Neuropsychopharmacology最新文献

{"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":"10.1038/s41386-025-02106-2","url":null,"abstract":"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.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 9","pages":"1319-1326"},"PeriodicalIF":6.6,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41386-025-02106-2.pdf","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":"OA","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,&nbsp;Julia Gallucci,&nbsp;On Yee Jones,&nbsp;Peter Zhukovsky,&nbsp;Stanley Wong,&nbsp;Karina Lakhani,&nbsp;Rayyan Farooqui,&nbsp;Lauren Stirpe,&nbsp;Ahmed K. Eltom Mohamed,&nbsp;Paramveer Love,&nbsp;Aristotle N. Voineskos,&nbsp;Colin Hawco,&nbsp;Abigail Ortiz,&nbsp;Benoit H. Mulsant,&nbsp;M. Ishrat Husain","doi":"10.1038/s41386-025-02096-1","DOIUrl":"10.1038/s41386-025-02096-1","url":null,"abstract":"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.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 8","pages":"1256-1264"},"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,&nbsp;Joseph DeBrosse,&nbsp;Sarah Keedy,&nbsp;Royce Lee,&nbsp;Harriet de Wit","doi":"10.1038/s41386-025-02110-6","DOIUrl":"10.1038/s41386-025-02110-6","url":null,"abstract":"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&nbsp;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.&nbsp;As expected, MA&nbsp;increased&nbsp;euphoria and feelings of well-being.&nbsp;MA had minimal effects on neural activation during either anticipation or receipt of reward, but&nbsp;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&nbsp;(placebo) session was correlated with euphoria induced by MA&nbsp;(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&nbsp;without the&nbsp;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.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 8","pages":"1298-1304"},"PeriodicalIF":6.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41386-025-02110-6.pdf","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":"OA","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}

{"title":"Rapid and sustained antidepressant effects of vaporized N,N-dimethyltryptamine: a phase 2a clinical trial in treatment-resistant depression","authors":"Marcelo Falchi-Carvalho,&nbsp;Fernanda Palhano-Fontes,&nbsp;Isabel Wießner,&nbsp;Handersson Barros,&nbsp;Raynara Bolcont,&nbsp;Sophie Laborde,&nbsp;Sérgio Ruschi B. Silva,&nbsp;Daniel Montanini,&nbsp;David C. Barbosa,&nbsp;Ewerton Teixeira,&nbsp;Rodrigo Florence-Vilela,&nbsp;Raissa Almeida,&nbsp;Rosana K. A. de Macedo,&nbsp;Flávia Arichelle,&nbsp;Érica J. Pantrigo,&nbsp;José V. Costa-Macedo,&nbsp;João Arthur da Cruz Nunes,&nbsp;Luiz Antonio de Araújo Costa Neto,&nbsp;Luis Fernando Nunes Ferreira,&nbsp;Luísa Dantas Corrêa,&nbsp;Romária Bárbara da Costa Bezerra,&nbsp;Emerson Arcoverde,&nbsp;Nicole Galvão-Coelho,&nbsp;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 &lt; 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":"Chronic, combinatorial targeting of NMDARs and 5-HT4Rs exerts extended behavioral effects against stress-induced perseverative behavior and hyponeophagia","authors":"Briana K. Chen,&nbsp;Alicia Whye,&nbsp;Louise C. Matthews,&nbsp;Taylor Moniz,&nbsp;Indira Mendez-David,&nbsp;Alain M. Gardier,&nbsp;Denis J. David,&nbsp;Stefanie Johns,&nbsp;Eric Weisblum,&nbsp;Christine A. Denny","doi":"10.1038/s41386-025-02107-1","DOIUrl":"10.1038/s41386-025-02107-1","url":null,"abstract":"Serotonin (5-HT) receptors and N-methyl-D-aspartate receptors (NMDARs) have both been implicated in stress-induced psychiatric disorders. However, there is a paucity of studies evaluating the effectiveness of novel combinatorial pharmacological treatments to treat stress-related disorders. Here, we evaluated whether administration of combinatorial (R,S)-ketamine, an NMDAR antagonist and Food and Drug Administration (FDA)-approved anesthetic, and prucalopride, a 5-HT type IV receptor (5-HT4R) agonist and FDA-approved drug for chronic idiopathic constipation (CIC), would have additional effects when administered after stress. A single injection of saline (Sal), (R,S)-ketamine (K), prucalopride (P), or a combined dose of (R,S)-ketamine and prucalopride (K + P) was administered for 1x, 2x, or 7x per week for 2 weeks after either contextual fear conditioning (CFC), learned helplessness (LH), stress enhanced fear learning (SEFL), or chronic corticosterone (CORT) stress in both sexes. Drug efficacy was assayed using assays to measure fear, behavioral despair, perseverative, and/or hyponeophagia. Combinatorial drug administration was also tested using intranasal delivery. We found that combinatorial K + P exerted additional effects, compared to either drug alone, in reducing a variety of stress-induced behaviors in both sexes. Moreover, intranasal dosing was also effective. Our results indicate that chronic administration of K + P has extended benefits for combating stress-induced pathophysiology. Our findings provide strong evidence that future clinical studies using this chronic treatment strategy may prove advantageous in decreasing a broad range of stress-induced psychiatric disorders.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 8","pages":"1210-1223"},"PeriodicalIF":6.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034554","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":"Ketamine-induced static and dynamic functional connectivity changes are modulated by opioid receptors and biological sex in rats.","authors":"Valeria Grasso, Joseph Tennyson, Raag D Airan, Tommaso Di Ianni","doi":"10.1038/s41386-025-02108-0","DOIUrl":"https://doi.org/10.1038/s41386-025-02108-0","url":null,"abstract":"<p><p>Subanesthetic ketamine is currently used as a rapid-acting treatment for varied neuropsychiatric disorders. However, the mechanistic underpinnings of its therapeutic action remain unclear, and emerging clinical and preclinical evidence highlights a potential involvement of the opioid system. We used pharmacological functional ultrasound imaging data acquired during and after ketamine administration in male and female rats pretreated with naltrexone, an opioid receptor antagonist, or vehicle. We found that ketamine-induced functional connectivity changes are modulated by opioid receptor blockade, and that these responses are dependent on biological sex. Specifically, naltrexone sex-dependently altered the connectivity patterns within the medial prefrontal cortex (mPFC), a key node of the brain's default-mode network, and between the mPFC and other functional nodes. Furthermore, ketamine produced an opioid-dependent shift toward states of increased dysconnectivity and brain entropy in male rats only. Our findings warrant further investigation into the neurophysiological underpinnings of ketamine action and potential sex-specific interactions with opioid receptors.</p>","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991338","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}