Neuropsychopharmacology Reports最新文献

{"title":"Evaluation of GABAergic and Glutamatergic Levels in the Dorsal Anterior Cingulate Cortex of Patients With Bipolar Disorder: A Cross-Sectional ¹H-MRS Study.","authors":"Sotaro Moriyama, Yoshihiro Noda, Shiori Honda, Richard A E Edden, Koki Takahashi, Keisuke Saito, Keita Taniguchi, Masataka Wada, Sakiko Tsugawa, Yui Tobari, Sunjun Huh, Yumina Nakane, Saki Homma, Mie Matsui, Shinsuke Koike, Masaru Mimura, Hiroyuki Uchida, Shinichiro Nakajima","doi":"10.1002/npr2.70085","DOIUrl":"10.1002/npr2.70085","url":null,"abstract":"<p><strong>Background: </strong>Imbalances between excitatory and inhibitory (E/I) neurotransmitters in the brain may contribute to the pathophysiology of bipolar disorder (BD). Proton magnetic resonance spectroscopy (¹H-MRS) measures glutamatergic neurometabolites and gamma-aminobutyric acid (GABA) as indices of E/I neurotransmission. Previous meta-analyses reported higher glutamatergic neurometabolite levels in the medial prefrontal cortex of BD, but findings on GABA levels in the anterior cingulate cortex (ACC) of BD patients remain inconsistent.</p><p><strong>Methods: </strong>We conducted a cross-sectional study using ¹H-MRS to compare GABA and glutamate plus glutamine (Glx) levels in the dorsal ACC (dACC) of 27 patients with BD and 27 age- and sex-matched healthy controls (HCs). We used the ¹H-MRS (3 T MRI, MEGAPRESS, 256 averages, TR = 1500 ms, TE = 68 ms). Clinical symptoms were evaluated using standardized rating scales. Statistical analyses were conducted to assess group differences in neurometabolite levels and to explore the associations between these neurometabolite levels and clinical symptom severity within the BD group.</p><p><strong>Results: </strong>No significant differences in dACC GABA levels, Glx levels, or Glx/GABA ratio were observed between the BD and HC groups. There were no significant differences within the BD group based on BD subtype (I or II) or clinical phase (depression or euthymic). Patients with lithium treatment had higher GABA levels compared to those without.</p><p><strong>Discussion: </strong>Our results suggest that GABAergic function in the dACC may not play a pivotal role in the pathophysiology of BD. Given possible GABAergic dysregulation in BD, further research using alternative methodologies is warranted to elucidate the pathological basis.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 1","pages":"e70085"},"PeriodicalIF":2.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12722104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145810737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of Vortioxetine in Patients With Depression: A Post-Marketing Surveillance Study of Intracranial Hemorrhage in a Japanese Health Insurance Claims Database.","authors":"Takeshi Inoue, Rie Otake, Tatsuya Hoshino","doi":"10.1002/npr2.70077","DOIUrl":"10.1002/npr2.70077","url":null,"abstract":"<p><strong>Aim: </strong>As part of a post-marketing commitment, this study evaluated the incidences of intracranial hemorrhage and serious (intracranial or gastrointestinal) hemorrhage requiring hospitalization in Japanese patients with depression prescribed vortioxetine or selective serotonin reuptake inhibitors (SSRIs).</p><p><strong>Methods: </strong>This real-world, retrospective cohort study used data from the JMDC claims database. Patients with depression who received an initial prescription for vortioxetine or SSRIs (index date) between November 2019 and November 2022, with an observation period of 6 months before (look-back period) and up to 360 days after (follow-up period) the index date were included. The primary analysis estimated the incidence of intracranial hemorrhage, while the secondary analysis estimated the incidence of serious hemorrhage requiring hospitalization. A multivariate model incorporating age, sex, antithrombotic and nonsteroidal anti-inflammatory drug prescriptions, and hypertension as covariates was used to calculate adjusted hazard ratios (aHRs). A propensity score incorporating 21 additional covariates assessed the robustness of the primary analysis (sensitivity analysis).</p><p><strong>Results: </strong>Overall, 147 777 patients were included; 22 827 were prescribed vortioxetine (exposure) and 124 950 were prescribed SSRIs (control). The incidence of intracranial hemorrhage was 1.5 per 10 000 person-years in the exposure group and 3.2 per 10 000 person-years in the control group (aHR: 0.5, 95% confidence interval [CI]: 0.1-1.9). The incidence of serious hemorrhage requiring hospitalization was 27.4 per 10 000 person-years in the exposure group and 31.4 per 10 000 person-years in the control group (aHR: 0.8, 95% CI: 0.6-1.2). The incidence of intracranial hemorrhage in the exposure group versus the control group in the sensitivity analysis was similar to the primary analysis (aHR: 0.4, 95% CI: 0.1-1.9).</p><p><strong>Conclusion: </strong>The incidence of intracranial hemorrhage and serious hemorrhage requiring hospitalization was low in Japanese patients with depression prescribed vortioxetine, and comparable with that observed in patients prescribed SSRIs.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov: NCT05932407.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 1","pages":"e70077"},"PeriodicalIF":2.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12741241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of the rs7858836 Single-Nucleotide Polymorphisms of the ASTN2 Gene on Pain-Related Phenotypes in Japanese Women Who Underwent Laparoscopic Gynecologic Surgery.","authors":"Rie Inoue, Daisuke Nishizawa, Shoko Okahara, Atsuko Hara, Hisako Okada, Junko Hasegawa, Yuko Ebata, Kyoko Nakayama, Masakazu Hayashida, Kazutaka Ikeda","doi":"10.1002/npr2.70083","DOIUrl":"10.1002/npr2.70083","url":null,"abstract":"<p><strong>Background: </strong>In our previous study, the minor T allele of the rs7858836 C/T single-nucleotide polymorphism (SNP) in the ASTN2 gene, which encodes astrotactin 2, was associated with reduced fentanyl requirements after laparoscopic-assisted colectomy and after mandibular osteotomy. In this study, we investigated the effects of this SNP on pain-related phenotypes in patients who underwent laparoscopic gynecologic surgery (LGS).</p><p><strong>Methods: </strong>We studied 333 Japanese women, 21-69 years, who underwent LGS at Juntendo University Hospital between 2017 and 2019. We evaluated associations between SNP genotypes and postoperative pain-related phenotypes, including fentanyl requirements, rescue analgesic requirements, and the average pain scores on an 11-point Numeric Rating Scale (NRS) during the 24-h postoperative period. Patients with the TT or CT genotype were compared with those with the CC genotype using the Mann-Whitney test or χ² test. Values of p < 0.05 were considered statistically significant.</p><p><strong>Results: </strong>The minor T allele frequency was 34.1%. Patients with the CT or TT genotype reported significantly lower average NRS pain scores (median, 1.6 vs. 2.0; p = 0.031) and required fewer rescue analgesics (5.5% vs. 15.0%; p = 0.003) compared to those with the CC genotype. Postoperative fentanyl requirements did not differ between the two groups (p = 0.940).</p><p><strong>Conclusion: </strong>The minor T allele of the rs7858836 SNP was significantly associated with lower postoperative pain intensity, albeit only slightly, and decreased the need for rescue analgesics under comparable fentanyl dosing conditions, potentially reflecting lower pain sensitivity. However, the magnitude of the effect was less than our previous findings.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 1","pages":"e70083"},"PeriodicalIF":2.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12722107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145810724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Data-Driven Psychiatric Disorder Subtype Defined by Significant Enlarged Ventricles and Cognitive Impairment: A Replication Study.","authors":"Toshiaki Onitsuka, Yuka Yasuda, Satsuki Ito, Junya Matsumoto, Naohiro Okada, Maeri Yamamoto, Kazutaka Ohi, Tsutomu Takahashi, Manabu Kubota, Naoki Hashimoto, Harumasa Takano, Naomi Hasegawa, Go Okada, Reiji Yoshimura, Shin Nakagawa, Hidenori Yamasue, Shusuke Numata, Ryota Hashimoto","doi":"10.1002/npr2.70078","DOIUrl":"10.1002/npr2.70078","url":null,"abstract":"<p><p>We previously performed data-driven classification based on large-scale neuroimaging datasets to identify a potential novel subtype of psychiatric disorders characterized by the pronounced enlarged ventricles and cognitive impairment (EVCI) in one cohort. However, these findings have yet to be validated across independent cohorts. Herein, we investigated the availability of cognitive data in other cohorts in the Cognitive Genetics Collaborative Research Organization (COCORO) project to assess the presence of cognitive impairment (CI). Subsequently, we compared the prevalence of CI, lateral ventricular volume, and demographic and clinical characteristics between individuals with EVCI and those with EV but without CI (EV-nonCI). Cognitive data were available for 27 individuals with EVCI from the other 8 cohorts. Among the 27 individuals in the EV group, 5 (18.5%) exhibited EVCI, all of whom were diagnosed with schizophrenia. Three individuals (60%) in the EVCI group were male. Compared with the EV-non-CI group, the EVCI group presented significantly lower current intellectual quotient (IQ) scores (p = 5.8 × 10^-4), but there was no significant difference in premorbid IQ (p = 0.56). Furthermore, there was no significant difference in the Z scores for lateral ventricular volume between the groups (p = 0.26). This study validated the existence of the EVCI subgroup in independent cohorts, thus supporting our previous findings.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 1","pages":"e70078"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12803960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145985271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heavy Episodic Drinking and Hazardous Drinking Among Japanese Young Adults: A Cross-Sectional Study on Prevalence and Associated Factors.","authors":"Kei Yoshida, Aya Kinjo, Yuki Kuwabara, Hongja Kim, Hanako Murase, Hitoshi Maesato, Ruriko Minobe, Susumu Higuchi, Yoneatsu Osaki, Sachio Matsushita","doi":"10.1002/npr2.70091","DOIUrl":"10.1002/npr2.70091","url":null,"abstract":"<p><strong>Background: </strong>No studies have investigated alcohol consumption patterns in a mixed sample of students and employees among Japanese young adults. This study estimated the prevalence of problematic drinking in a sample that includes 18- and 19-year-old individuals and aimed to identify factors related to problematic drinking, which may ultimately contribute to its prevention.</p><p><strong>Methods: </strong>This cross-sectional study conducted in 2019 included 5500 randomly selected adults (18-24 years) from 11 cities. Data on geographical and socioeconomic characteristics, alcohol consumption, and drinking patterns were collected. The prevalence of heavy episodic drinking (HED; consuming ≥ 60 g pure alcohol on a single occasion) and hazardous drinking (HD; daily ethanol intake ≥ 40 g for men and ≥ 20 g for women) was calculated. Binomial logistic regression analysis identified variables associated with HED + HD - group, HD + group, and HED + HD + group as dependent variables.</p><p><strong>Results: </strong>Among 1743 participants who were analyzed (response rate: 32.3%), the prevalence of HED and HD was 27.2% and 17.9%, respectively. Being a student (OR = 2.20, 95% CI: 1.43-3.37) and male sex (OR = 2.26, 95% CI: 1.60-3.19) were associated with HED + HD - group, while living with parents (OR = 0.64, 95% CI: 0.43-0.94) was negatively associated with HD. Underage drinking, all-you-can-drink use, smoking, and alcohol mixed with energy drinks were positively associated with all dependent variables.</p><p><strong>Conclusions: </strong>This study provided data on HED and HD prevalence and associated variables. These findings could help prioritize populations for targeted intervention programs.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 1","pages":"e70091"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12890438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Characteristics of Over-The-Counter Drug Misusers in Psychiatric Practice in Japan: Comparison Between Codeine Misusers and Dextromethorphan Misusers.","authors":"Yuko Tanibuchi, Soichiro Omiya, Takashi Usami, Takuya Shimane, Toshihiko Matsumoto","doi":"10.1002/npr2.70100","DOIUrl":"10.1002/npr2.70100","url":null,"abstract":"<p><strong>Purpose: </strong>In recent years, the misuse of over-the-counter (OTC) medications has been increasing in psychiatric clinical settings in Japan. This study aimed to compare individuals who misuse codeine (COD) with those who misuse dextromethorphan (DXM) to clarify the clinical characteristics of DXM misusers and to consider the support measures needed for this population.</p><p><strong>Methods: </strong>We used data from the 2024 National Survey on Drug-Related Disorders in Psychiatric Inpatient Facilities. Individuals who primarily misused OTC containing COD (COD group) and DXM (DXM group) were extracted from the database. We examined demographic characteristics, ICD-10 subcategories, and comorbid psychiatric disorders and compared the two groups using Fisher's exact test. Factors associated with DXM misuse were further analyzed using multivariable logistic regression.</p><p><strong>Results: </strong>The study included 160 individuals in the COD group and 72 in the DXM group. Compared with the COD group, the DXM group had higher proportions of females and younger individuals, as well as higher rates of drug use within the past year and a history of self-harm or suicide attempts. The DXM group also showed significantly higher comorbidity rates of \"acute intoxication\" and \"mood disorders (F3)\" based on ICD-10. In the multivariable logistic regression analysis, younger age (AOR = 2.558, 95% CI: 1.218-5.371), acute intoxication (AOR = 2.73, 95% CI: 1.254-5.942), and comorbid mood disorders (AOR = 2.201, 95% CI: 1.146-4.227) were significantly associated with DXM misuse.</p><p><strong>Conclusion: </strong>These findings highlight the importance of acute-phase management, assessment of comorbid psychiatric disorders, and interventions that include suicide-risk evaluation in supporting individuals who misuse DXM. Furthermore, preventive education incorporating perspectives on mental-health-focused suicide prevention, as well as regulatory measures for OTC medication sales, are urgently needed.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 1","pages":"e70100"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12914584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146220608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How Does the Public Perceive the Functions of Non-Suicidal Self-Injury? An Analysis by Gender and Age Group.","authors":"Masaru Takahashi","doi":"10.1002/npr2.70088","DOIUrl":"10.1002/npr2.70088","url":null,"abstract":"<p><p>Non-suicidal self-injury (NSSI) is a prevalent phenomenon among adolescents and poses significant public health concerns. Research has identified various functions of NSSI. However, public perceptions of these functions remain unclear. This cross-sectional study explored public understanding of the functions of NSSI and examined the relations between these perceptions and demographic factors of gender and age group. A nationwide online survey was conducted with 2000 Japanese adults (mean age 44.6 years, SD = 14.3) to assess their agreement with 20 statements about NSSI functions using a six-point scale. After conducting an exploratory factor analysis of the functions of NSSI, the study performed a two-factor analysis of variance with the factor scores for each function as the dependent variable and gender and age group as the independent variables. The exploratory factor analysis revealed a four-factor structure: (1) negative emotion regulation, (2) interpersonal effect, (3) avoidance of obligations, and (4) positive mood improvement. A series of two-way analyses of variance revealed gender and age differences, with women and younger individuals being more likely to endorse emotion regulation functions, and middle-aged and older adults more likely to support avoidance functions. Regarding interpersonal relationship factors, no statistically significant results were observed for either gender or age group. The findings suggest the importance of understanding public perceptions of NSSI functions for targeted psychological education and awareness. Future research should directly compare public perceptions with the perceptions of those who engaged in NSSI, considering other demographic factors.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 1","pages":"e70088"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12812855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased Cerebrospinal Fluid Lactate Levels in Schizophrenia and Major Depressive Disorder: NCNP Biobank Study in Japan.","authors":"Hideo Hagihara, Kotaro Hattori, Hiroshi Kunugi, Tsuyoshi Miyakawa","doi":"10.1002/npr2.70096","DOIUrl":"10.1002/npr2.70096","url":null,"abstract":"<p><strong>Aim: </strong>Altered brain energy metabolism related to neural hyperexcitation, which leads to increased lactate levels in the brain and cerebrospinal fluid (CSF), has been implicated in several neuropsychiatric disorders. This study aimed to investigate CSF levels of lactate and related metabolites in Japanese individuals with schizophrenia and major depressive disorder (MDD), using samples from the National Center for Neurology and Psychiatry biobank.</p><p><strong>Methods: </strong>CSF levels of lactate, pyruvate, and glucose were measured in 27 patients with schizophrenia, 26 patients with MDD, and 27 age-matched non-psychiatric controls. Analyses were conducted by diagnostic groups and demographic variables.</p><p><strong>Results: </strong>CSF lactate levels were significantly higher in individuals with schizophrenia and MDD compared with controls. CSF glucose levels were significantly elevated in individuals with MDD compared with controls. Pyruvate levels showed no significant group differences. Across all individuals, CSF lactate, pyruvate, and glucose levels were positively correlated. Lactate and glucose levels showed positive correlations with age. No significant associations were found between the three metabolites' levels and medication dosages, except for an effect of imipramine on glucose levels.</p><p><strong>Conclusion: </strong>This study confirmed elevated CSF lactate levels in Japanese individuals with schizophrenia and MDD, consistent with findings in other populations. The elevation of CSF lactate is unlikely to reflect medication effects and instead may represent an underlying pathophysiology associated with altered brain energy metabolism in the brain.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 1","pages":"e70096"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12956547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D3 Supplementation Modulates Inflammatory Protein CHI3L1/YKL-40 and Oxidative Stress Status in Multiple Sclerosis.","authors":"Sevda Asadpour, Mehrdokht Mazdeh, Jamshid Karimi, Iraj Khodadadi, Gholamreza Shafiee","doi":"10.1002/npr2.70076","DOIUrl":"10.1002/npr2.70076","url":null,"abstract":"<p><strong>Objective: </strong>Multiple sclerosis (MS) is characterized by chronic neuroinflammation and oxidative stress. Vitamin D is believed to exert immunomodulatory and antioxidant effects, yet its impact on specific inflammatory proteins such as CHI3L1 (YKL-40) in MS remains unclear. This study evaluated whether 8-week vitamin D3 supplementation affects serum CHI3L1 levels, oxidative stress markers, and antioxidant enzyme activities in patients with MS.</p><p><strong>Methods: </strong>In this single-arm pre-post clinical trial, 35 patients with MS (aged 30-56 years) received oral vitamin D3 supplementation (50 000 IU/week) for 8 weeks. Serum 25(OH)D and CHI3L1 levels were determined using commercial enzyme-linked immunosorbent assay (ELISA) kits. oxidative stress markers were measured pre- and post-intervention using commercial colorimetric kits. Statistical analysis was performed using paired t-tests or Wilcoxon signed-rank tests.</p><p><strong>Results: </strong>Vitamin D3 supplementation significantly increased serum 25(OH)D levels (20.80 ± 8.6 to 39.11 ± 12.26 ng/mL; p < 0.001). CHI3L1 concentration decreased by 21.7% (33.28 ± 8.9 to 26.05 ± 9.1 ng/mL; p < 0.001). oxidative stress was reduced, evidenced by lower TOS (1.55 ± 0.50 to 0.59 ± 0.23 mmol H₂O₂ equiv./L; p < 0.001) and MDA (0.08 ± 0.03 to 0.05 ± 0.026 nmol/mL; p < 0.001). Antioxidant capacity improved, as demonstrated by elevated TAC (0.622 ± 0.138 to 0.797 ± 0.15 mmol Fe²⁺/L; p < 0.001) and increased activities of SOD (10.5%; p < 0.001), CAT (19.5%; p < 0.001), and GPx (35.6%; p < 0.05). Significant inverse correlations were observed between serum 25(OH)D and CHI3L1 (r = -0.999, p < 0.001), TOS (r = -0.456, p = 0.0058), and MDA (r = -0.577, p < 0.001).</p><p><strong>Conclusion: </strong>Vitamin D3 supplementation was associated with reductions in CHI3L1 and oxidative stress markers, while suggesting enhancement of antioxidant capacity. This observed biomarker changes support vitamin D3 as a potential adjunct therapy targeting interconnected pathological pathways in MS.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"45 4","pages":"e70076"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12641099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145588156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Study on Multi-Timepoint DNA Methylation Levels of Serotonin Transporter Gene and Adolescent Psychological-Behavioral Development.","authors":"Tempei Ikegame, Miki Bundo, Daiki Nagaoka, Yutaro Yanagida, Yutaka Nakachi, Emi Kiyota, Naohiro Okada, Shinsuke Koike, Syudo Yamasaki, Shuntaro Ando, Atsushi Nishida, Kazuya Iwamoto, Kiyoto Kasai","doi":"10.1002/npr2.70081","DOIUrl":"10.1002/npr2.70081","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to investigate whether multi-timepoint DNA methylation levels at the SLC6A4 gene during early adolescence are associated with psychopathological and behavioral clusters, SLC6A4 encodes the serotonin transporter, which regulates the concentration of serotonin in the synaptic cleft. The clusters were previously identified by deep learning analysis of self- and parental-report questionnaires from participants in the Tokyo Teen Cohort (TTC) study in Japan.</p><p><strong>Methods: </strong>We extracted genomic DNA from saliva samples of a subset of TTC participants (N = 122) at ages 11, 13, and 15. DNA methylation levels at the functional CpG sites within the SLC6A4 promoter were measured using bisulfite pyrosequencing. Five psychopathological and behavioral clusters were applied from the previous study: minimal problems, persistent or worsening internalizing problems, subjective problems overlooked by caregivers, persistent externalizing problems, and chronic severe problems across symptoms. Linear mixed-effects models were applied to assess the associations between DNA methylation levels and psycho-behavioral clusters.</p><p><strong>Results: </strong>Males exhibited significantly lower mean methylation levels compared to females across all time points. Males classified as persistent externalizing problems showed notably lower methylation levels than those classified as minimal problems.</p><p><strong>Conclusions: </strong>DNA methylation levels in the SLC6A4 could potentially serve as epigenetic signatures for male adolescents exhibiting externalizing behavioral problems. To our knowledge, this is the first study to track SLC6A4 methylation at three developmental time points across early to mid-adolescence. Further epigenetic research is warranted to understand the role of environmental and genetic factors in the manifestation of adolescent behavioral problems.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"45 4","pages":"e70081"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12678003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145678210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}