Neuropsychopharmacology最新文献

{"title":"In memoriam - George R. Breese, Ph.D.","authors":"Fulton T Crews, Thomas L Kash","doi":"10.1038/s41386-024-02026-7","DOIUrl":"https://doi.org/10.1038/s41386-024-02026-7","url":null,"abstract":"","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676402","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":"Decoding threat neurocircuitry representations during traumatic memory recall in PTSD.","authors":"Kierra R Morris, Michael Jaeb, Joseph E Dunsmoor, Zachary N Stowe, Josh M Cisler","doi":"10.1038/s41386-024-02028-5","DOIUrl":"https://doi.org/10.1038/s41386-024-02028-5","url":null,"abstract":"<p><p>The neurocircuitry mechanisms underlying recall of traumatic memories remain unclear. This study investigated whether traumatic memory recall engages neurocircuitry representations that mirror activity patterns engaged during generalized threat stimulus processing in Post Traumatic Stress Disorder (PTSD). Multivariate pattern analysis was used to train 3 decoders. A \"trauma\" decoder was trained on fMRI patterns during idiographic trauma versus neutral narratives in a sample of 73 adult women with PTSD. A separate cohort of 125 adult participants completed a reward and threat learning task, from which \"shock\" and \"reward loss\" decoders were trained on neural patterns during threat or reward outcome delivery, respectively. These decoders were then cross-tested on the alternative datasets, allowing analyses of the degree to which traumatic memory recall engaged neurocircuitry representations that overlap with more general aversive stimuli. Decoders were trained and tested in four networks related to salience processing as well bilateral amygdala and hippocampal masks. The shock decoder trained in a midcingulate / posterior insula network demonstrated elevated predictions for shock during traumatic versus neutral memory recall. Similarly, the trauma decoder made elevated predictions about trauma recall during shock versus no shock delivery across multiple networks related to salience processing. There was no overlap between reward loss decoder predictions and trauma memory recall or vice versa. PTSD participants with elevated re-experiencing symptoms demonstrated the highest engagement of shock activity patterns during trauma memory recall. These results suggest that trauma memory recall engages neurocircuitry representations that overlap with threat, specifically painful, stimulus delivery.</p>","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676400","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":"Anterior piriform cortex dysfunction underlies autism spectrum disorders-related olfactory deficits in Fmr1 conditional deletion mice.","authors":"Lingzhi Zhang, Chi Geng, Shan Li, Qingnan Tang, Penglai Liu, Wei Liu, Gaoxue Qiu, Anan Li, Ankang Hu, Fengjiao Chen","doi":"10.1038/s41386-024-02027-6","DOIUrl":"https://doi.org/10.1038/s41386-024-02027-6","url":null,"abstract":"<p><p>Previous studies indicated that ASD-related olfactory dysfunctions are rooted in the piriform cortex. However, the direct evidence supporting a causal link between the dysfunction of the piriform cortex and olfactory disorders in ASD is limited. In the present study, we explored the role of anterior piriform cortex (aPC) in ASD-related olfactory disorders by specifically ablating Fmr1, a leading known monogenic cause for ASD, in the pyramidal neurons. Our data demonstrated that the targeted deletion of Fmr1 in aPC pyramidal neurons was sufficient to induce deficits in olfactory detection. In vivo and in vitro electrophysiological recordings showed that the deletion of Fmr1 increased the activity of pyramidal neurons, exhibiting an enhanced excitatory response and a reduced inhibitory response upon odor stimulation. Furthermore, specific deletion of Fmr1 enhanced the power of beta oscillations during odor stimuli, meanwhile, disturbed excitatory and inhibitory synaptic transmission. The abnormal morphology of pyramidal neurons induced by the deletion of Fmr1 may be responsible for the impaired aPC neuronal function. These findings suggest that dysfunction of the aPC may play a role in olfactory impairments observed in ASD models related to Fmr1 deficiency.</p>","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644592","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 Δ⁹-tetrahydrocannabinol exposure in adolescent nonhuman primates: persistent abnormalities in economic demand and brain functional connectivity.","authors":"Brian D Kangas, Harshawardhan U Deshpande, Sarah L Withey, Roger D Spealman, Jack Bergman, Stephen J Kohut","doi":"10.1038/s41386-024-02024-9","DOIUrl":"https://doi.org/10.1038/s41386-024-02024-9","url":null,"abstract":"<p><p>Although chronic cannabis use during adolescence can alter brain function and impair complex behavioral processes, it is unclear whether such deficits persist into adulthood. Using a coordinated awake neuroimaging and behavioral approach in nonhuman primates, we addressed this issue by examining the impact of chronic adolescent exposure to Δ⁹-tetrahydrocannabinol (THC) on brain functional connectivity and motivational processes during early adulthood. Female and male squirrel monkeys (n = 23) were treated daily for 6 months during adolescence with vehicle or either a low (0.32 mg/kg) or high dose (3.2 mg/kg) of THC. Regional homogeneity and seed-to-whole-brain functional connectivity were analyzed prior to, during, and following discontinuation of chronic treatment to examine changes in regions implicated in reward processing. Subsequently, motivation and reward sensitivity in these subjects, now young adults, were evaluated in economic demand studies by determining the relationship between escalating response requirements and consumption of differing magnitudes of a palatable food reinforcer. Results show that adolescent THC exposure led to persistent alterations in mOFC, caudate, and ventral striatum whole-brain connectivity. Moreover, subjects treated with vehicle during adolescence displayed an orderly and expected inverse relationship between reward magnitude and demand elasticity, whereas THC-treated subjects exhibited dosage-dependent disorder in reward sensitivity and motivational deficits. Changes in neural circuitry (local connectivity in ventral striatum and whole brain connectivity in mOFC) and economic demand were correlated with indices of reward sensitivity in vehicle- but not THC-treated subjects. Taken together, these data indicate that chronic adolescent THC exposure produced long-lasting neurocognitive abnormalities in reward processing.</p>","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624239","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 sleepy cannabis constituent: cannabinol and its active metabolite influence sleep architecture in rats.","authors":"Jonathon C Arnold, Cassandra V Occelli Hanbury-Brown, Lyndsey L Anderson, Miguel A Bedoya-Pérez, Michael Udoh, Laura A Sharman, Joel S Raymond, Peter T Doohan, Adam Ametovski, Iain S McGregor","doi":"10.1038/s41386-024-02018-7","DOIUrl":"https://doi.org/10.1038/s41386-024-02018-7","url":null,"abstract":"<p><p>Medicinal cannabis is being used worldwide and there is increasing use of novel cannabis products in the community. Cannabis contains the major cannabinoids, Δ⁹-tetrahydrocannabinol (Δ⁹-THC) and cannabidiol (CBD), but also an array of minor cannabinoids that have undergone much less pharmacological characterization. Cannabinol (CBN) is a minor cannabinoid used in the community in \"isolate' products and is claimed to have pro-sleep effects comparable to conventional sleep medications. However, no study has yet examined whether it impacts sleep architecture using objective sleep measures. The effects of CBN on sleep in rats using polysomnography were therefore examined. CBN increased total sleep time, although there was evidence of biphasic effects with initial sleep suppression before a dramatic increase in sleep. CBN increased both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. The magnitude of the effect of CBN on NREM was comparable to the sleep aid zolpidem, although, unlike CBN, zolpidem did not influence REM sleep. Following CBN dosing, 11-hydroxy-CBN, a primary metabolite of CBN surprisingly attained equivalently high brain concentrations to CBN. 11-hydroxy-CBN was active at cannabinoid CB₁ receptors with comparable potency and efficacy to Δ⁹-THC, however, CBN had much lower activity. We then discovered that the metabolite 11-hydroxy-CBN also influenced sleep architecture, albeit with some subtle differences from CBN itself. This study shows CBN affects sleep using objective sleep measures and suggests an active metabolite may contribute to its hypnotic action.</p>","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624231","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":"Mitogen-activated protein kinase dependent presynaptic potentiation in the lateral habenula mediates depressive-like behaviors in rats.","authors":"Hoyong Park, Hakyun Ryu, Seungjae Zhang, Sungmin Kim, ChiHye Chung","doi":"10.1038/s41386-024-02025-8","DOIUrl":"https://doi.org/10.1038/s41386-024-02025-8","url":null,"abstract":"<p><p>Emerging evidence suggests that the enhanced activity of lateral habenula (LHb) is involved in depressive disorders. This abnormal potentiation of LHb neurons was shown to originate from presynaptic alterations; however, the mechanisms underlying this presynaptic enhancement and physiological consequences are yet to be elucidated. Previously, we reported that presynaptic transmission in the LHb is temporally rhythmic, showing greater activity in the afternoon than in the morning. Here, we used a learned helpless rodent model of depression to show that exposure to a stressor or incubation with the stress hormone, corticosterone, abolished the presynaptic temporal variation in the LHb. In addition, selective inhibition of mitogen-activated protein kinase (MAPK) kinase (MAPKK, MEK) activity in the LHb restored the presynaptic alteration even after stress exposure. Moreover, we observed a slight increase in phosphorylated synapsin I after stress exposure. Finally, we found that a blockade of MAPK signaling before stress exposure successfully prevented the depression-like behaviors, including behavioral despair and helplessness, in an acute learned helpless animal model of depression. Our study delineates the cellular and molecular mechanisms responsible for the abnormal presynaptic enhancement of the LHb in depression, which may mediate depressive behaviors.</p>","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624292","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: Punishment-resistant alcohol intake is mediated by the nucleus accumbens shell in female rats.","authors":"Allison J McDonald, Panthea Nemat, Thijs van 't Hullenaar, Dustin Schetters, Yvar van Mourik, Isis Alonso-Lozares, Taco J De Vries, Nathan J Marchant","doi":"10.1038/s41386-024-02023-w","DOIUrl":"https://doi.org/10.1038/s41386-024-02023-w","url":null,"abstract":"","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605708","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":"Common and contrasting effects of 5-HTergic signaling in pyramidal cells and SOM interneurons of the mouse cortex.","authors":"Nathalie Schmitz, Sadat Hodzic, Therese Riedemann","doi":"10.1038/s41386-024-02022-x","DOIUrl":"https://doi.org/10.1038/s41386-024-02022-x","url":null,"abstract":"<p><p>Serotonin (5-hydroxytryptamine, 5-HT) is a powerful modulator of neuronal activity within the central nervous system and dysfunctions of the serotonergic system have been linked to several neuropsychiatric disorders such as major depressive disorders or schizophrenia. The anterior cingulate cortex (aCC) plays an important role in cognitive capture of stimuli and valence processing and it is densely innervated by serotonergic fibers from the nucleus raphe. In order to understand how pathophysiological 5-HT signalling can lead to neuropsychiatric diseases, it is important to understand the physiological actions of 5-HT on cortical circuits. Therefore, we combined electrophysiological recordings with pharmacology and immunocytochemistry to investigate the effects of 5-HT on Somatostatin-positive interneurons (SOM-INs) and compared these to supragranular pyramidal cells (PCs). This comparison allowed us to identify common and contrasting effects of 5-HT on SOM-INs and PCs of the aCC resulting in a specific modulation of the excitation-to-inhibition balance in PCs but not in SOM-INs.</p>","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605706","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":"Peptidomimetic inhibitors targeting TrkB/PSD-95 signaling improves cognition and seizure outcomes in an Angelman Syndrome mouse model.","authors":"Emily Z Huie, Xin Yang, Mengia S Rioult-Pedotti, Kyle Tran, Emma R Monsen, Kim Hansen, Michelle A Erickson, Mandar Naik, Anna Y Yotova, William A Banks, Yu-Wen Alvin Huang, Jill L Silverman, John Marshall","doi":"10.1038/s41386-024-02020-z","DOIUrl":"10.1038/s41386-024-02020-z","url":null,"abstract":"<p><p>Angelman syndrome (AS) is a rare genetic neurodevelopmental disorder with profoundly debilitating symptoms with no FDA-approved cure or therapeutic. Brain-derived neurotrophic factor (BDNF), and its receptor tropomyosin receptor kinase B (TrkB), have a well-established role as regulators of synaptic plasticity, dendritic outgrowth and spine formation. Previously, we reported that the association of postsynaptic density protein 95 (PSD-95) with TrkB is critical for intact BDNF signaling in the AS mouse model, as illustrated by attenuated PLCγ and PI3K signaling and intact MAPK pathway signaling. These data suggest that drugs tailored to enhance the TrkB-PSD-95 interaction may provide a novel approach for the treatment of AS and a variety of neurodevelopmental disorders (NDDs). To evaluate this critical interaction, we synthesized a class of high-affinity PSD-95 ligands that bind specifically to the PDZ3 domain of PSD-95, denoted as Syn3 peptidomimetic ligands. We evaluated Syn3 and its analog D-Syn3 (engineered using dextrorotary (D)-amino acids) in vivo using the Ube3a exon 2 deletion mouse model of AS. Following systemic administration of Syn3 and D-Syn3, we demonstrate improvement in the seizure domain of AS. Learning and memory using the novel object recognition assay also illustrated improved cognition following Syn3 and D-Syn3, along with restored long-term potentiation. A pharmacokinetic analysis of D-Syn3 demonstrates that it crosses the blood-brain barrier (BBB), and the brain influx rate is in the range of CNS therapeutics. Finally, D-Syn3 treated mice showed a partial rescue in motor learning. Neither Syn3 nor D-Syn3 improved gross exploratory locomotion deficits, nor gait impairments that have been well documented in the AS rodent models. These findings highlight the need for further investigation of this compound class as a potential therapeutic for AS and other genetic NDDs.</p>","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605710","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":"Improved patient identification by incorporating symptom severity in deep learning using neuroanatomic images in first episode schizophrenia.","authors":"Wenjing Zhang, Lituan Wang, Xusha Wu, Li Yao, Zhang Yi, Hong Yin, Lei Zhang, Su Lui, Qiyong Gong","doi":"10.1038/s41386-024-02021-y","DOIUrl":"https://doi.org/10.1038/s41386-024-02021-y","url":null,"abstract":"<p><p>Brain alterations associated with illness severity in schizophrenia remain poorly understood. Establishing linkages between imaging biomarkers and symptom expression may enhance mechanistic understanding of acute psychotic illness. Constructing models using MRI and clinical features together to maximize model validity may be particularly useful for these purposes. A multi-task deep learning model for standard case/control recognition incorporated with psychosis symptom severity regression was constructed with anatomic MRI collected from 286 patients with drug-naïve first-episode schizophrenia and 330 healthy controls from two datasets, and validated with an independent dataset including 40 first-episode schizophrenia. To evaluate the contribution of regression to the case/control recognition, a single-task classification model was constructed. Performance of unprocessed anatomical images and of predefined imaging features obtained using voxel-based morphometry (VBM) and surface-based morphometry (SBM), were examined and compared. Brain regions contributing to the symptom severity regression and illness identification were identified. Models developed with unprocessed images achieved greater group separation than either VBM or SBM measurements, differentiating schizophrenia patients from healthy controls with a balanced accuracy of 83.0% with sensitivity = 76.1% and specificity = 89.0%. The multi-task model also showed superior performance to single-task classification model without considering clinical symptoms. These findings showed high replication in the site-split validation and external validation analyses. Measurements in parietal, occipital and medial frontal cortex and bilateral cerebellum had the greatest contribution to the multi-task model. Incorporating illness severity regression in pattern recognition algorithms, our study developed an MRI-based model that was of high diagnostic value in acutely ill schizophrenia patients, highlighting clinical relevance of the model.</p>","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591193","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}