European Neuropsychopharmacology最新文献

{"title":"From first-episode psychosis to the future: Insights and challenges","authors":"Ana Catalán , Paolo Fusar-Poli","doi":"10.1016/j.euroneuro.2025.11.008","DOIUrl":"10.1016/j.euroneuro.2025.11.008","url":null,"abstract":"","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"103 ","pages":"Article 112731"},"PeriodicalIF":6.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833643","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":"Sodium benzoate treatment linked to increased glutathione levels and improved positive and negative symptoms, global function, and quality of life in patients with clozapine-resistant schizophrenia: secondary analysis of a randomized clinical trial","authors":"Chieh-Hsin Lin ,&nbsp;Hsien-Yuan Lane","doi":"10.1016/j.euroneuro.2025.11.010","DOIUrl":"10.1016/j.euroneuro.2025.11.010","url":null,"abstract":"<div><div>Oxidative stress is implicated in schizophrenia. Glutathione (GSH), a crucial endogenous antioxidant, is usually reduced in individuals with schizophrenia. GSH and its precursor, N-acetyl cysteine, have demonstrated potential as adjunctive treatment for schizophrenia; however, their effectiveness appears inconsistent, possibly because of their limited ability to penetrate the blood-brain barrier (BBB). Administration of sodium benzoate, capable of crossing BBB, enhanced GSH capacity and antipsychotic-like activity in animals. Further, adjunctive benzoate therapy improved clinical and functional outcomes in patients with schizophrenia, including clozapine-resistant schizophrenia (CRS). Whether sodium benzoate can also boost GSH to exert its therapeutic efficacy for schizophrenia deserves elucidation. This secondary analysis used data from a double-blind trial, in which 60 patients with CRS were randomized to receive addon treatment of sodium benzoate (n = 40) or placebo (n = 20) for 6 weeks. Clinical and functional assessments were conducted bi-weekly. Plasma levels of GSH were assayed at baseline and endpoint. As a result, six-week treatment of sodium benzoate was linked to increased GSH levels than placebo. Among the 40 benzoate receivers, the changes in GSH levels were correlated with the improvements in positive symptoms, negative symptoms, quality of life, and global function. In comparison, among placebo recipients, GSH changes were not associated with any changes in clinical or functional variables. The findings suggest that benzoate treatment may be related with elevation in GSH levels in CRS patients and improvement in functional outcomes as well as positive and negative symptoms. Longer-term studies in other populations are necessary in the future.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"103 ","pages":"Article 112733"},"PeriodicalIF":6.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145767508","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":"Ayahuasca modulation of traumatic-like fear memories requires infralimbic cortex BDNF-dependent mechanisms in rats","authors":"Isabel Werle ,&nbsp;Francisco S. Guimarães ,&nbsp;Rafael G. dos Santos ,&nbsp;Jaime E.C. Hallak ,&nbsp;Leandro J. Bertoglio","doi":"10.1016/j.euroneuro.2025.11.009","DOIUrl":"10.1016/j.euroneuro.2025.11.009","url":null,"abstract":"<div><div>Rodent studies have shown that psychedelic drugs can enhance fear extinction. However, investigations to date have relied on normative aversive conditioning procedures, which limit their relevance to trauma-related memories, as these tend to be overgeneralized and resistant to extinction. Fear extinction depends on activity and plasticity within the infralimbic (IL) region of the medial prefrontal cortex and is regulated by brain-derived neurotrophic factor (BDNF). Ayahuasca (AYA), a brew containing the serotonergic psychedelic <em>N,N</em>-dimethyltryptamine (DMT), facilitates fear extinction in rodents and increases BDNF levels/signaling. Here, we investigated whether AYA attenuates extinction deficits and generalized fear induced by preconditioning restraint stress or high-intensity contextual fear conditioning, and whether these effects depend on BDNF-TrkB receptor signaling in the IL cortex. Adult male and female rats underwent the protocols above and received oral AYA one hour before each of the two extinction sessions conducted on consecutive days. Repeated administration of AYA containing 0.3 mg/kg of DMT enhanced extinction learning and its retention, effects that were abolished by bilateral intra-IL cortex infusion of an anti-BDNF antibody or the TrkB receptor antagonist ANA-12. AYA treatment also reduced fear generalization, an action that was BDNF-dependent in the IL cortex of females but not males. Overall, these findings indicate that AYA can modulate maladaptive fear memories through cortical mechanisms involving BDNF signaling, highlighting the potential of psychedelics as enhancers for extinguishing difficult-to-treat memories like those underlying post-traumatic stress disorder.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"103 ","pages":"Article 112732"},"PeriodicalIF":6.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780511","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":"Dynamic functional network connectivity impairment in bipolar disorder and its relationship with global functioning","authors":"Daniele Olivo ,&nbsp;Alessandro Miola ,&nbsp;Francesco Folena Comini ,&nbsp;Nicolò Trevisan ,&nbsp;Giovanni Librizzi ,&nbsp;Tommaso Toffanin ,&nbsp;Renzo Manara ,&nbsp;Fabio Sambataro","doi":"10.1016/j.euroneuro.2025.11.015","DOIUrl":"10.1016/j.euroneuro.2025.11.015","url":null,"abstract":"<div><div>Abnormal functional connectivity (FC) has been consistently associated with bipolar disorders (BD). Classical FC analyses assume stationarity of brain interactions, although connectivity actually varies over time. Here, we examined alterations in dynamic functional network connectivity (dFNC) in BD, their associations with symptom severity and global functioning, and potential differences between bipolar disorder type I (BD1) and type II (BD2).</div><div>In this case-control study, we investigated dFNC in 57 patients with BD (29 BD1, 28 BD2) and 43 healthy controls (HCs). Most patients were euthymic at scanning (∼86 %), with only a minority showing residual depressive or hypomanic/mixed symptoms. Resting-state fMRI data were decomposed with spatially constrained independent component analysis and analyzed using a sliding-window approach. Meta-state metrics—number of meta-states, transitions, total distance, and span—were derived and compared across groups. Correlations with clinical measures and Global Assessment of Functioning (GAF) scores were tested. Dynamic metrics (number of meta-states, state transitions, and total distance) were reduced in BD relative to HCs, with the greatest reduction in BD1, followed by BD2. State span did not differ between groups. Across the BD sample, higher GAF scores were positively associated with greater dynamic fluidity, whereas no significant associations emerged with standard symptom scales.</div><div>In conclusion, BD is characterized by a graded disruption of the spatio-temporal dynamics of large-scale brain networks, most pronounced in BD1. Reduced neural flexibility is linked to poorer global functioning, suggesting that dFNC meta-state metrics may provide clinically relevant markers of illness burden in bipolar disorder.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"103 ","pages":"Article 112738"},"PeriodicalIF":6.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145750304","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":"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 ,&nbsp;Crystal Nok Yiu Yau ,&nbsp;Chris Chit Sze Fung ,&nbsp;Vivian Shi Cheng Fung ,&nbsp;Janet Hiu Ching Lei ,&nbsp;Gabbie Hou Sem Wong ,&nbsp;Sherry Kit Wa Chan ,&nbsp;Edwin Ho-Ming Lee ,&nbsp;Christy Lai-Ming Hui ,&nbsp;Eric Yu-Hai Chen ,&nbsp;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":"2026-01-01","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}

{"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 ,&nbsp;Dora Torok ,&nbsp;Nora Eszlari ,&nbsp;Gyorgy Bagdy ,&nbsp;Gabriella Juhasz ,&nbsp;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":"2026-01-01","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":"Psychedelics: The pathway to implementation in the European healthcare systems","authors":"Gerhard Gründer ,&nbsp;Lea J. Mertens ,&nbsp;Moritz Spangemacher ,&nbsp;Andreas Meyer-Lindenberg ,&nbsp;Henrik Jungaberle","doi":"10.1016/j.euroneuro.2025.11.007","DOIUrl":"10.1016/j.euroneuro.2025.11.007","url":null,"abstract":"<div><div>The integration of psychedelic therapies into European healthcare is a nuanced process that involves not only obtaining European Medicines Agency (EMA) approval but also successfully navigating Health Technology Assessment (HTA) evaluations across member states. After EMA approval, which focuses on the safety, efficacy, and quality of the therapeutic, HTA agencies assess these therapies for their “added therapeutic value,” considering factors like cost-effectiveness, clinical outcomes, and overall societal impact. Each country's HTA, including the UK’s National Institute for Health and Care Excellence (NICE), Germany’s Institute for Quality and Efficiency in Health Care (IQWiG), and France’s Haute Autorité de Santé (HAS), plays a pivotal role in determining reimbursement and access to these treatments. An added challenge is that HTA bodies in Europe often require active comparator studies rather than just placebo controls to establish a treatment’s advantage over existing standard of care – a particular hurdle for psychedelic-assisted therapies, where controlled trials against active comparators are almost completely lacking. Furthermore, psychedelics are typically integrated with psychotherapy, adding complexity to HTA evaluations, as few frameworks currently assess the value of combination therapies within healthcare systems. Creating a standardized HTA approach or a unified European guideline for such novel treatments could promote equitable access across countries, helping to overcome the discrepancies in market access and patient reach across Europe.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"102 ","pages":"Pages 41-48"},"PeriodicalIF":6.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667683","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":"Exploring clozapine dose adjustment strategy in acute-phase reaction of inflammation based on free drug concentrations and Kpuu","authors":"Yang Han ,&nbsp;Jing Guo ,&nbsp;Gaoyu Wang ,&nbsp;Fan Wang ,&nbsp;Wenyan Wang","doi":"10.1016/j.euroneuro.2025.10.007","DOIUrl":"10.1016/j.euroneuro.2025.10.007","url":null,"abstract":"","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"102 ","pages":"Pages 39-40"},"PeriodicalIF":6.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145616609","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":"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 ,&nbsp;Monika Budde ,&nbsp;Jonathan Laatsch ,&nbsp;Mathias Harrer ,&nbsp;Teuntje Pelgrim ,&nbsp;Alexandra Philipsen ,&nbsp;Urs Heilbronner ,&nbsp;Eduard Vieta ,&nbsp;Roos van Westrhenen ,&nbsp;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":"2026-01-01","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}

{"title":"Default mode network integrity across neuropsychiatric disorders and its relation to social dysfunction: A normative modelling approach","authors":"Simon Braak ,&nbsp;Marianne Oldehinkel ,&nbsp;Maarten Mennes ,&nbsp;Tanja Su ,&nbsp;Yolande Pijnenburg ,&nbsp;Celso Arango ,&nbsp;José Luis Ayuso-Mateos ,&nbsp;Nic van der Wee ,&nbsp;Gerard R. Dawson ,&nbsp;Hugh M. Marston ,&nbsp;Christian F. Beckmann ,&nbsp;Martien J.H. Kas ,&nbsp;Brenda W.J.H. Penninx","doi":"10.1016/j.euroneuro.2025.11.002","DOIUrl":"10.1016/j.euroneuro.2025.11.002","url":null,"abstract":"<div><div>Structural and functional default mode network (DMN) alterations are common in neuropsychiatric disorders and may contribute transdiagnostically to social dysfunction. Normative modelling enables assessment of DMN alterations at the individual level. This study investigates whether individual deviations in cortical thickness, surface area, and between-network functional connectivity of the DMN differ between schizophrenia (SZ), major depressive disorder (MDD), Alzheimer’s disease (AD), and healthy controls (HC), and whether these deviations transdiagnostically relate to social dysfunction. Social dysfunction was assessed using a composite score from the Social Functioning Scale and De Jong-Gierveld Loneliness scale. Structural MRI data was collected for 329 participants (SZ=86, MDD=44, AD=82, HC=117) and resting-state fMRI data for 317 participants. Individual deviation scores of DMN integrity were computed by adapting existing normative models of cortical thickness (<em>N</em> = 58,836), surface area (<em>N</em> = 43,524), and between-network functional connectivity (<em>N</em> = 21,515). Extreme deviations were quantified using a z-threshold of ±1.96. DMN deviation scores were not transdiagnostically associated with social dysfunction across the sample (<em>ps</em>&gt;0.05). AD patients had more extreme negative deviations in DMN cortical thickness than all other groups (<em>ps&lt;</em>0.0001; <em>z</em> = -4.14 to -6.34) and fewer extreme positive deviations in DMN surface area relative to SZ and HC (<em>ps</em>&lt;0.05; <em>z</em> = 2.10 to 2.71). For between-network functional connectivity of the DMN, AD and SZ patients had more extreme negative deviations than MDD and HC (<em>ps</em>&lt;0.05; <em>z</em> = -2.09 to -3.54). To conclude, normative modelling reveals differences in individual deviations of DMN integrity between neuropsychiatric groups, but these deviations do not transdiagnostically relate to social dysfunction.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"102 ","pages":"Pages 28-38"},"PeriodicalIF":6.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145616607","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}