Neuropsychopharmacology最新文献

{"title":"Less is more? Antidepressant effects of short-acting psychedelics","authors":"Johannes G. Ramaekers","doi":"10.1038/s41386-025-02103-5","DOIUrl":"10.1038/s41386-025-02103-5","url":null,"abstract":"","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 6","pages":"875-876"},"PeriodicalIF":6.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871901","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":"Rapid and sustained antidepressant effects of vaporized N,N-dimethyltryptamine: a phase 2a clinical trial in treatment-resistant depression","authors":"Marcelo Falchi-Carvalho, Fernanda Palhano-Fontes, Isabel Wießner, Handersson Barros, Raynara Bolcont, Sophie Laborde, Sérgio Ruschi B. Silva, Daniel Montanini, David C. Barbosa, Ewerton Teixeira, Rodrigo Florence-Vilela, Raissa Almeida, Rosana K. A. de Macedo, Flávia Arichelle, Érica J. Pantrigo, José V. Costa-Macedo, João Arthur da Cruz Nunes, Luiz Antonio de Araújo Costa Neto, Luis Fernando Nunes Ferreira, Luísa Dantas Corrêa, Romária Bárbara da Costa Bezerra, Emerson Arcoverde, Nicole Galvão-Coelho, Draulio B. Araujo","doi":"10.1038/s41386-025-02091-6","DOIUrl":"10.1038/s41386-025-02091-6","url":null,"abstract":"Depression affects over 185 million people worldwide, with approximately one-third classified as treatment-resistant depression (TRD). Current treatments, such as oral antidepressants, often take around 3 weeks to become effective, with no immediate anti-suicidal benefits. The field urgently needs innovative therapies that provide rapid relief. Psychedelics like psilocybin and ayahuasca have shown promising antidepressant effects; however, their long duration (several hours) makes them costly and impractical for public health systems. N,N-Dimethyltryptamine (DMT), an endogenous psychedelic also found in ayahuasca, offers a viable alternative with a short duration of action (10–20 min) and non-invasive inhalation administration. Unlike ayahuasca, which contains monoamine oxidase inhibitors, vaporized DMT acts quickly and poses fewer pharmacological interaction risks. This open-label trial evaluated inhaled DMT for TRD for the first time, within the framework of interventional psychiatry. Fourteen patients (Nfemale = 6) participated in a fixed-order, dose-escalation study (15 mg and 60 mg). The treatment was safe, well-tolerated, and produced manageable psychedelic effects with no serious adverse events. A subpopulation using antidepressants showed similar safety outcomes. Results showed rapid and sustained antidepressant effects, with an average reduction of 21.14 points on the Montgomery-Asberg Depression Rating Scale by day 7 (p < 0.001). The response rate was 85.71%, and the remission rate was 57.14% 7 days post-administration, lasting up to 3 months. Suicidal ideation significantly decreased, with no severe ideation the day after dosing. Vaporized DMT offers a non-invasive, time-efficient, and cost-effective alternative to other psychedelics and traditional antidepressants, supporting its role in interventional psychiatry and public health. Clinicaltrials.gov NCT06094907.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 6","pages":"895-903"},"PeriodicalIF":6.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871931","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":"Correction: Neuroactive steroid biosynthesis during pregnancy predicts future postpartum depression: a role for the 3α and/or 3β-HSD neurosteroidogenic enzymes?","authors":"Lauren M. Osborne, Semra Etyemez, Graziano Pinna, Rebecca Alemani, Lindsay R. Standeven, Xin-Qun Wang, Jennifer L. Payne","doi":"10.1038/s41386-025-02109-z","DOIUrl":"10.1038/s41386-025-02109-z","url":null,"abstract":"","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 6","pages":"1021-1021"},"PeriodicalIF":6.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41386-025-02109-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871904","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":"Heritable consequences of paternal heroin use: a role for miR-19b in drug-taking behavior.","authors":"Fair M Vassoler","doi":"10.1038/s41386-025-02100-8","DOIUrl":"https://doi.org/10.1038/s41386-025-02100-8","url":null,"abstract":"","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788284","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":"Correction: Lateral habenula induces cognitive and affective dysfunctions in mice with neuropathic pain via an indirect pathway to the ventral tegmental area.","authors":"Yue-Ying Liu, Ke Wu, Yu-Ting Dong, Ru Jia, Xing-Han Chen, An-Yu Ge, Jun-Li Cao, Yong-Mei Zhang","doi":"10.1038/s41386-025-02099-y","DOIUrl":"10.1038/s41386-025-02099-y","url":null,"abstract":"","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780720","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":"Neighborhood social fragmentation in relation to impaired mismatch negativity among youth at clinical high risk for psychosis and healthy comparisons.","authors":"Benson S Ku, Holly Hamilton, Qingyue Yuan, David A Parker, Brian J Roach, Peter M Bachman, Aysenil Belger, Ricardo E Carrión, Erica Duncan, Jason K Johannesen, Gregory A Light, Margaret A Niznikiewicz, Jean Addington, Carrie E Bearden, Kristin S Cadenhead, Tyrone D Cannon, Barbara A Cornblatt, Matcheri Keshavan, Diana O Perkins, William Stone, Scott W Woods, Elaine Walker, Daniel H Mathalon","doi":"10.1038/s41386-025-02093-4","DOIUrl":"10.1038/s41386-025-02093-4","url":null,"abstract":"<p><p>Impairments in mismatch negativity (MMN) are well-established in schizophrenia and have been observed in youth at clinical high-risk for psychosis (CHR-P). Prior animal studies have shown that social isolation may be related to neurobiological changes, including reduced MMN-like responses and schizophrenia-like behaviors. In parallel, neighborhood social fragmentation has been shown to be associated with the onset of psychosis. This study investigates the association between neighborhood social fragmentation and MMN impairment among CHR-P youth and healthy comparisons (HC). Data were collected from the North American Prodrome Longitudinal Study Phase 2. Electroencephalography was recorded during an unattended auditory oddball paradigm with duration-, pitch-, and double-deviant tones. Generalized linear mixed models tested the association between neighborhood social fragmentation and the frontal-central averaged MMN for three deviant types for youth at CHR-P and HC separately. The models adjusted for age, sex, race/ethnicity, parental education, parental history of psychosis, and neighborhood poverty. Participants (mean [SD] age: 18.69 [4.59], 41.9% females, 51.3% White non-Hispanic) included 304 CHR-P and 92 HC. In the CHR-P group, greater neighborhood social fragmentation was associated with impaired duration-deviant MMN (bootstrapped β = 0.18, 95% CI: 0.04 to 0.33, p = .022) but not for pitch-deviant (bootstrapped β = 0.09, 95% CI: -0.05 to 0.22, p = .199) or double-deviant MMN (bootstrapped β = 0.10, 95% CI: -0.09 to 0.17, p = .559). Greater neighborhood social fragmentation was associated with impaired duration-deviant MMN amplitude among high-risk individuals. Further research is needed to explore underlying mechanisms.</p>","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772881","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":"Random forest and Shapley Additive exPlanations predict oxytocin targeted effects on brain functional networks involved in salience and sensorimotor processing, in a randomized clinical trial in autism.","authors":"Elissar Andari, Kaundinya Gopinath, Erin O'Leary, Gabriella A Caceres, Shota Nishitani, Alicia K Smith, Opal Ousley, James K Rilling, Joseph F Cubells, Larry J Young","doi":"10.1038/s41386-025-02095-2","DOIUrl":"https://doi.org/10.1038/s41386-025-02095-2","url":null,"abstract":"<p><p>Intranasal oxytocin (IN-OXT) has shown some promises in rescuing social deficits in autism spectrum disorder (ASD) as well as some inconsistencies in long-term trials. We conducted a target engagement study to study the precise effects of different doses of IN-OXT on brain resting-state functional connectivity (rsFC) in ASD. We examined the effects of varying doses of IN-OXT (0 IU, 8 IU, 24 IU, 48 IU) on rsFC in a double-blind, placebo-controlled, within-subject design in 30 male adults with ASD and 17 neurotypical controls (NT) receiving placebo. Random forest analysis was used to classify individuals as ASD or NT. Shapely Additive explanations values were calculated to rank brain functional networks by level of contribution to ASD deficits and to evaluate IN-OXT dose effects. The model predicted ASD diagnosis with an AUC of 94%. Hypoconnectivity between salience/empathy and visual networks, and hyperconnectivity between reward and sensorimotor networks and theory of mind networks were among the strongest predictors of ASD deficits. IN-OXT had a dose-dependent effect on rescuing both deficits described above. Overall, 48 IU dose was more effective, and 24 IU dose was more effective in those who have lower DNA OXT receptor methylation and lower severity of clinical symptoms. Higher doses of OXT might be necessary to enhance empathic responses, and ASD individuals with less support needs and with a preserved OXT system might benefit most from OXT treatment. Applying machine learning approaches in OXT research can provide data-driven unbiased results that can inform future clinical trials.</p>","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772939","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":"Abnormal ventromedial-to-dorsolateral hierarchical topography of striatal circuits in cocaine use disorder and its modulations by brain stimulation.","authors":"Ran Zhang, Xiang Xiao, Debo Dong, Ting Xu, Yuzheng Hu, Feng Zhou, Tianye Zhai, Yawei Qi, Yihong Yang, Qinghua He","doi":"10.1038/s41386-025-02098-z","DOIUrl":"10.1038/s41386-025-02098-z","url":null,"abstract":"<p><p>Cocaine use disorder (CUD) has been linked to cortico-striatal dysfunctions, particularly within the prefrontal-striatal circuitry. However, previous studies have typically focused on discrete parcellations of the striatum, overlooking its continuous variations of neural organization. Moreover, while repetitive transcranial magnetic stimulation (rTMS) has shown benefits in CUD treatment, the neural effects of rTMS on striatal dysfunction in CUD remain poorly understood. Using connectome gradient-mapping techniques on three resting-state functional magnetic resonance imaging datasets, we derived the ventromedial-to-dorsolateral striatal functional topography. We identified specific alterations in this topography in the discovery cohort (41 CUD patients and 44 controls), validated findings in an independent cohort (53 CUD patients and 45 controls), and examined whether rTMS targeting the left dorsolateral prefrontal cortex (dlPFC) could normalize abnormalities in the rTMS-treatment cohort (44 patients). Across all datasets, we found a positive correlation between gradient variation and drug dependence severity in CUD. Compared to controls, CUD in both the discovery and replication cohorts exhibited elevated gradient values in the ventral striatum, while decreased values in the dorsal striatum were observed only in the discovery cohort. Furthermore, in the rTMS-treatment cohort, 5-Hz rTMS targeting the left dlPFC significantly normalized the aberrant gradient values in the ventral striatum, and these changes also related to cocaine craving changes. Overall, our study provides novel evidence of specific alterations in the ventromedial-to-dorsolateral functional topography of the striatum in CUD patients and highlights the impact of rTMS on striatal circuits through prefrontal modulation.</p>","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764560","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":"Four dimensions of individualization in brain stimulation for psychiatric disorders: context, target, dose, and timing","authors":"Ghazaleh Soleimani,&nbsp;Michael A. Nitsche,&nbsp;Colleen A. Hanlon,&nbsp;Kelvin O. Lim,&nbsp;Alexander Opitz,&nbsp;Hamed Ekhtiari","doi":"10.1038/s41386-025-02094-3","DOIUrl":"10.1038/s41386-025-02094-3","url":null,"abstract":"Non-invasive Brain Stimulation (NIBS) technologies, including transcranial electrical (tES) and magnetic (TMS) stimulation, have emerged as promising interventions for various psychiatric disorders. FDA-approved TMS protocols in depression, OCD and nicotine use disorder provide a meaningful improvement. Treatment efficacy however remains inconsistent across individuals, and one relevant reason is intervention effect variability based on individual factors. There is a growing effort to develop individualized interventions, reinforced recently by FDA approval of a new TMS protocol that includes individualized fMRI-based targeting along with other modifications with higher reported effect size than previous “one size fits all” protocols. This paper discusses the dimensions for individualizing tES/TMS protocols to enhance therapeutic efficacy. We propose a multifaceted approach to personalizing NIBS, considering four levels: (1) context, (2) target, (3) dose, and (4) timing. By addressing inter- and intra-individual variability, we highlight a path toward precision medicine using individualized Brain Stimulation to treat psychiatric diseases. Despite challenges and limitations, this approach encourages broader and more systematic adoption of personalized Brain Stimulation techniques to improve clinical outcomes.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 6","pages":"857-870"},"PeriodicalIF":6.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730914","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":"Early-life adversity alters adult nucleus incertus neurons: implications for neuronal mechanisms of increased stress and compulsive behavior vulnerability.","authors":"Anna Gugula, Patryk Sambak, Aleksandra Trenk, Sylwia Drabik, Aleksandra Nogaj, Zbigniew Soltys, Andrew L Gundlach, Anna Blasiak","doi":"10.1038/s41386-025-02089-0","DOIUrl":"10.1038/s41386-025-02089-0","url":null,"abstract":"<p><p>Early-life stress (ELS) arising from physical and emotional abuse disrupts normal brain development and impairs hypothalamic-pituitary-adrenal axis function, increasing the risk of psychopathological disorders and compulsive behaviors in adulthood. However, the underlying neural mechanisms remain unclear. The brainstem nucleus incertus (NI) is a highly stress-sensitive locus, involved in behavioral activation and stress-induced reward (food/alcohol) seeking, but its sensitivity to ELS remains unexplored. We used neonatal maternal separation stress in rats as a model for ELS and examined its impact on stress-related mRNA and neuropeptide expression in the NI, using fluorescent in situ hybridization and immunohistochemistry, respectively. Using whole-cell, patch-clamp recordings we determined the influence of ELS on the synaptic activity, excitability, and electrophysiological properties of NI neurons. Using c-Fos protein expression we also assessed the impact of ELS on the sensitivity of NI neurons to acute restraint stress in adulthood. ELS weakened the acute stress responsiveness of NI neurons, and caused dendritic shrinkage, impaired synaptic transmission and altered electrophysiological properties of NI neurons in a cell-type-specific manner. Additionally, ELS increased the expression of mRNA encoding corticotropin-releasing hormone receptor type 1 and the nerve-growth factor receptor, TrkA in adult NI. The multiple, cell-type specific changes in the expression of neuropeptides and molecules associated with stress and substance abuse in the NI, as well as impairments in NI neuron morphology and electrophysiology caused by ELS and observed in the adult brain, may contribute to the increased susceptibility to stress and compulsive behaviors observed in individuals with a history of ELS.</p>","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670199","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}