Neuropsychopharmacology最新文献

{"title":"Development of the McLean Hospital MENTOR Program to enhance mental health career pathways.","authors":"Courtney Beard, Michaela B Swee, Zelda McGhee, Fran Barth, Kimberly Arditte Hall, Nicole Rossi, Catharyn Gildesgame, Kerry Ressler","doi":"10.1038/s41386-025-02118-y","DOIUrl":"https://doi.org/10.1038/s41386-025-02118-y","url":null,"abstract":"","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009063","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":"Changes in nucleus accumbens core translatome accompanying incubation of cocaine craving.","authors":"Alex B Kawa, Joel G Hashimoto, Madelyn M Beutler, Marina Guizzetti, Marina E Wolf","doi":"10.1038/s41386-025-02112-4","DOIUrl":"https://doi.org/10.1038/s41386-025-02112-4","url":null,"abstract":"<p><p>In the 'incubation of cocaine craving' model of relapse, rats exhibit progressive intensification (incubation) of cue-induced craving over several weeks of forced abstinence from cocaine self-administration. The expression of incubated craving depends on plasticity of excitatory synaptic transmission in nucleus accumbens core (NAcC) medium spiny neurons (MSN). Previously, we found that the maintenance of this plasticity and the expression of incubation depends on ongoing protein translation, and the regulation of translation is altered after incubation of cocaine craving. Here we used male and female rats that express Cre recombinase in either dopamine D1 receptor- or adenosine 2a (A2a) receptor-expressing MSN to express a GFP-tagged ribosomal subunit in a cell-type specific manner, enabling us to use Translating Ribosome Affinity Purification (TRAP) to isolate actively translating mRNAs from both MSN subtypes for analysis by RNA-seq. We compared rats that self-administered saline or cocaine. Saline rats were assessed on abstinence day (AD) 1, while cocaine rats were assessed on AD1 or AD40-50. For both D1-MSN and A2a-MSN, there were few differentially translated genes between saline and cocaine AD1 groups. In contrast, pronounced differences in the translatome were observed between cocaine rats on AD1 and AD40-50, and this was far more robust in D1-MSN. Notably, all comparisons revealed sex differences in translating mRNAs. Sequencing results were validated by qRT-PCR for several genes of interest. This study, the first to combine TRAP-seq, transgenic rats, and a cocaine self-administration paradigm, identifies translating mRNAs linked to incubation of cocaine craving in D1-MSN and A2a-MSN of the NAcC.</p>","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026115","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":"A rat model of volitional mutual social interactions.","authors":"Cody A Lis, Antonino Casile, Bronte Feulner, Jonathan Garcia, Rajtarun Madangopal, Kimberly M Papastrat, Zhengyi Huang, Amanda Pacheco-Spiewak, Leslie A Ramsey, Marco Venniro","doi":"10.1038/s41386-025-02113-3","DOIUrl":"https://doi.org/10.1038/s41386-025-02113-3","url":null,"abstract":"<p><p>Social interactions are essential for building societies and fostering cooperation among individuals. These behaviors are governed by complex norms and signaling mechanisms promoting mutual engagement. While animal models are often used to study social behaviors, they typically focus on one individual, overlooking the role and motivation of an otherwise passive social partner. Here, we developed a model where resident and partner rats voluntarily engage in mutual social interactions. In this model, the resident initiates interaction by pressing a lever to activate cues for the partner, who responds by pressing an additional lever, leading to social interaction. To test motivation for mutual social interaction, we increased the effort required for both residents and partners either concurrently or independently. We further investigated the mechanisms underlying these interactions by manipulating the norepinephrine system both systemically and centrally during mutual social interactions. Both male and female paired rats consistently demonstrate mutual motivation to engage in social interactions, regardless of their roles. The rats effectively coordinate their actions, showing low latency and high engagement frequency even as effort demands increase. The average social score analysis identified a significant proportion of highly motivated social pairs. Manipulating the norepinephrine system selectively disrupted the distribution of highly motivated social pairs, emphasizing its role in regulating social interactions. Ablating norepinephrine terminals had no impact on motivation for food rewards, further confirming that central norepinephrine manipulation specifically affects mutual social interactions. Our findings provide insight into the fundamental behavioral and neurobiological mechanisms underlying sociability and complex social structures in rodents.</p>","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036683","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":"Comparing neuromodulation targets to reduce cigarette craving and withdrawal: a randomized clinical trial.","authors":"Nicole Petersen, Michael R Apostol, Timothy Jordan, Thuc Doan P Ngo, Nicholas W Kearley, Edythe D London, Andrew F Leuchter","doi":"10.1038/s41386-025-02106-2","DOIUrl":"https://doi.org/10.1038/s41386-025-02106-2","url":null,"abstract":"<p><p>Cigarette smoking remains the leading preventable cause of death, emphasizing the need for new therapeutics, such as repetitive transcranial magnetic stimulation (TMS). We tested the hypothesis that TMS to three targets would reduce cigarette craving and withdrawal by modulating connectivity within and between three canonical networks in a randomized clinical trial (ClinicalTrials.gov: NCT03827265). Participants (N = 72; DSM-5 tobacco use disorder, ≥1 year of daily smoking) received one session of TMS to hubs of canonical resting-state networks: the dorsolateral prefrontal cortex (dlPFC), superior frontal gyrus (SFG), posterior parietal cortex (PPC), and area v5 (control). Self-reports (craving, withdrawal, and negative affect) and resting-state functional connectivity were measured before and after stimulation. SFG stimulation significantly reduced craving (95% CI, 0.0476-7.9559) and withdrawal (95% CI, 0.9225-8.1063) versus control, with larger effects in men (D = 0.59) than in women (D = 0.30). SFG stimulation did not change network connectivity, whereas dlPFC stimulation increased somatomotor, default mode, and dorsal attention network connectivity. No severe or unexpected treatment-related adverse events occurred. These findings suggest that SFG shows promise as a target for smoking-cessation treatment, especially for men. Further trials are warranted to confirm efficacy and develop imaging biomarkers for precision neuromodulation.</p>","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994450","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":"Inflammation is associated with avolition and reduced resting state functional connectivity in corticostriatal reward circuitry in patients with schizophrenia.","authors":"David R Goldsmith, Courtney S Ning, Gregory P Strauss, Robin E Gross, Jessica A Cooper, Evanthia C Wommack, Ebrahim Haroon, Jennifer C Felger, Elaine F Walker, Michael T Treadway, Andrew H Miller","doi":"10.1038/s41386-025-02114-2","DOIUrl":"https://doi.org/10.1038/s41386-025-02114-2","url":null,"abstract":"<p><p>Low-grade inflammation has been associated with negative symptoms in patients with schizophrenia. Of these symptoms, deficits in motivation and pleasure, especially in the domain of avolition, are particularly disabling. Effects of inflammation on motivational deficits in patients with depression are associated with disruptions in corticostriatal reward circuitry involving the inferior ventral striatum (iVS) and ventromedial prefrontal cortex (vmPFC). Accordingly, we examined the relationships among inflammation, negative symptoms, and corticostriatal reward circuitry in patients with schizophrenia. Negative symptoms and high sensitivity C-reactive protein (hsCRP) were obtained in 57 individuals with schizophrenia. Resting state functional connectivity (rsFC) was obtained from a subset of 43 of these individuals. Associations were tested between hsCRP and the motivation and pleasure (MAP) and expressivity (EXP) dimensions of the Brief Negative Symptom Scale (BNSS) as well as targeted rsFC between iVS and vmPFC. Covariates in all statistical models included age, sex, race, smoking, body mass index, depression, and chlorpromazine equivalents. hsCRP was significantly associated with BNSS MAP (β = 0.34, p_corr = 0.022, specifically the domains of avolition and asociality (p < 0.05), but not BNSS EXP (β = -0.17, p_corr = 0.57) or the domains of blunted affect or alogia (both p > 0.05). hsCRP was also significantly associated with decreased rsFC from right iVS to vmPFC (β=-0.37, p_corr = 0.029), which in turn, was associated with increased avolition in individuals with higher (hsCRP >2 mg/L) but not lower inflammation (β=-14.01, p = 0.007 vs. β = 0.07, p = 0.77, respectively). hsCRP was associated with reduced avolition and corticostriatal rsFC in patients with schizophrenia and increased inflammation, underscoring the need for further research to replicate these associations with brain connectivity changes in this subgroup of individuals with schizophrenia.</p>","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041301","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":"Associations between structural brain measures and cognitive function in bipolar disorder: a systematic review and meta-analysis.","authors":"Brett D M Jones, Julia Gallucci, On Yee Jones, Peter Zhukovsky, Stanley Wong, Karina Lakhani, Rayyan Farooqui, Lauren Stirpe, Ahmed K Eltom Mohamed, Paramveer Love, Aristotle N Voineskos, Colin Hawco, Abigail Ortiz, Benoit H Mulsant, M Ishrat Husain","doi":"10.1038/s41386-025-02096-1","DOIUrl":"https://doi.org/10.1038/s41386-025-02096-1","url":null,"abstract":"<p><p>Bipolar disorder (BD) is a chronic condition characterized by recurrent mood episodes and persistent cognitive deficits that span multiple domains, ultimately impacting daily functioning. Understanding the neural underpinnings of these impairments is crucial. In a systematic review and meta-analysis examining 80 studies (with 50 meeting criteria for meta-analysis) of adults with BD, relationships between structural brain measures and cognitive performance were evaluated. Participants were diagnosed according to standard criteria, underwent structural and diffusion-weighted MRI, and completed standardized cognitive assessments. The meta-analyses indicated significant associations between both grey matter and white matter indices and cognitive functioning, reflected in moderate effect sizes. Notably, these associations exhibited substantial heterogeneity. Meta-regression revealed that bipolar subtype and current mood state moderated the observed brain-cognition relationships, with bipolar I and euthymic individuals showing higher associations with grey matter metrics. Cognitive domain differences also played a key role, indicating that certain cognitive functions are more strongly linked to structural brain measures than others. Brain networks emerged as a global influence on cognition, with limited differences in pairwise comparisons. Age, sex, psychosis, and mania were not found to significantly moderate these relationships. Overall, this work suggests that structural alterations in grey and white matter in individuals with BD may contribute meaningfully to cognitive difficulties, while brain networks may provide a broad integrative framework for these associations. These findings underscore the importance of considering both global and specific neural factors when exploring the pathophysiology of cognitive impairment in BD.</p>","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028860","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":"Effects of methamphetamine on two measures of reward: Euphoria and neural activation to reward cues.","authors":"Hanna Molla, Joseph DeBrosse, Sarah Keedy, Royce Lee, Harriet de Wit","doi":"10.1038/s41386-025-02110-6","DOIUrl":"https://doi.org/10.1038/s41386-025-02110-6","url":null,"abstract":"<p><p>Stimulants enhance dopamine function, affecting diverse aspects of reward function from neural processing of reward cues to feelings of well-being in humans. However, little is known about the relationships among different measures of reward function. Understanding relationships among different indices of reward processing could provide insight into the processes that control motivated behavior. The present study examined the effects of a single dose of methamphetamine on two measures of reward in healthy adults: feelings of well-being and neural activation with reward-related stimuli. In a randomized, within-subject, double-blind study, 88 healthy men and women received a single 20 mg oral dose of methamphetamine (MA) and placebo, across two sessions. Regional activations to reward-related cues were assessed using fMRI during the Monetary Incentive Delay task, and positive subjective effects of MA were assessed using standardized questionnaires. As expected, MA increased euphoria and feelings of well-being. MA had minimal effects on neural activation during either anticipation or receipt of reward, but it significantly increased ventral striatal activation during anticipation of monetary loss, suggesting heightened salience of loss-related cues. As reported previously, caudate activation during reward anticipation during the non-drug (placebo) session was correlated with euphoria induced by MA (on the MA session). However, this correlation between cue-induced neural activation and euphoria was not apparent on the MA session. Thus, MA-induced euphoria was related to reward cue-elicited neural activation only when participants were tested without the drug. MA increased neural reactivity to loss, and this was not correlated with euphoria. These findings suggest that MA can dampen reward-related neural activity normally detected in the drug-free state, and that it enhances brain responses to loss. Further research is needed to determine how neural responses to reward or loss cues are related to feelings of well-being, and how either of these affect reward-related behavior.</p>","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002947","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":"Mapping brain-wide activity networks: brainways as a tool for neurobiological discovery.","authors":"Ben Kantor, Keren Ruzal, Inbal Ben-Ami Bartal","doi":"10.1038/s41386-025-02105-3","DOIUrl":"https://doi.org/10.1038/s41386-025-02105-3","url":null,"abstract":"<p><p>Identifying brain-wide neural circuits and targeting these areas for neuropharmacological interventions are significant challenges in contemporary neuroscience. Traditional methods for registering and quantifying fluorescence in brain slices are labor-intensive and struggle to extract functional insights from complex datasets. To address these challenges, we introduce Brainways-an AI-based, open-source software that streamlines neural network identification from digital imaging to network analysis. Brainways facilitates neurobiological research by enabling automatic registration of coronal brain slices to any 3D brain atlas, along with precise quantification of fluorescent markers, such as activity markers and tracers, across brain regions. Brainways incorporates advanced statistical tools to identify neural patterns and functional networks associated with specific experimental contrasts. Trained on rat and mouse brain atlases, Brainways achieves over 93% atlas registration accuracy. The software also allows users to easily adjust the automatic registration through a user-friendly interface for enhanced accuracy. We present two experiment analyses demonstrating Brainways' capabilities. The first replicates and extends findings from a prior experiment on pro-social behavior in rats, wherein rats learned to free a trapped cagemate from a restrainer under ingroup and outgroup social conditions. Using Brainways, we analyzed approximately 300 times more tissue area than in our previous manual approach. The second experiment utilizes Multiplex RNAscope imaging for whole-brain registration, enabling combined quantification of cell type expression and activity markers. These analyses highlight Brainways' ability to link specific cell types and their activity to task conditions, providing detailed neural insights. Brainways offers a rapid and accurate solution for large-scale neurobiological projects, creating new opportunities to understand neural networks underlying complex behaviors.</p>","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006009","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":"Indirect, but not direct, lateral habenula projections to ventral tegmental area regulate the long-term consequences of neuropathic pain","authors":"Emily D. Prévost,&nbsp;David H. Root","doi":"10.1038/s41386-025-02111-5","DOIUrl":"10.1038/s41386-025-02111-5","url":null,"abstract":"","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 7","pages":"1025-1026"},"PeriodicalIF":6.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41386-025-02111-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991337","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":"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}