Neuropsychopharmacology最新文献

{"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":"Gamma-hydroxybutyrate to promote slow-wave sleep in major depressive disorder: a randomized crossover trial","authors":"Francesco Bavato, Laura K. Schnider, Dario A. Dornbierer, Julia R. Di Floriano, Benjamin Stucky, Nicole Friedli, Marina Janki, Boris B. Quednow, Hans-Peter Landolt, Oliver G. Bosch, Erich Seifritz","doi":"10.1038/s41386-025-02104-4","DOIUrl":"10.1038/s41386-025-02104-4","url":null,"abstract":"In major depressive disorder (MDD), main clinical features include insomnia and increased daytime sleepiness. However, specific treatment options to promote sleep in MDD are limited. Gamma-hydroxybutyrate (GHB, administered as sodium oxybate) is a GHB/GABAB receptor agonist used clinically in narcolepsy, where it promotes restorative slow-wave sleep (SWS) while reducing next-day sleepiness. Hence, we performed a randomized, placebo- and active comparator-controlled, double-blind, crossover trial to investigate the sleep-promoting properties of GHB in individuals with MDD. Outpatients aged 20–65 years fulfilling the DSM-5 criteria for MDD were enrolled. A single nocturnal dose of GHB (50 mg/kg) was compared with a single evening dose of the clinical competitor trazodone (1.5 mg/kg) and placebo. Of 29 randomized patients, 23 received at least one intervention and were included in the analysis. Primary outcomes were nocturnal slow wave sleep ([SWS] assessed by polysomnography), next-day vigilance (median response time and number of lapses on the psychomotor vigilance test [PVT]), next-day working memory (median speed and accuracy on an N-back task), and next-day plasma brain-derived neurotrophic factor (BDNF) levels. GHB robustly prolonged SWS compared to both trazodone and placebo. GHB also prolonged total sleep time and enhanced sleep efficiency, while reducing sleep stages N1, N2, and wake-after-sleep-onset. While the median response time on the next-day PVT was unaffected, GHB reduced the number of lapses compared to trazodone and placebo. No effects on next-day working memory performance and BDNF levels were observed. No serious adverse events occurred. Overall, a single nocturnal dose of GHB effectively promotes SWS and shows more favorable effects on next-day vigilance than trazodone and placebo. Future studies should investigate GHB in clinical settings, including repeated administration.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 8","pages":"1237-1244"},"PeriodicalIF":6.6,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41386-025-02104-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041295","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":"Prefrontal cortex excitatory neurons show distinct response to heroin-associated cue and social stimulus after prolonged heroin abstinence in mice","authors":"Yunwanbin Wang, Junting Liu, Shuwen Yue, Lu Chen, Archana Singh, Tianshi Yu, Erin S. Calipari, Zi-Jun Wang","doi":"10.1038/s41386-025-02102-6","DOIUrl":"10.1038/s41386-025-02102-6","url":null,"abstract":"Substance use disorder (SUD) has been linked with social impairments. The social cognitive dysfunctions can further increase the risk of the development of SUD or relapse. Therefore, understanding the neural mechanism of substance exposure-associated social impairments is beneficial for the development of novel prevention or treatment strategies for SUD. The prefrontal cortex (PFC) is a key brain region involved in both social cognition and drug addiction. Specifically, the prelimbic part of PFC (PrL) regulates social interaction and heroin-seeking behavior. Therefore, in this study, we explored how PFC excitatory neurons respond to social stimuli after prolonged abstinence from heroin self-administration (SA). Using fiber photometry calcium imaging, we monitored calcium-dependent fluorescent signals in PrL CaMKII-expressing neurons during drug seeking and social interaction tests following 14 days of abstinence from heroin SA. We found that GCaMP6f signals in PrL CaMKII-expressing neurons were increased when heroin-associated cues were presented during drug-seeking tests in both male and female mice after prolonged heroin abstinence, although the baseline neuronal activity in home cage is lower in the heroin group. Conversely, the calcium signals in PrL CaMKII-expressing neurons during social investigation were decreased after heroin abstinence in both sexes, along with reduced total social interaction time. In addition, drug-seeking behavior is partially negatively correlated with social investigation time. These findings provide direct evidence showing that opioid exposure impairs the PFC functional response to social stimuli, which may potentially increase the risk for opioid relapse.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 8","pages":"1284-1297"},"PeriodicalIF":6.6,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995499","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":"Alpha-2 agonism in the locus coeruleus impairs learning driven by negative prediction error","authors":"Ashleigh K. Brink, Simon K. C. Lui, Laura H. Corbit","doi":"10.1038/s41386-025-02092-5","DOIUrl":"10.1038/s41386-025-02092-5","url":null,"abstract":"Refining previous learning when environmental contingencies change is a critical adaptive function. Studies have shown that systemic noradrenaline (NA) manipulations, as well as optogenetic manipulations of the locus coeruleus (LC), the primary source of forebrain NA, can improve long-term retention of appetitive extinction. To determine whether the contribution of NA is specific to extinction or extends to other forms of learning where reward is less than expected, we suppressed LC activity with clonidine, an α2A-adrenergic receptor agonist, in two tasks: compound extinction, where two previously rewarded cues are presented together and no longer rewarded, and overexpectation, where animals are presented with two previously rewarded cues but receive a single reward rather than the expected two. In compound extinction, we found no differences between groups in training, extinction, or a spontaneous recovery test. However, animals that received clonidine reacquired responding to the previously extinguished cue significantly faster than saline-treated animals, suggesting weakened extinction learning. In overexpectation testing, the saline group responded significantly less to a stimulus that had undergone overexpectation relative to a control stimulus, indicating that they had recalibrated their estimation of reward magnitude following training where reward was less than expected. In contrast, clonidine-treated animals did not differ in responding to the overexpectation versus control stimuli, suggesting that clonidine impaired learning resulting from overexpectation. These results demonstrate that activity of the LC is important for learning to reduce responding in both extinction and overexpectation paradigms.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 7","pages":"1186-1193"},"PeriodicalIF":6.6,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41386-025-02092-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982839","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":"Psilocybin therapy for mood dysfunction in Parkinson’s disease: an open-label pilot trial","authors":"Ellen R. Bradley, Kimberly Sakai, Gisele Fernandes-Osterhold, Balázs Szigeti, Connie Ludwig, Jill L. Ostrem, Caroline M. Tanner, Meredith A. Bock, Katiah Llerena, Patrick R. Finley, Aoife O’Donovan, Jose Rafael P. Zuzuarregui, Zachary Busby, Amber McKernan, Andrew D. Penn, Aliss C. C. Wang, Raymond C. Rosen, Joshua D. Woolley","doi":"10.1038/s41386-025-02097-0","DOIUrl":"10.1038/s41386-025-02097-0","url":null,"abstract":"Mood dysfunction is highly prevalent in Parkinson’s disease (PD), a main predictor of functional decline, and difficult to treat—novel interventions are critically needed. Psilocybin shows early promise for treating depression and anxiety, but its potential in PD is unknown, as safety concerns have excluded people with neurodegenerative disease from previous trials. In this open-label pilot (NCT04932434), we examined the feasibility of psilocybin therapy among people with mild to moderate stage PD plus depression and/or anxiety. 12 participants (mean age 63.2 ± 8.2 years, 5 women) received psilocybin (one 10 mg followed by one 25 mg dose) with psychotherapy. There were no serious adverse events, no medical interventions required to manage effects of psilocybin, and no exacerbation of psychosis. Ten participants experienced treatment-emergent adverse events; the most frequent were anxiety, nausea, and increased blood pressure. We observed no worsening of PD symptomology measured by the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). On the contrary, non-motor (MDS-UPDRS Part I: –13.8 ± 1.3, p < 0.001, Hedges’ g = 3.0) and motor symptoms (Part II: –7.5 ± 0.9, p < 0.001, g = 1.2; Part III: –4.6 ± 1.3, p = 0.001; g = 0.3) as well as performance in select cognitive domains (Paired Associates Learning [-0.44 ± 0.14, p = .003, g = 0.4], Spatial Working Memory [–0.52 ± 0.17, p = 0.003, g = 0.7], and Probabilistic Reversal Learning [2.9 ± 0.9, p = 0.003, g = 1.3]) improved post-treatment, and improvements were sustained until the final safety assessment one month following drug exposure. Baseline Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale (HAM-A) scores were 21.0 ± 8.7 and 17.0 ± 3.7, respectively. Both improved to a clinically meaningful degree post-treatment; these improvements persisted to the final assessment three months following drug exposure (MADRS: -9.3 ± 2.7, p = .001, g = 1.0; HAM-A: –3.8 ± 1.7; p = 0.031, g = 0.7). This study provides the first data on psilocybin’s effects in any neurodegenerative disease. Results suggest that psilocybin therapy in PD warrants further investigation.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 8","pages":"1200-1209"},"PeriodicalIF":6.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41386-025-02097-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982841","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":"Aversion-induced dopamine reductions predict drug-taking and escape behaviors","authors":"Elaine M. Grafelman, Bridgitte E. Côté, Lisa Vlach, Ella Geise, G. Nino Padula, Daniel S. Wheeler, Matthew C. Hearing, John R. Mantsch, Robert A. Wheeler","doi":"10.1038/s41386-025-02101-7","DOIUrl":"10.1038/s41386-025-02101-7","url":null,"abstract":"Dopamine release in the nucleus accumbens core (NAcC) has long been associated with the promotion of motivated behavior. However, inhibited dopamine signaling can increase behavior in certain settings, such as during drug self-administration. While aversive environmental stimuli can reduce dopamine, it is unclear whether such stimuli reliably engage this mechanism in different contexts. Here we compared the physiological and behavioral responses to the same aversive stimulus in different designs to determine if there is uniformity in the manner that aversive stimuli are encoded and promote behavior. NAcC dopamine was measured using fiber photometry in male and female rats during cocaine self-administration sessions in which an acutely aversive 90 dB white noise was intermittently presented. In a separate group of rats, aversion-induced changes in dopamine were measured during an escape design in which operant responses terminated aversive white noise. Aversive white noise significantly reduced NAcC dopamine and increased cocaine self-administration in both male and female rats. The same relationship was observed in the escape design, in which white noise reduced dopamine and promoted the performance of escape behavior. In both designs, the magnitude of the dopamine reduction predicted behavioral performance. While prior research demonstrated that pharmacologically reduced dopamine signaling can promote intake, this report demonstrates that this physiological mechanism is naturally engaged by aversive environmental stimuli and is generalizable to non-drug contexts. These findings illustrate a common physiological signature in response to aversion that may promote both adaptive and maladaptive behavior.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 9","pages":"1376-1384"},"PeriodicalIF":6.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033849","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":"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":"10.1038/s41386-025-02100-8","url":null,"abstract":"","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 7","pages":"1023-1024"},"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":"50 7","pages":"1194-1194"},"PeriodicalIF":6.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41386-025-02099-y.pdf","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":"OA","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":"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.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 9","pages":"1446-1454"},"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":"10.1038/s41386-025-02095-2","url":null,"abstract":"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.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 9","pages":"1385-1394"},"PeriodicalIF":6.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41386-025-02095-2.pdf","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}