研究者業績
基本情報
- 所属
- 藤田医科大学 医学部 教授
- 学位
- 博士（医学）(名古屋大学)
- J-GLOBAL ID
- 200901048638344557
- researchmap会員ID
- 5000024641
- 外部リンク
1989年 名古屋大学医学部卒業
1993年 名古屋大学大学院修了 博士（医学）
1994年 名古屋大学医学部付属病院精神科 医員
1996年 National Institute of Health Visiting Fellow
1998年 藤田医科大学医学部精神神経科学 講師
2002年 藤田医科大学医学部精神神経科学 助教授
2003年 藤田医科大学医学部精神神経科学 教授（現職）
2011年 藤田医科大学研究支援推進本部 本部長（現職）
2015年 藤田医科大学医学部 医学部長（現職）
2016年 藤田医科大学 副学長（現職）
専門分野： 精神疾患の分子遺伝学、神経生化学、薬理遺伝学、臨床精神薬理学
1993年 名古屋大学大学院修了 博士（医学）
1994年 名古屋大学医学部付属病院精神科 医員
1996年 National Institute of Health Visiting Fellow
1998年 藤田医科大学医学部精神神経科学 講師
2002年 藤田医科大学医学部精神神経科学 助教授
2003年 藤田医科大学医学部精神神経科学 教授（現職）
2011年 藤田医科大学研究支援推進本部 本部長（現職）
2015年 藤田医科大学医学部 医学部長（現職）
2016年 藤田医科大学 副学長（現職）
専門分野： 精神疾患の分子遺伝学、神経生化学、薬理遺伝学、臨床精神薬理学
研究分野
1経歴
5-
2003年 - 現在
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2002年 - 2004年
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1998年 - 2002年
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1996年 - 1998年
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1994年 - 1996年
学歴
2-
1989年 - 1993年
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1983年 - 1989年
論文
659-
Psychiatry and clinical neurosciences 2026年2月10日AIM: This network meta-analysis of randomized controlled trials (RCTs) aimed to investigate which hypnotics are associated with the most favorable sleep architecture and respiratory outcomes in adults with obstructive sleep apnea. METHODS: Primary outcomes included total sleep time (TST) and apnea-hypopnea index (AHI) during TST. Other outcomes were rapid eye movement (REM) sleep time, latency to persistent sleep (LPS), wake after sleep onset (WASO), sleep efficiency (SE), AHI during non-REM or REM sleep, mean peripheral oxygen saturation (SpO2) during TST, mean SpO2 nadir during TST, arousal index (AI), all-cause discontinuation, adverse event-related discontinuation, and incidence of individual adverse events. Effect sizes with 95% confidence intervals were calculated. RESULTS: This systematic review included 32 RCTs (n = 1871, average age = 51.60 years, 62.52% male, mean AHI = 23.60). Our network meta-analysis evaluated brotizolam, daridorexant, eszopiclone, flurazepam, lemborexant, nitrazepam, ramelteon, temazepam, triazolam, zaleplon, zolpidem, zopiclone, and placebo. Compared with placebo, lemborexant increased TST, REM sleep time, and SE and decreased LPS and WASO, whereas both daridorexant and zolpidem increased TST and SE and decreased WASO. These three medications demonstrated respiratory safety and discontinuation profiles similar to those of placebo. Eszopiclone increased TST and SE and decreased LPS, WASO, AHI during TST, and AI, but its effects on LPS, WASO, AHI during TST, and AI disappeared in the sensitivity analysis, excluding continuous positive airway pressure titration studies. CONCLUSION: Our network meta-analysis identified different effects of various hypnotics on sleep architecture and respiratory parameters; however, the lack of data prevented a formal synthesis of subjective outcomes. Therefore, these results should be interpreted with caution in clinical practice.
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Schizophrenia research. Cognition 42 100390-100390 2025年12月BACKGROUND: Cognitive dysfunction has a significant impact on social functioning, such as employment, in patients with schizophrenia. However, existing cognitive assessments are time-consuming, impose a significant burden on patients, and require specialized training for evaluators, making them impractical for routine clinical use. Therefore, the present study investigated whether a simple and novel assessment tool, called Psychomotor Function Tests (PFT), correlates with existing Neuropsychological Tests (NT) and assessments with the Life Assessment Scale for the Mentally Ill (LASMI), which evaluates social functioning, including employment. METHODS: Cognitive function was examined in 24 patients with schizophrenia using NT (the Japanese Adult Reading Test, Trail Making Test (TMT), and word fluency test) and tablet-based PFT, while social functioning was evaluated using LASMI. Twenty-four healthy controls (HCs) underwent the same cognitive assessments. RESULTS: Psychomotor function, as evaluated by the choice reaction time, compensatory tracking test, and rapid visual information processing, was significantly worse in patients with schizophrenia than in HCs (p < 0.001). Furthermore, the composite score of PFT correlated with the time required for TMT (r = -0.707, -0.637) and LASMI subscales related to work, endurance & stability, self-recognition, required skills, and retention skills (r = -0.640, -0.689, -0.634, -0.420, -0.548). CONCLUSION: PFT correlated with existing NT, which are widely used in cognitive function assessments. Cognitive function examined by PFT was closely associated with social functioning. These results suggest the potential of PFT for evaluating cognitive function in routine clinical settings for patients with schizophrenia.
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Molecular psychiatry 2025年11月5日Sensory issues are common in autism spectrum disorders (ASD) and can significantly affect daily living. The phenomena of gating and habituation of event-related potentials (ERPs) to repetitive stimuli have been suggested as potential biomarkers reflecting atypical sensory processing in ASD. Sensory hypersensitivity and anxiety are closely related in ASD, and habituation to emotionally evocative stimuli may serve as a more sensitive biomarker for sensory hypersensitivity symptoms. However, previous studies have primarily used tonal stimuli, and there has been little investigation into whether habituation to emotionally evocative sounds is impaired in ASD patients. In this study, we compared the degree of habituation of the P1-N1 peak-to-peak amplitude in response to repeated tones and fearful vocalizations between control and ASD groups. Contrary to expectations, no significant difference was observed for fearful vocalizations between the groups, while ASD patients showed significantly reduced habituation to tonal sounds in the left parieto-occipital region. Furthermore, we found a significant correlation between the degree of habituation to tonal sounds in the left parieto-occipital region and sensory hypersensitivity symptoms in ASD patients, and similar abnormalities in BTBR mice, an animal model of ASD. These results suggest that habituation to tonal sounds, rather than emotionally evocative stimuli, may serve as a translational biomarker reflecting sensory hypersensitivity symptoms.
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Neuropsychopharmacology Reports 45(3) 2025年9月4日ABSTRACT Objective To examine the characteristics associated with happiness in Japanese individuals with schizophrenia. Methods A self‐reported online survey was conducted in 2022 among individuals aged 20–75 years, including 223 and 1776 individuals with and without schizophrenia, respectively. We used a modified Poisson regression to assess the factors associated with happiness by calculating the age‐ and sex‐adjusted prevalence ratios (PRs). We examined within‐schizophrenia group differences by age and sex strata, and compared these stratified PRs between groups with and without schizophrenia. Results Among participants with schizophrenia, happiness was significantly associated with self‐rated health status (PR = 1.75), Ikigai (PR = 5.02), depressive symptoms (PR = 0.43), perceived stress (PR = 0.52), cognitive social capital (PR = 2.07), structural social capital (PR = 1.70), social support (PR = 2.40), close friends (PR = 1.88), close relatives (PR = 2.34), and a cohabiting partner (PR = 1.57). Within the schizophrenia group, sex differences were significant for cognitive social capital (men: PR = 3.45; women: PR = 1.43) and cohabiting partners (men: PR = 2.26; women: PR = 1.25), whereas no significant age differences were found. Factors demonstrating a stronger association in participants with schizophrenia than in those without schizophrenia included: Ikigai (with, PR = 5.02; without, PR = 2.91), cognitive social capital (with, PR = 2.07; without, PR = 1.49), and structural social capital (with, PR = 1.70; without, PR = 1.24). Conclusion Happiness in individuals with schizophrenia is associated with physical, mental, and social factors, with social factors exhibiting sex‐related differences.
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Psychological medicine 55 e252 2025年8月28日BACKGROUND: The optimal duration for maintaining antidepressant treatment in individuals with obsessive-compulsive disorder (OCD) who achieve symptom stabilization remains unclear. METHODS: This systematic review and pairwise meta-analysis of double-blind randomized placebo-controlled trials (DBRPCTs) compared antidepressant maintenance and antidepressant discontinuation groups in terms of relapse rate at each DBRPCT study endpoint (primary outcome), OCD symptom improvement, all-cause discontinuation, and adverse event-related discontinuation. Furthermore, relapse rates at 4, 8, 12, 16, 20, and 24 weeks were compared between the groups. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. The absolute risk reduction (ARR) and number needed to treat to benefit (NNTB) for relapse rates were also estimated. RESULTS: Nine trials (n = 1084; mean age: 32.8 years; proportion of males: 53.3%) were included. The antidepressant maintenance group had lower relapse rates at each DBRPCT study endpoint (RR [95% CI] = 0.53 [0.42-0.68]; ARR = 21.0%; NNTB = 5) and lower all-cause and adverse event-related discontinuation rates than the antidepressant discontinuation group. The maintenance group also exhibited lower relapse rates at 4 weeks (RR [95% CI] = 0.47 [0.31-0.70]; ARR: not significant; NNTB: not significant), 8 weeks (0.42 [0.31-0.57]; 12.0%; 8), 12 weeks (0.43 [0.32-0.56]; 18.0%; 6), 16 weeks (0.41 [0.32-0.52]; 25.0%; 4), 20 weeks (0.43 [0.34-0.53]; 26.0%; 4), and 24 weeks (0.42 [0.33-0.52]; 27.0%; 4) than the discontinuation group. Moreover, the maintenance group outperformed the discontinuation group regarding OCD symptom improvement. CONCLUSIONS: Individuals with OCD may benefit from continued antidepressant treatment, provided that it is well tolerated.
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Translational Psychiatry 15(1) 2025年8月18日Abstract Light plays a crucial role in regulating nocturnal sleep patterns. This cross-sectional study evaluated the potential association between levels of light exposure in real-life settings and sleep parameters in individuals with bipolar disorder. We included 204 ambulatory individuals with bipolar disorder who participated in the APPLE (Association between Pathology of Bipolar Disorder and Light Exposure in Daily Life) cohort study. Daytime illuminance and sleep were assessed using actigraphy over a seven-day period. In addition, a portable light meter was used to evaluate the illuminance levels in the bedroom during nighttime. The median values of daytime illuminance and nighttime illuminance were 221.8 lux (interquartile range: 150.9–306.9 lux) and 2.3 lux (0.3–9.6 lux), respectively. Multivariable linear regression analyses, adjusting for potential confounders, revealed a significant association between greater daytime illuminance and higher sleep efficiency as well as shorter sleep onset latency and wake after sleep onset. Moreover, the interaction term of daytime and nighttime illuminance demonstrated a significant correlation with sleep efficiency (95% confidence interval [CI], −10.45 to −2.17; P = 0.003), sleep onset latency (95% CI, 0.18 to 0.91; P = 0.004), and wake after sleep onset (95% CI, 13.47 to 50.1; P < 0.001). Our findings indicate the existence of a significant positive correlation between daytime light exposure and sleep parameters in individuals with bipolar disorder. The interaction of increased daytime light and decreased nighttime light appears to be positively associated with sleep quality.
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Translational psychiatry 15(1) 211-211 2025年6月24日BACKGROUND: In order to appraise the risk-benefit balance of the three available dual orexin receptor antagonists (DORAs; daridorexant, lemborexant, and suvorexant) for the management of adults with insomnia, we conducted a systematic review and random-effects model network meta-analysis. METHODS: Included were all published double-blind, randomized, placebo-controlled trials of these agents. Outcomes included subjective time to sleep onset at month 1 (sTSO, primary), subjective total sleep time at month 1 (sTST, co-primary), subjective wake after sleep onset at month 1, Insomnia Severity Index scores at month 1, all-cause discontinuation, discontinuation due to adverse events, and the incidence of individual adverse events such as somnolence, dizziness, falls, headache, nasopharyngitis, and upper respiratory tract infection. RESULTS: This meta-analysis included eight trials (5198 adults, average age = 56.33 years, 67.84% female). The treatment arms included daridorexant 25 mg/day (DAR25), daridorexant 50 mg/day (DAR50), lemborexant 5 mg/day (LEM5), lemborexant 10 mg/day (LEM10), suvorexant 20 mg/day (15 mg/day for people ≥65years, SUV20/15), and placebo. All active-treatments outperformed placebo in terms of all efficacy outcomes. The standardized mean difference (95% CI) in primary outcomes ranged from; sTSO: -0.430 (-0.568, -0.292) for LEM10 to -0.164 (-0.296, -0.031) for SUV20/15 and sTST: -0.475 (-0.593, -0.357) for DRA50 to -0.206 ( -0.330, -0.082) for LEM5. An additional sensitivity analysis suggested that DRA25, LEM10, and SUV20/15 were associated with a higher incidence of somnolence compared to a placebo. CONCLUSIONS: Considering that there is no evidence that DORAs are associated with physiological tolerance, withdrawal symptoms, or rebound insomnia when abruptly discontinued, and that sleep architecture is not adversely affected, the DORAs appear to be a favorable choice in managing insomnia disorder in adults.
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Molecular psychiatry 2025年4月4日Dendritic spine abnormalities are believed to be one of the critical etiologies of autism spectrum disorder (ASD). Over the past decade, the importance of microglia in brain development, particularly in synaptic elimination, has become evident. Thus, microglial abnormalities may lead to synaptic dysfunction, which may underlie the pathogenesis of ASD. Several human studies have demonstrated aberrant microglial activation in the brains of individuals with ASD, and studies in animal models of ASD have also shown a relationship between microglial dysfunction and synaptic abnormalities. However, there are very few methods available to directly assess whether phagocytosis by human microglia is abnormal. Microglia are tissue-resident macrophages with phenotypic similarities to monocyte-derived macrophages, both of which consistently exhibit pathological phenotypes in individuals with ASD. Therefore, in this study, we examined the phagocytosis capacity of human macrophages derived from peripheral blood monocytes. These macrophages were polarized into two types: those induced by granulocyte-macrophage colony-stimulating factor (GM-CSF MΦ, traditionally referred to as "M1 MΦ") and those induced by macrophage colony-stimulating factor (M-CSF MΦ, traditionally referred to as "M2 MΦ"). Synaptosomes purified from human induced pluripotent stem cell-derived neuron were used to assess phagocytosis capacity. Our results revealed that M-CSF MΦ exhibited higher phagocytosis capacity compared to GM-CSF MΦ, whereas ASD-M-CSF MΦ showed a marked impairment in phagocytosis. Additionally, we found a positive correlation between phagocytosis capacity and cluster of differentiation 209 expression. This research contributes to a deeper understanding of the pathobiology of ASD and offers new insights into potential therapeutic targets for the disorder.
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PCN reports : psychiatry and clinical neurosciences 4(1) e70064 2025年3月BACKGROUND: With 30%-50% of people with bipolar depression (BDep) not responding to multiple pharmacological treatments, alternative therapies are needed. Accelerated intermittent theta burst stimulation (aiTBS) over the left dorsolateral prefrontal cortex (L-DLPFC) has been employed for individuals with pharmacological treatment-resistant major depressive disorder (TR-MDD). Imaging studies have revealed reduced regional activity of the L-DLPFC for both TR-MDD and pharmacological treatment-resistant BDep (TR-BDep), suggesting that aiTBS over the L-DLPFC may be beneficial for people with TR-BDep. METHODS: A 6-week, double-blind, sham-controlled, randomized trial will be conducted to compare the efficacy and safety of aiTBS to the L-DLPFC in people with TR-BDep (jRCTs042240019). Fifty iTBS sessions (1800 pulses/session) will be delivered in 10 daily sessions over 5 consecutive days at 90% resting motor threshold. This aiTBS protocol is termed as Fujita Neuromodulation Therapy for Bipolar Depression (FNT-BD). Twenty-two participants (both sexes, aged 18-64 years) with TR-BDep (DSM-5-TR, Type I) will be recruited. The response rate at any given week of follow-up will be the primary efficacy outcome, defined as a reduction of ≥50% in the Montgomery Åsberg Depression Rating Scale (MADRS) score. Other outcomes will include MADRS score changes, remission rate (10 ≥ MADRS score), Clinical Global Impression-Improvement score, Clinical Global Impression-Severity score, discontinuation rate, and incidence of individual adverse events. RESULTS: We anticipate that individuals who receive the aiTBS treatment show significant improvement in depressing symptoms compared to those receiving sham treatment. CONCLUSIONS: This study will provide valuable evidence for both patients with TR-BDep and clinicians.
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Translational psychiatry 15(1) 63-63 2025年2月20日Suicidal ideation (SI) and behavior (SB) are major public health concerns, but risk factors for their development and progression are poorly understood. We used ICD codes and a natural language processing algorithm to identify individuals in a hospital biobank with SI-only, SB, and controls without either. We compared the profiles of SB and SI-only patients to controls, and each other, using phenome-wide association studies (PheWAS) and polygenic risk scores (PRS). PheWAS identified many risk factors for SB and SI-only, plus specific psychiatric disorders which may be involved in progression from SI-only to SB. PRS for suicide attempt were only associated with SB, and even after accounting for psychiatric disorder PRS. SI PRS were only associated with SI-only, although not after accounting for psychiatric disorder PRS. These findings advance understanding of distinct genetic and clinical risk factors for SB and SI-only, which will aid in early detection and intervention efforts.
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Chronobiology international 42(2) 235-243 2025年2月Procrastination behavior has been reportedly associated with the evening preference. This study aimed to evaluate its difference between patients with circadian rhythm sleep-wake disorders with phase delay (CRSWDswPD) and healthy controls in terms of evening preference and comorbid psychiatric disorders. Thirty patients with CRSWDswPD and 29 healthy participants were included. In both groups, the general procrastination scale (GPS), Beck Depression Inventory (BDI), and Morningness-Eveningness Questionnaire (MEQ) were administered. Additionally, Adult ADHD Self-Report Scale (ASRS) and autism spectrum quotient (AQ) were also assessed in the patient group. Unexpectedly, GPS was not statistically different between patients with CRSWDswPD and healthy controls. GPS was significantly higher with lower MEQ in the healthy group, whereas the opposite tendency was observed in the patient group. Higher AQ, ASRS, and BDI tended to be associated with higher GPS in the patient group, with the first two being statistically significant. The results suggest that general procrastination is not significantly associated with CRSWDswPD, although it is associated with evening preference in healthy participants. Procrastination in the patient group may be associated with developmental disorders or depression tendencies. Future studies should include simultaneous measurement of circadian markers, other behavioral assessments, a larger population, and untreated patients.
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Pharmacopsychiatry 2025年1月29日The United States Food and Drug Administration approved the xanomeline-trospium combination in September 2024 for treating schizophrenia, based in part on three double-blind, randomized placebo-controlled trials in adults with schizophrenia experiencing acute psychosis. This random-effects model pairwise meta-analysis of those three trials found that xanomeline-trospium was comparable to placebo in terms of all-cause discontinuation, discontinuation rate due to adverse events, Simpson-Angus Scale score change, Barnes Akathisia Rating Scale score change, body weight change, body mass index change, blood pressure change, serum total cholesterol change, blood glucose change, QTc interval changes, and the incidence of headache, somnolence, insomnia, dizziness, akathisia, agitation, tachycardia, gastroesophageal reflux disease, diarrhea, increased weight, and decreased appetite. However, xanomeline-trospium was associated with a higher incidence of at least one adverse event, dry mouth, hypertension, nausea, vomiting, dyspepsia, and constipation, and increased serum triglyceride compared with placebo. Notably, xanomeline-trospium demonstrated superior efficacy than placebo in improving the Positive and Negative Syndrome Scale (PANSS) total score, PANSS positive subscale score, and PANSS negative subscale score.
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JMIR formative research 9 e66330 2025年1月29日BACKGROUND: Estimating the prevalence of schizophrenia in the general population remains a challenge worldwide, as well as in Japan. Few studies have estimated schizophrenia prevalence in the Japanese population and have often relied on reports from hospitals and self-reported physician diagnoses or typical schizophrenia symptoms. These approaches are likely to underestimate the true prevalence owing to stigma, poor insight, or lack of access to health care among respondents. To address these issues, we previously developed an artificial neural network (ANN)-based schizophrenia classification model (SZ classifier) using data from a large-scale Japanese web-based survey to enhance the comprehensiveness of schizophrenia case identification in the general population. In addition, we also plan to introduce a population-based survey to collect general information and sample participants matching the population's demographic structure, thereby achieving a precise estimate of the prevalence of schizophrenia in Japan. OBJECTIVE: This study aimed to estimate the prevalence of schizophrenia by applying the SZ classifier to random samples from the Japanese population. METHODS: We randomly selected a sample of 750 participants where the age, sex, and regional distributions were similar to Japan's demographic structure from a large-scale Japanese web-based survey. Demographic data, health-related backgrounds, physical comorbidities, psychiatric comorbidities, and social comorbidities were collected and applied to the SZ classifier, as this information was also used for developing the SZ classifier. The crude prevalence of schizophrenia was calculated through the proportion of positive cases detected by the SZ classifier. The crude estimate was further refined by excluding false-positive cases and including false-negative cases to determine the actual prevalence of schizophrenia. RESULTS: Out of 750 participants, 62 were classified as schizophrenia cases by the SZ classifier, resulting in a crude prevalence of schizophrenia in the general population of Japan of 8.3% (95% CI 6.6%-10.1%). Among these 62 cases, 53 were presumed to be false positives, and 3 were presumed to be false negatives. After adjustment, the actual prevalence of schizophrenia in the general population was estimated to be 1.6% (95% CI 0.7%-2.5%). CONCLUSIONS: This estimated prevalence was slightly higher than that reported in previous studies, possibly due to a more comprehensive disease classification methodology or, conversely, model limitations. This study demonstrates the capability of an ANN-based model to improve the estimation of schizophrenia prevalence in the general population, offering a novel approach to public health analysis.
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Nature 2025年1月22日Bipolar disorder is a leading contributor to the global burden of disease1. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown2. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.8 million controls), combining clinical, community and self-reported samples. We identified 298 genome-wide significant loci in the multi-ancestry meta-analysis, a fourfold increase over previous findings3, and identified an ancestry-specific association in the East Asian cohort. Integrating results from fine-mapping and other variant-to-gene mapping approaches identified 36 credible genes in the aetiology of bipolar disorder. Genes prioritized through fine-mapping were enriched for ultra-rare damaging missense and protein-truncating variations in cases with bipolar disorder4, highlighting convergence of common and rare variant signals. We report differences in the genetic architecture of bipolar disorder depending on the source of patient ascertainment and on bipolar disorder subtype (type I or type II). Several analyses implicate specific cell types in the pathophysiology of bipolar disorder, including GABAergic interneurons and medium spiny neurons. Together, these analyses provide additional insights into the genetic architecture and biological underpinnings of bipolar disorder.
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Brain stimulation 2025年1月15日
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Journal of affective disorders 2025年1月15日Dummy.
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Frontiers in psychiatry 16 1542000-1542000 2025年BACKGROUND: Although several guidelines provide dosing recommendations for antidepressants based on patients' genetic information, pharmacogenetic testing for antidepressant use is rarely routinely performed in Japan. To clarify the clinical impact of pharmacogenetic testing, this study estimated the potential drug-gene interactions for first-time antidepressant treatment in Japanese patients with major depressive disorder. METHODS: This study retrospectively included Japanese patients who were registered for depressive episodes (F32, International Classification of Diseases, Tenth Revision) and initiated on antidepressants between July 2022 and March 2023. Antidepressant prescription rates were calculated using a nationwide hospital-based database (Medical Data Vision Co., Ltd). The incidence of actionable drug-gene interactions was estimated by multiplying the first-time prescription rate of each relevant antidepressant by the frequency of its corresponding actionable phenotype. RESULTS: A total of 3,197 patients were included in the analysis. Escitalopram was the most frequently prescribed antidepressant (18.7%, n = 597), followed by mirtazapine (17.5%, n = 561), and sertraline (15.4%, n = 493). Of the patients receiving their first treatment of major depressive disorder, 56.5% (n = 1,807) were prescribed a drug with actionable pharmacogenetic implications, and 26.4% (n = 844) were estimated to have required actionable therapeutic recommendations. The highest incidence of actionable drug-gene interactions was observed in escitalopram and CYP2C19 pairs (12.4%, n = 398). For sertraline and CYP2C19 or CYP2B6 pairs, the incidence was 11.0% (n = 352). Among all antidepressants, paroxetine had the highest incidence of actionable drug-gene interactions related to CYP2D6 at 1.8% (n = 56); this interaction was rarely observed with other antidepressants (<1%). CONCLUSIONS: We estimated that one in four Japanese patients with major depressive disorder who were prescribed first-time antidepressants had actionable drug-gene interactions. These results suggest that pre-emptive pharmacogenetic testing in the treatment of major depressive disorder could have important clinical implications.
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Fujita Medical Journal 2024年12月 査読有り
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Psychiatry and clinical neurosciences 2024年10月15日AIM: Bipolar disorder (BD) is a common psychiatric disorder characterized by alterations between manic/hypomanic and depressive states. Rare pathogenic copy number variations (CNVs) that overlap with exons of synaptic genes have been associated with BD. However, no study has comprehensively explored CNVs in synaptic genes associated with BD. Here, we evaluated the relationship between BD and rare CNVs that overlap with synaptic genes, not limited to exons, in the Japanese population. METHODS: Using array comparative genome hybridization, we detected CNVs in 1839 patients with BD and 2760 controls. We used the Synaptic Gene Ontology database to identify rare CNVs that overlap with synaptic genes. Using gene-based analysis, we compared their frequencies between the BD and control groups. We also searched for synaptic gene sets related to BD. The significance level was set to a false discovery rate of 10%. RESULTS: The RNF216 gene was significantly associated with BD (odds ratio, 4.51 [95% confidence interval, 1.66-14.89], false discovery rate < 10%). The BD-associated CNV that corresponded with RNF216 also partially overlapped with the minimal critical region of the 7p22.1 microduplication syndrome. The integral component of the postsynaptic membrane (Gene Ontology:0099055) was significantly associated with BD. The CNV overlapping with the intron region of GRM5 in this gene set showed a nominal significant association between cases and controls (P < 0.05). CONCLUSION: We provide evidence that CNVs in RNF216 and postsynaptic membrane-related genes confer a risk of BD, contributing to a better understanding of the pathogenesis of BD.
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Translational Psychiatry 14(1) 2024年10月14日Abstract Recent genome-wide association studies (GWASs) have identified fatty acid desaturase (FADS) genes, which code key enzymes involved in polyunsaturated fatty acid (PUFA) desaturation as susceptibility genes for bipolar disorder (BD). Several quantitative changes in PUFAs suggest their involvement in BD pathogenesis. Therefore, this study aimed to clarify the relationship between BD and PUFAs by conducting lipidomics covariating with the FADS gene variant (rs174550), which is associated with PUFA levels and BD susceptibility. The concentrations of 23 fatty acids were measured using plasma samples from the BD group (n = 535) and the control group (n = 107). Differences in each PUFA concentration ratio were compared between the two groups. Also, differences in each PUFA concentration ratio were compared for each genotype in rs174550. Our results showed that the BD group had significantly lower concentrations of linoleic acid (LA) (β = −0.36, p = 0.023) and arachidonic acid (AA) (β = −0.18, p = 0.013) than the control group. Concerning the effect of FADS on the PUFA concentration ratio, carriers of C-allele at rs174550 had significantly decreased γ-linolenic acid and AA concentration ratios. A previous GWAS reported that the presence of a C-allele at rs174550 increased the BD risk. This direction is consistent with the lipidomic results of the present study. In conclusion, both the FADS and BD were considered to regulate the AA concentration. Thus, as the FADS gene variant is crucial for conducting lipidomics of BD we believe that the allele frequency of FADS must be analyzed.
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Nature genetics 56(10) 2027-2035 2024年10月Human genetic variants are associated with many traits through largely unknown mechanisms. Here, combining approximately 260,000 Japanese study participants, a Japanese-specific genotype reference panel and statistical fine-mapping, we identified 4,423 significant loci across 63 quantitative traits, among which 601 were new, and 9,406 putatively causal variants. New associations included Japanese-specific coding, splicing and noncoding variants, exemplified by a damaging missense variant rs730881101 in TNNT2 associated with lower heart function and increased risk for heart failure (P = 1.4 × 10-15 and odds ratio = 4.5, 95% confidence interval = 3.1-6.5). Putative causal noncoding variants were supported by state-of-art in silico functional assays and had comparable effect sizes to coding variants. A plausible example of new mechanisms of causal variants is an enrichment of causal variants in 3' untranslated regions (UTRs), including the Japanese-specific rs13306436 in IL6 associated with pro-inflammatory traits and protection against tuberculosis. We experimentally showed that transcripts with rs13306436 are resistant to mRNA degradation by regnase-1, an RNA-binding protein. Our study provides a list of fine-mapped causal variants to be tested for functionality and underscores the importance of sequencing, genotyping and association efforts in diverse populations.
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JAMA network open 7(10) e2441159 2024年10月1日IMPORTANCE: To date, several theta burst stimulation (TBS) protocols, such as intermittent TBS (iTBS), have been proposed; however, previous systematic reviews have revealed inconsistent efficacy findings in individual TBS studies for schizophrenia. OBJECTIVE: To examine which TBS protocols are associated with the most favorable and acceptable outcomes in adults with schizophrenia. DATA SOURCES: The Cochrane Library, PubMed, and Embase databases were searched for studies published before May 22, 2024. STUDY SELECTION: The inclusion criteria were as follows: (1) published and unpublished randomized clinical trials (RCTs) of any TBS treatment and (2) RCTs including individuals with schizophrenia spectrum disorders, other psychotic disorders, or both. DATA EXTRACTION AND SYNTHESIS: This study followed the Cochrane standards for data extraction and data quality assessment and used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline for reporting. The risk of bias of individual studies was assessed using the second version of the Cochrane risk of bias tool, and the Confidence in Network Meta-Analysis application was used to rate the certainty of evidence for meta-analysis results. At least 2 authors double-checked the literature search, data transfer accuracy, and calculations. MAIN OUTCOMES AND MEASURES: The primary outcome of this study was improvement in scores related to negative symptoms. Our frequentist network meta-analysis used a random-effects model. The standardized mean difference (SMD) or odds ratio for continuous or dichotomous variables, respectively, was calculated with 95% CIs. RESULTS: A total of 30 RCTs of 9 TBS protocols, with 1424 participants, were included. Only iTBS over the left dorsolateral prefrontal cortex (L-DLPFC) was associated with reduced negative symptom scores (SMD, -0.89; 95% CI, -1.24 to -0.55), overall symptom scores (SMD, -0.81; 95% CI, -1.15 to -0.48), Positive and Negative Syndrome Scale general subscale scores (SMD, -0.57; 95% CI, -0.89 to -0.25), depressive symptom scores (SMD, -0.70; 95% CI, -1.04 to -0.37), and anxiety symptom scores (SMD, -0.58; 95% CI, -0.92 to -0.24) and improved overall cognitive impairment scores (SMD, -0.52; 95% CI, -0.89 to -0.15) compared with a sham. However, positive symptom score changes, all-cause discontinuation rate, discontinuation rate due to adverse events, headache incidence, and dizziness incidence did not significantly differ between any TBS protocols and sham. CONCLUSIONS AND RELEVANCE: In this network meta-analysis, iTBS over the L-DLPFC was associated with improved scores for negative, depressive, anxiety, and cognitive symptoms in individuals with schizophrenia and was well tolerated by the participants. Other forms of TBS were not associated with benefit. Further research is needed to assess the potential role of TBS in the treatment of schizophrenia.
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medRxiv : the preprint server for health sciences 2024年9月17日Bipolar disorder (BD) is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 BD risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci, and prioritized 17 likely causal SNPs for BD. We mapped these SNPs to genes, and investigated their likely functional consequences by integrating variant annotations, brain cell-type epigenomic annotations, brain quantitative trait loci, and results from rare variant exome sequencing in BD. Convergent lines of evidence supported the roles of genes involved in neurotransmission and neurodevelopment including SCN2A, TRANK1, DCLK3, INSYN2B, SYNE1, THSD7A, CACNA1B, TUBBP5, PLCB3, PRDX5, KCNK4, CRTC3, AP001453.3, TRPT1, FKBP2, DNAJC4, RASGRP1, FURIN, FES, DPH1, GSDMB, MED24 and THRA in BD. These represent promising candidates for functional experiments to understand biological mechanisms and therapeutic potential. Additionally, we demonstrated that fine-mapping effect sizes can improve performance of BD polygenic risk scores across diverse populations, and present a high-throughput fine-mapping pipeline (https://github.com/mkoromina/SAFFARI).
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BMC psychiatry 24(1) 600-600 2024年9月5日BACKGROUND: We report the final results of treatment with aripiprazole, blonanserin, and paliperidone from the Japan Useful Medication Program for Schizophrenia (JUMPs), a 104-week naturalistic study. METHODS: JUMPs was an open-label, three-arm, randomized, parallel-group, 104-week study. Patients aged ≥ 20 years with schizophrenia requiring antipsychotic treatment or a switch from previous therapy were enrolled. The primary endpoint was treatment discontinuation rate over 104 weeks. Secondary endpoints included remission rate, Personal and Social Performance (PSP), safety, Positive and Negative Syndrome Scale (PANSS), and quality of life (QOL; EuroQol-5 dimension). RESULTS: In total, 251 patients received aripiprazole (n = 82), blonanserin (n = 85), or paliperidone (n = 84). Treatment discontinuation rates (aripiprazole, 80.5%; blonanserin, 81.2%; paliperidone, 71.4%) were not significantly different (p = 0.2385) among the treatment groups at 104 weeks; comparable outcomes were observed for endpoints, including remission (42.9%, 46.7%, and 45.8%), PANSS, and safety. In the overall cohort, while the improvement in the PSP total score at Week 104 was not significantly different from baseline, a significant improvement (p < 0.05) in QOL and total PANSS scores (including all subscales) was observed at Week 104 compared with baseline. Multivariable analysis identified a shorter disease duration and a higher chlorpromazine-equivalent antipsychotic dosage level (≥ 1000 mg) before switching to monotherapy as predictors of treatment discontinuation. CONCLUSIONS: The 104-week treatment outcomes were comparable between groups; the overall trend of improvement in remission rate, safety, and QOL suggests the importance of continued treatment. CLINICAL TRIAL REGISTRATION: UMIN-Clinical Trials Registry UMIN000007942 (public release date: 14/05/2012).
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Psychiatry and clinical neurosciences 2024年7月22日AIM: Adverse childhood experiences are potentially traumatic events with long-lasting effects on the health and well-being of patients with autism spectrum disorder (ASD). It is important to clarify which types of long-lasting autism-related symptoms are influenced by childhood experiences to design future intervention studies. However, few studies have examined the association between childhood experiences and autistic symptoms in large samples of adults with ASD and individuals with typical development (TD). In this study, we evaluate the effects of adverse childhood experiences on multiple ASD phenotypes among both individuals with ASD and those with TD. METHOD: We combined questionnaire evaluations; Childhood Abuse and Trauma Scale, the Japanese version of the Autism-Spectrum Quotient, Conners' Adult ADHD Rating Scale, the Japanese version of the Impact of Event Scale-Revised, and the Japanese version of the Adolescent/Adult Sensory Profile. RESULTS: Individuals with ASD and those with TD (n = 205 and 104, respectively) were included. There were significant correlations between the extent of adverse childhood experiences and severity of attention-deficit/hyperactivity disorder symptoms, posttraumatic stress disorder symptoms, and hypersensitivity in both participants with ASD and those with TD. By contrast, ASD core symptoms showed no significant correlation with adverse childhood experiences in either group. These results remained consistent after adjusting for age, sex, and the estimated intelligence quotient. CONCLUSION: These findings suggest the need for a detailed disentanglement of ASD-related core and peripheral symptoms of adverse childhood experiences, which may help to appropriately set outcomes for future early interventions for the childhood experiences of individuals with ASD.
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Molecular psychiatry 2024年6月6日In clinical practice, theta burst stimulation (TBS) presents as a more efficient and potentially more effective therapeutic modality than conventional repetitive transcranial magnetic stimulation (rTMS), as it allows for the delivery of more stimuli in less time and at similar intensities. To date, accelerated treatment plans according to various continuous (cTBS) and intermittent TBS (iTBS) protocols for depression have been proposed. To investigate which of the TBS protocols provided a favorable risk-benefit balance for individuals with depression, this systematic review and random-effects model network meta-analysis was conducted. The study outcomes included response rate (primary), depression symptom improvement, remission rate, all-cause discontinuation rate, incidence of switch to mania, and incidence of headache/discomfort at treatment site. In this meta-analysis, a total of 23 randomized controlled trials (n = 960, mean age = 41.88 years, with 60.78% females) were included. Approximately 69.57% of the trials included individuals with an exclusive diagnosis of major depressive disorder. The following six TBS protocols (target) were evaluated: cTBS (right-dorsolateral prefrontal cortex [R-DLPFC]), cTBS (R-DLPFC) + iTBS (left-DLPFC [L-DLPFC]), iTBS (L-DLPFC), iTBS (L-DLPFC) + iTBS (R-DLPFC), iTBS (left-dorsomedial prefrontal cortex) + iTBS (right-dorsomedial prefrontal cortex), and iTBS (occipital lobe). Compared to sham, cTBS (R-DLPFC) + iTBS (L-DLPFC), iTBS (L-DLPFC), and iTBS (occipital lobe) had a higher response rate (k = 23); cTBS (R-DLPFC) + iTBS (L-DLPFC) and iTBS (L-DLPFC) dominated in the depression symptom improvement (k = 23); and iTBS (L-DLPFC) had a higher remission rate (k = 15). No significant differences were found for all-cause discontinuation rate (k = 17), incidence of switch to mania (k = 7), and incidence of headache/discomfort at treatment site (k = 10) between any TBS protocols and sham. Thus, cTBS (R-DLPFC) + iTBS (L-DLPFC) and iTBS (L-DLPFC) demonstrate favorable risk-benefit balance for the treatment of depression.
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Journal of Clinical Medicine 13(10) 2970-2970 2024年5月17日Background and Objective: Excellent generalizability is the precondition for the widespread practical implementation of machine learning models. In our previous study, we developed the schizophrenia classification model (SZ classifier) to identify potential schizophrenia patients in the Japanese population. The SZ classifier has exhibited impressive performance during internal validation. However, ensuring the robustness and generalizability of the SZ classifier requires external validation across independent sample sets. In this study, we aimed to present an external validation of the SZ classifier using outpatient data. Methods: The SZ classifier was trained by using online survey data, which incorporate demographic, health-related, and social comorbidity features. External validation was conducted using an outpatient sample set which is independent from the sample set during the model development phase. The model performance was assessed based on the sensitivity and misclassification rates for schizophrenia, bipolar disorder, and major depression patients. Results: The SZ classifier demonstrated a sensitivity of 0.75 when applied to schizophrenia patients. The misclassification rates were 59% and 55% for bipolar disorder and major depression patients, respectively. Conclusions: The SZ classifier currently encounters challenges in accurately determining the presence or absence of schizophrenia at the individual level. Prior to widespread practical implementation, enhancements are necessary to bolster the accuracy and diminish the misclassification rates. Despite the current limitations of the model, such as poor specificity for certain psychiatric disorders, there is potential for improvement if including multiple types of psychiatric disorders during model development.
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Neuropsychopharmacology Reports 44(1) 165-175 2024年3月
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Neuropsychopharmacology reports 2024年2月6日AIM: To update the major depressive disorder (MDD) treatment guidelines of the Japanese Society of Mood Disorders, we conducted a systematic review and pairwise meta-analysis of double-blind, randomized, placebo-controlled trials of available antidepressants in Japan for older adults with MDD. METHODS: Outcome measures included response rate (primary), improvement in depressive symptom scale score, remission rate, all-cause discontinuation, discontinuation due to adverse events, and at least one adverse event. A random-effects model was used to calculate the risk ratio (RR) and standardized mean difference (SMD) with a 95% confidence interval (95% CI). RESULTS: Nine double-blind, randomized, placebo-controlled trials (n = 2145) were identified. No study has been conducted in Japan. Our meta-analysis included the following antidepressants: duloxetine, escitalopram, imipramine, sertraline, venlafaxine, and vortioxetine. Antidepressants have significantly higher response rates than placebo (RR [95% CI] = 1.38 [1.04, 1.83], p = 0.02). Antidepressants outperformed placebo in terms of improving depressive symptom scale score (SMD [95% CI] = -0.62 [-0.92, -0.33], p < 0.0001). However, antidepressants were associated with a higher discontinuation rate due to adverse events (RR [95% CI] = 1.94 [1.30, 2.88], p = 0.001) and a higher incidence of at least one adverse event (RR [95% CI] = 1.11 [1.02, 1.21], p = 0.02) compared to placebo. The groups did not differ significantly in terms of remission rate or all-cause discontinuation. CONCLUSIONS: Our meta-analysis concluded that treatment with antidepressants available in Japan is only weakly recommended for moderate to severe MDD in older adults.
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Psychiatry and clinical neurosciences 2023年11月20日
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JMIR Formative Research 7 e50193-e50193 2023年11月15日Background In Japan, challenges were reported in accurately estimating the prevalence of schizophrenia among the general population. Retrieving previous studies, we investigated that patients with schizophrenia were more likely to experience poor subjective well-being and various physical, psychiatric, and social comorbidities. These factors might have great potential for precisely classifying schizophrenia cases in order to estimate the prevalence. Machine learning has shown a positive impact on many fields, including epidemiology, due to its high-precision modeling capability. It has been applied in research on mental disorders. However, few studies have applied machine learning technology to the precise classification of schizophrenia cases by variables of demographic and health-related backgrounds, especially using large-scale web-based surveys. Objective The aim of the study is to construct an artificial neural network (ANN) model that can accurately classify schizophrenia cases from large-scale Japanese web-based survey data and to verify the generalizability of the model. Methods Data were obtained from a large Japanese internet research pooled panel (Rakuten Insight, Inc) in 2021. A total of 223 individuals, aged 20-75 years, having schizophrenia, and 1776 healthy controls were included. Answers to the questions in a web-based survey were formatted as 1 response variable (self-report diagnosed with schizophrenia) and multiple feature variables (demographic, health-related backgrounds, physical comorbidities, psychiatric comorbidities, and social comorbidities). An ANN was applied to construct a model for classifying schizophrenia cases. Logistic regression (LR) was used as a reference. The performances of the models and algorithms were then compared. Results The model trained by the ANN performed better than LR in terms of area under the receiver operating characteristic curve (0.86 vs 0.78), accuracy (0.93 vs 0.91), and specificity (0.96 vs 0.94), while the model trained by LR showed better sensitivity (0.63 vs 0.56). Comparing the performances of the ANN and LR, the ANN was better in terms of area under the receiver operating characteristic curve (bootstrapping: 0.847 vs 0.773 and cross-validation: 0.81 vs 0.72), while LR performed better in terms of accuracy (0.894 vs 0.856). Sleep medication use, age, household income, and employment type were the top 4 variables in terms of importance. Conclusions This study constructed an ANN model to classify schizophrenia cases using web-based survey data. Our model showed a high internal validity. The findings are expected to provide evidence for estimating the prevalence of schizophrenia in the Japanese population and informing future epidemiological studies.
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Neuropsychopharmacology reports 2023年11月1日AIM: The present study aimed to examine the association between copy number variations (CNVs) in parkin (PRKN) and schizophrenia (SCZ) and autism spectrum disorder (ASD) in a large case-control sample. METHOD: Array comparative genomic hybridization was performed on 3111 cases with SCZ, 1236 cases with ASD, and 2713 controls. We systematically prioritized likely pathogenic CNVs (LP-CNVs) in PRKN and examined their association with SCZ and ASD. RESULTS: In total, 3014 SCZ cases (96.9%), 1205 ASD cases (97.5%), and 2671 controls (98.5%) passed quality control. We found that monoallelic carriers of LP-CNVs in PRKN were common (70/6890, 1.02%) and were not at higher risk of SCZ (p = 0.29) or ASD (p = 0.72). We observed that the distribution pattern of LP-CNVs in the Japanese population was consistent with those in other populations. We also identified a patient diagnosed with SCZ and early-onset Parkinson's disease carrying biallelic pathogenic CNVs in PRKN. The absence of Parkinson's symptoms in 10 other monoallelic carriers of the same pathogenic CNV further reflects the lack of effect of monoallelic pathogenic variants in PRKN in the absence of a second hit. CONCLUSION: The present findings suggest that monoallelic CNVs in PRKN do not confer a significant risk for SCZ or ASD. However, further studies to investigate the association between biallelic CNVs in PRKN and SCZ and ASD are warranted.
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Journal of psychiatric research 167 132-138 2023年10月16日The benefits of serotonin 3 receptor antagonists (5-HT3R-As) in obsessive-compulsive disorder (OCD) treatment remain unclear. Thus, this study aimed to perform a systematic review and a random-effects meta-analysis, including double-blind, randomized, placebo-controlled trials (DBRPCTs). The outcomes include the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) total score (primary), Y-BOCS obsession subscale score, Y-BOCS compulsive subscale score, treatment response, remission rate, all-cause discontinuation, and incidence of individual adverse events (nervousness/restlessness/anxiety, insomnia, headache, dizziness/lightheadedness, decreased appetite, constipation, nausea/vomiting, diarrhea, dry mouth, sweating/increased perspiration, itching/pruritus, tremor, and sexual dysfunction/decreased libido). The mean differences (MD) for continuous outcomes and risk ratios for dichotomous outcomes with 95% confidence intervals (CIs) were calculated. Our study included 10 DBRPCTs (n = 628). Pooled 5-HT3R-As outperformed placebo regarding Y-BOCS total score (MD = -5.08, 95% CI = -7.04, -3.12, N = 9, n = 560), Y-BOCS obsession subscale score, Y-BOCS compulsive subscale score, treatment response, and remission rate. Individually, all 5-HT3R-As outperformed placebo regarding Y-BOCS total score (granisetron: MD = -5.59, 95% CI = -8.79, -2.39, N = 3, n = 178, ondansetron: MD = -5.72, 95% CI = -8.06, -3.37, N = 6, n = 331, tropisetron: MD = -2.87, 95% CI = -5.19, -0.550, N = 1, n = 96). However, all-cause discontinuation and incidence of individual adverse events between pooled 5-HT3R-As and placebo were not significantly different. In conclusion, our meta-analysis suggested 5-HT3R-As as efficacious for symptom improvement in individuals with OCD. However, the number of individuals included in each study was small; thus, a replication randomized trial of 5-HT3R-As should be conducted using a larger sample size.
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日本睡眠学会定期学術集会・日本時間生物学会学術大会合同大会プログラム・抄録集 45回・30回 276-276 2023年9月
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Neuropsychopharmacology reports 2023年8月30日INTRODUCTION: The question remains to be elucidated: "Is treatment with antidepressants at doses approved in Japan effective for Japanese patients with MDD?" It is crucial to confirm this in order to provide appropriate treatments for Japanese patients with major depressive disorder (MDD). Therefore, we conducted a systematic review and random-effects pairwise meta-analysis including these nine double-blind, randomized, placebo-controlled trials. METHODS: We calculated the standardized mean difference (SMD) and risk ratio (RR) with a 95% confidence interval (95% CI). RESULTS: Pooled newer antidepressants outperformed placebo regarding improvement of depressive symptom scale scores [SMD (95% CI) = -0.20 (-0.27, -0.12), p < 0.00001], response to treatment [RR (95% CI) = 1.23 (1.13, 1.32), p < 0.00001], and remission rate [RR (95% CI) = 1.30 (1.16, 1.45), p < 0.00001]. Although all-cause discontinuation was not significantly different between the treatment groups, the pooled antidepressant group showed a higher discontinuation rate due to adverse event [RR (95% CI) = 1.60 (1.13, 2.26), p = 0.007] and a higher incidence of at least one adverse event than the placebo group [RR (95% CI) = 1.13 (1.08, 1.18), p < 0.00001]. DISCUSSION: We concluded that newer antidepressants are effective for Japanese adults with MDD although the clinicians must monitor the health conditions of these individuals.
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Psychiatry research 328 115452-115452 2023年8月28日Our meta-analysis demonstrated that intermittent theta burst stimulation (iTBS)/bilateral-TBS (Bi-TBS) and high-frequency repetitive transcranial magnetic stimulation (HF-rTMS)/bilateral-rTMS (Bi-rTMS) had similar efficacy, acceptability, and safety profiles for antidepressant treatment-resistant major depressive disorder (AD-TRD). In our sensitivity analysis that excluded a study that compared Bi-TBS with Bi-rTMS for older adults, all efficacy outcomes were also comparable between iTBS and HF-rTMS. Because iTBS does not require higher stimulation intensity and a longer stimulus time than conventional HF-rTMS protocols, we speculated that for those with AD-TRD, iTBS/Bi-TBS is a more helpful therapeutic modality in clinical practice than HF-rTMS/Bi-rTMS.
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Fujita medical journal 9(3) 218-224 2023年8月OBJECTIVES: We evaluated the continuity and effectiveness of oral appliances (OAs) for treating obstructive sleep apnea (OSA) in a psychiatric sleep clinic, specifically focusing on mild cases and those with psychiatric comorbidity. METHODS: We retrospectively examined the medical records of 106 OSA patients treated with OA. Survival analysis was performed to assess the discontinuation of OA use. Clinical Global Impression-Improvement (CGI-I) scale were obtained from medical records. The apnea-hypopnea index (AHI), measured by polysomnography (PSG), and Epworth Sleepiness Scale (ESS) were compared between diagnosis and after post-OA treatment if a second PSG for efficacy assessment was conducted. RESULTS: Among all 106 patients, Kaplan-Meier analysis estimated a discontinuation rate of 16.8% at 1 year. This tended to be higher for OSA patients with psychiatric comorbidity (22.7%) than those without (11.6%), though it was not statistically significant (P=0.08). The overall rate of improvement in CGI-I scale was 37.7% and was significantly lower in OSA patients with psychiatric comorbidity (25.0%) than those without (48.3%). Among the 74 patients who underwent a second PSG, AHI and ESS were significantly lower after OA treatment for the entire group and subgroups of OSA severity at diagnosis and psychiatric comorbidity, except for ESS in the moderate OSA severity subgroup. CONCLUSION: OA continuation was relatively good, and sleepiness was relieved by OA use, even in mild OSA patients and those with psychiatric comorbidity. However, the continuation and subjective improvement of symptoms were slightly lower in OSA patients with psychiatric comorbidity.
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Fujita medical journal 9(3) 231-235 2023年8月OBJECTIVES: To investigate the subjective assessments of an antipsychotic treatment with brexpiprazole. METHODS: This was a 14-week prospective observational study. Nineteen patients participated in the study between February 2019 and January 2020. RESULTS: Patients had a mean age of 40.6±14.2 years and a Clinical Global Impressions-Severity of Illness scale (CGI-S) score of 4.6±1.2 at the initiation of brexpiprazole treatment. The Subjective Well-being under Neuroleptic drug treatment Short form, Japanese version (SWNS-J) total score significantly improved from 68.1±22.3 in week 2 to 79.5±21.0 in week 14 (p=0.0084). The SWNS-J subscales of self-control and social integration status also significantly improved from 14.0±4.7 and 13.9±6.0 in week 2 to 17.0±4.7 and 16.0±5.1 in week 14, respectively (p=0.0053 and 0.012, respectively). No significant improvements were observed in any other SWNS-J subscales or the Drug Attitude Inventory-10 (DAI-10) in the 14-week observation period. Moreover, the SWNS-J total score did not correlate with the DAI-10 (r=0.31, p=0.19), or CGI-S (r=-0.18, p=0.47) scores. CONCLUSIONS: The present results suggest that brexpiprazole might improve subjective well-being, although this may not necessarily reflect psychopathological improvements. To enhance medication adherence, it is important to perform subjective assessments on patients over time.
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Research in Clinical Pharmacy 1(1) 10-21 2023年6月30日
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iScience 26(5) 106701-106701 2023年5月
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Psychiatry and clinical neurosciences 2023年4月24日AIM: Sleep disturbance, a core feature of bipolar disorder, is closely associated with mood symptoms. We examined the association between actigraphy sleep parameters and mood episode relapses in patients with bipolar disorder. METHODS: This prospective cohort study analyzed 193 outpatients with bipolar disorder who participated in the Association between the Pathology of Bipolar Disorder and Light Exposure in Daily Life (APPLE) cohort study. The participants' sleep was objectively evaluated via actigraphy over 7 consecutive days for the baseline assessment and then at the 2-year follow-up appointment for mood episode relapses. The actigraphy sleep parameters were presented using the mean and variability (standard deviation) of each sleep parameter for 7 days. RESULTS: Of the 193 participants, 110 (57%) experienced mood episodes during follow-up. The participants with higher variability in total sleep time had a significantly shorter mean estimated time to mood episode relapses than those with lower variability (12.5 vs. 16.8 months; P < 0.001). The Cox proportional hazards model, when adjusted for potential confounders, demonstrated that variability in total sleep time was significantly associated with an increase in the mood episode relapses (per hour; hazard ratio [HR], 1.407; 95% confidence interval (CI), 1.057-1.873), mainly in the depressive episodes (per hour; HR, 1.477; 95% CI, 1.088-2.006). CONCLUSIONS: Our findings suggest that consistency in sleep time might be useful, as an adjunct therapy, in preventing the recurrence or relapse of mood episodes in bipolar disorder. This article is protected by copyright. All rights reserved.
MISC
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精神神経学雑誌 = Psychiatria et neurologia Japonica 126(4) 243-250 2024年
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BIPOLAR DISORDERS 24 58-59 2022年7月
書籍等出版物
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共同研究・競争的資金等の研究課題
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日本学術振興会 科学研究費助成事業 2022年4月 - 2025年3月
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日本学術振興会 科学研究費助成事業 2022年4月 - 2025年3月
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日本学術振興会 科学研究費助成事業 2016年4月 - 2019年3月
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日本学術振興会 科学研究費助成事業 2013年4月 - 2016年3月
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日本学術振興会 科学研究費助成事業 2010年 - 2012年