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":"https://doi.org/10.1093/ijnp/pyaf073","url":null,"abstract":"","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of the AMPK/SIRT1 pathway in gut dysbiosis-mediated postoperative cognitive dysfunction in aged mice.","authors":"Fu Xu, Yang Yue, Defeng Sun","doi":"10.1093/ijnp/pyaf066","DOIUrl":"https://doi.org/10.1093/ijnp/pyaf066","url":null,"abstract":"<p><strong>Objective: </strong>Postoperative cognitive dysfunction (POCD) is a prevalent complication in older patients who undergo surgery that requires anesthesia. This study explored the role of the AMPK/SIRT1 pathway in gut dysbiosis-mediated POCD in aged mice.</p><p><strong>Methods: </strong>POCD was induced in aged male mice via open tibial fracture surgery under isoflurane anesthesia. Mice then received the probiotic VSL#3, the SIRT1 inhibitor EX527, and the AMPK/SIRT1 activator resveratrol. Fecal microbiota transplantation was conducted in aged POCD mice. Mouse cognitive function was assessed using the Morris water maze and novel object recognition tests. Mouse histopathological changes were observed via HE staining. Iba1+/GFAP+ activation was assessed via immunofluorescence, and pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 [IL]-1β, IL-6) in the hippocampus were determined via ELISA. Gut microbiota compositions were detected via 16S rRNA sequencing. Hippocampal pAMPK/AMPK and SIRT1 levels were assessed by western blot.</p><p><strong>Results: </strong>Aged POCD mice exhibited prolonged escape latency, reduced platform crossings, and an impaired object discrimination rate on postoperative day 7. Severe hippocampal CA1 damage, increased Iba1+/GFAP+ cell numbers, elevated pro-inflammatory cytokines, and gut dysbiosis were also observed. The probiotic VSL#3 ameliorated gut dysbiosis, alleviated POCD, and reduced neuroinflammation. Gut microbiota from POCD mice exacerbated cognitive deficits and neuroinflammation in aged mice, while clearance of gut microbiota improved outcomes. VSL#3 improved POCD in aged mice by balancing gut microbiota through the AMPK/SIRT1 pathway. The AMPK/SIRT1 pathway activation mitigated POCD.</p><p><strong>Conclusion: </strong>VSL#3 balanced gut microbiota and suppressed neuroinflammation in hippocampal CA1 region by activating the AMPK/SIRT1 pathway, thereby alleviating POCD in aged mice.</p>","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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","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":3.7,"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":"https://doi.org/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. In the current study, we used a mouse model of post-acute sequelae of SARS-CoV-2 infection (PASC) to evaluate the neurobiological nature of the sequelae without the interference of the contextual effects on behavior following SARS-CoV-2 infection.</p><p><strong>Results: </strong>SARS-CoV-2 infection resulted in behavioral deficits related to cognition but not anxiety- or depression-like behavior. The cognitive deficits were affected by the severity of the acute disease. Cytokine and chemokine levels as well as kynurenine pathway metabolites were significantly altered in the brains of infected mice. Both cytokine/chemokine levels and kynurenine pathway metabolites correlated with the severity of the acute disease. Microbiome taxonomic profiling revealed significant differences between groups, suggesting that specific bacterial species may be associated with the development of PASC.</p><p><strong>Conclusions: </strong>These results suggest that SARS-CoV-2 infection leads to cognitive deficits in PASC, influenced by the severity of the acute disease. In contrast, PASC anxiety- and depression-like behavior was not related to the viral infection itself. This could indicate that PASC anxiety and depression is more linked to contextual stressors related to the pandemic, rather than the viral infection per se. Additionally, our results points to a role of cytokines and in particular metabolites of the kynurenine pathway in PASC, suggesting their potential as biomarkers and targets for pharmacological treatment.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":"https://doi.org/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 non-response 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>Blood metabolome was measured in a sample of 89 patients with BD either under prophylactic lithium treatment (n = 47), and characterized as responders (R) or non-responders (NR), or with other mood stabilizers (MS, n = 42). For each patient plasma metabolome was measured with 1H-NMR and 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 non-responders to lithium.</p><p><strong>Conclusions and relevance: </strong>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":3.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":"https://doi.org/10.1093/ijnp/pyaf070","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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":3.7,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific prolactin disturbance and divergent gonadal hormone correlates in first-episode schizophrenia.","authors":"Anle Pan, Jindong Wang, Jing Liang, Meihong Xiu, Qiang Hu, Shuangli Zhang","doi":"10.1093/ijnp/pyaf068","DOIUrl":"https://doi.org/10.1093/ijnp/pyaf068","url":null,"abstract":"<p><strong>Background: </strong>Hyperprolactinemia and altered prolactin (PRL) levels are well-documented in schizophrenia. However, very few studies have investigated sex-specific differences in the prevalence of PRL disturbances in first-episode patients with schizophrenia. This cross-sectional study investigated sex-specific PRL dysregulation and its interplay with gonadal hormones in first-episode schizophrenia patients.</p><p><strong>Methods: </strong>One hundred eighty-nine first-episode patients (96 males, 93 females) with minimally treated (≤2 weeks) were recruited. PRL levels and gonadal hormones were measured in all participants.</p><p><strong>Results: </strong>We found a significantly higher prevalence of abnormal PRL levels in males compared to females (32.3% vs. 8.6%, χ2 = 16.2, p<.001). Comparative analysis of gonadal hormones between elevated PRL (n = 39) and normal PRL (n = 150) groups demonstrated elevated follicle-stimulating hormone (Z = 2.7, p=.007) and testosterone (Z = 3.7, p<.001) in the hyperprolactinemic group. In the elevated PRL group, PRL positively correlated with progesterone and testosterone, whereas in the normal PRL group, PRL showed positive associations with estradiol and luteinizing hormone, but negative correlations with progesterone.</p><p><strong>Conclusions: </strong>Our findings underscore the complex and sex-specific nature of PRL dysregulation and its association with gonadal hormones in first-episode schizophrenia patients.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Individual differences in dopamine-related traits influence mood effects of dopamine D2-antagonist and antidepressant treatment expectations.","authors":"Li-Ching Chuang, Nick Augustat, Philipp Bierwirth, Ty Lees, Diego A Pizzagalli, Dominik Endres, Erik M Mueller","doi":"10.1093/ijnp/pyaf067","DOIUrl":"https://doi.org/10.1093/ijnp/pyaf067","url":null,"abstract":"<p><strong>Background: </strong>High trait anhedonia and low trait extraversion have both been previously related to not only low state positive affect but also depressive disorders, disrupted reward processing, and altered mesolimbic dopaminergic signaling. Research on placebo responses suggests that treatment expectations may alter dopamine signaling, elevate positive affect, and reduce depressive symptoms in anhedonic individuals. However, it remains unclear whether such antidepressant placebo responses depend on putative low baseline dopaminergic functioning in high anhedonia and low extraversion. The present study investigates how interindividual differences in these traits influence positive affective responses under manipulation of dopamine and treatment expectations.</p><p><strong>Materials and methods: </strong>In a randomized, double-blind 2×2 design (N = 297), we administered either placebo or the dopamine D2 receptor antagonist sulpiride (400 mg), and manipulated treatment expectations by telling participants that they received either a mood-elevating drug or an inactive substance. Moreover, we assessed trait anhedonia and extraversion, and had participants rate their state positive affect at 6 different time points before and after treatment.</p><p><strong>Results: </strong>Trait anhedonia and extraversion, as well as a broad trait positive affectivity factor, predicted state positive affect across time points. Importantly, effects of sulpiride and antidepressant treatment expectations on positive affect were moderated by dopaminergic traits such that sulpiride increased state positive affect in high anhedonia but decreased it in low anhedonia. Similarly, antidepressant treatment expectations raised positive affect in low extraversion but reduced it in high extraversion.</p><p><strong>Conclusions: </strong>This study demonstrates that dopamine-related individual differences moderate the effects of both sulpiride and a placebo intervention on positive affective state.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","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":3.7,"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":"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":3.7,"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}