Journal of Psychopharmacology最新文献

{"title":"GABA and Glx levels in cortico-subcortical networks predict catecholaminergic effects on response inhibition.","authors":"Anna Helin Koyun, Annett Werner, Paul Kuntke, Veit Roessner, Christian Beste, Ann-Kathrin Stock","doi":"10.1177/02698811251340893","DOIUrl":"10.1177/02698811251340893","url":null,"abstract":"<p><strong>Background: </strong>Cortico-subcortical networks play a fundamental role in cognitive control. Within these circuits, neurotransmitters such as gamma-aminobutyric acid (GABA), glutamate, and catecholamines crucially modulate response control and (motor) response inhibition. Despite the evident interrelation between these transmitter systems, the role of baseline GABA and glutamate-glutamine (Glx) levels in predicting/influencing catecholaminergic effects has remained rather unclear.</p><p><strong>Aims: </strong>Addressing this knowledge gap, we investigated the question how much (and which facets) of behavioral effects attributed to catecholamines are due to GABAergic and glutamatergic levels in control-relevant cortical networks.</p><p><strong>Methods: </strong>Using proton-magnetic resonance spectroscopy, we assessed baseline GABA+ and Glx levels within the striatum, the anterior cingulate cortex, and the (pre-)supplementary motor cortex ((pre-)SMA), and their predictive value for catecholaminergic modulation of response selection and inhibition performance. For this purpose, we administered low and high doses of methylphenidate (MPH) to healthy adults and examined whether baseline GABA+ and Glx were associated with dose-dependent MPH effects on response control.</p><p><strong>Results/outcomes: </strong>For the first time in a sample of healthy adults, we demonstrate that GABA+/Glx levels in cognitive control-relevant cortical areas are indicative of the magnitude of MPH-induced effects on response inhibition. Specifically, striatal GABA+/Glx levels predicted better response inhibition performance under the administration of low MPH doses. In contrast, (pre-)SMA GABA+/Glx levels were associated with high MPH dose-induced impairments of response inhibition performance.</p><p><strong>Conclusion/interpretation: </strong>The predictive relevance of GABA+/Glx levels for MPH dose-dependent effects on cognitive control processes provides valuable insights into the neural mechanisms underlying the previously reported heterogeneous MPH effects.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251340893"},"PeriodicalIF":4.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adolescent substance use trajectories are associated with nucleus accumbens functional connectivity.","authors":"Juliann B Purcell, Heather E Dark, Sylvie Mrug, Marc N Elliott, Susan Tortolero Emery, Mark A Schuster, David C Knight","doi":"10.1177/02698811251344691","DOIUrl":"10.1177/02698811251344691","url":null,"abstract":"<p><strong>Background: </strong>Adolescent substance use is associated with disrupted communication among brain regions underlying reward-driven behaviors (e.g., nucleus accumbens (NAcc)) and cognitive/emotional control (e.g., prefrontal cortex (PFC); medial temporal lobe), which may be linked to poor future outcomes (e.g., substance use disorder). However, the relationship functional brain connectivity has with trajectories of adolescent alcohol, tobacco, and cannabis use has received limited attention.</p><p><strong>Aims: </strong>Investigate relationships between adolescent substance use trajectories and young adult whole-brain NAcc resting-state functional connectivity (rsFC).</p><p><strong>Methods: </strong>Substance use was assessed at ages 11, 13, 16, and 19. Subsequently (age 20), a subset of participants (<i>N</i> = 299) completed a single neuroimaging session. Latent growth curve models estimated substance use trajectories that included the intercept (age 14 use), linear slope (progression), and quadratic slope (acceleration), which served as predictors in neuroimaging analyses.</p><p><strong>Hypotheses: </strong>Substance use trajectories representing greater age 14 usage, faster progression of use, and acceleration of use across adolescence would show stronger NAcc rsFC with regions implicated in cognitive/emotional control.</p><p><strong>Results: </strong>Age 14 use (alcohol, tobacco, and cannabis) was associated with NAcc rsFC with dorsolateral PFC, dorsomedial PFC, parahippocampal gyrus (PHG), hippocampus, and amygdala. Progression of use was associated with NAcc rsFC with dorsolateral PFC, dorsomedial PFC, ventrolateral PFC, PHG, and amygdala. Finally, acceleration of use was linked with NAcc rsFC with dorsolateral PFC, ventromedial PFC, PHG, and hippocampus.</p><p><strong>Conclusions: </strong>NAcc rsFC with several brain regions (e.g., PFC subregions) varied with adolescent substance use, which may represent common neural mechanisms linking adolescent substance use with common psychological outcomes.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251344691"},"PeriodicalIF":4.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional connectivity alterations of the pregenual anterior cingulate cortex by ketamine and the modulation by lamotrigine.","authors":"David Weigner, Marvin Sören Meiering, Anne Weigand, Luisa Carstens, Christian Keicher, Rita Hertrampf, Christian Beckmann, Maarten Mennes, Andreas Wunder, Matti Gärtner, Simone Grimm","doi":"10.1177/02698811251346705","DOIUrl":"https://doi.org/10.1177/02698811251346705","url":null,"abstract":"<p><strong>Background: </strong>Neuroimaging studies have linked the beneficial effects of subanaesthetic ketamine doses in psychiatric conditions characterized by chronic stress pathology (CSP) to altered functional connectivity (FC) within the pregenual anterior cingulate cortex (pgACC). Previous research indicates a potential role of glutamate concentration in FC changes; however, the precise relationship between glutamate release and increased FC remains unclear. Lamotrigine, a glutamate-release inhibitor, allows deeper exploration of this relationship. Additionally, CSP and treatment efficacy are closely associated with alterations in working memory (WM), necessitating the examination of FC during resting state and WM tasks.</p><p><strong>Aims: </strong>This study aimed to investigate the acute and sustained effects of altered glutamate transmission induced by ketamine and lamotrigine on pgACC FC during rest and WM.</p><p><strong>Methods: </strong>In this double-blind, placebo-controlled, randomized, single-dose, parallel-group study, resting-state and task-related functional Magnetic Resonance Imaging (fMRI) data were collected at baseline, during and 24 h after ketamine administration in 75 healthy participants. Participants were randomized to receive ketamine, ketamine with lamotrigine pretreatment or placebo. FC analyses utilized pgACC masks derived from the Julich Brain Atlas.</p><p><strong>Results: </strong>Ketamine infusion significantly enhanced FC between the pgACC and dorsomedial prefrontal cortex during the WM task, and increased resting-state FC between the pgACC and left insula. These effects were absent following lamotrigine pretreatment.</p><p><strong>Conclusions: </strong>The findings support the hypothesis that ketamine's favourable effects, reflected by enhanced FC within key neural networks, may be attributable to glutamate release.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251346705"},"PeriodicalIF":4.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nucleus accumbens serotonin 1A receptor expression is altered by female reproduction and regulates postpartum affective and caregiving behaviors.","authors":"Erika M Vitale, Emma G Ford, Margaret S Ahern, Joseph S Lonstein","doi":"10.1177/02698811251340909","DOIUrl":"https://doi.org/10.1177/02698811251340909","url":null,"abstract":"<p><strong>Background: </strong>Motherhood is often characterized by a positive affective state and high motivation to interact with potentially rewarding offspring. However, many mothers suffer from postpartum mental health issues that can degrade their maternal motivation and caregiving abilities. Serotonin-modulating drugs are commonly used to treat distressed mothers, but how serotonin (5-HT) in brain sites underlying motivation influences postpartum behaviors is mostly unknown.</p><p><strong>Aims: </strong>Because 5-HT in the nucleus accumbens (NAcs) regulates dopamine release, we hypothesized that the NAc is a critical site where serotonin signaling influences postpartum affective and caregiving behaviors.</p><p><strong>Methods: </strong>We used RT-qPCR and autoradiographic binding to determine changes in NAc 5-HT1A, 5-HT2A, and 5-HT2C receptor expression across pregnancy and postpartum; shRNA-mediated knockdown of NAc 5-HT1A receptors to determine its effects on postpartum behavior; and repeated pregnancy stress to determine its effects on both NAc 5-HT1A and postpartum behavior.</p><p><strong>Results: </strong>Recently parturient rats had higher 5-HT1A (but not 5-HT2A or 5-HT2C) receptor mRNA and 5-HT1A binding in the NAc shell (NAcSh) compared with nulliparae. 5-HT1A knockdown in the maternal NAcSh to prevent this normative increase in receptor expression resulted in high anxiety-like behavior, more off-nest behaviors, and delayed pup retrieval. 5-HT1A knockdown also reduced NAcSh tyrosine hydroxylase. Pregnancy stress reduced postpartum NAcSh 5-HT1A receptor binding at some rostrocaudal levels, as well as disrupted the display of caregiving behaviors.</p><p><strong>Conclusions: </strong>These results provide new insights into how 5-HT signaling in the NAcSh contributes to postpartum affective and caregiving behaviors and offer a mechanism through which serotonin-based pharmacotherapies may help improve maternal caregiving motivation in anxious, depressed, or chronically stressed mothers.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251340909"},"PeriodicalIF":4.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of the Comprehensive Cannabis Motives Questionnaire (CCMQ).","authors":"John Moffitt, Carl Roberts, Paul Christiansen","doi":"10.1177/02698811251341371","DOIUrl":"10.1177/02698811251341371","url":null,"abstract":"<p><strong>Background: </strong>Existing scales that measure cannabis use motives have failed to incorporate the full range of motives that underpin cannabis consumption, especially with the increased use of medical cannabis. The current research aimed to develop a novel, psychometrically robust scale that comprehensively measures cannabis use motives. Here, we report the development and validation of the Comprehensive Cannabis Motives Questionnaire (CCMQ).</p><p><strong>Method: </strong>Cannabis users completed a 45-item questionnaire measuring a range of cannabis use motives. A UK English-speaking sample (<i>n</i> = 450) provided data for exploratory factor analysis. A second UK English-speaking sample (<i>n</i> = 200) was used for confirmatory factor analysis. Test-retest reliability was based on a third English-speaking sample (<i>n</i> = 45) who completed the revised, 41-item CCMQ twice across 2 weeks. A US-based sample (<i>N</i> = 216) was used to test measurement invariance of the scale across countries.</p><p><strong>Results: </strong>Exploratory and subsequent confirmatory factor analysis provided an eight-factor solution. The eight factors were food, medicinal, sleep, social, high, coping, conformity and creative. All the factors had good to excellent internal reliability with McDonald's ω ranging between 0.85 and 0.97. Test-retest reliability was obtained for the revised 41-item questionnaire (Intraclass correlation's 0.5+ for Total Cannabinoid Eating Experience Questionnaire and each subscale). The eight factors were correlated with Cannabis Use Disorder Identification Test - Revised to assess relationships with problematic use. Finally, strict measurement invariance was achieved in comparisons between males and females and a UK sample against a US sample.</p><p><strong>Conclusion: </strong>The CCMQ provided a valid, reliable assessment of the motivations that underlie cannabis use.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251341371"},"PeriodicalIF":4.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing mindfulness and compassion through an ayahuasca-inspired formulation containing N,N-DMT and harmine: A randomized controlled trial in healthy subjects.","authors":"Helena D Aicher, Ilhui A Wicki, Daniel Meling, Michael J Mueller, Dario A Dornbierer, Milan Scheidegger","doi":"10.1177/02698811251344689","DOIUrl":"https://doi.org/10.1177/02698811251344689","url":null,"abstract":"<p><strong>Background: </strong>Mindfulness and compassion are therapeutically relevant and can be increased through different forms of meditation practices. However, meditation practice needs time and commitment. These resources are often limited in patients with mood disorders. Therefore, efficacious remedies that increase mindfulness and compassion could provide therapeutic options. This study aimed to investigate the relationship between psychedelic experiences induced by an ayahuasca-inspired N,N-dimethyltryptamine (DMT)/harmine formulation on mindfulness and compassion in healthy subjects.</p><p><strong>Methods: </strong>This study applies a randomized, double-blind, placebo-controlled within-subjects design in a laboratory setting with 31 healthy participants. Each subject received a formulation comprising DMT + harmine, harmine + placebo, and placebo only on three different study days. Primary outcomes were mindfulness (MINDSENS) and compassion (SOCS).</p><p><strong>Results: </strong>A significant effect of the drug on mindfulness (<i>p</i> < 0.05, <i>F</i> = 3.41), self-compassion (SOCS-S; <i>p</i> < 0.01, <i>F</i> = 7.53), and compassion with others (SOCS-O; <i>p</i> < 0.05, <i>F</i> = 3.37) 1 day post-treatment was found. Significant differences between the high- and low-sensitivity groups were found for mindfulness (<i>p</i> < 0.05, <i>F</i> = 6.54), self-compassion (<i>p</i> < 0.05, <i>F</i> = 4.21), and compassion with others (<i>p</i> < 0.05, <i>F</i> = 4.42).</p><p><strong>Conclusions: </strong>In line with previous studies on traditional botanical ayahuasca, our findings support the notion that the DMT/harmine formulation might have therapeutic potential through its ability to acutely enhance mindfulness and compassion. Continuing studies in therapeutic settings are needed to further elucidate the mechanisms of action of ayahuasca-inspired formulations.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251344689"},"PeriodicalIF":4.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Naturalistic use of psychedelics is associated with longitudinal improvements in anxiety and depression during global crisis times.","authors":"Maria Bălăeţ, William Trender, Annalaura Lerede, Peter J Hellyer, Adam Hampshire","doi":"10.1177/02698811251346729","DOIUrl":"https://doi.org/10.1177/02698811251346729","url":null,"abstract":"<p><strong>Background: </strong>Mental health implications of COVID-19 drug use patterns are still unclear.</p><p><strong>Methods: </strong>We used data-driven clustering in a large citizen science cohort recruited agnostically to an interest in drug-use to categorise people according to common patterns of drug use and analysed their mental health symptoms (GAD-7 and PHQ-9 items), from recruitment prior to COVID-19 restrictions in 2020 (<i>N</i> = 242,260) to three follow-ups in 2020-2022 (<i>N</i> = 68,416). Mixed effects modelling examined how mental health scores related to drug-use clusters cross-sectionally and how changes in those scores longitudinally related to changes in consumption frequencies.</p><p><strong>Results: </strong>We identified six common patterns of drug use during the COVID-19 pandemic, with cannabis cross cutting most of them. The majority of drug use clusters had worse average mental health scores relative to drug-naive individuals at all timepoints. The average mental health scores of those who used more drugs during the pandemic worsened over time relative to individual baselines. However, psychedelics and cannabis users showed average improvements in depression (β = -0.26 SD, 95% CI: -0.44, -0.08, <i>p</i> = 0.003), anxiety (β = -0.24 SD, 95% CI: -0.41, -0.06, <i>p</i> = 0.007) and overall mental health (β = -0.2 SD, 95% CI: -0.35, -0.04, <i>p</i> = 0.01) from pre-pandemic to January 2022, becoming on par with the drug-naive group. This was not the case for cannabis-only users, whose worse mental health scores persisted.</p><p><strong>Conclusion: </strong>Those who used psychedelics may have experienced some improvements in mental health across the pandemic timeframe, which supports the idea that beneficial effects on mood and anxiety associated with these substances may extend beyond controlled conditions.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251346729"},"PeriodicalIF":4.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncertainty about lithium and suicide: A response to Nassir Ghaemi.","authors":"Joanna Moncrieff, Jacki Stansfeld, Lisa Wood, Martin Plöderl","doi":"10.1177/02698811251346706","DOIUrl":"https://doi.org/10.1177/02698811251346706","url":null,"abstract":"","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251346706"},"PeriodicalIF":4.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A model training curriculum for psychedelic, psycholytic, and entactogen-assisted psychotherapy.","authors":"Torsten Passie, Anja Loizaga-Velder, Alicia Danforth, Charles S Grob, George R Greer, David Erritzoe, Peter Oehen, Juraj Styk, Michael Schlichting, Eric Vermetten, Ivar W Goksøyr, Tomas Palenicek, Michael C Mithoefer, Annie Mithoefer, Brian Anderson, Erwin Krediet, Peter Gasser, Elizabeth M Nielson, Ingmar Gorman, Janis Phelps, Alexander B Belser, Jeffrey Guss","doi":"10.1177/02698811241282759","DOIUrl":"https://doi.org/10.1177/02698811241282759","url":null,"abstract":"<p><p>The authors offer a model for curriculum for education and training in substance-assisted psychotherapy (SAP), that is, psychedelic, psycholytic, and entactogen/MDMA (3,4-methylenedioxymethamphetamine)-assisted psychotherapy, addressing both the detailed contents of training and the question of experiential training. All authors of this model have an abiding interest and extensive experience in both the theory and practical aspects of SAP and questions relating to training. The model curriculum has been written through an international consensus building process and represents a consensus statement about the topic. The model includes an enumeration of theoretical themes and topics, which we suggest for inclusion in an SAP curriculum. The practical part of the curriculum includes experiential training with the following components: (1) apprenticeship observation: learning from observing experienced therapists, (2) ongoing clinical supervision: conducting treatment under direct supervision of experienced SAP therapists, and (3) a proposal for the inclusion of self-experiences for the trainees. Other parts address the use of peer supervision and conventional supervision. The authors are aware of the abiding need for respect of intercultural differences. We are conscious that the proposed model is one largely adapted to western industrialized countries with established graduate level education and training procedures for psychotherapists. However, the model curriculum includes teachings about the use of related substances and treatment techniques in indigenous cultures and traditions. This curriculum model may be valuable to psychedelic researchers, those endeavoring to train therapists for research studies, and those preparing for the clinical work to follow, once SAP is conducted outside of research settings.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811241282759"},"PeriodicalIF":4.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute subanesthetic ketamine-induced effects on the mismatch negativity and their relationship to early and sustained treatment response in major depressive disorder.","authors":"Sara de la Salle, Jennifer L Phillips, Pierre Blier, Verner Knott","doi":"10.1177/02698811251319456","DOIUrl":"10.1177/02698811251319456","url":null,"abstract":"<p><strong>Background: </strong>A sub-anesthetic dose of ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, produces robust antidepressant effects in treatment-resistant major depressive disorder (MDD). The mismatch negativity (MMN) is reliant on glutamatergic neurotransmission and reduced by NMDAR antagonists. The MMN may characterise the neural mechanisms underlying ketamine's effects.</p><p><strong>Aims: </strong>This study examined the acute effects of ketamine and midazolam on the MMN and its relationship to early and sustained decreases in depressive symptoms.</p><p><strong>Methods: </strong>Treatment-resistant MDD patients (<i>N</i> = 24), enrolled in a multi-phase clinical ketamine trial, received two intravenous infusions within an initial double-blind crossover phase: ketamine (0.5 mg/kg) and midazolam (30 μg/kg). Three recordings were carried out per session (pre-, immediately post- and 2 h post-infusion). Peak MMN amplitude (μV), latency (ms), theta event-related oscillations (EROs), theta phase locking factor (PLF) and source-localised MMN generator activity were assessed. Relationships between changes in MMN indices and early (Phase 1: double-blind, cross-over phase) and sustained (Phases 2, 3: open-label repeated and maintenance phases, respectively) changes in depressive symptoms (Montgomery-Åsberg Depression Rating Scale score) were examined.</p><p><strong>Results: </strong>Ketamine reduced frontal MMN amplitudes, theta ERO immediately post- and 2 h post-infusion and source-localised peak MMN frontal generator activity. Select baseline and ketamine-induced MMN decreases correlated and predicted greater early (left frontal MMN decreases in amplitude and theta ERO, baseline left PLF) and sustained (baseline left PLF, right inferior temporal activity) symptom reductions.</p><p><strong>Conclusions: </strong>Acute NMDARs blockade reduced frontal MMN, with larger MMN reductions predicting greater symptom improvement. The MMN may serve as a non-invasive biomarker predicting antidepressant response to glutamatergic agents.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"577-592"},"PeriodicalIF":4.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}