International Journal of Neuropsychopharmacology最新文献

{"title":"Life Engagement Improvements with Cariprazine in Schizophrenia: A Post-Hoc Analysis of PANSS Data from Short-Term Studies.","authors":"Réka Csehi, Péter Szabó, Zsófia Borbála Dombi, Thomas Brevig, Balázs Szatmári, Ágota Barabássy","doi":"10.1093/ijnp/pyag027","DOIUrl":"https://doi.org/10.1093/ijnp/pyag027","url":null,"abstract":"<p><strong>Objective: </strong>Patient life engagement (PLE) is increasingly recognised as a meaningful treatment goal in schizophrenia, yet it remains under-researched, partly due to the lack of validated PLE measures. This post-hoc analysis evaluated the effect of cariprazine on PLE using a 14-item subset of the Positive and Negative Syndrome Scale (PANSS).</p><p><strong>Methods: </strong>Data from three 6-week, randomized, double-blind, placebo-controlled trials were pooled and analysed post-hoc. The 14-item PANSS subset measured PLE across four domains: Cognitive, Social, Emotional, and Physical. Changes from baseline to Week 6 in PLE Total Score and domain scores were analysed using mixed models for repeated measures. Responder rates (≥5- and ≥10-point reductions) were further assessed.</p><p><strong>Results: </strong>Cariprazine (n=880; 1.5-6.0 mg/day) showed significantly greater improvements than placebo (n=446) on PLE Total Score (LS mean difference [LSMD] = -3.23; 95% CI: -4.59 to -1.87; Cohen's d = 0.79, p < 0.001) and across Emotional (LSMD: -0.59; 95% CI: -0.97 to -0.22; Cohen's d = 0.49, p < 0.001), Social (LSMD: -1.13; 95% CI: -1.65 to -0.6; Cohen's d = 0.71, p < 0.001), and Cognitive (LSMD: -1.34; 95% CI: -1.91 to -0.76; Cohen's d = 0.77, p < 0.001) domains, and numerically greater improvement on the Physical (LSMD: -0.25; 95% CI: -0.5 to 0.01; Cohen's d = 0.30, p = 0.071) domain. Statistically significant improvements emerged by Week 2 on the PLE Total and were sustained through Week 6. Responder analyses showed that 81% and 57% of cariprazine-treated patients met the ≥5- and ≥10-point thresholds, respectively, versus 64% and 43% with placebo (both p < 0.001).</p><p><strong>Conclusion: </strong>The results suggest that cariprazine is associated with significant improvements in patient life engagement in schizophrenia based on the 14-item subset of the PANSS, with early and clinically meaningful benefits across domains. These findings support the value of cariprazine in addressing patient-centred treatment goals.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856286","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":"The introduction of measurement-based care for patients with schizophrenia may improve psychiatric symptoms and guideline adherence rate.","authors":"Keisuke Mori, Junya Matsumoto, Satsuki Ito, Kentaro Fukumoto, Ken Inada, Fumitoshi Kodaka, Harumasa Takano, Shinsuke Kito, Ryota Hashimoto","doi":"10.1093/ijnp/pyag026","DOIUrl":"https://doi.org/10.1093/ijnp/pyag026","url":null,"abstract":"<p><strong>Background: </strong>Measurement-Based Care (MBC) is a clinical approach that uses objective measurements to quantitatively assess patients' symptoms and conditions as the basis for treatment, with the assessments shared with patients and used in practice. One indicator of MBC, the Guideline Adherence Rate (GAR), provides a comprehensive evaluation of the extent to which psychiatrists' prescribing practices conform to clinical practice guidelines. Although the practice of MBC has been reported to improve clinical outcomes in depressive disorders, improvements in clinical outcomes with MBC have not been reported in schizophrenia. We examined longitudinal changes in psychiatric symptoms and the GAR among patients with schizophrenia receiving MBC.</p><p><strong>Methods: </strong>Sixty-five patients with schizophrenia were included. The Positive and Negative Syndrome Scale (PANSS) total score and the GAR were compared longitudinally between time point 1 (T1) and time point 2 (T2).</p><p><strong>Results: </strong>The PANSS total score was significantly lower at T2 than at T1. The GAR was significantly higher at T2 than at T1.</p><p><strong>Conclusion: </strong>Improvements in psychiatric symptoms were consistent with previous findings on MBC reported in depressive disorders. In addition, improvements in the GAR indicated that psychiatrists' prescribing practices aligned more closely with the guideline over time within an MBC environment. These findings suggest that the MBC framework may also be clinically useful in the treatment of schizophrenia. The results were obtained from a specialized schizophrenia outpatient clinic in a national center, which represents a best-case environment for guideline adherence and monitoring. Therefore, further studies are needed to examine the generalizability of these findings.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856291","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":"Heterogeneity in adverse events associated with lumateperone: a study on potential subgroup-specific differences.","authors":"Cheng Jiang, Luhan Tang, Mingqian Li, Guoqin Xia","doi":"10.1093/ijnp/pyag022","DOIUrl":"https://doi.org/10.1093/ijnp/pyag022","url":null,"abstract":"<p><strong>Background: </strong>Lumateperone, a novel atypical antipsychotic, has emerged as an illuminating hope for patients with schizophrenia and bipolar disorder. While prior studies have employed spontaneous reporting databases and identified over 100 novel adverse events associated with lumateperone, the differences in these adverse events across subgroups remain unclear.</p><p><strong>Objective: </strong>This study provides a comprehensive evaluation of the adverse event profile of lumateperone using the Food and Drug Administration Adverse Event Reporting System database, focusing on the potential differences in reporting adverse events across subgroups.</p><p><strong>Methods: </strong>Based on the results of clinical characteristics and signal detection, the potential differences in reporting lumateperone-associated adverse events across specific subgroups regarding report year, reporter type, sex, age, outcome, indication, and concomitant drug were analyzed using the ROR algorithm and Fisher's exact test with Bonferroni correction. The observed differences were further validated using sensitivity analyses, stratified analyses, and comparative analyses.</p><p><strong>Results: </strong>This study identified 1762 reports and 5074 adverse events associated with lumateperone. Notably, females had a higher frequency of reporting nervous system disorders. Tardive dyskinesia was more frequently resulted in serious consequences. Moreover, bipolar disorder patients more frequently reported nervous system disorders, while schizophrenia patients more frequently reported psychiatric disorders.</p><p><strong>Conclusions: </strong>This study underscores the need for future confirmatory studies into the potential sex, outcome and indication differences in adverse events associated with lumateperone. The findings should be considered preliminary and require further validation.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856218","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":"Late-onset major depression and subthreshold depressive symptoms as early clinical correlates of brain small vessel disease.","authors":"Calypso Α Mitkani, Thomas J Tegos, Vasilios K Kimiskidis, Stavroula Koukou, Konstantinos N Fountoulakis","doi":"10.1093/ijnp/pyag024","DOIUrl":"https://doi.org/10.1093/ijnp/pyag024","url":null,"abstract":"<p><strong>Background: </strong>Late-onset depression (LOD) and subthreshold depressive symptoms (SDS) have been associated with cerebral small vessel disease (SVD), but the evidence regarding pre-stroke depression remains limited. This study examined the frequency of DSM-5 LOD and SDS prior to the first non-embolic lacunar stroke.</p><p><strong>Methods: </strong>Fifty-eight patients (mean age 62.2 ± 8.2 years; 41.4% female) with a first lacunar ischemic stroke underwent MRI (T1, T2, FLAIR sequences) and psychiatric evaluation using the MINI, with data from caregivers and medical records. Patients were classified as having LOD (D), SDS (S), combined (S/D), or none (nD/S). Statistical analyses included Mann-Whitney U and Fisher's Exact tests.</p><p><strong>Results: </strong>Of the total sample, 63.8% (n = 37) exhibited LOD or SDS, with reported onset on average 5-7 years prior to stroke (mean onset age: 55.5 years). Females exhibited higher prevalence of depressive symptoms (87.5% vs. 47.1%, p = 0.001). Hypertension (75.7%) and dyslipidemia (62.2%) were the most common vascular risk factors. No patient had manic or hypomanic episodes.</p><p><strong>Conclusions: </strong>Premorbid depressive symptoms were common and may precede the clinical manifestation of cerebrovascular disease. Given the retrospective and observational design, these findings should be regarded as hypothesis-generating rather than causal. Prospective longitudinal studies incorporating quantitative SVD imaging markers are required.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856251","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":"Increase of the AMPA-evoked response of pyramidal neurons in the rat medial prefrontal cortex following acute administration of ketamine and S-ketamine, but not R-ketamine.","authors":"Mostafa El Mansari, Naomichi Okamoto, Pierre Blier","doi":"10.1093/ijnp/pyag020","DOIUrl":"https://doi.org/10.1093/ijnp/pyag020","url":null,"abstract":"<p><strong>Background: </strong>In preclinical studies, an increase in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) to N-methyl-D-aspartate receptor (NMDA) throughput is the predominant hypothesis posited to explain the rapid antidepressant effect of ketamine and S-ketamine. Several lines of evidence show that this AMPA increase takes place in the medial prefrontal cortex (mPFC), which activation has been shown to induce antidepressant-like effects. The present electrophysiological study was aimed at investigating whether a single dose of drugs with antidepressant-like effects that act on glutamate receptors as a primary target induce an increase of evoked AMPA-induced response of pyramidal neurons in the mPFC.</p><p><strong>Methods: </strong>Microiontophoretic applications of AMPA and NMDA were carried out in male anesthetized rats, following acute administration racemic ketamine, S-ketamine, R-ketamine and ifenprodil to first assess their effects on their evoked response of mPFC pyramidal neurons. In a second series of experiments, the effects of these drugs were also assessed on the spontaneous firing activity of these neurons.</p><p><strong>Results: </strong>An increase in the AMPA-, but not NMDA-evoked response was observed following a single acute injection of ketamine and S-ketamine, when compared to saline treated rats. However, R-ketamine and the NMDA receptor GluN2B subunit antagonist ifenprodil had no effect on AMPA- and NMDA-induced responses of mPFC pyramidal neurons. The spontaneous firing activity of pyramidal neurons was enhanced by S-ketamine and ifenprodil.</p><p><strong>Conclusion: </strong>An increase in the AMPA-induced response appears to constitute a common factor underlying the antidepressant-like effects of ketamine and S-ketamine. This increase did not correlate with change in mPFC pyramidal neurons firing activity.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837669","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":"Global Perspectives on CNS Drug Innovation: Achievements, Barriers, and Priorities for the Next Decade.","authors":"Hiroyuki Uchida, Gabriella Gobbi, Joseph Zohar, Allan H Young, Dan Rujescu, Ming-Chyi Huang, Suresh Sundram, Lukoye Atwoli, Jana Vukovic, Kazutaka Ikeda","doi":"10.1093/ijnp/pyag023","DOIUrl":"https://doi.org/10.1093/ijnp/pyag023","url":null,"abstract":"<p><strong>Background: </strong>Over the past decade, neuropsychopharmacology has shifted from stagnation to momentum, with first-in-class mechanisms and biomarker-enabled trials spanning psychiatry and neurology.</p><p><strong>Methods: </strong>We narratively synthesized advances from 2013 to 2026 across central nervous system (CNS) discovery and development, including pivotal trials, regulatory actions, digital/real-world evidence, genetics, artificial intelligence (AI), and implementation/global-access themes that are endorsed by international societies.</p><p><strong>Results: </strong>Therapeutic gains include rapid-acting drugs for treatment-resistant depression (intranasal esketamine); psychedelic-assisted therapy for posttraumatic stress disorder and depression; neuroactive steroid γ-aminobutyric acid-A receptor positive allosteric modulators (brexanolone, zuranolone) for postpartum depression; non-dopaminergic muscarinic agonists (xanomeline-trospium) for schizophrenia; orexin receptor antagonists for insomnia; and anti-amyloid monoclonal antibodies (lecanemab, donanemab) for early Alzheimer's disease. Persistent barriers include high mid-/late-stage attrition that is driven by placebo effects, subjective endpoints, and preclinical-to-clinical gaps; regulatory and economic headwinds; and limited generalizability from tightly run trials. Emerging enablers include adaptive/platform designs, digital health technologies, patient-reported outcomes, and clinical outcome assessments, real-world evidence (RWE), AI/machine learning (ML), genetics for target de-risking and biomarker-guided stratification, and publicly accessible large CNS relevant biological datasets.</p><p><strong>Conclusions: </strong>To convert momentum into durable progress, we recommend: (i) deeper academia-industry/stakeholder collaboration and sustained funding for high-risk/high-reward science from industry, governments and non-for profit foundations; (ii) modernized regulation (flexible evidentiary paths, novel endpoints, and clear guidance on adaptive/platform trials); (iii) data-driven development integrating RWE, AI/ML, and precision medicine; (iv) the adoption of Neuroscience-based Nomenclature (NbN); and (v) a global-access mandate with essential-medicine inclusion, equitable pricing/licensing, capacity building, tele-enabled mental health, and geographically diverse research. Aligning scientific innovation with implementation and equity can accelerate translation and ensure new treatments benefit patients worldwide.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837682","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":"Structural and functional neuroimaging correlates of suicidal ideation in treatment-resistant major depressive disorder.","authors":"Patricia Burhunduli, Katie L Vandeloo, Zhuo Fang, Pierre Blier, Jennifer L Phillips","doi":"10.1093/ijnp/pyag016","DOIUrl":"10.1093/ijnp/pyag016","url":null,"abstract":"<p><strong>Background: </strong>Treatment-resistant depression (TRD) is a severe form of major depressive disorder associated with elevated suicide risk. Identifying neurobiological correlates of suicidal ideation (SI), a key modifiable risk factor, has important clinical implications. This study examined structural and functional magnetic resonance imaging (MRI) correlates of SI severity in individuals with TRD.</p><p><strong>Methods: </strong>Structural and resting-state functional MRI data were collected from 41 participants with TRD and a history of SI. Investigator-rated past-week depression and SI severity was evaluated using the Montgomery-Åsberg Depression Rating Scale and the Columbia Scale of Suicide Severity Rating Scale, respectively. Cortical thickness and subcortical gray matter volumes were measured using FreeSurfer, and resting-state functional connectivity measures were determined using the CONN functional connectivity toolbox. Associations between SI severity and cortical thickness, subcortical gray matter volume, and resting-state functional connectivity were assessed.</p><p><strong>Results: </strong>Whole-brain vertex-wise surface-based structural analyses revealed a significant negative correlation between right lateral occipital cortical thickness and past-week SI severity, covaried for age, sex, and depression severity (P = .03, cluster-corrected). Network-based statistics analyses among 58 preselected regions of interest revealed a significant association between SI severity and resting-state functional connectivity between the right posterior parietal cortex and the left anterior insula, bilateral temporooccipital middle temporal gyrus and left frontal orbital cortex (pFDR = 0.017), covaried for depression severity. Post-hoc analyses further characterized effects, revealing negative associations between SI and functional connectivity measures (pFDR < 0.0001).</p><p><strong>Conclusions: </strong>This multimodal imaging study identified distinct structural and functional correlates of SI severity in TRD. These findings highlight the need to further investigate neurobiological underpinnings of SI to better inform suicide risk assessments and intervention strategies in this high-risk population.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147591875","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 Therapeutic Profiles of Ketamine in Treatment-Resistant Depression: An Exploratory Analysis.","authors":"Kuan-I Liu, Wei-Chen Lin, Cheng-Ta Li, Ya-Mei Bai, Tung-Ping Su, Mu-Hong Chen","doi":"10.1093/ijnp/pyag021","DOIUrl":"https://doi.org/10.1093/ijnp/pyag021","url":null,"abstract":"<p><strong>Objective: </strong>Intravenous ketamine demonstrates rapid efficacy for treatment-resistant depression (TRD). However, its impact on individual depressive symptoms and whether the degree of treatment resistance moderates these effects remain unclear. This study aimed to dissect symptom-specific trajectories and examine the moderating role of the degree of treatment resistance.</p><p><strong>Methods: </strong>We conducted a post-hoc analysis of pooled data from two randomized, double-blind, controlled trials involving 154 adults with TRD receiving subanesthetic ketamine or control. Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) over 15 days. Linear mixed-effect models (LMM) analyzed total scores, while generalized estimating equations (GEE) assessed item-level improvement. The Maudsley Staging Method (MSM) was used to quantify the degree of treatment resistance and evaluate its moderating effect.</p><p><strong>Results: </strong>Ketamine elicited a significant reduction in MADRS total scores (p < .001). Item-level analysis revealed significant improvements in seven symptoms, including apparent sadness, inner tension, and suicidal thoughts (p < .05). Crucially, a significant treatment x MSM interaction was found for apparent sadness (p = .002) and inner tension (p = .024), indicating attenuated efficacy in patients with higher resistance. Conversely, anti-suicidal efficacy was robust and not significantly moderated by resistance severity (p = .083).</p><p><strong>Conclusions: </strong>Ketamine demonstrates broad efficacy in TRD but may exhibit symptom-specific divergence: anti-suicidal effects appear robust across resistance levels, whereas improvements in apparent sadness and inner tension may be attenuated by greater resistance severity. These exploratory findings warrant confirmation in prospective studies.</p><p><strong>Significant outcomes: </strong>Intravenous ketamine showed rapid anti-suicidal efficacy in patients with treatment-resistant depression (TRD), which was not significantly moderated by the baseline severity of treatment resistance. Improvement in apparent sadness and inner tension was significantly moderated by the degree of treatment resistance, with attenuated efficacy observed in patients with higher Maudsley Staging Method (MSM) scores. These exploratory findings raise the hypothesis that a symptom-specific stratified therapeutic approach may be warranted. Future research should examine whether ketamine could serve as an acute intervention for suicidal crises across the resistance spectrum, and whether improvements in specific affective symptoms may require augmentation strategies in highly refractory cases.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770740","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":"Three-week effect of amisulpride, aripiprazole, and olanzapine on gene expression in peripheral blood in individuals with schizophrenia spectrum disorders.","authors":"Anja Torsvik, Andrea Trentani, Tomasz K Stokowy, Silje Skrede, Inge Joa, Solveig M Klæbo Reitan, Maria Rettenbacher, Rune A Kroken, Erik Johnsen, Vidar M Steen","doi":"10.1093/ijnp/pyag019","DOIUrl":"https://doi.org/10.1093/ijnp/pyag019","url":null,"abstract":"<p><strong>Objective: </strong>Antipsychotics drugs are to varying degrees associated with hematological side-effects and peripheral metabolic and immunological changes. Here, we aimed to characterize the initial transcriptional changes in peripheral leukocytes from individuals with schizophrenia spectrum disorder (SSD) after starting antipsychotic treatment with amisulpride, aripiprazole, or olanzapine.</p><p><strong>Methods: </strong>We analyzed RNA sequencing data obtained from peripheral whole blood samples from 100 individuals with SSD (41 antipsychotic-naïve, 10 antipsychotic-free and 49 antipsychotic-switching at inclusion) collected at baseline and after one week and three weeks of antipsychotic drug use. Data from 36 healthy controls (HC) collected at baseline and after three weeks without any intervention were included. We analyzed age- and sex-adjusted differentially expressed genes between SSD and HC before and after treatment and stratified by previous antipsychotic use. A linear mixed model was applied to study longitudinal gene expression changes associated with the antipsychotic drug that was used.</p><p><strong>Results: </strong>After three weeks of antipsychotic use, the antipsychotic-switching group had the most significant transcriptional changes, characterized by increased expression of genes typically transcribed by immature erythroid cells and immature neutrophil cells. This gene profile showed no correlation with symptoms score. Interestingly, the immature neutrophil-associated gene signature was more pronounced in participants receiving olanzapine, and partly also amisulpride, but not aripiprazole. In contrast, only minor transcriptional changes were observed in the antipsychotic-naïve participants.</p><p><strong>Conclusions: </strong>These findings suggest that prior antipsychotic exposure may have a priming effect on leukocyte gene expression, which results in a transcriptional response indicative of stress erythropoiesis and neutropoiesis when switching to a new antipsychotic drug. This response appears to be independent of psychosis symptom severity.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770660","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":"Effects of adjunctive brexpiprazole with selective serotonin reuptake inhibitor treatment on anxiety and sleep architecture in mice.","authors":"Junya Maruoka, Kohei Kozuka, Ryo Egami, Yusuke Kubo, Yusuke Kakumoto, Tetsuro Kikuchi, Kazuhiko Kume","doi":"10.1093/ijnp/pyag007","DOIUrl":"10.1093/ijnp/pyag007","url":null,"abstract":"<p><strong>Introduction: </strong>Major depressive disorder (MDD) is frequently accompanied by residual symptoms such as anxiety and sleep disturbances, even after adequate antidepressant treatment. Brexpiprazole, a serotonin-dopamine activity modulator, has shown efficacy as adjunctive therapy for MDD. However, its mechanistic contribution to anxiety and sleep regulation remains unclear. This study aimed to evaluate the combined effects of brexpiprazole and paroxetine, a selective serotonin reuptake inhibitor (SSRI), on anxiety-like behavior and sleep architecture in mice.</p><p><strong>Methods: </strong>We used male Crl:CD1 and C57BL/6J mice. Anxiety-like behavior was assessed using the marble-burying behavior (MBB) test using Crl:CD1 mice. We also evaluated locomotor activity (LA) monitored to exclude sedative effects. Sleep architecture was evaluated via cortical electroencephalography and electromyography, quantifying Wake, rapid eye movement (REM) sleep, and non-REM (NREM) sleep stages using C57BL/6J mice.</p><p><strong>Results: </strong>In MBB test, paroxetine reduced buried marbles without affecting LA, whereas brexpiprazole alone was ineffective. The combination of brexpiprazole (0.1 mg/kg) and paroxetine (0.75 mg/kg) significantly decreased buried marbles. Next, to explore the role of α2C adrenoreceptor (AR) antagonism, JP-1302 (a selective α2C AR antagonist) was also tested. Similarly, JP-1302 (30 mg/kg) combined with paroxetine (0.75 mg/kg) decreased buried marbles. In sleep architecture, brexpiprazole dose-dependently decreased Wake and increased NREM sleep, while paroxetine primarily reduced REM sleep. Combined administration decreased Wake and REM sleep and increased NREM sleep. The combination showed effects comparable to each drug administered alone.</p><p><strong>Conclusions: </strong>In this study, we demonstrated that the combination of brexpiprazole and paroxetine produced anxiolytic-like effects and altered sleep architecture in mice. Furthermore, the anxiolytic-like effect of the combination suggests that brexpiprazole's α2C AR antagonistic activity may be one of several plausible contributors. Adjunctive brexpiprazole may influence anxiety and sleep architecture, potentially contributing to the management of residual symptoms in MDD.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146226476","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}