Marcela Verginia de Medeiros , Eduardo Antonio Rosa , Gabriela Vissintainer , Cilene Lino de Oliveira , Bruno Jacson Martynhak
{"title":"Lack of antidepressant-like effect of imipramine, fluoxetine and ketamine in the forced swim test in mice: How much standardization does a positive control require?","authors":"Marcela Verginia de Medeiros , Eduardo Antonio Rosa , Gabriela Vissintainer , Cilene Lino de Oliveira , Bruno Jacson Martynhak","doi":"10.1016/j.euroneuro.2024.12.012","DOIUrl":"10.1016/j.euroneuro.2024.12.012","url":null,"abstract":"","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"93 ","pages":"Pages 24-26"},"PeriodicalIF":6.1,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074357","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":"Disease continuum centered on Parkinson's disease","authors":"Ming Zheng","doi":"10.1016/j.euroneuro.2025.01.002","DOIUrl":"10.1016/j.euroneuro.2025.01.002","url":null,"abstract":"<div><div>Parkinson’s disease (PD), once viewed as a neurodegenerative disorder, is now increasingly recognized as part of a broader disease continuum, intricately linked to comorbidities across various organ systems. This study provides a snapshot of the disease continuum centered on PD, using a disease-wide association study (DWAS) involving 392,423 individuals—including 4,235 PD cases. This DWAS identifies disease clusters of PD comorbidities across the musculoskeletal, circulatory, digestive, and respiratory systems. Moreover, comorbidities were classified based on their temporal relationship to PD diagnosis: pre-PD comorbidities, such as hypertension and autoimmune disorders, may act as risk factors of PD onset, while post-PD comorbidities, including Alzheimer’s disease and renal disorders, highlight the systemic consequences of PD progression. These findings emphasize the critical need for early detection and intervention to manage comorbidities and potentially delay PD onset. Furthermore, this study advocates for integrated diagnostic and therapeutic strategies targeting shared risk factors, advancing a precision-medicine approach to improve patient care and long-term management of PD.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"93 ","pages":"Pages 19-21"},"PeriodicalIF":6.1,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064811","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}
Bonnie L. Quigley , Adem T. Can , Megan Dutton , Cyrana C. Gallay , Grace Forsyth , Monique Jones , Fiona Randall , Trish Wilson , Jim Lagopoulos , Daniel F. Hermens
{"title":"Low dose oral ketamine treatment on post-traumatic stress disorder (PTSD) (OKTOP): An open-label pilot study","authors":"Bonnie L. Quigley , Adem T. Can , Megan Dutton , Cyrana C. Gallay , Grace Forsyth , Monique Jones , Fiona Randall , Trish Wilson , Jim Lagopoulos , Daniel F. Hermens","doi":"10.1016/j.euroneuro.2025.01.003","DOIUrl":"10.1016/j.euroneuro.2025.01.003","url":null,"abstract":"","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"93 ","pages":"Pages 17-18"},"PeriodicalIF":6.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064814","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}
Riccardo De Giorgi , Nima Norbu Sherpa , Edoardo Giuseppe Ostinelli
{"title":"Preliminary evidence should be treated as such: Response to “Is creatine useful as adjuvant in cognitive-behavioural therapy for depression?”","authors":"Riccardo De Giorgi , Nima Norbu Sherpa , Edoardo Giuseppe Ostinelli","doi":"10.1016/j.euroneuro.2024.12.015","DOIUrl":"10.1016/j.euroneuro.2024.12.015","url":null,"abstract":"","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"93 ","pages":"Pages 15-16"},"PeriodicalIF":6.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064817","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}
Montaine Lion , El Chérif Ibrahim , Elodie Caccomo-Garcia , Julie Bourret , Guillaume Cinquanta , Olfa Khalfallah , Nicolas Glaichenhaus , Laetitia Davidovic , Philippe Courtet , Gustavo Turecki , Eleni Tzavara , Raoul Belzeaux
{"title":"A specific GPR56/ADGRG1 splicing isoform is associated with antidepressant response in major depressive disorder","authors":"Montaine Lion , El Chérif Ibrahim , Elodie Caccomo-Garcia , Julie Bourret , Guillaume Cinquanta , Olfa Khalfallah , Nicolas Glaichenhaus , Laetitia Davidovic , Philippe Courtet , Gustavo Turecki , Eleni Tzavara , Raoul Belzeaux","doi":"10.1016/j.euroneuro.2025.01.001","DOIUrl":"10.1016/j.euroneuro.2025.01.001","url":null,"abstract":"<div><div>Major Depressive Episode (MDE) is one of the most common psychiatric disorders. Often difficult to treat, this disease is one of the leading causes of suicide. A recent study showed an association between <em>GPR56/ADGRG1</em> mRNA, MDE and response to antidepressant treatment in blood and in brain. Among <em>GPR56</em> splicing variant, the S4 isoform has recently been associated with microglial synaptic pruning, while microglia are already known as a central player in MDE. Therefore, we hypothesized that S4 is the specific isoform associated to MDE and antidepressant response. To test our hypothesis, an <em>in silico</em> analysis was first performed to identify the different proteins and transcript isoforms of <em>GPR56</em>. This analysis allowed to design PCR and qPCR primers. <em>GPR56</em> total, S4 and S3 were assessed by RT-qPCR in leukocytes from a cohort of 46 MDE patients including non-responders (NR, <em>n</em> = 31) and responders-remitters (R, <em>n</em> = 17) to antidepressant treatment. We replicated the result of one of our previous studies, which described an increase in total <em>GPR56</em> mRNA in Rs. Additionally, we observed that this variation differs among mRNA splicing variants, with S4 exhibiting a similar pattern of variation while S3 shows no significant change. The differences observed withstood statistical correction for covariates of interest such as smoking, gender and suicidal ideation, demonstrating the robustness of the model. These findings confirm our hypothesis that certain mRNA splicing variants of <em>GPR56</em> may play a more significant role in depression. This study highlighted a link between the <em>GPR56-S4</em> and response to antidepressant treatment.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"93 ","pages":"Pages 5-14"},"PeriodicalIF":6.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058503","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":"3D imaging and geometric morphometrics of facial dysmorphology and asymmetry indicate gestational timings of dysmorphogenesis in schizophrenia and bipolar disorder","authors":"John L. Waddington , Federico M. Sukno","doi":"10.1016/j.euroneuro.2024.12.007","DOIUrl":"10.1016/j.euroneuro.2024.12.007","url":null,"abstract":"","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"93 ","pages":"Pages 1-2"},"PeriodicalIF":6.1,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926887","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":"Disease-wide association study uncovers disease continuum network of unipolar depression","authors":"Ming Zheng","doi":"10.1016/j.euroneuro.2024.12.009","DOIUrl":"10.1016/j.euroneuro.2024.12.009","url":null,"abstract":"<div><div>Unipolar depression is typically regarded as a psychiatric disorder, yet it frequently coexists with various major diseases. This study employs a Disease-Wide Association Study (DWAS) approach to map the disease continuum surrounding unipolar depression, analyzing data from a registry cohort of 392,423 individuals, including 43,280 diagnosed cases of unipolar depression. Significant associations were identified between depression and comorbidities across multiple organ systems, including both mental and physical disorders. Next, temporal analysis categorized these comorbidities based on their onset relative to depression into short-term (1-year), mid-term (5-year), and long-term (15-year) periods, discovering temporal consistent associations with comorbidities such as schizophrenia, anxiety disorders, post-traumatic stress disorder (PTSD), asthma, hypothyroidism, type 2 diabetes, cardiac arrhythmias, and cancer. These findings highlight the interconnected nature of depression within a broader disease continuum network. Recognizing depression within this systemic framework supports the adoption of personalized medicine strategies tailored to individual comorbidity profiles, enabling therapeutic targeting of shared pathogenic mechanisms that concurrently address both depression and its associated comorbidities.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"92 ","pages":"Pages 74-76"},"PeriodicalIF":6.1,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902368","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}
Nicholas Fabiano , Stanley Wong , Carl Zhou , Christoph U. Correll , Mikkel Højlund , Marco Solmi
{"title":"Efficacy, tolerability, and safety of xanomeline-trospium chloride for schizophrenia: A systematic review and meta-analysis","authors":"Nicholas Fabiano , Stanley Wong , Carl Zhou , Christoph U. Correll , Mikkel Højlund , Marco Solmi","doi":"10.1016/j.euroneuro.2024.11.013","DOIUrl":"10.1016/j.euroneuro.2024.11.013","url":null,"abstract":"<div><div>The United States Food and Drug Administration approved xanomeline-trospium combination for schizophrenia on September-26–2024. We conducted a PRISMA 2020-compliant systematic review with random-effects meta-analysis on the efficacy and safety of xanomeline-trospium in randomized controlled trials in patients with schizophrenia (MEDLINE, EMBASE, Cochrane, PsycINFO, October-01–2024). Co-primary outcomes were Positive And Negative Syndrome Scale (PANSS) total score (standardized mean difference=SMD), and all-cause discontinuation (risk ratio=RR). Cochrane's Risk of Bias (RoB) Tool 2 and GRADE were used. Xanomeline-trospium (<em>k</em> = 3, schizophrenia acute exacerbation, RoB=low, baseline <em>N</em> = 690, males=75.5 %, age=44.3 + 11.0, duration=5 weeks) outperformed placebo on PANSS total (SMD=-0.56, 95 % confidence interval/CI=-0.72/-0.40), positive (SMD=-0.59, 95 %CI=-0.75/-0.43), negative (SMD=-0.33, 95 %CI=-0.49/-0.17), and Marder Factor negative symptom score (SMD=-0.36, 95 %CI=-0.60/-0.13), Clinical Global Impression-Severity (SMD=-0.54, 95 %CI=-0.71/-0.37) (GRADE=moderate), and response (≥30 % reduction from baseline: RR=2.13, 95 %CI=1.66–2.75). Risk of ≥7 % weight gain (RR=0.46, 95 %CI=0.25–0.87, NNT=19), low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol levels were reduced, while risk was increased for vomiting, hypertension, nausea, dry mouth, dyspepsia, constipation (RR=7.60, 95 %CI=1.50–38.57 to RR=2.72, 95 %CI=1.63–4.55), any adverse event (RR=1.33, 95 %CI=1.18–1.51, NNT=6), triglyceride levels and supine heart rate (GRADE=moderate to high). Conversely, the risk was not increased for any other, serious, or severe adverse events or all-cause discontinuation. In post-hoc analyses, xanomeline-trospium outperformed placebo regarding response (≥20 % and ≥30 % threshold) starting at week 2, negative symptoms in patients with prominent negative symptoms, and cognitive symptoms in patients ≥1 standard deviation below the general population norm. Further, pro-/anti-cholinergic side effects were mild-moderate and mostly transient. Xanomeline-trospium is an effective treatment for schizophrenia with a unique tolerability profile, potentially addressing unmet needs.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"92 ","pages":"Pages 62-73"},"PeriodicalIF":6.1,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gustavo J. Gil-Berrozpe , Alex G. Segura , Ana M. Sánchez-Torres , Silvia Amoretti , Eloi Giné-Servén , Eduard Vieta , Gisela Mezquida , Antonio Lobo , Ana Gonzalez-Pinto , Alvaro Andreu-Bernabeu , Alexandra Roldán , Maria Florencia Forte , Josefina Castro , Daniel Bergé , Natalia Rodríguez , Alejandro Ballesteros , Sergi Mas , Manuel J. Cuesta , Miquel Bernardo , PEPs group
{"title":"Interrelationships between polygenic risk scores, cognition, symptoms, and functioning in first-episode psychosis: A network analysis approach","authors":"Gustavo J. Gil-Berrozpe , Alex G. Segura , Ana M. Sánchez-Torres , Silvia Amoretti , Eloi Giné-Servén , Eduard Vieta , Gisela Mezquida , Antonio Lobo , Ana Gonzalez-Pinto , Alvaro Andreu-Bernabeu , Alexandra Roldán , Maria Florencia Forte , Josefina Castro , Daniel Bergé , Natalia Rodríguez , Alejandro Ballesteros , Sergi Mas , Manuel J. Cuesta , Miquel Bernardo , PEPs group","doi":"10.1016/j.euroneuro.2024.12.002","DOIUrl":"10.1016/j.euroneuro.2024.12.002","url":null,"abstract":"<div><div>Psychopathological manifestations and cognitive impairments are core features of psychotic disorders. Polygenic risk scores (PRS) offer insights into the relationships between genetic vulnerability, symptomatology, and cognitive impairments. This study used a network analysis to explore the connections between PRS, cognition, psychopathology, and overall functional outcomes in individuals experiencing a first episode of psychosis (FEP). The study sample comprised 132 patients with FEP. Genetic data were used to construct PRS for mental disorders and cognitive traits via PRS-continuous shrinkage. We conducted comprehensive clinical and neuropsychological assessments at 2 months post-diagnosis and again at a 2-year follow-up. A network analysis was performed to generate two distinct networks and their centrality indices, encompassing 19 variables across domains such as symptoms, cognition, functioning, and PRS. Variables were grouped within related domains, and stronger relationships were observed within domains than between them. PRS for schizophrenia showed weak negative associations with attention, working memory, and verbal memory, while PRS for cognitive performance showed weak positive associations with attention. Negative symptoms were negatively associated with functioning and verbal memory at both the 2-month and 2-year assessments, as well as with social cognition at 2 years. Poor functioning was moderately related to greater severity of Positive and Negative Syndrome Scale dimensions. This study identified pathways linking PRS, cognition, symptoms, and functioning, suggesting that genetic risk may serve as a marker of vulnerability and disorder progression. The findings also highlight the importance of considering genetic predispositions alongside clinical and cognitive factors to better understand the heterogeneity of psychotic disorders.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"92 ","pages":"Pages 52-61"},"PeriodicalIF":6.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893342","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}