International Journal of Neuropsychopharmacology最新文献

{"title":"Methodological considerations for interpreting ketamine-naltrexone trials in depression.","authors":"Igor D Bandeira, Luke A Jelen, Jason M Tucciarone, Boris D Heifets, Carolyn I Rodriguez, Alan F Schatzberg","doi":"10.1093/ijnp/pyaf073","DOIUrl":"10.1093/ijnp/pyaf073","url":null,"abstract":"","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12530182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjunctive brexpiprazole in patients with major depressive disorder who show minimal or partial response to antidepressant treatment: post hoc analysis of randomized controlled trials.","authors":"Shivani Kapadia, Zhen Zhang, Ferhat Ardic, Mehul Patel, Michael E Thase, George I Papakostas","doi":"10.1093/ijnp/pyaf074","DOIUrl":"10.1093/ijnp/pyaf074","url":null,"abstract":"<p><strong>Introduction: </strong>Many patients with major depressive disorder (MDD) have <50% symptom reduction on antidepressant treatment, and may benefit from an adjunctive atypical antipsychotic. This post hoc analysis aimed to investigate the efficacy and safety of adjunctive brexpiprazole in patients with minimal (>0% to <25%) and partial (≥25% to <50%) response to antidepressant treatment.</p><p><strong>Methods: </strong>Data were pooled from three international, randomized, double-blind, placebo-controlled, Phase 3 trials. Adult outpatients with MDD and inadequate response to antidepressant treatments were enrolled. Patients were stratified post hoc into minimal and partial response subgroups based on their response over an 8-week prospective antidepressant treatment period. Adjunctive brexpiprazole 2-3 mg/day (versus adjunctive placebo) was investigated in a 6-week randomized treatment period. Efficacy was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impressions - Severity of illness (CGI-S). Safety was assessed by treatment-emergent adverse events (TEAEs).</p><p><strong>Results: </strong>In patients with minimal response to antidepressant treatment (n = 663), least squares (LS) mean (SE) MADRS total score change over the randomized treatment period was -8.8 (0.3) points for antidepressant + brexpiprazole and -6.3 (0.3) points for antidepressant + placebo; the LS mean difference at Week 6 was -2.47 (95% CI, -3.38 to -1.55); P<.001; Cohen's d, 0.41. In patients with partial response to antidepressant treatment (n = 235), corresponding changes were -6.4 (0.5) and -4.9 (0.5) points; LS mean difference, -1.53 (-2.94 to -0.11); P = .035; Cohen's d, 0.28. CGI-S results aligned with MADRS results. In patients with minimal response to antidepressant treatment, the incidence of TEAEs was 196/328 (59.8%) for antidepressant + brexpiprazole and 160/335 (47.8%) for antidepressant + placebo. In patients with partial response to antidepressant treatment, corresponding values were 63/115 (54.8%) and 49/120 (40.8%).</p><p><strong>Conclusions: </strong>Adjunctive brexpiprazole may be efficacious in MDD regardless of whether patients show minimal or partial response to antidepressant treatment.</p><p><strong>Trial registration: </strong>Post hoc analysis of NCT01360645, NCT01360632, NCT02196506 (ClinicalTrials.gov). Significance Statement Depression is a common mental disorder associated with a constant feeling of sadness or lack of interest in daily life. Treatment with antidepressant medication can help to improve symptoms of depression. However, the amount of improvement varies from person to person. For people who still have symptoms on antidepressants, one option is to add brexpiprazole. Brexpiprazole is a medication that can help to improve symptoms of depression when taken with an antidepressant. Our study used data from clinical trials to look at the effects of brexpiprazole in people with either \"mi","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12554155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of peripheral biomarkers through metabolomic analysis in patients with bipolar disorder treated with mood stabilizers: an exploratory study.","authors":"Cristina Piras, Claudia Pisanu, Martina Spada, Anna Meloni, Donatella Congiu, Vanessa Palmas, Giovanni Severino, Raffaella Ardau, Caterina Chillotti, Martina Contu, Pasquale Paribello, Marco Pinna, Federico Suprani, Maria Del Zompo, Bernardo Carpiniello, Aldo Manzin, Mirko Manchia, Luigi Atzori, Alessio Squassina","doi":"10.1093/ijnp/pyaf071","DOIUrl":"10.1093/ijnp/pyaf071","url":null,"abstract":"<p><strong>Importance: </strong>Bipolar disorder (BD) is mainly treated with mood stabilizers, among which lithium represents the gold standard. Despite its high clinical efficacy, the molecular players involved in lithium response and nonresponse remain partly unclear. Therefore, the identification of peripheral biomarkers would significantly improve the management of pharmacological interventions in BD.</p><p><strong>Objective and design: </strong>In this study, we sought to investigate the blood metabolome in patients with BD to identify biosignatures of treatment with different mood stabilizers as well as possible biomarkers of response to lithium.</p><p><strong>Setting and participants: </strong>The blood metabolome was measured in a sample of 89 patients with BD either under prophylactic lithium treatment (n = 47), and characterized as responders or nonresponders, or with other mood stabilizers (MS, n = 42). For each patient the plasma metabolome was measured with hydrogen nuclear magnetic resonance (1H-NMR) and gas chromatography-mass spectrometry (GC-MS). Data were investigated with multivariate analyses accounting for covariates.</p><p><strong>Results: </strong>Patients exposed to lithium or to other MS showed different, specific metabolic signatures, with different levels of metabolites belonging to pathways involved in glucose, pyruvate, and glutamate metabolism, which were previously suggested to be implicated in BD and to be regulated by lithium. On the other hand, we were not able to identify significant differences in the metabolomic profile between responders and nonresponders to lithium.</p><p><strong>Conclusions and relevance: </strong>The findings from this exploratory study suggest that patients treated with lithium show distinctive metabolomic biosignatures, specifically pointing to energy metabolism and mitochondria functioning, thus potentially suggesting possible biosignatures of mood-stabilizing treatments.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12539573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A longitudinal PET study on changes in brain norepinephrine transporter availability following duloxetine treatment in major depressive disorder.","authors":"Sho Moriguchi, Keisuke Takahata, Harumasa Takano, Hironobu Endo, Kenji Tagai, Soichiro Kitamura, Hiroyuki Uchida, Masaru Mimura, Manabu Kubota, Ming-Rong Zhang, Makoto Higuchi","doi":"10.1093/ijnp/pyaf064","DOIUrl":"10.1093/ijnp/pyaf064","url":null,"abstract":"<p><strong>Importance: </strong>The norepinephrine transporter (NET) plays a crucial role in major depressive disorder (MDD). Serotonin and norepinephrine reuptake inhibitors, such as duloxetine, are first-line treatments for MDD. Duloxetine inhibits the reuptake of both serotonin and norepinephrine. However, its precise mechanism, particularly regarding NET occupancy and changes in transporter availability, remains unclear. Norepinephrine transmission, mediated by NET, may be instrumental in treating MDD. Therefore, NET occupancy could serve as a potential biomarker to evaluate treatment efficacy.</p><p><strong>Objective: </strong>This study evaluated duloxetine's impact on brain NET availability in patients with MDD using positron emission tomography (PET) with (S,S)-[18F]FMeNER-D2 and its correlation with clinical symptoms using the Hamilton Depression Rating Scale (HAM-D).</p><p><strong>Design: </strong>Longitudinal study.</p><p><strong>Setting: </strong>Psychiatric hospitals and clinics.</p><p><strong>Participants: </strong>Fifteen patients with MDD.</p><p><strong>Interventions: </strong>Duloxetine (20-60 mg daily).</p><p><strong>Main outcomes and measures: </strong>Baseline PET examinations were conducted for all patients, followed by treatment with duloxetine (20-60 mg daily). After 4-6 weeks of duloxetine administration, a second PET examination was performed, and plasma concentrations of duloxetine were measured immediately before and after the second examination using gas chromatography-mass spectrometry. Seven patients showing symptom improvement over the course of time discontinued duloxetine and underwent a third PET examination after a 2-month washout period.</p><p><strong>Results: </strong>Norepinephrine transporter occupancy by duloxetine was 30%-40% across the doses studied. A paired t-test comparing NET availability before and after duloxetine treatment showed no significant differences, suggesting that duloxetine did not significantly alter NET availability in the short term. Further analysis revealed a significant positive correlation between the change in NET availability and HAM-D scores after treatment. Patients with greater reductions in HAM-D scores exhibited more pronounced reductions in NET availability.</p><p><strong>Conclusions: </strong>These findings underscore the potential role of NET occupancy by duloxetine in the treatment of MDD and its relationship with clinical outcomes.</p><p><strong>Relevance: </strong>Understanding changes in NET and their implications enhances our comprehension of the complex mechanisms behind antidepressants and may reveal new therapeutic targets for MDD and other neuropsychiatric disorders.</p><p><strong>Clinical trial registration number: </strong>UMIN000008251.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":"28 10","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12489337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropsychiatric- and cognitive post-acute sequelae of SARS-CoV-2 infection - evidence from K18-hACE C57BL/6 J mice.","authors":"Marco Maria Santi, Eleonora Genovese, Thor Mertz Schou, Matheus da Silva, Sophie Erhardt, Lilly Schwieler, Jacob Ahlberg Weidenfors, Giorgia Marino, Søren Riis Paludan, Samia Joca, Gregers Wegener, Line Reinert, Cecilie Bay-Richter","doi":"10.1093/ijnp/pyaf072","DOIUrl":"10.1093/ijnp/pyaf072","url":null,"abstract":"<p><strong>Background: </strong>Survivors of COVID-19 frequently report psychiatric and cognitive sequelae. The origin of such sequelae has not been determined, as it has been a challenge to resolve whether these symptoms have a viral origin or are related to the contextual stressors associated with the pandemic. Using a mouse model of post-acute sequelae of SARS-CoV-2 infection (PASC), we examined neurobiological mechanisms underlying these effects without the confounding influence of contextual factors.</p><p><strong>Results: </strong>SARS-CoV-2 infection induced cognitive, but not anxiety- or depression-like, behavioral deficits. Cognitive impairments correlated with severity of the acute disease. Infected mice showed significant alterations in brain cytokine levels, as well as in kynurenine pathway (KP) metabolites, both of which were associated with acute disease severity. Microbiome taxonomic profiling revealed group-specific differences, indicating that certain bacterial species may contribute to PASC development.</p><p><strong>Conclusions: </strong>Our findings suggest that SARS-CoV-2 infection causes cognitive deficits in PASC, modulated by acute disease severity, while anxiety- and depression-like behaviors appear unrelated to the viral infection itself. This supports the idea that such psychiatric symptoms may stem from pandemic-related stressors rather than infection. Altered cytokine signaling and KP metabolism may play key roles in the pathophysiology of PASC, identifying potential biomarkers and therapeutic targets.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12542986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-differences in catecholamine transporter expression in the rodent prefrontal cortex following repetitive mild traumatic brain injury and methylphenidate treatment.","authors":"Eleni Papadopoulos, Anna Abrimian, Christopher P Knapp, Jessica A Loweth, Barry D Waterhouse, Rachel L Navarra","doi":"10.1093/ijnp/pyaf070","DOIUrl":"10.1093/ijnp/pyaf070","url":null,"abstract":"<p><p>Irregular transmitter activity is theorized to underly impaired prefrontal cortex (PFC)-mediated executive functions following repetitive mild traumatic brain injury (rmTBI). The psychostimulant, methylphenidate (MPH), enhances catecholamine neurotransmission by blocking reuptake transporters and is used off-label to treat post-TBI executive dysfunction. Both rmTBI and MPH are known to independently alter catecholamine transporter levels. The present report evaluated the interactive effects of rmTBI and a sub-chronic therapeutic dose of MPH on expression levels of vesicular monoamine transporter-2 (VMAT2) and norepinephrine reuptake transporter (NET) within the medial, anterior cingulate, and orbitofrontal subregions of the PFC in both male and female rats. MPH failed to rescue, and in some cases exacerbated, rmTBI-induced reductions in VMAT2 and NET expression in males, whereas transporter expression was largely unaltered in females. These results suggest MPH treatment produces further protein-level perturbations of catecholaminergic activity that are proposed to underlie executive dysfunction in males, but negligible effects in females, following rmTBI.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12513166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal Administration of KCNN2 Blocking Peptide Improves Deficits in Cognitive Flexibility in Mouse Model of Fetal Alcohol Spectrum Disorders.","authors":"Shahid Mohammad, Li Wang, Masaaki Torii, Kazue Hashimoto-Torii","doi":"10.1093/ijnp/pyaf055","DOIUrl":"10.1093/ijnp/pyaf055","url":null,"abstract":"<p><strong>Background: </strong>Fetal alcohol spectrum disorders (FASD) show a myriad of cognitive and neurological deficits, with the prevalence estimated to be 1% to 5 % in children. To date, there are no effective treatments for these deficits in FASD. In a mouse model of FASD, daily intraperitoneal administration of a potassium calcium-activated channel subfamily N member 2 (KCNN2) blocking peptide has been shown to improve motor learning deficits due to upregulation of KCNN2 channels. This study investigates whether intranasal administration of a KCNN2 blocking peptide, Leiurotoxin-1 Dab7 (Lei-Dab7), can improve cognitive flexibility, specifically reversal learning deficits, in these mice.</p><p><strong>Methods: </strong>We utilized a mouse model of prenatal alcohol exposure. Cognitive flexibility was assessed using the water T-maze test at postnatal day 40. Lei-Dab7's specificity and cytotoxicity were evaluated in vitro, and intranasal delivery efficiency was confirmed through immunohistochemistry, quantifying its distribution and binding to neurons with elevated KCNN2 expression in the prefrontal cortex.</p><p><strong>Results: </strong>Lei-Dab7 showed high specificity and negligible cytotoxicity in vitro. Intranasal administration efficiently delivered Lei-Dab7 to the prefrontal cortex, where it specifically bound to neurons expressing increased KCNN2 channels. Behavioral tests demonstrated that Lei-Dab7 significantly improved cognitive flexibility, reversing the deficits in the water T-maze test seen in ethanol-exposed mice, without apparent acute physiological adverse effects.</p><p><strong>Conclusions: </strong>Intranasal administration of KCNN2 blockers, such as Lei-Dab7, represents a promising, non-invasive therapeutic approach for treating cognitive inflexibility and possibly other cognitive dysfunctions associated with FASD.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trajectory of efficacy and safety across ulotaront dose levels in schizophrenia: a systematic review and dose-response meta-analysis.","authors":"Yu-Chia Hsu, Tzu-Yen Hung, Yang-Chieh Brian Chen, Kuo-Chuan Hung, Chih-Sung Liang, Ping-Tao Tseng, Yu-Kang Tu, Christoph U Correll, Chih-Wei Hsu, Marco Solmi","doi":"10.1093/ijnp/pyaf059","DOIUrl":"10.1093/ijnp/pyaf059","url":null,"abstract":"<p><strong>Background: </strong>Ulotaront is an experimental antipsychotic for schizophrenia, but its optimal dose is unclear. This study aimed to evaluate dose-response relationships for efficacy and safety in people with schizophrenia.</p><p><strong>Methods: </strong>A systematic review of four databases (until January 22, 2025; INPLASY202510091) identified randomized clinical trials assessing ulotaront. Outcomes included efficacy, measured by changes in the Positive and Negative Syndrome Scale (PANSS) total score (primary outcome), positive and negative subdomains, and the Clinical Global Impression Scale-Severity, and safety, assessed by all-cause dropout (co-primary outcome, dropout due to adverse event, serious, non-serious, and specific adverse events). We employed one-stage dose-response meta-analysis (random-effects model) calculating standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (CIs).</p><p><strong>Results: </strong>Analysis of three randomized clinical trials (n = 1144) indicated that the 100 mg dose of ulotaront provided the greatest improvement in PANSS total score (standardized mean difference = -0.23 [95% CI: -0.43, -0.02]), PANSS positive symptom score (-0.30 [-0.70, 0.10]), and PANSS negative symptom score (-0.28 [-0.48, -0.08]). However, Clinical Global Impression Scale-Severity scores did not exhibit a clear dose-response relationship. Regarding safety, all-cause dropout (RR at 100 mg = 1.10 [95% CI: 0.57, 2.12]), adverse event-related dropout, serious, non-serious, and most specific adverse events showed no significant dose-response relationship. The risk of anxiety-related adverse events was significantly higher than placebo at 50 and 75 mg doses (RR at 75 mg = 2.06 [95% CI: 1.11, 3.80]).</p><p><strong>Conclusion: </strong>Ulotaront 100 mg appears greatest efficacy with favorable safety for acute schizophrenia. However, effect sizes were small, and higher ulotaront doses should be tested. Significance Statement Ulotaront is a new medication being tested for treating schizophrenia. Unlike most existing antipsychotic drugs that block dopamine receptors in the brain, ulotaront works through a different mechanism by activating trace amine-associated receptor 1 and serotonin 1A receptors. These novel targets may help reduce both hallucinations and negative symptoms like social withdrawal and lack of motivation, with fewer side effects. In this study, we analyzed data from several clinical trials to understand how different doses of ulotaront affect patients. We found that higher doses-especially around 100 mg-can improve schizophrenia symptoms without increasing safety concerns. These findings are important because they suggest that ulotaront may offer a new and safer treatment option for people with schizophrenia, and they help guide doctors toward the most effective dose.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12421877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct neural activation patterns in executive functions of schizophrenia patients with predominant positive and negative symptoms: an fNIRS study.","authors":"Yinqing Xu, Xiaoning Huo, Xiaolong Yang, Yutai Ma, Yongjie Wang, Jibao Deng, Haozhong Zheng, Meihong Xiu, Fengchun Wu","doi":"10.1093/ijnp/pyaf058","DOIUrl":"10.1093/ijnp/pyaf058","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the differences in executive functions, specifically cognitive flexibility and inhibitory control, between schizophrenia (SCH) patients with predominantly positive symptoms (PSD) and those with predominantly negative symptoms (NSD), compared to healthy controls, using functional near-infrared spectroscopy (fNIRS).</p><p><strong>Methods: </strong>Fifty-two patients with SCH and 29 control subjects were recruited in the study. We employed fNIRS to measure brain activation while participants performed 2 tasks: a cognitive flexibility-switching task and the Stroop task, which assesses inhibitory control. Performance metrics included accuracy and reaction time. The study included 3 groups: SCH patients with PSD, SCH patients with NSD, and healthy controls.</p><p><strong>Results: </strong>Patients with SCH exhibited lower accuracy and longer reaction times compared to healthy controls. In terms of brain activation, the PSD group showed the highest levels of prefrontal activation, followed by healthy controls, while the NSD group had the lowest activation levels. Patients had lower accuracy and longer reaction times than healthy controls. The PSD group showed excessive activation in both prefrontal cortex and the dorsolateral prefrontal cortex during both the congruent condition and incongruent condition of the Stroop task. In contrast, the NSD group exhibited higher prefrontal activation under congruent conditions but significantly reduced activation under incongruent conditions.</p><p><strong>Conclusion: </strong>Our findings highlight distinct patterns of executive function deficits and brain activation in SCH patients with PSD and NSD. These results suggest that symptom profiles may influence the nature and severity of cognitive impairments and associated neural mechanisms. Future research should further explore these differences to inform targeted interventions and improve clinical outcomes for individuals with SCH.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acquisition of trace fear conditioning without functional nucleus reuniens did not require dorsal or ventral hippocampus NMDA receptor activation in male Long-Evans rats.","authors":"Ru-Hsuan Liu, Chun-Hui Chang","doi":"10.1093/ijnp/pyaf065","DOIUrl":"10.1093/ijnp/pyaf065","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;The nucleus reuniens (RE) is a crucial component that interconnects the medial prefrontal cortex (mPFC) and hippocampus (HPC), completing the HPC-dependent circuit underlying the regulation of trace fear. We previously demonstrated that RE inactivation during acquisition impaired the encoding of trace fear, while RE inactivation during both the acquisition and retrieval led to heightened trace fear throughout the test session, raising questions about the involvement of HPC-independent circuit in trace fear acquisition without functional RE.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To investigate whether rats without functional RE throughout the entire behavioral sessions can acquire trace fear using an HPC-independent circuit.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;A balanced factorial design was used to assess the role of the dorsal hippocampus (DH) or ventral hippocampus (VH) in trace fear acquisition with or without functional RE.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Setting: &lt;/strong&gt;The study was conducted in a controlled laboratory environment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants: &lt;/strong&gt;Adult male Long-Evans rats were used as experimental subjects.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interventions: &lt;/strong&gt;Consecutive intracranial micro-infusions of either GABAA receptor agonist \"Muscimol\" or vehicle targeted the RE during both trace fear acquisition and retrieval. Micro-infusions of the N-methyl-D-aspartate (NMDA) receptor antagonist \"DL-2-amino-5-phosphonovaleric acid\" or saline targeted the DH or VH during trace fear acquisition.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes: &lt;/strong&gt;Fear level of respective groups was measured.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Measures: &lt;/strong&gt;Freezing was quantified as immobility during baseline and conditioned stimulus during trace fear acquisition and retrieval.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Control animals required proper DH or VH NMDA receptor activation for the acquisition of trace fear. Rats without functional RE still acquired trace fear, but independent of DH or VH NMDA receptor activation, suggesting the reliance of an HPC-independent circuit during fear encoding.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and relevance: &lt;/strong&gt;These findings highlighted potential alternative neural pathways that may support and compensate trace fear acquisition under pathological conditions. Significance Statement Impaired fear regulation resulted in psychiatric disorders like panic disorder and anxiety. Pavlovian trace fear conditioning using male Long-Evans rats as the subjects models human emotional learning. Although hippocampus (HPC)-medial prefrontal cortex (mPFC) interactions facilitate trace fear acquisition, the role of thalamic nucleus reuniens (RE), which connects these regions, is unclear. In this study, we found that in terms of within-session fear expression during acquisition, dorsal hippocampus (DH) N-methyl-D-aspartate (NMDA) receptor blockade impaired fear response only in RE-intact rats, whereas ventral hippocampus (VH) blockade impaired the response regardless of the ","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}