International Journal of Neuropsychopharmacology最新文献

{"title":"Genetic predispositions for anxiety disorders and major depressive disorder affect current dietary habits in older patients with lifestyle-related diseases.","authors":"Kazutaka Ohi, Daisuke Nishizawa, Daisuke Fujikane, Junko Hasegawa, Naomi Sato, Fumihiko Tanioka, Haruhiko Sugimura, Kazutaka Ikeda, Toshiki Shioiri","doi":"10.1093/ijnp/pyag014","DOIUrl":"10.1093/ijnp/pyag014","url":null,"abstract":"<p><strong>Background: </strong>Dietary intake is critical for the prevention and management of physical and mental disorders and may also be influenced by genetic predispositions for anxiety disorders and major depressive disorder (MDD). This study examined the effects of polygenic risk scores (PRSs) for anxiety disorders and MDD on current dietary intake in older patients with lifestyle-related diseases.</p><p><strong>Methods: </strong>Current dietary intake was assessed across 8 categories: miso soup, Japanese tea, green and yellow vegetables, light-colored vegetables, fruits, pickles, meats, and soybeans in 730 older outpatients diagnosed with or suspected of having lifestyle-related diseases, such as hypertension, diabetes mellitus, and cancer, at Iwata City Hospital, Shizuoka, Japan, during the recruitment period from 2003 to 2008. Polygenic risk scores for anxiety disorders and MDD were calculated using large-scale genome-wide association studies datasets, and their correlations with dietary intake patterns in these patients were investigated. Furthermore, genetic correlations between these disorders and specific dietary intake were explored in an independent general cohort from the UK Biobank.</p><p><strong>Results: </strong>Higher PRSs for anxiety disorders were significantly correlated with increased fruit intake (R2 = 0.010, P = 2.62 × 10-3) in these patients. Conversely, higher PRSs for MDD were nominally correlated with decreased intake of fruits (R2 = 0.0056, P = .021), Japanese tea (R2 = 0.0069, P = .014), green vegetables (R2 = 0.0076, P = 7.82 × 10-3), light-colored vegetables (R2 = 0.0049, P = .029), and soybeans (R2 = 0.0054, P = .025) and with increased intake of meats (R2 = 0.0082, P = 8.02 × 10-3). In contrast, in the independent general cohort, both disorders were commonly genetically correlated with decreased fruit intake (anxiety disorders: rg = -0.10, P = 2.10 × 10-3; MDD: rg = -0.17, P = 2.01 × 10-9).</p><p><strong>Conclusions: </strong>Our findings suggest that genetic factors related to anxiety disorders may shape dietary habits, potentially influencing compensatory healthy dietary behaviors in response to anxiety and worry related to physical health issues. Significance statement Genetic predispositions for anxiety disorders may contribute to compensatory healthy dietary behaviors in response to physical health-related anxiety, whereas those for major depressive disorder (MDD) may be related to unhealthy eating patterns in patients with lifestyle-related diseases. Genetic factors for anxiety disorders and MDD distinctly influence dietary behaviors.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13076931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147494027","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}

{"title":"Responsible artificial intelligence integration framework for psychiatric guidelines.","authors":"Shlomo Mendlovic, Iryna Frankova, Eric Vermetten, Danuta Wasserman, Thomas G Schulze, Peter Falkai, Konstantinos N Fountoulakis, Kristina Adorjan, Hiroyuki Uchida, Eyal Fruchter, Gabriella Gobbi, Joseph Zohar","doi":"10.1093/ijnp/pyag010","DOIUrl":"10.1093/ijnp/pyag010","url":null,"abstract":"<p><p>Artificial intelligence (AI) is reshaping medicine, promising advances in diagnosis, monitoring, and treatment, and psychiatry will be no exception. Yet the field remains fragmented: ethical guidelines, technical standards, and clinical workflows have evolved in parallel, creating uncertainty about how to integrate AI safely and meaningfully into psychiatric care. Existing frameworks often address isolated domains (explainability, data protection, or harm prevention [HP]) without providing a coherent structure that connects them to everyday clinical realities. This article introduces a global framework for the responsible integration of AI in psychiatry, built on 4 non-negotiable system capabilities: Explainable AI to ensure transparency and trust; Shared Decision-Making to protect patient autonomy; Electronic Health Record integration to secure continuity and accountability; and HP to embed multilayered safety controls. Together, these pillars define a responsibility-by-design approach that aligns technological development with psychiatry's ethical foundations. The framework offers clinicians, policymakers, and developers a roadmap for aligning innovation with human values and measurable improvements in clinical outcomes. By translating ethical commitments into auditable, non-negotiable system capabilities, it establishes a concrete foundation for regulatory oversight, guideline endorsement, and responsible AI deployment in psychiatry.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":"29 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770927","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}

{"title":"Functional inputs to the subgenual cingulate cortex differentiate levels of depressive symptom severity in neurotypical young adults: granger causality and clustering analyses.","authors":"Huey-Ting Li, Yu Chen, Shefali Chaudhary, Jaime S Ide, Chiang-Shan R Li","doi":"10.1093/ijnp/pyag005","DOIUrl":"10.1093/ijnp/pyag005","url":null,"abstract":"<p><strong>Introduction: </strong>Extant research has implicated functional connectivity of the subgenual anterior cingulate cortex (sgACC) in major depressive disorders or depressive traits in neurotypical populations. However, prior studies have not distinguished the inputs and outputs of the sgACC, and the \"diagnostic\" accuracy of these connectivity metrics remains elusive.</p><p><strong>Methods: </strong>Here, we analyzed data of 890 neurotypical young adults (459 women, age 22-35) from the Human Connectome Project using Granger causality analyses (GCA) with the sgACC as the seed and 268 regions of interest from the Shen's atlas as targets. Depressive and other comorbid symptoms were assessed using the Adult Self Report. Individual connectivities were assessed with an F test and group results were evaluated with a binomial test, both at a corrected threshold.</p><p><strong>Results: </strong>We identified brain regions with significant inputs to and outputs from the sgACC. Clustering analyses of Granger causality inputs, but not Granger causality outputs or resting state connectivity features revealed distinct subject clusters, effectively distinguishing individuals with different levels of depressive symptom severity and those with comorbidities. Specifically, weaker projections from the fronto-parietal and orbitofrontal cortices, anterior insula, temporal cortices, and cerebellum to the sgACC characterized five clusters with low to high scores of depression as well as comorbid internalizing and externalizing problems. Machine learning using a logistic classifier with the significant \"GCA-in\" features and 5-fold cross-validation achieved 87% accuracy in distinguishing subject clusters, including those with high vs. low depressive symptom severity levels.</p><p><strong>Discussion: </strong>These new findings specify the functional inputs and outputs of the sgACC and highlight an outsized role of sgACC inputs in distinguishing individuals' depressive symptom severity in a neurotypical population.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12962302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149659","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}

{"title":"Conceptual and pragmatic clinical implications of dichotomizing psychotropics as targeting physiology-physiomodal and pathology-pathomodal.","authors":"Michael Berk, Stephen M Stahl, Lakshmi Yatham, Janardhanan C Narayanaswamy, Seetal Dodd","doi":"10.1093/ijnp/pyag006","DOIUrl":"10.1093/ijnp/pyag006","url":null,"abstract":"<p><p>Conventional antidepressant, antipsychotics and mood stabilizing drugs share several characteristics. Firstly, they have a slow onset of action with benefits accruing late that is broadly mediated by long term homeostatic processes. Response generally predicts long term maintenance effects. They have little or no effect on the mental state of healthy individuals and can be conceptualized as targeting elements of pathophysiology. We can term them pathomodal. In contrast, psychotropic agents that are repurposed recreational drugs also share several effects. They have a rapid effect on mood states or perception and risk withdrawal symptoms that are generally the phenomenological mirror image of their acute effects and hence risks accrue late. Notwithstanding some heterogeneity, long term benefits are less clear than acute effects. Lastly, their effects are evident in all people who take them, and they can therefore be conceptualized as targeting elements of physiology. We can term them physiomodal. This categorization has several implications for both research design and clinical care.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12981678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146201545","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}

{"title":"Auricular transcutaneous vagus nerve stimulation stabilizes event segmentation through modulation of working memory representations.","authors":"Xianzhen Zhou, Foroogh Ghorbani, Veit Roessner, Bernhard Hommel, Astrid Prochnow, Christian Beste","doi":"10.1093/ijnp/pyag002","DOIUrl":"10.1093/ijnp/pyag002","url":null,"abstract":"<p><strong>Background: </strong>Segmenting continuous experience into discrete units-event segmentation-is fundamental for situational awareness and adaptive action. Based on Event Segmentation Theory, we used auricular transcutaneous vagus nerve stimulation (atVNS) to test whether the control of event segmentation is moderated by norepinephrine and/or GABAergic systems.</p><p><strong>Methods: </strong>Healthy adults (N = 40) completed a double-blind, counterbalanced experiment in which they watched a narrative movie and indicated perceived event boundaries under active atVNS and sham stimulation while the electroencephalogram (EEG) was recorded. Multivariate pattern analysis (MVPA) quantified the decodability of boundary interval (BI) vs no-boundary interval (NBI), and EEG source reconstruction assessed cortical activation.</p><p><strong>Results: </strong>Relative to sham, active atVNS reduced the likelihood of segmentation. Converging neurophysiological evidence mirrored this behavioral effect: MVPA revealed lower decoding accuracy for BI and NBI, indicating less distinct neural representational patterns. Source reconstruction showed reduced activation in the prefrontal cortex, a region involved in working memory.</p><p><strong>Conclusions: </strong>Across behavioral and neural measures, atVNS stabilized ongoing event representation and restricted the updating of the current event working model, consistent with a GABAergic modulation of event segmentation. These findings extend prior work linking atVNS to working memory gating and demonstrate its impact on an ecologically relevant cognitive process-event segmentation. Significance Statement This study tests whether 2 neuromodulators-norepinephrine (NE) and GABA-causally change how people divide continuous experience into meaningful events-a process called event segmentation. We used auricular vagus nerve stimulation (atVNS) to nudge these systems and compared active stimulation with a sham control. Compared to sham, active atVNS reduced the probability of setting event boundaries. In parallel, the brain activity patterns before the moments of segmenting were less distinct from the no-boundary period than in the sham condition, with lower activity in prefrontal regions. Together, these converging behavioral and neural findings indicate that atVNS stabilizes ongoing event representations and restricts the updating of the current event working model, a pattern that more parsimoniously supports a GABAergic inhibitory gating account over an NE arousal account of event segmentation.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12911928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029453","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}

{"title":"Exploring the association between sweet liking and treatment response to naltrexone in patients with alcohol use disorder.","authors":"Min-Chiao Chang, Chun-Hsin Chen, Shih-Chun Meng, Shu-Hao Shu, Hu-Ming Chang, Ming-Chyi Huang","doi":"10.1093/ijnp/pyag004","DOIUrl":"10.1093/ijnp/pyag004","url":null,"abstract":"<p><strong>Background: </strong>Response to naltrexone varies among individuals with alcohol use disorder (AUD). Studies in Western populations have linked the sweet-liking (SL) phenotype, reflecting an individual's hedonic response to sweet taste, to improved outcomes with naltrexone. However, cultural and ethnic variations in SL raise questions about the generalizability of this association. This exploratory investigation examined the relationship between SL phenotype and naltrexone treatment outcomes in Taiwanese patients with AUD.</p><p><strong>Methods: </strong>Patients with DSM-5-defined severe AUD who had completed alcohol withdrawal were enrolled in an 8-week open-label naltrexone trial. Participants completed a sweet taste test and were categorized into SL or sweet-disliking (SDL) groups. Outcomes included alcohol consumption (drinking days per week, heavy drinking days per week, drinks per drinking day, abstinent days), alcohol craving, and depression and anxiety severity. Generalized estimating equations were used to assess the effects of time, group, and their interaction.</p><p><strong>Results: </strong>Ninety-one patients were enrolled (SL: n = 44; SDL: n = 47). Baseline characteristics were comparable between groups, except for smoking-related variables. After adjusting for smoking, both groups showed improvements in alcohol use and psychological measures over time. A significant group-by-time interaction was found for drinks per drinking day, with the SL group showing more favorable outcomes than the SDL group (P = .03).</p><p><strong>Conclusions: </strong>This is the first exploratory investigation in Asians to assess SL phenotype in relation to naltrexone response in AUD patients. The SL phenotype was associated with reduced alcohol consumption over 8 weeks of naltrexone treatment, supporting SL phenotype as a potential biomarker for personalized AUD treatment.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12931563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029448","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}

{"title":"Diazepam modulates anterior cingulate glutamate levels in people at clinical high-risk for psychosis.","authors":"Amanda Kiemes, Nicholas R Livingston, Paulina B Lukow, Samuel Knight, Luke Jelen, Thomas Reilly, Aikaterini Dima, Maria A Nettis, David J Lythgoe, Cecilia Casetta, Alice Egerton, Thomas Spencer, Andrea De Micheli, Paolo Fusar-Poli, Anthony A Grace, Steven C R Williams, Philip McGuire, Cathy Davies, James M Stone, Gemma Modinos","doi":"10.1093/ijnp/pyaf078","DOIUrl":"10.1093/ijnp/pyaf078","url":null,"abstract":"<p><strong>Objective: </strong>Preclinical evidence suggests that modulating neural excitation through administration of diazepam, a positive allosteric modulator of GABAA receptors, can prevent the emergence of behavioral and neurobiological alterations relevant to psychosis in adulthood.</p><p><strong>Design and participants: </strong>Here, we examine this neurochemical mechanism in individuals at clinical high risk for psychosis in a randomized, double-blind, placebo-controlled crossover study. Twenty-four individuals (15 female and 9 male) aged 18-35 were scanned twice using proton magnetic resonance spectroscopy to measure anterior cingulate cortex Glx (glutamate and glutamine) levels, once after a single dose of diazepam (5 mg) and once after placebo.</p><p><strong>Results: </strong>Mixed-effects model analyses revealed that diazepam reduced anterior cingulate cortex Glx levels compared to placebo (t(20.8) = -2.14, P = .04). The effect of diazepam on Glx levels was greater in older individuals at clinical high risk for psychosis (t(12) = -4.36, P = .001).</p><p><strong>Conclusion: </strong>These findings suggest that pharmacological modulation of GABAA receptors can alter Glx changes in and support a novel therapeutic mechanism of benefit for individuals at clinical high risk of psychosis.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12874875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145742495","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}

{"title":"The efficacy of nutritional phytochemical compounds in improving cognition.","authors":"Alexander Marsh, Darren Quelch, Marion Mackonochie, Momna Hejmadi, Vivien Rolfe","doi":"10.1093/ijnp/pyag003","DOIUrl":"10.1093/ijnp/pyag003","url":null,"abstract":"<p><p>The incidence of cognitive disorders is rising, and medications to address cognitive impairments are limited. Phytochemical compounds have had some success in improving cognitive outcomes in preclinical studies. However, the evidence surrounding the implementation of these compounds routinely in (1) improving cognition in healthy individuals or (2) as prophylaxis and treatment against the cognitive sequelae of neurological insult has not been collated. To address this, the evidence base surrounding the impact of phytochemical agents on cognitive function in healthy individuals was reviewed. Web of Science, PubMed, PsycNET, and AYUSH Research Portal were systematically searched for double-blind and single-blind randomized controlled trials assessing the efficacy of Curcuma longa, Bacopa monnieri, Ocimum tenuiflorum, Camellia sinensis, Centella asiatica, Ganoderma lingzhi, and Rosmarinus officinalis on cognitive function. Seven studies met inclusion. These examined the impact of B. monnieri, O. tenuiflorum, or C. sinensis. There was no benefit of B. monnieri or C. sinensis on processing speed, attention, working memory, language, psychomotor function, or overall cognitive performance. O. tenuiflorum improved reaction times on an executive function task. Further, more methodologically robust trials of longer duration are recommended to investigate the efficacy of phytochemical supplementation for cognition.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12935010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029483","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}

{"title":"Pharmacokinetic and pharmacodynamic results from a randomized controlled study with the growth hormone secretagogue receptor blocker PF-5190457 in recently abstinent patients with alcohol use disorder.","authors":"Ryan E Tyler, Rabea K Pfaff, Raja Muhammad Naseer Khan, Anna Loften, Ryan Zurick, Yi Zeng, Oluwatobi T Arisa, Charlotte Harvey, Fatemeh Akhlaghi, William D Figg, Mehdi Farokhnia, Lorenzo Leggio","doi":"10.1093/ijnp/pyaf081","DOIUrl":"10.1093/ijnp/pyaf081","url":null,"abstract":"<p><strong>Objective: </strong>Ghrelin and liver-expressed antimicrobial peptide 2 (LEAP2) act via the growth hormone secretagogue receptor (GHSR), which modulates feeding, alcohol use, and endocrine and immune system function. The GHSR blocker PF-5190457 has potential as a novel pharmacotherapy for alcohol use disorder (AUD). This study aimed to characterize the effects of PF-5190457 on endocrine and immune markers in individuals with AUD.</p><p><strong>Methods: </strong>Pre-planned analyses used data from a randomized, double-blind, placebo-controlled, crossover human laboratory study in recently abstinent inpatients with AUD (N = 29; 8 females). Participants received PF-5190457 (100 mg twice daily) or matched placebo for 5+ days, separated by 2+ washout days. Blood was collected daily prior to dosing (T1). On days 4+, behavioral testing occurred post-dosing, followed by an additional blood collection ~2 hours post dosing (T2). Pharmacokinetic (PK: PF-5190457 and its active metabolite PF-6870961) and pharmacodynamic (PD: comprehensive panel of endocrine and immune markers) parameters were assessed over the course of dosing days. Additional exploratory analyses examined relationships between PK, PD, and behavioral measures.</p><p><strong>Results: </strong>PF-5190457 and PF-6870961 concentrations peaked at T2 and were elevated at T1 under drug vs placebo. LEAP2 levels were reduced under drug vs placebo but rebounded on the first washout day. PF-5190457 dramatically reduced growth hormone (GH) at T2, followed by an elevation of GH at T1 the following day. No other endocrine or immune markers differed significantly between drug and placebo. GH at T1 negatively correlated with the number of calories selected during a cafeteria-like virtual reality buffet experiment under drug, but not placebo conditions.</p><p><strong>Conclusions: </strong>GHSR blockade with repeated dosing of PF-5190457 changed LEAP2 and GH concentrations but produced overall negligible effects on the endocrine and immune systems. These results further characterize the ghrelin system in AUD and its potential as a therapeutic target.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT02707055; registered November 3, 2016.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12866918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145862237","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}

{"title":"Identification of antidepressant response-related changes to DNA methylation and gene expression.","authors":"Laura M Fiori, Corina Nagy, Gustavo Turecki","doi":"10.1093/ijnp/pyag001","DOIUrl":"10.1093/ijnp/pyag001","url":null,"abstract":"<p><strong>Background: </strong>Major depressive disorder (MDD) is a debilitating condition that is commonly treated with antidepressants. However, many people do not respond to treatment, and the molecular mechanisms underlying antidepressant response remain poorly understood. Baseline DNA methylation differences have been observed between individuals who respond to treatment compared to those who do not respond; however, little is known regarding DNA methylation changes that occur during treatment or how they may relate to clinical response.</p><p><strong>Methods: </strong>We assessed peripheral levels of DNA methylation and gene expression at baseline and after 8 weeks of treatment in 154 individuals with MDD who were treated with escitalopram or desvenlafaxine, using the Infinium MethylationEPIC Beadchip and RNA sequencing. We identified methylation sites whose levels changed over time in relation to changes in depressive symptoms, as well as corresponding changes to gene expression levels after 8 weeks of treatment.</p><p><strong>Results: </strong>We identified 2 sites, in sodium voltage-gated channel alpha subunit 7 and IQ Motif and ankyrin repeat containing 1, whose methylation changes over time were correlated with changes in depressive symptoms at the epigenome-wide level. Gene ontology analyses of genes displaying response-related methylation changes highlighted several processes previously implicated in depression, including small GTPase-related signaling and the Wnt signaling pathway. Additionally, we identified methylation sites in 10 genes that displayed significant changes in methylation over time in relation to improvement of depressive symptoms, whose expression levels at week 8 were correlated with the level of depressive symptoms, and for which methylation levels were functionally related to gene expression.</p><p><strong>Conclusions: </strong>Antidepressant treatment response is associated with changes in peripheral DNA methylation over time, as well as corresponding alterations in gene expression. Significance Statement Major depressive disorder (MDD) is commonly treated with antidepressants; however, many people do not respond to treatment. In order to better understand the molecular changes that occur during antidepressant treatment, we analyzed DNA methylation and gene expression in the blood of 154 individuals with MDD who were treated with escitalopram or desvenlafaxine. We found 10 methylation sites within 10 genes whose methylation levels changed over time in relation to clinical improvement, and whose levels of expression were related to both methylation and antidepressant response.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12903956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146062882","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}