Neuropsychopharmacology Reports最新文献

{"title":"Beyond Diagnosis: Transdiagnostic Cognitive Subgroups in Mood Disorders Linked to Work-Related Disability.","authors":"Ryo Sawagashira, Takuro Tsutsumi, Hayato Watanabe, Atsuhito Toyomaki, Ryo Okubo, Naoki Hashimoto, Takahiro A Kato","doi":"10.1002/npr2.70116","DOIUrl":"10.1002/npr2.70116","url":null,"abstract":"<p><strong>Aim: </strong>Cognitive dysfunction is a transdiagnostic feature of mood disorders and a key determinant of functional outcomes. This study aimed to identify transdiagnostic cognitive heterogeneity among patients with mood disorders using a data-driven approach and to examine its association with social functioning. Characterizing cognitive subtypes and their association with subjective functional disability is an essential first step toward stratified interventions and personalized care.</p><p><strong>Methods: </strong>We analyzed data from 264 age- and sex-matched patients (132 each with major depressive disorder [MDD] or bipolar disorder [BD]). Participants completed six neurocognitive tests to assess executive function, memory, attention, and processing speed. Cognitive variables were adjusted for age and sex, and unsupervised K-means clustering was used to identify transdiagnostic subgroups. Functional impairment was evaluated using the Sheehan Disability Scale.</p><p><strong>Results: </strong>After matching participants based on age and sex, we compared the cognitive performance between the diagnostic groups. Significant differences were observed in only two cognitive variables with a small effect size (mean |Cohen's d| = 0.14). No differences were found in the social functioning measures. Cluster analysis identified two cognitive subtypes: higher-performance group (n = 200) and lower-performance group (n = 64) with a large effect size (mean |Cohen's d| = 0.99). Both clusters included patients with MDD and BD in similar proportions (p = 0.11), indicating a diagnostic overlap. The lower-performance group also showed significantly greater work-related and total functional impairments.</p><p><strong>Conclusion: </strong>Unsupervised clustering revealed transdiagnostic cognitive subgroups in mood disorders independent of diagnostic labels. Cognitive phenotyping may inform personalized treatment strategies and improve functional outcomes by identifying high-risk patients for cognitive remediation or neuromodulation therapies.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 2","pages":"e70116"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593409","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 Preliminary Open-Label Pilot Study of a Pillow-Based ELF-ELME (Extremely Low-Frequency, Extremely Low Magnetic Environment) Intervention for Major Depressive Disorder.","authors":"Ibuki Tomita, Masako Tachibana, Yoshihiro Nawa, Mikako Ito, Fumie Kinoshita, Yachiyo Kuwatsuka, Daisuke Mori, Masashi Ikeda, Kinji Ohno, Toshiya Inada","doi":"10.1002/npr2.70139","DOIUrl":"10.1002/npr2.70139","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial dysfunction has been implicated in the pathogenesis of depression. Major depressive disorder (MDD) is a prevalent condition with substantial individual and societal burden. A novel approach-exposure to an extremely low-frequency, extremely low magnetic environment (ELF-ELME)-has shown promise. This preliminary study builds on a previous trial using a head-mounted ELF-ELME device and explores the potential efficacy and safety of a pillow-based ELF-ELME device in patients with MDD.</p><p><strong>Methods: </strong>In this preliminary open-label pilot study, four patients with MDD were treated using a pillow-based ELF-ELME device (10 μTesla, 4 ms, 1-8 Hz/8 s) for 2 h daily over 8 weeks. The primary outcome was change in Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline to Week 8. Artificial Intelligence-based MADRS (AI-MADRS) scores were also assessed.</p><p><strong>Results: </strong>Total MADRS scores showed a unidirectional decrease from baseline (33.8 ± 7.3) to Week 8 (21.5 ± 8.7; p = 0.050, FDR = 0.067), and no time point reached statistical significance after FDR correction. In contrast, AI-MADRS scores significantly decreased from baseline (34.0 ± 8.3) to Week 8 (19.8 ± 6.8; p = 0.040). No serious adverse events were reported.</p><p><strong>Conclusion: </strong>These preliminary findings suggest that an 8-week course of pillow-based ELF-ELME intervention may have potential to alleviate depressive symptoms in patients with MDD. However, given the small sample size and open-label design, the results should be interpreted with caution. Larger controlled studies are warranted to confirm these findings.</p><p><strong>Trial registration: </strong>jRCT number: jRCTs042240061; https://jrct.mhlw.go.jp/en-latest-detail/jRCTs042240061.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 2","pages":"e70139"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13238718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148144012","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":"Vipr2 Gene Expression Is Upregulated in the Nucleus Accumbens of Spontaneous Hypertensive Rats During Early Life.","authors":"Ryota Araki, Ayami Kita, Yukio Ago, Takeshi Yabe","doi":"10.1002/npr2.70143","DOIUrl":"10.1002/npr2.70143","url":null,"abstract":"<p><strong>Aim: </strong>Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders. Recent methylome analyses have shown that peripheral DNA methylation levels in the VIPR2 gene, which encodes vasoactive intestinal peptide receptor 2, are correlated with ADHD symptoms. However, mRNA expression and DNA methylation levels of the VIPR2 gene in the brain in ADHD are unknown. In this study, we examined the mRNA expression and DNA methylation levels of the Vipr2 gene in the brains of spontaneous hypertensive rats (SHRs), which are used as an animal model of ADHD.</p><p><strong>Methods: </strong>The mRNA levels of Vipr2 and related genes were analyzed in the prefrontal cortex, nucleus accumbens (NAc), amygdala, and hippocampus of SHRs and Wistar Kyoto rats (WKYs), a reference strain, by quantitative reverse transcription polymerase chain reaction. DNA methylation levels at the cytosine-phosphate-guanine (CpG) islands of the Vipr2 gene were evaluated in the NAc of WKYs and SHRs by bisulfite sequencing.</p><p><strong>Results: </strong>The mRNA level of Vipr2 was significantly higher in the NAc, but not in the prefrontal cortex, amygdala, or hippocampus, of male SHRs compared with male WKYs at 4 weeks old. Upregulation of the mRNA level of Vipr2 was observed before 4 weeks old and in females. In contrast, there were no differences in DNA methylation levels at the CpG islands of the Vipr2 gene in the NAc between WKYs and SHRs.</p><p><strong>Conclusion: </strong>DNA methylation was not correlated with upregulation of Vipr2 mRNA in SHRs. Further studies are needed to clarify the involvement of Vipr2 mRNA upregulation in ADHD-like symptoms.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 2","pages":"e70143"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13275169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148272261","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":"Serum Amyloid β Oligomer May Predict Treatment Response in Middle-Aged and Late-Life Patients With Depression.","authors":"Kentaro Shimizu, Seita Yasuda, Hitoshi Maeshima, Tomoya Ichikawa, Hajime Baba","doi":"10.1002/npr2.70109","DOIUrl":"10.1002/npr2.70109","url":null,"abstract":"<p><strong>Aim: </strong>Late-life patients with depression are reportedly less responsive to antidepressant treatment than younger patients. Additionally, patients who have depression comorbid with Alzheimer's disease (AD) and those with an amyloid β (Aβ) burden have shown a poor response to antidepressant treatment, suggesting that AD pathology may contribute to treatment resistance. A recent report indicated that Aβ oligomers in blood have increased in patients with AD and are associated with AD pathology. This study was performed to reveal the relationship between blood Aβ oligomers and the response to antidepressant treatment in middle-aged and late-life patients with depression.</p><p><strong>Methods: </strong>In this observational study, serum levels of Aβ40, Aβ42, and Aβ oligomers were evaluated in 80 inpatients with major depressive disorder aged ≥ 40 years. Depressive symptoms were assessed at admission (baseline) and after 4 weeks of treatment.</p><p><strong>Results: </strong>There were significantly fewer treatment responders among patients with than without serum Aβ oligomers (p = 0.016). Serum Aβ oligomers were found to influence the treatment response even after control for age, sex, number of depressive episodes, severity of depression, and Mini-Mental State Examination scores (p = 0.031).</p><p><strong>Conclusions: </strong>These results suggest that serum Aβ oligomers may predict a poor response to antidepressant treatment in middle-aged and late-life patients with depression. Our findings also lead us to speculate that elderly patients with a poor treatment response may share AD-related pathophysiological features or neural vulnerability.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 2","pages":"e70109"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13581076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147463485","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 by Type of Drug Misused for the First Time.","authors":"Soichiro Omiya, Yuko Tanibuchi, Takashi Usami, Takuya Shimane, Toshihiko Matsumoto","doi":"10.1002/npr2.70108","DOIUrl":"10.1002/npr2.70108","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to understand the clinical characteristics of individuals who misuse over-the-counter (OTC) drugs in psychiatric clinical settings in Japan, and to reconsider approaches to current drug misuse prevention education and support strategies in Japan.</p><p><strong>Methods: </strong>Data were obtained from the 2024 Nationwide Survey on Drug-Related Disorders in Psychiatric Inpatient Facilities in Japan. Patients for whom OTC drugs were the primary substance of abuse were identified, and their demographic profiles, ICD-10 subcategories, and comorbid psychiatric disorders were examined. On the basis of the substance initially misused, participants were classified into three groups: illicit drugs, prescription drugs, and OTC drugs. Comparative analyses were conducted to assess clinical characteristics across these groups.</p><p><strong>Results: </strong>A total of 389 participants were included in the analysis: 36 in the illicit drug group, 47 in the prescription drug group, and 306 in the OTC drug group. Compared with the other groups, the OTC drug group exhibited a significantly higher proportion of female patients, adolescents, and individuals enrolled in junior or senior high school. Furthermore, this group demonstrated significantly lower rates of criminal history and engagement with support or treatment services, such as self-help groups, addiction-focused group therapy, and psychiatric hospitalization. In contrast, the prevalence of comorbid psychiatric disorders was significantly higher in the OTC drug group compared with the other two groups. Within the ICD-10 subcategories, \"harmful use\" was notably more frequent in the OTC drug group compared with the other groups.</p><p><strong>Conclusion: </strong>The findings of this study indicate that OTC drug misuse has become a significant public health concern among adolescent females in Japan. The present findings underscore the necessity of reconsidering existing drug misuse prevention education and support frameworks, which have traditionally been oriented toward illicit substances.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 2","pages":"e70108"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13581093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574385","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":"Pain-Related Smoking Expectancies Across Tobacco Product Use Patterns, Including Heated Tobacco Products: Psychometric Validation of the Japanese Pain and Smoking Inventory.","authors":"Keiko Yamada, Takashi Kimura, Naoki Mizunuma, Takahiro Tabuchi","doi":"10.1002/npr2.70119","DOIUrl":"10.1002/npr2.70119","url":null,"abstract":"<p><strong>Aim: </strong>With the rapid proliferation of heated tobacco products (HTPs) in Japan, understanding pain-related smoking expectancies across tobacco use patterns has become increasingly important. In this study, we aimed to profile these expectancies among adults with pain using the Pain and Smoking Inventory (PSI) and to evaluate its psychometric properties in a Japanese context.</p><p><strong>Methods: </strong>We conducted a cross-sectional internet-based survey in 2024 among 300 Japanese adults with pain who smoked daily. Participants were categorized as combustible-only, HTP-only, switchers (from cigarettes to HTPs), or dual users. Psychometric evaluation included assessment of factor structure, internal consistency, and convergent validity. We used a structural equation model to examine associations between the latent PSI score and pain-related outcomes. We then conducted analyses of covariance to compare PSI scores across tobacco use groups (adjusted for age and gender).</p><p><strong>Results: </strong>Psychometric validation indicated high internal consistency (α = 0.93), mixed but essentially unidimensional fit, and expected correlations with nicotine dependence, pain, and psychological measures. The structural equation model demonstrated significant positive associations between the latent PSI factor and pain intensity (β = 0.29, p < 0.001) as well as pain-related disability (β = 0.39, p < 0.001). Exploratory group comparisons revealed higher PSI scores among dual users than switchers, reflecting stronger perceived pain-smoking relationships. HTP-only users also showed descriptively elevated profiles similar to combustible and dual users.</p><p><strong>Conclusions: </strong>Pain-related smoking expectancies differed across tobacco product use patterns, with dual users showing higher-risk expectancy profiles. The PSI may serve as a useful tool for screening and tailored intervention in pain and tobacco use contexts.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 2","pages":"e70119"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13068504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147654541","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":"High Adherence to Pharmacological Treatment Guidelines in Recovery and Remission States Among Patients With Schizophrenia: A Cross-Sectional Study.","authors":"Ryo Asada, Hitoshi Iida, Leo Gotoh, Kiyohiro Yasumatsu, Hikaru Hori","doi":"10.1002/npr2.70136","DOIUrl":"10.1002/npr2.70136","url":null,"abstract":"<p><strong>Background: </strong>Several schizophrenia guidelines have been published, showing treatment efficacy. However, no studies have examined recovery and pharmacological therapy or guideline adherence's impact on various schizophrenia states. This study aimed to investigate adherence to pharmacological guidelines across recovery, remission, and non-remission states in patients with schizophrenia.</p><p><strong>Methods: </strong>This cross-sectional study included 72 patients with schizophrenia who met the criteria for recovery, remission, or non-remission. Adherence to pharmacological guidelines was measured using the Individual Fitness Score (IFS).</p><p><strong>Results: </strong>IFS was significantly higher in the recovery (88.1 ± 18.9) and remission (89.0 ± 16.7) groups than in the non-remission group (65.59 ± 21.8) (p < 0.01). However, no significant differences were observed between the recovery and remission groups. Receiver operating characteristic analysis identified 72 points on the IFS as a potential cutoff point between remission and non-remission.</p><p><strong>Conclusion: </strong>These results show that higher adherence to pharmacological guidelines may be associated with recovery and remission state, compared with non-remission state. The cutoff point between remission and non-remission should be considered preliminary and exploratory because of a small sample. Clinical practice guidelines have been developed to standardize and improve the quality of medical care. Treatments following these guidelines have been reported to be effective.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 2","pages":"e70136"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13250629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148211955","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":"Aligning Measurement, Scoring, and Interpretation in Survey-Based NSSI Research.","authors":"Kenjiro Shiraishi","doi":"10.1002/npr2.70118","DOIUrl":"10.1002/npr2.70118","url":null,"abstract":"<p><p>This graphical abstract highlights the central interpretive point of the Letter: the survey measured public views about possible functions of NSSI, not the actual motives of people who engage in NSSI. Clearer alignment between measurement target, scoring, and inference may improve reproducibility and interpretation.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 2","pages":"e70118"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13056422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633968","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":"Age and Overdose at the Index Attempt Predict Suicide Reattempts After Emergency Admission: A Multicenter Cohort Study.","authors":"Taro Sasaki, Norio Sugawara, Motoharu Furukawa, Hirotaka Iwaki, Shiro Suda, Norio Yasui-Furukori","doi":"10.1002/npr2.70127","DOIUrl":"10.1002/npr2.70127","url":null,"abstract":"<p><strong>Aim: </strong>A history of suicide attempts is a well-established predictor of future suicidal behavior; however, longitudinal evidence from real-world emergency settings remains limited. Because age and self-poisoning/overdose are readily available at emergency presentation and may inform post-discharge care, we examined whether age and overdose at the index suicide attempt predict medically attended suicide reattempts after emergency admission.</p><p><strong>Methods: </strong>We conducted a multicenter retrospective cohort study of 1038 patients admitted to emergency departments after suicide attempts between 2020 and 2025 at three tertiary hospitals in Japan (Dokkyo Medical University Hospital, Jichi Medical University Hospital, and Hachinohe City Hospital). Patients were followed longitudinally to identify suicide reattempts requiring medical attention. Time-to-event analyses were performed using Kaplan-Meier methods and Cox proportional hazards models. Age (< 40 vs. ≥ 40 years) and sex were included as baseline covariates, and overdose at the index attempt was examined as an explanatory variable. Sensitivity analyses were performed using a stricter definition of overdose (overdose alone).</p><p><strong>Results: </strong>During follow-up, 58 medically attended suicide reattempts were identified. Kaplan-Meier analyses showed higher cumulative reattempt risk in females and in patients aged 39 years or younger. In Cox proportional hazards models, age ≥ 40 years was associated with a lower risk of suicide reattempt, whereas overdose at the index attempt was associated with a significantly increased risk of suicide reattempt. These findings were consistent in sensitivity analyses.</p><p><strong>Conclusion: </strong>Younger age and overdose at the index suicide attempt were independently associated with an increased risk of medically attended suicide reattempt. Assessment of the initial suicide method may help identify patients requiring intensive post-discharge monitoring.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 2","pages":"e70127"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777322","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":"Japanese Cohort Study Identifies an Association Between the Serotonin Transporter-Linked Polymorphic Region and Suicide Death.","authors":"Shohei Okada, Toshiyuki Shirai, Masao Miyachi, Gentaro Yamasaki, Kiriko Minami, Ryo Tsukamoto, Kentaro Mouri, Takaki Tanifuji, Ryuichi Katada, Satoshi Okazaki, Ikuo Otsuka, Akitoyo Hishimoto","doi":"10.1002/npr2.70120","DOIUrl":"10.1002/npr2.70120","url":null,"abstract":"<p><strong>Introduction: </strong>More than 720 000 individuals die by suicide annually worldwide, making it a major public health concern and a leading cause of death among young people, particularly in Asian populations. Dysregulation of the 5-hydroxytryptamine system has been implicated in suicide risk. The SLC6A4 gene encodes the serotonin transporter, which regulates synaptic 5-hydroxytryptamine levels. Its promoter region contains a 44-base-pair insertion/deletion polymorphism, known as the serotonin-transporter-linked polymorphic region (5-HTTLPR). We examined the association between the 5-HTTLPR polymorphism and suicide death in a Japanese cohort, representing the largest sample from an Asian population to date.</p><p><strong>Methods: </strong>We included 448 suicide decedents and 361 controls. Genomic DNA was extracted from peripheral blood, and 5-HTTLPR genotypes were determined using PCR. We evaluated genotype- and allele-level associations with suicide. Additionally, we conducted a meta-analysis incorporating previous studies.</p><p><strong>Results: </strong>The distributions of 5-HTTLPR genotypes and alleles differed significantly between suicide decedents and controls (S allele: OR = 1.62, 95% CI = 1.26-2.09, p < 0.001). The associations remained significant in subgroup analyses by sex, age group, and violent methods. Age- and sex-matched analyses yielded consistent results. However, the random-effects meta-analysis did not demonstrate a significant association.</p><p><strong>Conclusion: </strong>Our findings indicate a potential association between 5-HTTLPR polymorphisms and suicide death in a Japanese population. Although further research in larger and diverse samples is warranted, these results may contribute to a better understanding of the biological underpinnings of suicide risk.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 2","pages":"e70120"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147675266","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}