis of preclinical rodent studies. Our goal was to systematically evaluate, within controlled experimental paradigms: (1) how, to what extent, and in which brain regions CS affects the KP; (2) which neurochemical pathways are most impacted by CS. We searched PubMed/MEDLINE, EMBASE, Scopus for preclinical studies until 06/27/2025. We performed a systematic review and meta-analysis following a pre-determined protocol (PROSPERO:CRD42023459414), considering KP metabolites and enzymes as outcomes (Standardized Mean Difference=SMD). SYRCLE/CAMARADES tools assessed quality and risk-of-bias. 59 studies entered the meta-analyses. CS proved to increase hippocampal and cortical overall concentrations of kynurenine (SMD=1.71,95 %C.I.[0.99,2.42], p < 0.01,I2=91.3 %,k = 23,n = 508; SMD=1.54,95 %C.I.[1.08,2.01],p < 0.01,I2=57.77 %,k = 16,n = 247), as well as kynurenine/tryptophan ratio and quinolinic acid. KYNA concentrations decreased in the hippocampus and cortex. KP enzyme expression/activity, including Indoleamine-2,3-Dioxygenase, Tryptophan-2,3-Dioxygenase, Kynurenine-3-Monoxygenase, increased. These findings support a shift of tryptophan metabolism towards the KP following CS. Particularly, the increase in neurotoxic quinolinic acid (NMDAR-agonist) and decrease in KYNA (NMDA-antagonist) may disrupt the neuroprotection/excitotoxic neuronal balance, influencing neuroplasticity. The KP may play a key role in the pathophysiology of CS-associated behaviors, and could serve to highlight potential targets for novel therapeutic strategies, specifically for treatment resistance.
{"title":"Chronic stress and brain kynurenine pathway: addressing unresolved issues with a meta-analytic approach of preclinical studies, translational implication for psychiatric disorders","authors":"Andrea de Bartolomeis , Michele Fornaro , Elena Scopetta , Claudio Ricci , Antonella Irano , Giuseppe De Simone , Stefano Comai , Felice Iasevoli , Claudio Caiazza","doi":"10.1016/j.euroneuro.2025.10.005","DOIUrl":"10.1016/j.euroneuro.2025.10.005","url":null,"abstract":"<div><div>The kynurenine pathway (KP) has emerged as a key mediator of inflammation and synaptic plasticity, which play a significant role in the pathophysiology of chronic stress (CS). CS, in turn, is a major environmental factor in the development of psychiatric disorders. Despite growing evidence linking the KP to psychiatric disorders, the mechanisms underlying its alterations under CS remain poorly understood. To address this gap, we conducted the first comprehensive meta-analysis of preclinical rodent studies. Our goal was to systematically evaluate, within controlled experimental paradigms: (1) how, to what extent, and in which brain regions CS affects the KP; (2) which neurochemical pathways are most impacted by CS. We searched PubMed/MEDLINE, EMBASE, Scopus for preclinical studies until 06/27/2025. We performed a systematic review and meta-analysis following a pre-determined protocol (PROSPERO:CRD42023459414), considering KP metabolites and enzymes as outcomes (Standardized Mean Difference=SMD). SYRCLE/CAMARADES tools assessed quality and risk-of-bias. 59 studies entered the meta-analyses. CS proved to increase hippocampal and cortical overall concentrations of kynurenine (SMD=1.71,95 %C.I.[0.99,2.42], <em>p</em> < 0.01,I<sup>2</sup>=91.3 %,<em>k</em> = 23,<em>n</em> = 508; SMD=1.54,95 %C.I.[1.08,2.01],<em>p</em> < 0.01,I<sup>2</sup>=57.77 %,<em>k</em> = 16,<em>n</em> = 247), as well as kynurenine/tryptophan ratio and quinolinic acid. KYNA concentrations decreased in the hippocampus and cortex. KP enzyme expression/activity, including Indoleamine-2,3-Dioxygenase, Tryptophan-2,3-Dioxygenase, Kynurenine-3-Monoxygenase, increased. These findings support a shift of tryptophan metabolism towards the KP following CS. Particularly, the increase in neurotoxic quinolinic acid (NMDAR-agonist) and decrease in KYNA (NMDA-antagonist) may disrupt the neuroprotection/excitotoxic neuronal balance, influencing neuroplasticity. The KP may play a key role in the pathophysiology of CS-associated behaviors, and could serve to highlight potential targets for novel therapeutic strategies, specifically for treatment resistance.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"101 ","pages":"Pages 22-40"},"PeriodicalIF":6.7,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145470939","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}
Pub Date : 2025-10-27DOI: 10.1016/j.euroneuro.2025.10.004
Yuxuan Gao, Weili Wang, Jiapeng Leng
{"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":"2025-10-27","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}
Pub Date : 2025-10-27DOI: 10.1016/j.euroneuro.2025.09.012
Souichi Oka , Kota Takemura , Yoshiyasu Takefuji
{"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":"2025-10-27","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}
Pub Date : 2025-10-26DOI: 10.1016/j.euroneuro.2025.09.010
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
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 (agerange=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 (RPL31P11 and KCNJ5) for peripheral blood, and, in cord blood, in monocytes (PDE6B), CD8T cells (KCNA3 and HAND2), and NK cells (KIFC1). Notably, several significant sites detected in peripheral blood (RPL31P11 and KCNJ5) 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.
研究DNA甲基化（DNAm）可以深入了解注意力缺陷/多动障碍（ADHD）的基因调控机制。虽然大多数DNAm研究是在大块组织中进行的，但本研究使用统计反褶积来确定与儿童多动症症状相关的五种主要血细胞类型的细胞类型特异性DNAm谱。我们对儿童时期收集的外周血和脐带血中ADHD症状（年龄范围为4-16岁）的甲基组全关联研究（MWAS）进行了荟萃分析。研究队列包括七个基于阵列的甲基化数据集，分析了来自妊娠和儿童表观遗传学协会（N=2 934外周血；N=2 546脐带血）的多达450 K CpGs，以及一个基于测序的甲基化数据集，分析了来自大烟山研究（GSMS； N=583）的几乎所有2800万CpGs血液。荟萃分析结果显示，外周血CD8T细胞（RPL31P11和KCNJ5）、脐带血单核细胞（PDE6B）、CD8T细胞（KCNA3和HAND2）和NK细胞（KIFC1）在甲基组范围内存在显著（FDR<0.05） ADHD关联。值得注意的是，在外周血中检测到的几个重要位点（RPL31P11和KCNJ5）也在脐带血中检测到。此外，GSMS所有可用位点的扩展MWAS分别在单核细胞和粒细胞中检测到69和17个额外的CpGs。在这首个针对ADHD的细胞类型特异性MWAS中，我们确定了DNAm与ADHD症状的关联；在外周血和脐带血中都发现了一些关联，提示ADHD风险增加的潜在易感性标记。这些发现表明，细胞类型特异性分析和基于测序的方法可以增加对与儿童多动症症状相关的表观遗传模式的了解。
{"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":"2025-10-26","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号