International Journal of Neuropsychopharmacology最新文献

{"title":"Multimodal Evidence for Large-scale Network Imbalance in Etomidate Use Disorder.","authors":"Juan Le, Xingmin Wang, Ying Tang, Hao Chen, Xinxin Chen, Xuhao Wang, Yunde Tang, Lishun Zhao, Lin Zhao, Hongxian Shen, Qiuping Huang, Zhenjiang Liao","doi":"10.1093/ijnp/pyag049","DOIUrl":"https://doi.org/10.1093/ijnp/pyag049","url":null,"abstract":"<p><strong>Background: </strong>Etomidate use disorder (EUD) is an escalating public health issue in East and Southeast Asia, yet its neuroimaging features remain poorly understood. This study used simultaneous electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) to examine multimodal functional connectivity alterations in individuals with EUD.</p><p><strong>Methods: </strong>A total of 54 individuals with EUD and 46 healthy controls (HCs) were recruited and underwent simultaneous resting-state EEG and fNIRS recordings. Psychological dimensions including impulsivity, aggression, and craving were evaluated using standardized and validated scales. Source-level EEG functional connectivity and fNIRS hemodynamic connectivity were analyzed to identify group differences. Associations between altered connectivity features and clinical measures were examined within the EUD group. Machine learning analyses were conducted as exploratory assessments of the discriminative information contained in multimodal connectivity features.</p><p><strong>Results: </strong>In unadjusted exploratory analyses of BIS-11 and BPAQ subscales, the EUD group showed higher cognitive impulsivity, non-planning impulsivity, physical aggression, anger and self-directed aggression (t=2.32 to 4.54, p<0.05), but lower motor impulsivity, compared with HCs. Source-level EEG analysis revealed significant group differences only in the delta band, with reduced large-scale connectivity in EUD involving default mode, dorsal attention, visual and sensorimotor systems. fNIRS analysis showed reduced hemodynamic connectivity across multiple frontal subregions and motor-related areas. Weaker connectivity between the primary motor cortex and the triangular part of the inferior frontal gyrus was associated with stronger negative reinforcement craving (rho=-0.471, p_FDR<0.05). Exploratory machine learning analysis showed preliminary discriminative performance, with the random forest model producing the numerically highest test-set AUC (0.80) in this particular data split.</p><p><strong>Conclusions: </strong>Convergent EEG-fNIRS findings suggest delta-band network decoupling and reduced frontal hemodynamic connectivity as multimodal neural features of EUD. These findings provide preliminary evidence for the neural mechanisms of EUD and may inform future objective assessment and treatment-monitoring studies.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181754","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":"Disruption of ultrasonic vocalizations with systemic administration of the non-competitive N-methyl-D-aspartate receptor antagonist MK-801 in adult male mice.","authors":"Ryuto Tamura, Mizuki Yamamoto, Yusuke Ujihara, Haruki Kasahara, Shuntaro Matsushima, Daiki Nasukawa, Kazuko Hayashi, Kota Yamada, Masashi Tanaka, Koji Toda","doi":"10.1093/ijnp/pyag048","DOIUrl":"10.1093/ijnp/pyag048","url":null,"abstract":"<p><strong>Objective: </strong>Social behavior and communication, including ultrasonic vocalizations (USVs), are important for survival and reproductive success across species. N-methyl-D-aspartate (NMDA) receptors contribute to the neural mechanisms underlying social behavior, and pharmacological modulation of these receptors can alter both social behavior and USVs in rodents. However, the effects of NMDA receptor blockade on dyadic USVs and social approach during male-female interactions in mice remain incompletely understood. We therefore investigated the effects of systemic administration of MK-801, a non-competitive NMDA receptor antagonist, on dyadic vocal activity, social approach, locomotor behavior, and excretory outcomes in adult male mice.</p><p><strong>Methods: </strong>Sexually experienced male mice were tested in male-female interaction and same-sex social-preference tasks. Using VocalMat, a machine-learning-based tool, we classified the USVs recorded during male-female interactions into 11 call categories and examined their temporal relationship to the proximity of the male subject to the female stimulus.</p><p><strong>Results: </strong>Administration of MK-801 to the male dose-dependently reduced the total number of USVs recorded from the male-female dyad, with a marked reduction at the highest dose, while leaving the treated male's proximity to the female stimulus unchanged. In the same-sex social-preference task, MK-801 reduced the time spent near the social stimulus at the highest dose, although preference for the social stimulus over the non-social object remained significant under all treatment conditions. MK-801 also increased locomotor activity and reduced fecal output and estimated urine output in the open-field task. These findings demonstrate that systemic NMDA receptor blockade differentially affects dyadic vocal communication, social approach, locomotor activity, and excretory outcomes.</p><p><strong>Conclusion: </strong>Systemic MK-801 administration to the male reduced the number of USVs recorded during male-female interactions and produced distinct effects on social approach, locomotor activity, and excretory outcomes. These findings indicate that NMDA receptor blockade differentially affects multiple behavioral domains, although the mechanisms underlying the reduction in USVs remain to be determined.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13647287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148989755","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":"From depression to bone health: examining the skeletal effects of classical and rapid-acting antidepressants.","authors":"Polymnia Louka, Andrew A Pitsillides, Morfeas Koumas, Charalambos Papacharalambous, Antonia Sophocleous, Panos Zanos","doi":"10.1093/ijnp/pyag044","DOIUrl":"10.1093/ijnp/pyag044","url":null,"abstract":"<p><p>Depression is a brain disorder with systemic consequences including effects on bone health. Clinical and preclinical evidence has associated major depressive disorder (MDD) with reduced bone mineral density (BMD), increased bone resorption, and higher fracture risk, particularly in older adults and postmenopausal women. Plausible mediators include chronic stress, hypothalamic-pituitary-adrenal axis dysregulation, pro-inflammatory cytokines, and altered serotonergic signaling, each of which can affect bone remodeling. Classical antidepressants, particularly selective serotonin reuptake inhibitors, have been associated with adverse skeletal outcomes in human studies, while in vitro evidence indicates effects on osteoblast differentiation, mineralization, and osteoclast activity. Human biomarker studies and preclinical evidence suggest that ketamine-related compounds can modulate bone-related pathways, although these effects appear context-, dose-, exposure-, and model-dependent. Acute and repeated ketamine administration in patients with depression has been associated with changes in bone-turnover markers, including osteoprotegerin (OPG)/receptor activator of nuclear factor kappa-B ligand (RANKL)-related, while rodent studies suggest that arketamine may attenuate stress- and ovariectomy-induced reductions in BMD and normalize the OPG/RANKL ratio. Conversely, preclinical bone-regeneration and explant data indicate that ketamine can reduce bone-cell viability and impair bone healing under specific experimental conditions. The skeletal effects of ketamine, its enantiomers, and its metabolites, including (2R,6R)-hydroxynorketamine, remain preliminary and is limited to human biomarker studies and preclinical rodent/in vitro models; no clinical longitudinal BMD, bone-microarchitecture, or fracture-outcome data are currently available. This review summarizes the evidence linking depression, classical, and rapid-acting antidepressant use and bone health, and identifies gaps and priorities for future investigation, including skeletal monitoring and physiotherapy-informed rehabilitation as adjunctive clinical considerations.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792635","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":"Parvalbumin interneurons under stress: converging mechanisms of vulnerability.","authors":"Thamyris Santos-Silva, Lívea Dornela Godoy, Francisco S Guimarães, Felipe V Gomes","doi":"10.1093/ijnp/pyag043","DOIUrl":"10.1093/ijnp/pyag043","url":null,"abstract":"<p><p>From early life to adulthood, stress shapes brain circuits by impacting vulnerable neuron populations, with parvalbumin-expressing interneurons (PVIs) emerging as particularly sensitive targets. These fast-spiking interneurons orchestrate inhibitory control, maintain excitatory/inhibitory balance, and regulate network oscillations, all of which are crucial for cognitive and emotional function. In addition, PVIs play a central role in regulating stress vulnerability and resilience. Several cellular and molecular mechanisms have been implicated in stress-induced PVI deficits, including disrupted developmental trajectories, redox and metabolic vulnerabilities, inflammatory and microglia-associated signaling, and epigenetic modulation. Stress also remodels perineuronal nets (PNNs), specialized extracellular matrix structures that enwrap PVIs and contribute to their stabilization, the regulation of synaptic function, and protection against oxidative stress. This review synthesizes evidence from rodent models of stress, detailing putative mechanisms through which stress alters PVIs, their associated PNNs, and their circuit-level consequences across development and brain regions, including sex-dependent effects. It further discusses pharmacological and adjuvant interventions that may mitigate stress-induced PVI dysfunction, including monoaminergic modulators, ketamine and its derivatives, as well as anti-inflammatory and antioxidant strategies. By integrating mechanistic insights with potential strategies to protect or restore PVI function, we aim to provide a framework for understanding and reducing stress-induced psychiatric outcomes.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13561109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759492","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":"Vornorexant versus lemborexant for insomnia disorder: a systematic review and network meta-analysis.","authors":"Taro Kishi, Kenji Sakuma, Tsuyoshi Kitajima, Nakao Iwata","doi":"10.1093/ijnp/pyag047","DOIUrl":"10.1093/ijnp/pyag047","url":null,"abstract":"<p><strong>Objective: </strong>This frequentist network meta-analysis was conducted to compare vornorexant (VOR) and lemborexant (LEM) in terms of efficacy, tolerability, and safety outcomes in adults with insomnia disorder.</p><p><strong>Methods: </strong>Efficacy outcomes evaluated at weeks 1 and 2 included subjective time to sleep onset (sTSO), which served as the primary outcome at week 2, as well as subjective total sleep time (sTST), subjective wake after sleep onset (sWASO), and subjective sleep efficiency. Tolerability outcome was treatment discontinuation due to adverse events. Safety outcomes included the incidence of death, suicidal behavior or ideation, at least one adverse event, somnolence, fatigue, dizziness, falls, headache, nightmares, cataplexy, and sleep paralysis.</p><p><strong>Results: </strong>This network meta-analysis included seven trials (n = 2805, average age = 55.14 years, 69.22% female). Treatment arms comprised VOR 5 mg/day (VOR5), VOR 10 mg/day (VOR10), LEM 5 mg/day (LEM5), LEM 10 mg/day (LEM10), and placebo. All active treatments were associated with significantly greater improvements in sTSO at week 2 than placebo. The mean differences in sTSO at week 2 were -11.997 min (95% CI, -15.236 to -8.757) for LEM5, -14.856 min (95% CI, -18.038 to -11.674) for LEM10, -11.364 min (95% CI, -14.733 to -7.996) for VOR5, and - 9.758 min (95% CI, -13.186 to -6.330) for VOR10. LEM5, LEM10, and VOR5 demonstrated significant improvements across all efficacy outcomes at weeks 1 and 2 over placebo. However, although VOR10 did not demonstrate superiority over placebo for sWASO at weeks 1 and 2, it was superior to placebo for all other efficacy outcomes. LEM5 and LEM10 were associated with a higher incidence of at least one adverse event and somnolence compared with placebo, whereas no significant differences in tolerability or safety outcomes were observed for VOR5 or VOR10 versus placebo.</p><p><strong>Conclusions: </strong>Dosage variations could influence both the clinical efficacy and safety profile of these agents.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874061","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":"Multiomic single-nucleus profiling reveals cell-type-specific epigenetic and transcriptional dysregulation in major depressive disorder brain.","authors":"Aleena Francis, Yogesh Dwivedi","doi":"10.1093/ijnp/pyag045","DOIUrl":"10.1093/ijnp/pyag045","url":null,"abstract":"<p><strong>Objective: </strong>Major depressive disorder (MDD) is a leading global cause of disability, marked by persistent mood disturbances, cognitive deficits, and changes in prefrontal cortex neural circuitry. In this study, we aimed to define cell-type-specific molecular and regulatory mechanisms underlying MDD by mapping gene-expression and chromatin-accessibility changes in the dorsolateral prefrontal cortex (PFC) (dlPFC).</p><p><strong>Methods: </strong>Postmortem dlPFC (BA9) tissue from 7 MDD and 8 well-matched controls was analyzed using 10× Genomics snRNA-seq and paired ATAC+RNA multiome sequencing. Sequencing data were processed with Cell Ranger pipelines, nuclei were filtered for quality and doublets/debris, and datasets were integrated and clustered using Seurat/Signac packages. Differential gene expression, chromatin accessibility, and transcription factor motif activity were tested between MDD and controls within each cell type, followed by peak-to-gene linkage and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and PsyGeNET enrichment to interpret dysregulated regulatory mechanisms.</p><p><strong>Results: </strong>A total of 20 distinct clusters encompassing major neuronal and non-neuronal populations were identified. Differential analyses uncovered extensive cell type-specific changes in chromatin accessibility and gene expression, particularly within excitatory layer 5/6 and inhibitory Pvalb neurons, as well as glial and vascular populations. Functional enrichment indicated dysregulation of synaptic organization, neurotransmission, myelination, stress-response, and immune-regulatory pathways across neuronal and non-neuronal cells. Notably, glucocorticoid-responsive transcription factors NR3C1/NR3C2 exhibited conserved regulatory networks implicating stress signaling in MDD pathophysiology.</p><p><strong>Conclusions: </strong>Together, these findings provide a comprehensive single-nucleus atlas of gene regulation in the MDD PFC, highlighting coordinated dysfunction across neurons, glia, and vascular cells.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792646","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":"Effects of lavender oil preparation silexan on different symptoms of major depression - results from a randomized, controlled trial.","authors":"Hans-Jürgen Möller, Ion-George Anghelescu, Hans-Peter Volz, Erich Seifritz, Sandra Schläfke, Siegfried Kasper","doi":"10.1093/ijnp/pyag041","DOIUrl":"10.1093/ijnp/pyag041","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Major depressive disorder (MDD) is characterized by depressed mood, anhedonia, and loss of energy, which can be accompanied by associated symptoms and co-morbidities. Psychiatric scales such as the Montgomery Åsberg Depression Rating Scale (MADRS) must account for the complex nature of depression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The MADRS total score change between baseline and week 8 was the primary outcome measure in a randomized, double-blind clinical trial investigating the antidepressant efficacy of 8 weeks' treatment with silexan compared to sertraline and placebo in patients with mild or moderate MDD. We report on a pre-planned, exploratory analysis of the individual MADRS items. Treatment effects were assessed using analyses of covariance with baseline adjustment, based on an estimand strategy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;498 subjects (silexan 170, sertraline 171, placebo 157) were treated and analyzed. After 8 weeks, silexan was superior to placebo for 5 out of the 9 MADRS items analyzed (\"apparent sadness\", \"reported sadness\", \"reduced appetite\", \"concentration difficulties\", \"lassitude\"; P &lt; .05) and showed clinically important adjusted mean value differences &gt;0.2 points for 7 out of the 9 items. Item-level results for silexan and sertraline were mainly comparable.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Silexan had a strong over-all antidepressant effect, with the most pronounced improvements affecting the cardinal symptoms of depression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Trial registration: &lt;/strong&gt;EudraCT2020-000688-22 first entered on 12/08/2020. Significance statement Patients with depressive disorders can show many different symptoms. To better characterize the clinical action of an antidepressant, it is therefore important to analyze not only the overall value of a depression scale but also the individual items that describe these symptoms. Silexan is a preparation from lavender oil whose antidepressant effect has been proven in a randomized, double-blind, placebo-controlled 8-week study in patients with mild or moderate major depressive disorder. Based on the individual items of the Montgomery Åsberg Depression Rating Scale that was used as the main outcome for efficacy, we found in an exploratory, hypothesis-generating analysis that silexan had a rather broad antidepressant effect in the participants of our study, with potentially clinically meaningful advantages over placebo for 7 out of the 9 individual items investigated. This applied in particular to the main symptoms of depression, namely sadness and lassitude. Our single-item analysis thus helps to understand the antidepressant effects of silexan in more detail. Significant outcomes In patients with mild to moderate major depressive disorder, lavender oil preparation silexan has a clinical profile similar to that of the selective serotonin re-uptake inhibitor sertraline based on an item-level analysis of the Montgomery-Åsberg Depression Rating Scale (MADRS).","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13533546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669506","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":"Weight and metabolic changes in patients with schizophrenia treated with paliperidone palmitate 6-month formulation versus paliperidone palmitate 3-month formulation: a post-hoc analysis.","authors":"Mark Guirguis, Robert Karl Knight, Panna Sanga, John Han, Silvana Galderisi","doi":"10.1093/ijnp/pyag042","DOIUrl":"10.1093/ijnp/pyag042","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To determine the effect that paliperidone palmitate 6-month long-acting injectable formulation (PP6M) had on metabolic parameters including body weight (BW), and blood lipid profiles, a post-hoc analysis was conducted to assess changes in BW from baseline to the end of study based on age, body mass index (BMI), and changes in blood lipid profiles during a 12-month, phase 3, double-blind (DB) clinical study. Long term effects of PP6M on BW and BMI were further explored during a 24-month extension study in which participants were treated exclusively with PP6M.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method: &lt;/strong&gt;In the 12-month DB phase, participants were randomized to receive PP6M or paliperidone palmitate 3-month long-acting injectable formulation (PP3M). The mean change in BW and abnormal weight percent change from baseline were calculated at endpoint by age, gender, and BMI. Additionally, treatment-emergent shifts from baseline for the four key lipid parameters (fasting low density lipoprotein [LDL], fasting triglycerides [TG], fasting total cholesterol [TC], and fasting high density lipoprotein [HDL]) during DB were assessed. Following this study, participants were given the opportunity to transition to a 24-month extension study and be treated with PP6M. The mean change and percent change in BW, and the mean change in BMI from DB baseline to the end of the extension study (36 months total) were calculated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Participants who were treated with PP6M showed numerically less weight gain, BMI, waist circumference, and more weight decrease compared to PP3M group during 12-month DB phase, though the proportion of participants reporting an abnormal change (≥7% change) in BW did not significantly differ between PP3M and PP6M. The weight differences were more pronounced in the younger age group (18-25 years) and those who were overweight (BMI: 25 to &lt;30 kg/m2. Numerical differences in favor of PP6M were found in fasting blood lipids (HDL, LDL, TG, and TC). The changes in BW and BMI over time remained consistent throughout the 24-month extension, favoring PP6M in each instance.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This post-hoc analysis demonstrated that PP6M was comparable to PP3M in terms of metabolic parameters; however, it may have a beneficial effect on weight gain, especially in young patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Trial registration: &lt;/strong&gt;Post-Hoc Analysis of Studies NCT03345342 and NCT04072575 (ClinicalTrials.gov). Significant outcomes The findings from this study have highlighted that participants who were treated with the 6-month long-acting injectable formulation of paliperidone exhibited less weight gain during treatment overall, and significantly less weight gain in adolescents and young adults. Importantly, this trend continued over the course of long-term treatment, regardless of age. Participants treated with the 6-month formulation also had fewer shifts in blood lipids outside of the normal range and h","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13533545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792716","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":"Chronic social defeat stress induces a hypoglycemic shift and depression-related behaviors, both prevented by antidiabetic drugs.","authors":"Wenran Qiu, Hirotaka Nagai, Kohei Ota, Midori Nagai, Tomoyuki Furuyashiki","doi":"10.1093/ijnp/pyag046","DOIUrl":"10.1093/ijnp/pyag046","url":null,"abstract":"<p><strong>Objective: </strong>Stress-related mental illnesses, including depression, are associated with altered glucose metabolism. However, it is unclear how chronic stress alters glucose metabolism along with depression-related behaviors, and how antidiabetic drugs normalize these alterations.</p><p><strong>Methods: </strong>Using a mouse model of social defeat stress, we compared stress-induced glycemic responses among strains that differ in stress susceptibility (C57BL/6N, C57BL/6J, and BALB/c). Blood glucose was measured before stress and after the last stress exposure of acute and chronic stress. Circulating metabolic hormones and inflammatory cytokines were quantified, and depression-related behaviors (social avoidance, anhedonia-like behavior and cognitive deficits) were assessed. In C57BL/6N mice, the antidiabetic drug glyburide or liraglutide was administered 30 min before each of the 10 stress exposures, and their effects on glycemic responses and behavioral outcomes were evaluated.</p><p><strong>Results: </strong>Acute stress elevates blood glucose in the relatively stress-resilient C57BL/6N and C57BL/6J strains, but not in the more stress-susceptible BALB/c strain. After chronic stress, this stress-induced hyperglycemic response was abolished in C57BL/6N and C57BL/6J mice, whereas BALB/c mice showed stress-induced hypoglycemia. Chronic stress also produced largely coordinated changes in circulating metabolic hormones and inflammatory cytokines, with strain-dependent differences in a subset of these molecules. In C57BL/6N mice, treatment with glyburide or liraglutide, antidiabetic drugs with distinct primary mechanisms of action, before each stress exposure reduced the development of anhedonia-like behavior and cognitive deficits without affecting social avoidance, while restoring stress-induced hyperglycemia.</p><p><strong>Conclusions: </strong>These results demonstrate that chronic stress drives a hypoglycemic shift accompanied by depression-related behaviors, and that the development of both metabolic and behavioral alterations can be prevented by antidiabetic drugs with distinct primary mechanisms administered during the stress period. Thus, this study supports metabolically targeted interventions as a potential preventive strategy for stress-related mental illnesses, whereas their efficacy against an already established phenotype remains to be tested.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792673","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":"Viloxazine occupies the 5-HT2C receptor in the Macaca fascicularis brain in vivo: a [11C]CIMBI-36 positron emission tomography study.","authors":"Jennie Garcia-Olivares, Brittney Yegla, Khanum Ridler, Gaia Rizzo, Zhen Fan, Amy Llopis Amenta, Anton Forsberg Moren, Christer Halldin, Vladimir Stepanov, Jennifer Koch, Chungping Yu, Jonathan Rubin, Vladimir Maletic, Eugenii A Rabiner","doi":"10.1093/ijnp/pyag034","DOIUrl":"10.1093/ijnp/pyag034","url":null,"abstract":"<p><strong>Objective: </strong>Efficacy of viloxazine ER (extended-release capsules; Qelbree®) for attention-deficit/hyperactivity disorder (ADHD) is attributed to its ability to increase extracellular norepinephrine and dopamine in the medial prefrontal cortex by inhibiting norepinephrine transporters (NET); however, studies also suggest potentially relevant activity at serotonin (5-HT) receptors. In this study, we evaluated the target engagement by viloxazine at 5-HT2 receptor subtypes, in species with close similarities with humans, and whether viloxazine engages 5-HT2 receptor subtypes within a clinically relevant plasma concentration range.</p><p><strong>Methods: </strong>This study utilized positron emission tomography (PET) and was conducted to measure the relationship between viloxazine plasma concentration and the changes in binding of the agonist radioligand [11C]CIMBI-36 to 5-HT2C/5-HT2A receptors in the brain of Macaca fascicularis monkeys.</p><p><strong>Results: </strong>Viloxazine administration reduced the binding of [11C]CIMBI-36 at 5-HT2C receptors at a concentration 10- to 20-fold lower than at 5-HT2A receptors (EC50: 4.1 vs 45.1 μM, respectively), consistent with receptor binding affinities previously measured in vitro (Ki: 0.66 vs 16.0 μM, respectively). Unbound viloxazine plasma concentrations during these PET scans were compared to human unbound concentrations at doses used to treat ADHD. Our data suggest that at clinically relevant plasma concentrations, viloxazine occupies 60%-72% of 5-HT2C receptors.</p><p><strong>Conclusion: </strong>Our results demonstrate that at unbound viloxazine plasma concentrations comparable with those clinically relevant for the treatment of ADHD, viloxazine occupies a high proportion of 5-HT2C receptors. Occupancy of and potential functional activity at 5-HT2C receptors could therefore contribute to the therapeutic activity of viloxazine in addition to inhibition of NET.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308157","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}