Neuropsychopharmacology最新文献

{"title":"Cigarette smoking is associated with reduced neuroinflammation and better cognitive control in people living with HIV","authors":"Arthur L. Brody, Anna K. Mischel, Andre Y. Sanavi, Alvin Wong, Ji Hye Bahn, Arpi Minassian, Erin E. Morgan, Brinda Rana, Carl K. Hoh, David R. Vera, Kishore K. Kotta, Alannah H. Miranda, Nina Pocuca, Thomas J. Walter, Natalie Guggino, Renee Beverly-Aylwin, Jeffrey H. Meyer, Neil Vasdev, Jared W. Young","doi":"10.1038/s41386-024-02035-6","DOIUrl":"10.1038/s41386-024-02035-6","url":null,"abstract":"People living with HIV (HIV+) are roughly twice as likely to smoke cigarettes (Smok+) as the general population. With the advent of effective antiretroviral therapies, it is increasingly important to understand the effects of chronic HIV infection and cigarette smoking on brain function and cognition since HIV+ individuals have heightened neuroinflammation and cognitive deficits even with such therapies. Based on prior studies demonstrating that smoking reduces a marker for neuroinflammation in HIV- individuals, we hypothesized that HIV+/Smok+ individuals would have less neuroinflammation and better cognitive control than HIV+/Smok- individuals. Fifty-nine participants (HIV-/Smok- [n = 16], HIV-/Smok+ [n=14], HIV+/Smok- [n = 18], and HIV+/Smok+ [n = 11]) underwent baseline eligibility tests, positron emission tomography (PET) scanning to determine levels of a marker for neuroinflammation, and assessment of cognitive control with the reverse-translated 5-choice continuous performance test (5C-CPT), with smokers having smoked to satiety prior to testing. For the PET data, a significant effect of smoking status on whole brain (WB) standardized uptake value (SUV) was found between HIV+/Smok+ and HIV+/Smok- participants (due to 18.8% lower WB SUV in the HIV+/Smok+ group). HIV+/Smok- participants exhibited a mean 13.5% higher WB SUV than HIV-/Smok- participants. For the 5C-CPT, HIV+/Smok+ participants performed significantly better than HIV+/Smok- participants (d prime), and HIV+/Smok- participants performed worse than HIV-/Smok- participants. Thus, HIV+/Smok+ individuals demonstrated lower levels of the neuroinflammation marker and better cognitive control than HIV+/Smok- individuals. Given that HIV+ individuals whose HIV is well-controlled can still have chronic neurocognitive complications, study results suggest possible paths for future research into nicotine-related treatments to prevent such complications.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 4","pages":"695-704"},"PeriodicalIF":6.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11845771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142910099","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":"Relative effectiveness of antidepressant treatments in treatment-resistant depression: a systematic review and network meta-analysis of randomized controlled trials","authors":"Johan Saelens, Anna Gramser, Victoria Watzal, Carlos A. Zarate Jr., Rupert Lanzenberger, Christoph Kraus","doi":"10.1038/s41386-024-02044-5","DOIUrl":"10.1038/s41386-024-02044-5","url":null,"abstract":"This systematic review and network meta-analysis (NMA) sought to compare different antidepressant treatments for treatment-resistant depression (TRD) in order to facilitate evidence-based choices. A literature search of PubMed, Cochrane Library, and Embase from inception until April 13th, 2023 identified randomized, controlled trials (RCTs) of adults with depression who had not responded to at least two antidepressant trials; all RCTs had ≥10 participants per study arm, and participants with bipolar or psychotic depression were excluded. The Cochrane Risk of Bias Tool-2 was used to assess study quality. Response rate was the primary outcome measure. Odds ratios (ORs) using a random effects NMA are reported. From 8234 records, 69 RCTs were included in this analysis, encompassing 10,285 participants (5662 F/4623 M) and 25 separate treatments. Six of the 25 treatments demonstrated a higher response rate versus placebo or sham treatment: electroconvulsive therapy (ECT), minocycline, theta-burst stimulation (TBS), repetitive transcranial magnetic stimulation (rTMS), ketamine, and aripiprazole. ORs ranged from 1.9 (95%CI = [1.25; 2.91]) for aripiprazole to 12.86 (95%CI = [4.07; 40.63]) for ECT. Moderate heterogeneity of the model was observed (I2 = 47.3% (95%CI [26.8–62%]). Of the included studies, 12.5% were rated as having high risk of bias, 28.13% as having low risk, and 59.38% as showing some concerns. Several effective treatments for TRD showed robust treatment effects across outcomes (ECT, TBS, rTMS, and ketamine), and others showed promising results for some, but not all, outcomes (minocycline, aripiprazole). These findings may help guide evidence-based treatment choices for TRD. Study Registration: PROSPERO (#CRD42023420584).","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 6","pages":"913-919"},"PeriodicalIF":6.6,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41386-024-02044-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142910098","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":"Safety and cognitive pharmacodynamics following dose escalations with 3-methylmethcathinone (3-MMC): a first in human, designer drug study","authors":"Johannes G. Ramaekers, Johannes T. Reckweg, Natasha L. Mason, Kim P. C. Kuypers, Stefan W. Toennes, Eef L. Theunissen","doi":"10.1038/s41386-024-02042-7","DOIUrl":"10.1038/s41386-024-02042-7","url":null,"abstract":"3-Methylmethcathinone (3-MMC) is a designer drug that belongs to the group of synthetic cathinones. The compound has been scheduled in many jurisdictions because of public health concerns associated with excessive use. To date, there are no clinical studies that have evaluated the risk profile of 3-MMC in the recreational range of low to moderate doses. The current, first-in-human study (N = 14) assessed the impact of three escalating doses of 3-MMC (25, 50 and 100 mg) on vital signs, neurocognitive function, state of consciousness, appetite and drug desire, in a cross-over, placebo-controlled trial. A battery of neurocognitive tests and questionnaires as well as measures of vital signs were repeatedly administered up to 5 h after dosing. Overall, 3-MMC caused dose-dependent increases in heart rate and blood pressure, though not of clinical significance, and feelings of subjective high. Additionally, 3-MMC induced dose-related enhancement of task performance across several neurocognitive domains, including processing speed, cognitive flexibility, psychomotor function, attention and memory. Impulse control was not affected by 3-MMC. Participants also reported mild increases in dissociative and psychedelic effects, decreased appetite, and gave greater ratings of liking and wanting for 3-MMC that were transient over time. Overall, the cardiovascular, psychostimulant and psychotomimetic profile of 3-MMC appears consistent with that of compounds structurally related to amphetamine. It is concluded that low to moderate doses of 3-MMC were well tolerated and safe and that potential health risks might only occur at high or excessive doses of 3-MMC.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 7","pages":"1084-1092"},"PeriodicalIF":6.6,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41386-024-02042-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886063","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":"Acute dose-dependent effects and self-guided titration of continuous N,N-dimethyltryptamine infusions in a double-blind placebo-controlled study in healthy participants","authors":"Livio Erne, Severin B. Vogt, Lorenz Müller, Albiona Nuraj, Anna Becker, Aaron Klaiber, Melani Zuparic, Nimmy Varghese, Anne Eckert, Deborah Rudin, Dino Luethi, Matthias E. Liechti","doi":"10.1038/s41386-024-02041-8","DOIUrl":"10.1038/s41386-024-02041-8","url":null,"abstract":"N,N-dimethyltryptamine (DMT) is a serotonergic psychedelic that is known for its short-lasting effects when administered intravenously. Several studies have investigated the administration of intravenous boluses or combinations of a bolus and a subsequent continuous infusion. However, data on dose-dependent acute effects and pharmacokinetics of continuous DMT infusions are lacking. We used a double-blind, randomized, placebo-controlled, crossover design in 22 healthy participants (11 women, 11 men) who received placebo and DMT (0.6, 1.2, 1.8, and 2.4 mg/min) over an infusion duration of 120 min. We also tested a self-guided titration scheme that allowed participants to adjust the DMT dose rate at prespecified time points to achieve their desired level of subjective effects. Outcome measures included subjective effects, autonomic effects, adverse effects, plasma hormone concentrations, and pharmacokinetics up to 3 h after starting the infusion. DMT infusions exhibited dose-proportional pharmacokinetics and rapidly induced dose-dependent subjective effects that reached a plateau after 30 min. A ceiling effect was observed for “good drug effect” at 1.8 mg/min. The 2.4 mg/min dose of DMT induced greater anxious ego dissolution than the 1.8 mg/min dose and induced significant anxiety compared with placebo. We observed moderate acute tolerance to acute effects of DMT. In the self-guided titration session, the participants opted for moderate to strong psychedelic effects, comparable in intensity to the 1.8 mg/min DMT dose rate in the randomized dosing sessions. These results may assist with dose finding for future DMT research and demonstrate that acute subjective effects of DMT can be rapidly adjusted through dose titration.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 6","pages":"1008-1016"},"PeriodicalIF":6.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41386-024-02041-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864332","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":"Epac2-mediated synaptic insertion of Ca2+-permeable AMPARs in the nucleus accumbens contributes to incubation of cocaine craving","authors":"Xiaojie Liu, Yao Huang, Lianwei Mu, Vladislav Friedman, Thomas J. Kelly, Ying Hu, Dong Yuan, Qing-song Liu","doi":"10.1038/s41386-024-02030-x","DOIUrl":"10.1038/s41386-024-02030-x","url":null,"abstract":"The accumulation of GluA2-lacking Ca2+-permeable AMPARs (CP-AMPARs) in the medium spiny neurons (MSNs) of the nucleus accumbens (NAc) is required for the expression of incubation of cocaine craving. The exchange protein directly activated by cAMP (Epac) is an intracellular effector of cAMP and a guanine nucleotide exchange factor for the small GTPase Rap1. Epac2 has been implicated in the trafficking of AMPA receptors at central synapses. We tested the hypothesis that Epac2 activation contributes to the accumulation of CP-AMPARs in NAc MSNs and incubation of cocaine craving. Here we demonstrate that the selective Epac2 agonist S-220 facilitated the synaptic insertion of GluA2-lacking CP-AMPARs at excitatory synapses onto NAc MSNs. In addition, prolonged abstinence from cocaine self-administration in rats resulted in elevated Rap1-GTP levels in the NAc, implying that Epac2 is activated during incubation. Importantly, we show that AAV-mediated shRNA knockdown of Epac2 in the NAc core attenuated the accumulation of CP-AMPARs and cue-induced drug-seeking behavior after prolonged abstinence from cocaine self-administration. In contrast, acute pharmacological inhibition of Epac2 with the selective Epac2 inhibitor ESI-05 did not alter CP-AMPARs that had already accumulated during incubation, and intra-NAc application of ESI-05 did not significantly affect cue-induced drug seeking following prolonged abstinence. Taken together, these results suggest that Epac2 activation during the period of incubation, but not during cue-induced drug seeking, leads to the accumulation of CP-AMPARs in NAc MSNs, which in turn contributes to incubation of cocaine craving.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 4","pages":"620-629"},"PeriodicalIF":6.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864479","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":"Neural basis of adolescent THC-induced potentiation of opioid responses later in life","authors":"Elizabeth Hubbard, Pieter Derdeyn, Vivienne Mae Galinato, Andrew Wu, Katrina Bartas, Stephen V. Mahler, Kevin T. Beier","doi":"10.1038/s41386-024-02033-8","DOIUrl":"10.1038/s41386-024-02033-8","url":null,"abstract":"Use of one addictive drug typically influences the behavioral response to other drugs, either administered at the same time or a subsequent time point. The nature of the drugs being used, as well as the timing and dosing, also influence how these drugs interact. Here, we tested the effects of adolescent THC exposure on the development of morphine-induced behavioral adaptations following repeated morphine exposure during adulthood. We found that adolescent THC administration paradoxically prevented the development of anxiety-related behaviors that emerge during a forced abstinence period following morphine administration but facilitated reinstatement of morphine CPP. Following forced abstinence, we then mapped the whole-brain response to a moderate dose of morphine and found that adolescent THC administration led to an overall increase in brain-wide neuronal activity and increased the functional connectivity between frontal cortical regions and the ventral tegmental area. Last, we show using rabies virus-based circuit mapping that adolescent THC exposure triggers a long-lasting elevation in connectivity from the frontal cortex regions onto ventral tegmental dopamine cells. Our study adds to the rich literature on the interaction between drugs, including THC and opioids, and provides potential neural substates by which adolescent THC exposure influences responses to morphine later in life.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 5","pages":"818-827"},"PeriodicalIF":6.6,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41386-024-02033-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807188","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":"Correction: The might of light for revealing neuropsychiatric mechanisms","authors":"Kutlu Kaya, Hilary P. Blumberg","doi":"10.1038/s41386-024-02032-9","DOIUrl":"10.1038/s41386-024-02032-9","url":null,"abstract":"","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 3","pages":"607-607"},"PeriodicalIF":6.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801770","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":"The efficacy and cerebral mechanism of intradermal acupuncture for major depressive disorder: a multicenter randomized controlled trial","authors":"Xiaoting Wu, Mingqi Tu, Zelin Yu, Zhijian Cao, Siying Qu, Nisang Chen, Junyan Jin, Sangsang Xiong, Jiajia Yang, Shuangyi Pei, Maosheng Xu, Jia Wang, Yan Shi, Lishu Gao, Jian Xie, Xinwei Li, Jianqiao Fang, Xiaomei Shao","doi":"10.1038/s41386-024-02036-5","DOIUrl":"10.1038/s41386-024-02036-5","url":null,"abstract":"New combinations or alternative therapies for major depressive disorder (MDD) are necessary. Intradermal acupuncture (IA) shows promise but requires further investigation regarding its efficacy, safety, and mechanisms. Conducted across 3 centers from November 2022 to January 2024, our randomized controlled trial included 120 participants with moderate to severe MDD, divided into the selective serotonin reuptake inhibitors (SSRIs), SSRIs plus sham IA (SSRIs + SIA), and SSRIs plus active IA (SSRIs + AIA) groups. Acupuncture groups received 10 sessions over 6 weeks at Shenmen (HT7), Neiguan (PC6), Sanyinjiao (SP6) and Taichong (LR3) bilaterally, followed by a 4-week follow-up. The primary outcome was changes in Hamilton Depression Rating Scale-17 (HAMD-17) scores at week 6. Furthermore, healthy controls (HCs) and MDD patients underwent magnetic resonance imaging (MRI) scans for functional connectivity (FC) analysis. After 6 weeks of treatment, the SSRIs + AIA group showed a greater reduction in HAMD-17 score than the SSRIs + SIA group (MD, −4.9 [CI, −7.6 to −2.2], P < 0.001) and SSRIs group (MD, −5.1 [CI, −7.8 to −2.3], P < 0.001). No serious adverse events occurred. SSRIs + AIA resulted in lower incidences of palpitations (vs.SSRIs + SIA: OR, 0.1% [CI, 0.0–1.0%]; vs. SSRIs: OR, 0.1% [CI, 0.0–0.7%]; P < 0.05), somnolence (vs.SSRIs + SIA: OR, 0.1% [CI, 0.0–0.9%]; vs.SSRIs: OR, 0.1% [CI, 0.0–0.7%]; P < 0.05), and nausea (vs.SSRIs + SIA: OR, 0.1% [CI, 0.0–1.0%]; vs. SSRIs: OR, 0.1% [CI, 0.0–0.9%]; P < 0.05). MDD patients showed abnormal FCs, and IA enhanced FCs between striatum and frontal_inf_tri, and striatum and cerebellum in the MRI study. Overall, IA as adjunctive therapy provides clinical efficacy and safety for MDD, and it may exert antidepressant effects by modulating striatal FCs.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 7","pages":"1075-1083"},"PeriodicalIF":6.6,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41386-024-02036-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795041","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":"Genome-wide methylome-based molecular pathologies associated with depression and suicide","authors":"Yogesh Dwivedi, Bhaskar Roy, Praveen Kumar Korla","doi":"10.1038/s41386-024-02040-9","DOIUrl":"10.1038/s41386-024-02040-9","url":null,"abstract":"Major depressive disorder (MDD) is a debilitating disorder. Suicide attempts are 5-times higher in MDD patients than in the general population. Interestingly, not all MDD patients develop suicidal thoughts or complete suicide. Thus, it is important to study the risk factors that can distinguish suicidality among MDD patients. The present study examined if DNA methylation changes can distinguish suicidal behavior among depressed subjects. Genome-wide DNA methylation was examined in the dorsolateral prefrontal cortex of depressed suicide (MDD+S; n = 15), depressed non-suicide (MDD−S; n = 17), and nonpsychiatric control (C; n = 16) subjects using 850 K Infinium Methylation EPIC BeadChip. The significantly differentially methylated genes were used to determine the functional enrichment of genes for ontological clustering and pathway analysis. Based on the number of CpG content and their relative distribution from specific landmark regions of genes, 32,958 methylation sites were identified across 12,574 genes in C vs. MDD+/−S subjects, 30,852 methylation sites across 12,019 genes in C vs. MDD−S, 41,648 methylation sites across 13,941 genes in C vs. MDD+S, and 49,848 methylation sites across 15,015 genes in MDD−S vs. MDD+S groups. A comparison of methylation sites showed 33,129 unique methylation sites and 5451 genes in the MDD−S group compared to the MDD+S group. Functional analysis suggested oxytocin, GABA, VGFA, TNFA, and mTOR pathways associated with suicide in the MDD group. Altogether, our data show a distinct pattern of DNA methylation, the genomic distribution of differentially methylated sites, gene enrichment, and pathways in MDD suicide compared to non-suicide MDD subjects.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 4","pages":"705-716"},"PeriodicalIF":6.6,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11845511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792027","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":"The activation of the piriform cortex to lateral septum pathway during chronic social defeat stress is crucial for the induction of behavioral disturbance in mice","authors":"Yuki Okuda, Dongrui Li, Yuzuki Maruyama, Hirokazu Sonobe, Tomoyuki Mano, Kazuki Tainaka, Ryota Shinohara, Tomoyuki Furuyashiki","doi":"10.1038/s41386-024-02034-7","DOIUrl":"10.1038/s41386-024-02034-7","url":null,"abstract":"Chronic stress induces neural dysfunctions and risks mental illnesses. Clinical and preclinical studies have established the roles of brain regions underlying emotional and cognitive functions in stress and depression. However, neural pathways to perceive sensory stimuli as stress to cause behavioral disturbance remain unknown. Using whole-brain imaging of Arc-dVenus neuronal response reporter mice and machine learning analysis, here we unbiasedly demonstrated different patterns of contribution of widely distributed brain regions to neural responses to acute and chronic social defeat stress (SDS). Among these brain regions, multiple sensory cortices, especially the piriform (olfactory) cortex, primarily contributed to classifying neural responses to chronic SDS. Indeed, SDS-induced activation of the piriform cortex was augmented with repetition of SDS, accompanied by impaired odor discrimination. Axonal tracing and chemogenetic manipulation showed that excitatory neurons in the piriform cortex directly project to the lateral septum and activate it in response to chronic SDS, thereby inducing behavioral disturbance. These results pave the way for identifying a spatially defined sequence of neural consequences of stress and the roles of sensory pathways in perceiving chronic stress in mental illness pathology.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 5","pages":"828-840"},"PeriodicalIF":6.6,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41386-024-02034-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786313","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}