International Journal of Neuropsychopharmacology最新文献

{"title":"Hexahydrocannabinol (HHC): pharmacokinetics, systemic toxicity, and acute behavioural effects in Wistar rats.","authors":"Klára Šíchová, Barbara Mallarino, Lucie Janečková, Petr Palivec, Magdaléna Vágnerová, Čestmír Vejmola, Marek Nikolič, Lucie Ladislavová, Kristýna Mazochová, Pavel Ryšánek, Martin Šíma, Adam Šafanda, Bui Quang Hiep, Isis Rita Anzel Koutrouli, Martin Kuchař, Tomáš Páleníček","doi":"10.1093/ijnp/pyaf041","DOIUrl":"https://doi.org/10.1093/ijnp/pyaf041","url":null,"abstract":"<p><strong>Background: </strong>Hexahydrocannabinol (HHC) is a new psychoactive substance known for its mind-altering effects and temporary legal status. It is widely used in parts of the EU and UK as a legal alternative to ∆9-tetrahydrocannabinol (∆9-THC), yet little research has explored its effects and safety. This study examined how HHC is processed in the body, its toxicity, and its impact on behaviour in male Wistar rats.</p><p><strong>Methods: </strong>A 1:1 mixture of (9R)-HHC and (9S)-HHC was administered via intragastric gavage at doses of 1, 5, and 10 mg/kg. Behavioural effects were assessed using the Open Field test and the Prepulse Inhibition of Acoustic Startle Response.</p><p><strong>Results: </strong>Two hours after the highest dose (10 mg/kg), peak concentrations of HHC were detected in blood and brain tissue. The OECD 423 toxicity test classified HHC as a Category 4 substance, estimating a lethal dose of 1000 mg/kg. Compared to controls (administered by sunflower oil), 10 mg/kg HHC reduced movement, increased anxiety, and impaired sensory processing.</p><p><strong>Conclusions: </strong>Overall, HHC crosses the bloodbrain barrier, exhibits mild toxicity, and induces behavioural effects similar to THC. Its dose-dependent anxiogenic properties and impact on information processing highlight the importance of the appropriate dosing in any potential therapeutic use.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608315","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":"Illicit Substance Exposure in Pregnancy and Infant Mortality Risk: A Nationwide Taiwan Study.","authors":"Chun Lin, Mu-Hong Chen, Wei-Szu Lin, Shiow-Ing Wu, Yuan-Chun Liao, Yu-Hsuan Lin, Ching-Heng Lin","doi":"10.1093/ijnp/pyaf046","DOIUrl":"https://doi.org/10.1093/ijnp/pyaf046","url":null,"abstract":"<p><strong>Background: </strong>To investigate the association between prenatal illicit substance exposure and infant mortality, addressing the unclear links between specific and multiple substances and increased mortality.</p><p><strong>Materials and methods: </strong>This 16-year retrospective cohort study used Taiwan's National Health Insurance Research Database, the Taiwan Maternal and Child Health dataset, and the Integrated Illegal Drug Database, including 1 937 301 pregnant women who delivered from 2004 to 2019. Among them, 11 477 used illicit drugs during pregnancy, with a matched control group of 45 908 non-users based on maternal age, income, and childbirth year. Of the drug users, 26.9% used multiple substances, primarily methamphetamine and opioids. The primary outcome was all-cause mortality within the first year of life, with analyses stratified by substance type and timing of exposure. Cox regression models were employed to assess mortality, with results presented as adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). A p-value below 0.05 was considered statistically significant.</p><p><strong>Results: </strong>Infant from illicit drug-exposed mothers had a higher all-cause mortality rate (0.7%) compared to the control group (0.4%). Polysubstance use, which in most cases involved methamphetamine or opioids, was significantly associated with increased mortality risk (aHR 1.53, 95% CI 1.00-2.34), whereas no single substance alone-including methamphetamine (aHR 1.38, 95% CI 0.87-2.19) or opioids (aHR 1.63, 95% CI 0.98-2.72)-showed a statistically significant association. MDMA, ketamine, and cannabis were likewise not linked to increased mortality. Mortality risk increased with drug exposure during pregnancy, with borderline significant associations in the first (aHR 1.82, 95% CI 0.98-3.37) and second trimesters (aHR 1.96, 95% CI 0.99-3.86), suggesting heightened vulnerability during early to mid-gestation.</p><p><strong>Conclusion: </strong>One-year infant mortality is elevated among women with illicit substance use, with a higher proportion of deaths attributed to preterm birth and hypoxic events. The highest mortality risk was observed among those with polysubstance use. The findings underscore a dire public health issue, associating prenatal illicit substance exposure, notably multiple substances use, opioids, and methamphetamine, with heightened infant mortality rates, calling for targeted interventions and further research.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591199","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":"Efficacy and Safety of the Muscarinic Receptor Agonist KarXT (Xanomeline-Trospium) in Schizophrenia: A Systematic Review, Meta-Analysis and Bayesian Sensitivity Analysis.","authors":"Nikhil Sharma, Mahalaqua Nazli Khatib, R Roopashree, Mandeep Kaur, Manish Srivastava, Amit Barwal, G V Siva Prasad, Pranchal Rajput, Vinamra Mittal, Muhammed Shabil, Amit Kumar, Ganesh Bushi, Rachana Mehta, Prakasini Satapathy, Sanjit Sah","doi":"10.1093/ijnp/pyaf045","DOIUrl":"https://doi.org/10.1093/ijnp/pyaf045","url":null,"abstract":"<p><strong>Background: </strong>Schizophrenia significantly impacts global health, with existing treatments primarily focusing on positive symptoms and often causing considerable side effects. KarXT, a novel treatment combining xanomeline, a muscarinic M1/M4 receptor agonist, and trospium, targets a broader range of symptoms including negative and cognitive deficits, potentially with fewer side effects. This systematic review and meta-analysis evaluates the efficacy and safety of KarXT in treating schizophrenia, assessing symptom reduction and safety profiles compared to placebo.</p><p><strong>Methods: </strong>We searched PubMed, Embase, and Web of Science up to November 10, 2024, for randomized controlled trials (RCTs) assessing the efficacy and safety of KarXT in schizophrenia. Data were pooled using a random-effects model, assessing outcomes like Positive and Negative Syndrome Scale (PANSS) scores and incidence of treatment-emergent adverse events (TEAEs). R software (Version 4.4.) was used for meta-analysis.</p><p><strong>Results: </strong>Three RCTs involving 674 participants were included. KarXT significantly reduced total PANSS scores of mean difference (MD) -9.707 (95% CI: -12.329 to -7.085), with notable improvements in both negative (MD = -1.623; 95% CI: -2.461 to -0.785) and positive symptom subscales (MD = -3.213; 95% CI: -4.033 to -2.393). The treatment was associated with a higher incidence of TEAEs, predominantly constipation (RR: 2.77; 95% CI: 1.72-4.45) and nausea (RR: 4.87; 95% CI: 2.73-8.68) compared to placebo. Bayesian meta-analysis confirmed the results.</p><p><strong>Conclusion: </strong>KarXT offers significant improvements in both negative and positive symptoms of schizophrenia with a manageable safety profile. Its potential as a transformative treatment for schizophrenia highlights the need for further research to confirm these findings and to fully understand its long-term efficacy and safety.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575424","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":"Sleep Deprivation Engages the Orexin/Hypocretin System to Regulate Food Reward Seeking.","authors":"Ana L Almeida Rojo, Tyler R Barnhardt, Thien Quy Pham, Benjamin Heim, Li Cai, George C Tseng, Yanhua H Huang","doi":"10.1093/ijnp/pyaf047","DOIUrl":"https://doi.org/10.1093/ijnp/pyaf047","url":null,"abstract":"<p><strong>Background: </strong>Inadequate sleep is a prevalent health issue in modern society, with unintended consequences in dysregulation of the reward system. For example, acute sleep deprivation (SD) in humans increases craving for and intake of calorie-dense foods, which lead to further health concerns. The circuit and molecular mechanisms underlying sleep-regulation of reward, however, remain poorly understood. The hypothalamic orexin (also called hypocretin) system is phylogenetically conserved to dually regulate sleep/arousal and reward. Here, we tested the hypothesis that acute SD engages the orexin system to modulate food reward-seeking.</p><p><strong>Methods: </strong>We used sucrose self-administration model in male and female mice to test how acute SD by gentle handling regulates sucrose reward seeking. We then administered specific orexin receptor antagonists systemically (Ox1R antagonist SB-334867 10 mg/kg or Ox2R antagonist seltorexant 10 mg/kg) or in selective brain regions (up to 100 μM) to assess their respective roles.</p><p><strong>Results: </strong>We found that under normal sleep conditions the orexin system is minimally involved in sucrose reward seeking. By contrast, SD increased sucrose self-administration in both male and female mice, and preferentially engaged orexin receptor 2 (Ox2R) signaling in females to mediate this effect. Moreover, in nucleus accumbens (NAc) or paraventricular nucleus of hypothalamus (PVN), key reward regulatory regions enriched in Ox2Rs, blocking Ox2R signaling in each individually did not counteract the SD effects in females. Finally, c-Fos analysis showed highly correlative activity levels between diverse cortical and subcortical regions during sucrose self-administration in females, revealing differential network engagement following SD, which was partially restored by systemic Ox2R antagonism following SD in females.</p><p><strong>Conclusion: </strong>These results highlight Ox2R signaling in counteracting the acute SD effects on food reward seeking in females.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560050","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":"Adjunctive Brexpiprazole in Patients With Unresolved Symptoms of Depression on Antidepressant Treatment Who are Early in the Disease Course: Post Hoc Analysis of Randomized Controlled Trials.","authors":"Shivani Kapadia, Zhen Zhang, Csilla Csoboth, Mehul Patel, Michael E Thase, George I Papakostas","doi":"10.1093/ijnp/pyaf050","DOIUrl":"https://doi.org/10.1093/ijnp/pyaf050","url":null,"abstract":"<p><strong>Background: </strong>Treatment for major depressive disorder (MDD) should be optimized as early as possible in the disease course to minimize patient suffering and maximize clinical benefits. This post hoc analysis aimed to investigate the efficacy and safety of adjunctive brexpiprazole in patients who were earlier and later in the disease course.</p><p><strong>Methods: </strong>Data were pooled from three 6-week, randomized, double-blind, placebo-controlled trials of adjunctive brexpiprazole in adult outpatients with MDD and inadequate response to antidepressant treatment. \"Earlier\" and \"later\" disease course subgroups were defined based on proxies of median age, age at diagnosis, number of episodes, episode duration, and number of prior antidepressants. Efficacy was assessed by changes in Montgomery-Åsberg Depression Rating Scale (MADRS) total score, and safety by treatment-emergent adverse events.</p><p><strong>Results: </strong>Greater improvement in MADRS total score at Week 6 (p<.05) was observed for antidepressant + brexpiprazole 2-3 mg/day (n = 579) versus antidepressant + placebo (n = 583) in all subgroups representing earlier and later disease, with treatment effects ranging from -1.79 to -2.92 points. The incidence of treatment-emergent adverse events across subgroups was 53.1-67.2% for antidepressant + brexpiprazole 2-3 mg/day and 43.0-51.8% for antidepressant + placebo, with no consistent differences in earlier or later disease.</p><p><strong>Conclusions: </strong>Adjunctive brexpiprazole improved depressive symptoms earlier in the disease course, when benefits to patients and healthcare systems can be maximized. Adjunctive brexpiprazole also improved depressive symptoms later in the disease course; there was no advantage of delaying brexpiprazole treatment.</p><p><strong>Trial registration: </strong>Post hoc analysis of NCT01360645, NCT01360632, NCT02196506 (ClinicalTrials.gov).</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553469","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":"The Role of Affective States in Computational Psychiatry.","authors":"David Benrimoh, Ryan Smith, Andreea O Diaconescu, Timothy Friesen, Sara Jalali, Nace Mikus, Laura Gschwandtner, Jay Gandhi, Guillermo Horga, Albert Powers","doi":"10.1093/ijnp/pyaf049","DOIUrl":"https://doi.org/10.1093/ijnp/pyaf049","url":null,"abstract":"<p><p>Studying psychiatric illness has often been limited by difficulties in connecting symptoms and behavior to neurobiology. Computational psychiatry approaches promise to bridge this gap by providing formal accounts of the latent information processing changes that underlie the development and maintenance of psychiatric phenomena. Models based on these theories generate individual-level parameter estimates which can then be tested for relationships to neurobiology. In this review, we explore computational modelling approaches to one key aspect of health and illness: affect. We discuss strengths and limitations of key approaches to modelling affect, with a focus on reinforcement learning, active inference, the hierarchical gaussian filter, and drift-diffusion models. We find that, in this literature, affect is an important source of modulation in decision making, and has a bidirectional influence on how individuals infer both internal and external states. Highlighting the potential role of affect in information processing changes underlying symptom development, we extend an existing model of psychosis, where affective changes are influenced by increasing cortical noise and consequent increases in either perceived environmental instability or expected noise in sensory input, becoming part of a self-reinforcing process generating negatively valenced, over-weighted priors underlying positive symptom development. We then provide testable predictions from this model at computational, neurobiological, and phenomenological levels of description.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540104","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":"Association between anhedonia severity and clinical, humanistic, and economic outcomes among US adults with major depressive disorder.","authors":"Hrishikesh Kale, M Janelle Cambron-Mellott, Tiina Drissen, Kacper Perkowski, Kristen King-Concialdi, Manish K Jha","doi":"10.1093/ijnp/pyaf048","DOIUrl":"https://doi.org/10.1093/ijnp/pyaf048","url":null,"abstract":"<p><strong>Background: </strong>Anhedonia is a key symptom and part of the diagnostic criterion of major depressive disorder (MDD). However, the relationship between anhedonia severity and the clinical, humanistic, and economic burden among patients with MDD is poorly understood.</p><p><strong>Methods: </strong>Adults diagnosed with depression were identified from the 2022 US National Health and Wellness Survey (NHWS). Participants with depression were recontacted to participate in an online cross-sectional survey to collect data on anhedonia, using the Snaith-Hamilton Pleasure Scale (SHAPS). Multivariable analyses assessed the association of SHAPS score with health-related outcomes, while controlling for age, sex, race, comorbidity burden, and insurance status. The SHAPS (score range: 14 to 56) assesses the ability to experience pleasure, with higher scores indicating greater levels of anhedonia.</p><p><strong>Results: </strong>Of the 8,270 NHWS respondents with depression who met inclusion criteria, 665 completed the recontact survey (mean age, 58.4 years; female, 78.3%). Mean SHAPS score was 25.4 (range, 14-47). After adjustments for covariates, higher SHAPS scores were significantly (all p <0.05) associated with higher levels of depression (β = 0.211) and anxiety (β = 0.126), poorer mental (β = -0.339) and physical health-related quality of life (β = -0.178), greater impairment while working [Rate Ratio (RR) = 1.02], and higher direct medical costs (RR = 1.02).</p><p><strong>Conclusions: </strong>In adults with depression, higher levels of anhedonia were associated with greater clinical, humanistic, and economic burden. These results highlight the need for targeted treatments to help patients with MDD with prominent anhedonia attain improved clinical, humanistic, and work productivity outcomes.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540102","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":"m6A Methylation: A Novel Key to Unlocking Mental Disorders.","authors":"Yinuo Wang, Xiaobing Li, Min Liu, Xiaoxu Xu, Yue Ma, Yang Luo, Yue Wang","doi":"10.1093/ijnp/pyaf044","DOIUrl":"https://doi.org/10.1093/ijnp/pyaf044","url":null,"abstract":"<p><p>More than 100 types of RNA modifications have been identified in mammalian cells, among which N6-methyladenosine (m6A) is the most prevalent. This reversible and dynamic modification involves methyltransferases, demethylases, and reader proteins. Aberrant expression of m6A-related regulatory proteins in the nervous system significantly impacts neuronal physiology, contributing to mental disorders such as depression, autism spectrum disorder, and schizophrenia. This review summarizes the role of m6A methylation in the pathogenesis of mental disorders and highlights its potential as a biomarker and therapeutic target, providing a comprehensive reference for future research and clinical interventions.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540103","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":"Involvement of a stress-responsive orbito-striatal projection in impulsive action in male rats.","authors":"Milena Girotti, Maisie G Boehmer-Cortez, Kathleen Tuite, David A Morilak","doi":"10.1093/ijnp/pyaf043","DOIUrl":"https://doi.org/10.1093/ijnp/pyaf043","url":null,"abstract":"<p><strong>Background: </strong>Motor impulsivity is a symptom shared by several psychiatric disorders. Stress exacerbates impulsivity, but the neurocircuits involved are unknown. We have shown that the orbitofrontal cortex (OFC) is activated during a rodent motor impulsivity task and that chronic unpredictable stress (CUS) increases premature responding. In this study we examine the role of the OFC projection to dorsomedial striatum (DMS) in motor control, and test whether this pathway mediates the effects of stress on impulsive action.</p><p><strong>Methods: </strong>Motor impulsivity was measured with the 1-choice serial reaction time test (1-CSRTT). To determine if OFC-DMS projections are involved in controlling impulsivity, we used pathway-specific chemogenetic manipulation during 1-CSRTT. We examined stress effects on OFC-DMS neuronal activation using Fos immunohistochemistry. To assess if stress increases impulsivity through OFC-DMS projections, we chemogenetically manipulated the pathway in stressed rats during behavior.</p><p><strong>Results: </strong>We found OFC-DMS projections inhibit premature responding in a well-mastered task. Stress attenuated OFC neuronal activation, including the OFC-DMS projection neurons, during behavior. However, selectively activating the projection in stressed rats was not sufficient to abolish the stress effects. Finally, the response to stress depended on baseline trait impulsivity. Rats with low trait impulsivity were more vulnerable to stress, and showed attenuated activation of OFC-DMS neurons but increased activation of other OFC cell populations.</p><p><strong>Conclusions: </strong>These results suggest the OFC-DMS pathway modulates impulsivity in concert with other OFC neuronal populations. Furthermore, stress effects are baseline-dependent and affect only low impulsivity rats, possibily by altering the balance of activation in functionally opposing neuronal populations.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505646","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":"Predicting Antidepressant Responsiveness in MDD patients via EEG Gamma-Band Dynamic Functional Connectivity in Response to Salient Auditory Stimuli.","authors":"Kang-Min Choi, Taegyeong Lee, Seung-Hwan Lee, Chang-Hwan Im","doi":"10.1093/ijnp/pyaf042","DOIUrl":"https://doi.org/10.1093/ijnp/pyaf042","url":null,"abstract":"<p><strong>Background: </strong>Heterogeneous pathophysiological characteristics in patients with major depressive disorder (MDD) lead to individually differentiated sensitivities to antidepressants. Based on the hypothesis that gamma-band dynamic fluctuations in cortical functional connectivity (FC) in response to salient stimuli are linked to pathophysiological characteristics, we conducted a classification analysis for antidepressant responsiveness prediction.</p><p><strong>Methods: </strong>Biosignals and psychological measures were acquired from 47 patients with MDD prior to treatment. After eight weeks of vortioxetine therapy, patients were divided into non-remitted MDD (nrMDD; aged 42.55±11.52 years; n = 20) and remitted MDD (rMDD; aged 47.22±11.59 years; n = 27) groups based on their depressive symptom reduction. Electroencephalography (EEG) signals were acquired during the duration-variant auditory mismatch negativity (MMN) paradigm. From the deviant condition, gamma-band weighted phase-lag index-based dynamic fluctuations were evaluated using a template generated from 21 demography-matched healthy control (HC, aged 43.81±14.10 years) data.</p><p><strong>Results: </strong>Using these dynamic FC (dFC) features, a machine-learning-based classification analysis was performed for nrMDD and rMDD. Using leave-one-out cross-validation, the linear discriminant analysis classifier achieved the best accuracy (82.98%) for classifying nrMDD and rMDD. Further simple effect analyses identified three core dFC features for nrMDD: (i) relatively intact time-dependent FC between the left frontal and right temporal regions; (ii) disrupted right frontoparietal FC; and (iii) disrupted left fronto-temporal FC. These dFC features commonly exhibit transient hyperconnections in patients with nrMDD.</p><p><strong>Conclusions: </strong>We demonstrated that gamma-band dynamic FC responses to salient stimuli could serve as potential biomarkers for antidepressant responsiveness prediction in patients with MDD.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511906","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}