Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology最新文献

{"title":"Network homeostasis: functional brain network alterations and relapse in remitted late-life depression.","authors":"Andrew R Gerlach, Helmet T Karim, Antonija Kolobaric, Brian D Boyd, Kevin Kahru, Robert T Krafty, Olusola Ajilore, Warren D Taylor, Carmen Andreescu","doi":"10.1038/s41386-025-02138-8","DOIUrl":"10.1038/s41386-025-02138-8","url":null,"abstract":"<p><p>Late-life depression (LLD) is highly recurrent and associated with disability and increased mortality. In this study, we aim to identify neurobiological factors that are prospectively associated with relapse risk in late-life depression. We recruited 145 older adults (age ≥ 60): 102 recently remitted LLD participants and 43 healthy comparisons. Participants underwent baseline MRI and evaluation of depression symptoms/status for up to 2 years. We evaluated intrinsic network connectivity for 111 participants (39 healthy comparisons, 47 stable remitted, 25 relapsed). Compared to healthy comparisons, LLD participants had lower connectivity within the somatomotor network and greater connectivity between the executive control and default mode networks (DMN). Lower connectivity of DMN to somatomotor and salience networks was associated with relapse. Overall, connectivity of relapse participants was more similar to healthy comparisons than connectivity of stable remitted participants was. We found robust differences in network functional connectivity between stable remitted and relapsed participants. We also found evidence of neural \"scarring,\" or persistent functional network differences at baseline in all participants with a history of depression. Alterations in DMN connectivity were observed most prominently. Notably, the network structure of relapsed participants was more similar to healthy comparisons than stable remitted participants. These findings indicate that remission is associated with persistent functional network alterations while vulnerability to relapse is associated with a failure to establish a new stable homeostatic functional network structure.</p>","PeriodicalId":520722,"journal":{"name":"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct structural deficits in treatment-resistant schizophrenia and their putative neurotransmitter basis: a source-based morphometry analysis.","authors":"Huan Huang, Xiaowei Wang, Xuan Qin, Rui Xu, Ying Xiong, Cheng Chen, Qirong Wan, Hao Liu, Chang Shu, Wei Yuan, Yunlong Peng, Yuan Zhou, Huiling Wang, Lena Palaniyappan","doi":"10.1038/s41386-025-02135-x","DOIUrl":"https://doi.org/10.1038/s41386-025-02135-x","url":null,"abstract":"<p><p>Schizophrenia is associated with widespread gray matter reduction. This is influenced by the underlying connectivity, resulting in covarying patterns of structural changes that are more pronounced in treatment-resistant individuals. However, it remains uncertain whether a distinct network of brain regions, with specific neurotransmitter basis, forms the substrate for treatment resistance in schizophrenia. We investigated the structural covariance networks (SCN) in 198 individuals; 55 with treatment-resistant schizophrenia (TRS) and 79 without TRS (non-TRS) in active symptomatic phase, and 64 healthy controls (HC) using Calhoun's Source-Based Morphometry. We mapped the putative neurotransmitter basis of the SCNs using a PET-based chemoarchitectural atlas. Twelve independent components (i.e., SCNs) were identified. A prefrontal-limbic SCN had lower gray matter volume (GMV) in TRS compared to HC and non-TRS (F = 7.757, p < 0.001, FDR-corrected). Spatial correlation with chemoarchitectural atlas revealed predominant contributions from serotonergic [5HT_1b and 5HT_2a], glutamatergic [mGluR₅], histaminergic [H₃], and opioid [MOR] receptors for this TRS-related SCN (all p_{spin-permutation} < 0.05, FDR-corrected). A different SCN comprised of dorsal fronto-temporal and parieto-occipital regions, not associated with  any specific neurotransmitter distribution, exhibited reduced GMV in both TRS and non-TRS groups vs. HC (F = 7.239, p < 0.001, FDR-corrected). Amidst the generic GMV reduction that is shared with non-TRS patients, patients with TRS have specific prefrontal-limbic structural deficits with a unique non-dopaminergic chemoarchitecture. These findings indicate a putative molecular and structural basis for poor treatment response, guiding the development of second- and third-line pharmacotherapies for TRS.</p>","PeriodicalId":520722,"journal":{"name":"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FGF21 analogue PF-05231023 on alcohol consumption and neuronal activity in the nucleus accumbens.","authors":"Bart J Cooley, Cassandra V Occelli Hanbury-Brown, Eun A Choi, Willow A Heller, Alyssa W Lim, Andrew J Lawrence, Paul S Haber, Gavan P McNally, E Zayra Millan","doi":"10.1038/s41386-025-02133-z","DOIUrl":"https://doi.org/10.1038/s41386-025-02133-z","url":null,"abstract":"<p><p>Fibroblast growth factor 21 (FGF21) is a liver-derived hormone known to suppress alcohol consumption in mice and non-human primates. However, the role of FGF21 in modulating environmental and behavioural factors driving alcohol consumption-such as cue-driven responses and effortful actions to obtain alcohol-and its effects on neural activity related to consumption, remain unclear. Here, we evaluated the impact of PF-05231023, a long-acting FGF21 analogue, across multiple dimensions of alcohol consumption and motivation and examined consumption-related activity in the nucleus accumbens. PF-05231023 reduced alcohol intake and preference in a dose- and sex-specific manner; diminished approach behaviours following an alcohol but not sucrose cue; and decreased lever-pressing under a progressive-ratio schedule, both alone and when combined with the Glucagon-like peptide-1 (GLP-1) agonist Exendin-4; it did not reduce lever-pressing for sucrose in alcohol-naïve mice. Additionally, PF-05231023 altered the microstructure of alcohol consumption by shortening drinking bouts and increased the recruitment of nucleus accumbens (Acb) neurons associated with bout termination as determined by micro-endoscopy of GCaMP7f. These findings demonstrate that PF-05231023 broadly suppresses alcohol-motivated behaviours without impacting natural reward and that targeting FGF21 signaling in combination with GLP-1 agonists may enhance therapeutic efficacy. Mechanistically, the observed reductions in alcohol consumption following PF-05231023 may involve diminished alcohol palatability and modulation of neuronal activity from distinct subsets of Acb neurons.</p>","PeriodicalId":520722,"journal":{"name":"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DLPFC: The Decade circLe CCNP Family Cohort.","authors":"Zhe Zhang, Ning Yang","doi":"10.1038/s41386-025-02131-1","DOIUrl":"https://doi.org/10.1038/s41386-025-02131-1","url":null,"abstract":"","PeriodicalId":520722,"journal":{"name":"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep patterns predicting stress resilience are dependent on sex.","authors":"Brittany J Bush, Affra Mohamed, Eva-Jeneé Andrews, Gabrielle Cain, Ayobami Fawole, Hadiya Johnson, Ashton Arocho, Zhimei Qiao, Ketema N Paul, J Christopher Ehlen","doi":"10.1038/s41386-025-02124-0","DOIUrl":"10.1038/s41386-025-02124-0","url":null,"abstract":"<p><p>Sleep disturbances and stress have a well-established link with neuropsychiatric illness; however, the nature of this relationship remains unclear. Recently, studies using the mouse social-defeat stress model revealed a causal role for non-rapid eye movement (NREM) sleep in the maladaptive behavioral responses to stress. These results suggest a novel function for NREM sleep; as a response by cortical neurons to mitigate the maladaptive effects of stress. A major limitation in many social defeat studies has been the exclusion of females. Women exhibit a greater prevalence of both affective disorders and sleep disturbances compared to men, thus there is a clear need to understand sleep-stress interactions in females. The present study adapts recently developed female social-defeat stress models to allow social-defeat and EEG in male-female pairs. Our findings duplicate the behavioral responses that occur in other female, nondiscriminatory, and male models of social-defeat stress. Analysis of electroencephalographic (EEG) recordings, before exposure to stress, reveal that resilience is associated with differences in both NREM and REM sleep that are dependent on sex. After social defeat stress, NREM sleep was increased only in resilient males. In females, susceptibility to stress was associated with increased durations in NREM-sleep bouts. A potential cause of these sleep differences was also identified prior to stress exposure, sex differences in recovery from NREM-sleep loss; thus, suggesting an underlying sex-difference in the homeostatic process regulating sleep interactions with social-defeat stress. These findings suggest that NREM sleep quality is lower in resilient females, whereas the amount of REM sleep is decreased in susceptible females-when compared to males of the same behavioral phenotype. Overall, our findings reveal sexual dimorphism in both the sleep characteristics predicting resilience and sleep changes induced by social-defeat stress.</p>","PeriodicalId":520722,"journal":{"name":"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144096765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The efficacy of elevating anandamide via inhibition of fatty acid amide hydrolase (FAAH) combined with internet-delivered cognitive behavioral therapy in the treatment of post-traumatic stress disorder: a randomized, placebo-controlled clinical trial.","authors":"Leah M Mayo, Emelie Gauffin, Gavin N Petrie, Ryann Tansey, Raegan Mazurka, Connor J Haggarty, Madeleine R Jones, Hilda Engelbrektsson, Victoria Aminoff, Anisja Hühne-Landgraf, Mark E Schmidt, Darrel J Pemberton, Cecilia Fredlund, Lars Östman, Hanna Karlsson, Andreas Löfberg, Michal Pietrzak, Gerhard Andersson, Andrea Johansson Capusan, Matthew N Hill, Markus Heilig","doi":"10.1038/s41386-025-02128-w","DOIUrl":"https://doi.org/10.1038/s41386-025-02128-w","url":null,"abstract":"<p><p>Post-traumatic stress disorder (PTSD) is a severe mental health disorder with limited treatment options. Gold standard treatment includes cognitive behavioral therapies (CBT) that incorporate exposure to traumatic memories to facilitate extinction. CBT can be effective in PTSD, but effects are incomplete and symptoms are prone to spontaneous return. Pharmacologically facilitating fear extinction could potentiate the effects of exposure-based therapy. Here, we explored whether targeting the endocannabinoid (eCB) system, a neuromodulatory system critically involved in fear extinction, would promote the efficacy of exposure-based CBT. Specifically, we tested the effects of elevating the eCB ligand anandamide (AEA) via inhibition of its main degradative enzyme, fatty acid amide hydrolase (FAAH). In this double-blind, placebo-controlled study, patients with PTSD (N = 100; 85 women) were randomized to the FAAH inhibitor (FAAHi) JNJ-42165279 (25 mg b.i.d.) or placebo for 12 weeks. In weeks 5-12, all participants completed an internet-delivered CBT that included exposure-based modules. The primary outcome was clinician-assessed PTSD symptom severity (CAPS-5). Secondary outcomes included self-reported symptoms of PTSD, depression, anxiety, and sleep quality. Blood samples were taken to measure levels of drug and eCBs. Overall, PTSD symptoms improved over time. While FAAHi increased AEA levels, there was no effect of FAAHi on PTSD symptoms or any secondary measure. FAAHi combined with internet-delivered CBT did not improve PTSD symptoms to a greater extent than internet-delivered CBT alone. Thus, FAAH inhibition does not appear to be a suitable adjunct treatment for enhancing CBT in PTSD. This study was registered as Eudra-CT 2020-001965-36.</p>","PeriodicalId":520722,"journal":{"name":"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144096766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ACNP 61st Annual Meeting: Author Index.","authors":"","doi":"10.1038/s41386-022-01488-x","DOIUrl":"https://doi.org/10.1038/s41386-022-01488-x","url":null,"abstract":"","PeriodicalId":520722,"journal":{"name":"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology","volume":" ","pages":"521-554"},"PeriodicalIF":7.6,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9721317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40569006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}