Neuropsychopharmacology最新文献

{"title":"Proximity in mice induced by an auditory-conditioned stimulus","authors":"Wataru Ito, Alexei Morozov","doi":"10.1038/s41386-026-02492-1","DOIUrl":"10.1038/s41386-026-02492-1","url":null,"abstract":"Social affiliation promotes survival and well-being across species, and proximity to conspecifics is a necessary precondition for affiliative contact. While innate threats reliably increase proximity among conspecifics, whether learned threats have the same effect remains unknown. Here, we report that an auditory conditioned stimulus (CS) induces proximity in mice. In same-sex dyads, fear-conditioned mice increased proximity during CS presentation, independent of freezing levels. This CS-evoked proximity required familiarity between partners and intact basolateral amygdala-to-ventral hippocampus inputs, demonstrated by DREADD-mediated suppression. It also required oxytocin receptor signaling, demonstrated by systemic administration of the antagonist L368,899. These findings suggest that learned and innate threats engage shared neural circuitry for social proximity.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"51 10","pages":"1-8"},"PeriodicalIF":7.6,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41386-026-02492-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148458271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is abnormal brain insulin action implicated in the biology of depression? A pilot neuroimaging study in adolescents","authors":"Kateryna Maksyutynska, Nicolette Stogios, Vittal Korann, Laurie Hamel, Daphne Korczak, Benjamin I. Goldstein, Gary Remington, Marcos Sanches, Margaret K. Hahn, Ariel Graff-Guerrero, Sri Mahavir Agarwal","doi":"10.1038/s41386-026-02498-9","DOIUrl":"10.1038/s41386-026-02498-9","url":null,"abstract":"Brain insulin action was measured in adolescents with (cases) and without (controls) depression, by calculating the difference in resting-state functional connectivity (ΔrsFC) following an intranasal insulin challenge. A significant Group × Condition interaction effect was identified: controls exhibited greater ΔrsFC with intranasal insulin compared to cases in brain regions regulating cognitive/emotional processing.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"51 10","pages":"1902-1905"},"PeriodicalIF":7.6,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The neuroanatomy of depression: weak but replicable effects in 4021 individuals from three clinical cohorts","authors":"Udo Dannlowski, Nils R. Winter, Susanne Meinert, Dominik Grotegerd, Anna Kraus, Kira Flinkenflügel, Elisabeth Leehr, Joscha Böhnlein, Tiana Borgers, Lukas Fisch, Michael Bauer, Andrea Pfennig, Maike Richter, Nils Opel, Jonathan Repple, Marius Gruber, Heike Minnerup, Marco Hermesdorf, Robert Nitsch, Joachim Groß, Andreas Jansen, Nina Alexander, Frederike Stein, Igor Nenadić, Klaus Berger, Tilo Kircher, Tim Hahn, Janik Goltermann","doi":"10.1038/s41386-026-02491-2","DOIUrl":"10.1038/s41386-026-02491-2","url":null,"abstract":"The structural neuroanatomy underlying Major Depressive Disorder (MDD) remains elusive and even large-scale neuroimaging studies and meta-analyses produced inconsistent outcomes with marginal effect sizes. Furthermore, the replicability of brain-psychopathology associations is under scrutiny, attributable to inadequately powered sample sizes and inflated effect sizes. The present study aimed to examine the effect sizes, replicability, and generalizability of brain structural alterations in MDD, harnessing the wealth of three large-scale clinical cohorts. We used three independent cohorts totaling n = 4021 deeply characterized participants (aged 15–65 years), encompassing MDD patients (n = 1764), and healthy controls (HC; n = 2257) with individual MRI data. The diagnosis was confirmed by structured clinical interviews. Brain-wide case-control differences in voxel-based morphometry were tested. We conducted pooled analyses to maximize statistical power, and further investigated cross-cohort replicability and generalizability by inspecting 1) correlations between t-maps from each cohort, 2) converging significance across the three cohorts, and 3) by using a cross-validation framework, iterating through cohorts as independent test sets. Pooling all individuals together yielded reduced gray matter volumes in patients with MDD in widespread bilateral clusters, covering the insula, thalamus, orbitofrontal cortex, and a parahippocampal-fusiform-lingual complex. No evidence was found for differences within the hippocampus. The largest effect size was found in the bilateral anterior insula (partial R2 = 0.01). Analyzing cohorts separately yielded 1) t-map correlations between cohorts (r = 0.212 to r = 0.281), 2) replicability indicated by overlapping significance in multiple areas exceeding thresholds in each single cohort, and 3) generalizability of case-control differences in clusters that were deemed non-significant in single cohorts, implicating further frontal, temporal and cerebellar regions. Results indicate that gray matter correlates of MDD are subtle but nevertheless replicable and generalizable. These alterations are localized in an array of regions involved in emotion regulation and sensory processing. Our investigation underscores the need to investigate the replicability and generalizability of mental health neuroimaging findings and provides a tangible framework for this endeavor.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"51 11","pages":"2016-2025"},"PeriodicalIF":7.6,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does a monoclonal antibody targeting immune cells affect glutamatergic level in schizophrenia? A multimodal PET/MRS brain imaging study","authors":"Guy Hindley, Yuya Mizuno, Katherine Beck, Ines Carreira Figueiredo, Toby Pillinger, Sami Jeljeli, Joel Dunn, Alexander Hammers, Ramla Awais, Kerstin Sander, Erik Årstad, David J. Lythgoe, Julia J. Schubert, Mattia Veronese, Federico Turkheimer, Oliver D. Howes, Tiago Reis Marques","doi":"10.1038/s41386-026-02466-3","DOIUrl":"10.1038/s41386-026-02466-3","url":null,"abstract":"Microglial dysfunction and glutamatergic dysregulation are implicated in the neurobiology of schizophrenia. Microglia regulate brain glutamate levels through mechanisms including the cysteine-glutamate antiporter, raising the possibility that microglial dysfunction could underlie glutamatergic dysregulation in schizophrenia. We tested this using a combined cross-sectional/longitudinal study of individuals with first episode psychosis and healthy controls. We investigated two hypotheses: (1) increase in a positron emission tomography (PET) imaging marker of microglia is associated with increased anterior cingulate (ACC) glutamate levels; and (2) reducing immune trafficking into the CNS using the monoclonal antibody natalizumab would reduce ACC glutamate levels in people with first-episode psychosis. A total of 108 participants (68 patients and 40 healthy controls) underwent simultaneous proton magnetic resonance spectroscopy to quantify ACC glutamate and glutamate/glutamine (glx) levels and PET imaging with [18 F]DPA-714 to quantify translocator protein (TSPO) levels, a protein highly expressed by microglia in neuroinflammatory conditions. In the longitudinal arm, 50 first-episode psychosis patients were included and either randomised to receive natalizumab or placebo double-blind, or received open-label natalizumab. At baseline, there was no significant association between ACC glutamate concentration and ACC TSPO binding in the entire sample (β = -0.003, SE = 0.006, p = 0.55). In the longitudinal arm, natalizumab did not significantly alter ACC glutamate levels (mean difference = 0.227 i.u., t = 1.52, p = 0.139). These findings do not support the hypothesis that microglial dysfunction drives ACC glutamatergic dysregulation in early psychosis. Microglial dysfunction and glutamatergic dysregulation may therefore represent distinct mechanisms within the neurobiology of schizophrenia.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"51 11","pages":"2083-2092"},"PeriodicalIF":7.6,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41386-026-02466-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term effects of adolescent risperidone treatment on the mouse cortex","authors":"Abneil D. Alicea-Pauneto, Hyowon Choi, Wenyu Zhang, Xinjian Li, Laurence. A. Busque, Mingxuan Li, Andrew Wu, Evan Zhang, Adam D. Marc, Jonathan Preall, Kuan Hong Wang, Robert E. Featherstone, Steven J. Siegel, Chang-Gyu Hahn, Karin E. Borgmann-Winter","doi":"10.1038/s41386-026-02483-2","DOIUrl":"10.1038/s41386-026-02483-2","url":null,"abstract":"Since the introduction of second-generation antipsychotics, antipsychotics have been increasingly prescribed for children and adolescents, raising concerns about their long-term impact on neurodevelopment. Antipsychotics block dopaminergic and serotonergic receptors, potentially disrupting the maturation of neurocognitive processes, which is a public health concern. Previous studies have reported that adolescent antipsychotic treatment can cause persistent neurocognitive dysfunction in rodents, yet the neurobiological underpinnings remain unknown. To address this, we administered risperidone, a commonly used antipsychotic, to C57BL/6 mice during adolescence (3 to 6 weeks of age) and examined behavioral and neurobiological outcomes nine weeks post-treatment. Risperidone-treated mice exhibited subtle deficits in behavioral correlates of anxiety-like behavior. In vivo, two-photon calcium imaging of cortical neurons revealed a remarkable increase in the amplitude of calcium events with subtle sex-specific changes in the frequency, consistent with increased neuronal excitability. Single-nucleus RNA-sequencing (snRNA-seq) analyses showed widespread reductions in transcripts for voltage-sensitive and inwardly rectifying potassium channels in both pyramidal neurons and interneurons. Additionally, both cell types exhibited reduced Grin2a and Grin2b, as well as scaffolding proteins, indicative of weakened synaptic connectivity between excitatory and inhibitory neurons. Interestingly, we observed sex-dependent differences in the directionality of correlation between certain gene co-expression modules and risperidone treatment. Our results suggest that adolescent risperidone treatment induces lasting transcriptomic and functional changes associated with altered excitatory-inhibitory neuronal interactions that may underline cognitive and behavioral dysregulations.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"51 10","pages":"1-11"},"PeriodicalIF":7.6,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41386-026-02483-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148414703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Cue labeling reduces cigarette craving and associated neural activity","authors":"Golnaz Tabibnia, Dara G. Ghahremani, Hilary A. Tindle, J. David Creswell, Cecilia Westbrook, Thomas E. Kraynak, Erica Julson, Edythe D. London","doi":"10.1038/s41386-026-02488-x","DOIUrl":"10.1038/s41386-026-02488-x","url":null,"abstract":"","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"51 10","pages":"1-1"},"PeriodicalIF":7.6,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41386-026-02488-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148414701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In memoriam – Ming T. Tsuang, M.D., Ph.D., D.Sc","authors":"Debby W. Tsuang, Stephen J. Glatt, Stephen V. Faraone","doi":"10.1038/s41386-026-02481-4","DOIUrl":"10.1038/s41386-026-02481-4","url":null,"abstract":"","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"51 10","pages":"1906-1906"},"PeriodicalIF":7.6,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41386-026-02481-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148414696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CSF galanin and noradrenaline downregulation by psilocybin therapy in major depressive disorder","authors":"Wojciech Paslawski, Daniel Doyon, Carl Johan Ekman, Hampus Yngwe, Dejan Mamula, Justyna Zareba-Paslawska, Maria Beckman, Zhi-Qing David Xu, Tomas Hökfelt, Mikael Tiger, Johan Lundberg, Per Svenningsson","doi":"10.1038/s41386-026-02490-3","DOIUrl":"10.1038/s41386-026-02490-3","url":null,"abstract":"Psilocybin is a rapid-acting antidepressant, but its mechanism of action in major depressive disorder remains unclear. In this secondary analysis of randomized, placebo-controlled trial with multimodal CSF and blood biomarker measurements, psilocybin selectively reduced CSF galanin and noradrenaline, implicating that normalization of these co-transmitters is a key pharmacodynamic signature.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"51 10","pages":"1898-1901"},"PeriodicalIF":7.6,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41386-026-02490-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148407802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In memoriam: Jon Kar Zubieta, M.D., Ph.D.","authors":"Stephan F. Taylor","doi":"10.1038/s41386-026-02493-0","DOIUrl":"10.1038/s41386-026-02493-0","url":null,"abstract":"","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"51 10","pages":"1907-1907"},"PeriodicalIF":7.6,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41386-026-02493-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148407826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Auditory event-related potentials and psychosis dimensions","authors":"Jadyn Trayvick, Greg Perlman, Katherine G. Jonas, Kayla R. Donaldson, Dan Foti, Evelyn J. Bromet, Roman Kotov, Brady D. Nelson","doi":"10.1038/s41386-026-02487-y","DOIUrl":"10.1038/s41386-026-02487-y","url":null,"abstract":"The auditory event-related potential (ERP) components N1 and P3 have been identified as potential neural markers of psychotic disorders. However, the literature has largely examined categorical disorders, and the auditory N1 and P3 have also been associated with internalizing disorders. It is unclear whether the auditory N1 and P3 relate to specific features of psychosis, broad psychosis, or general psychopathology. The present study examined the relationship between the auditory N1, P3a, and P3b and dimensional representations of psychosis and comorbid psychopathology. We tested whether auditory ERPs (1) were associated with specific psychosis dimensions (thought disorder, detachment, cognition, functioning) or the psychosis superspectrum, and (2) demonstrated specificity to psychosis compared to comorbid internalizing psychopathology. Participants (Mage = 49.57, 45.2% female) were 202 individuals with a history of hospitalization for a psychotic disorder and 304 demographically matched comparisons. All participants completed an auditory oddball task while we recorded electroencephalography, diagnostic interviews, self-report questionnaires, and a neuropsychological battery. A more blunted auditory N1, P3a, and P3b were associated with greater scores on the psychosis superspectrum. After controlling for the psychosis superspectrum, the N1 and P3a were not independently related to any specific psychosis dimension, but a smaller P3b was associated with poorer cognition. The N1 and P3b, but not P3a, demonstrated specificity to the psychosis superspectrum compared to the internalizing spectrum. A blunted auditory N1 and P3b are uniquely associated with the psychosis superspectrum, while a blunted P3a was common to both the psychosis superspectrum and internalizing spectrum.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"51 11","pages":"2102-2110"},"PeriodicalIF":7.6,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148388525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}