研究者詳細 - 内田　裕之

論文 - 内田　裕之

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Relapse in Schizophrenia: A Systematic Review of Criteria for Clinical Studies and International Consensus Guidelines to Improve Them.

Howes OD, Bukala BR, Chen EYH, Correll CU, Hasan A, Honer WG, Kane JM, Leucht S, Siafis S, Agid O, Akena D, Arango C, Atwoli L, Barnes TRE, Birnbaum ML, Bitter I, Breier A, Buchanan RW, Citrome L, Cotter DR, Crossley N, Davidson M, de Bartolomeis A, DeLisi LE, Dollfus S, Dursun SM, Ebdrup BH, Elkis H, Emsley R, Falkai P, Fernández-Egea E, Fleischhacker W, Freudenreich O, Gadelha A, Gaebel W, Graff-Guerrero A, Gridley A, Hallak JEC, Homan P, Kahn RS, Kaiser S, Kapi M, Kennedy JL, Kim E, Kinon BJ, Soo Kwon J, Lawrie SM, Lee J, Leweke FM, Li T, Libiger J, Marder SR, Melle I, Meltzer H, Mucci A, Naber D, Nakajima S, Nielsen J, O'Brien O, Ojagbemi A, Omlor W, Pantelis C, Peuskens J, Raedler TJ, Ran MS, Marques TR, Remington G, Rossell S, Rubio JM, Sachs G, Scott J, Si T, Siskind D, Siu CO, Sommer IE, Suzuki T, Takeuchi H, Tandon R, Taylor D, Teferra S, Thomas N, Tiihonen J, Uchida H, Ucok A, Umbricht D, Venkatasubramanian G, Wagner E, Walters JTR, Wang C, Weiser M, Wright C, Yu X, McCutcheon RA

The American journal of psychiatry 182 （ 11 ） 969 - 983 2025年11月

ISSN 0002-953X

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Long-interval intracortical inhibition in individuals with autism spectrum disorders: A TMS-EEG study with source estimation analyses

Mimura Y., Nakajima S., Takano M., Wada M., Taniguchi K., Honda S., Uchida H., Mimura M., Noda Y.

Clinical Neurophysiology 178 2110936 2025年10月

ISSN 13882457

Objective: This study aimed to evaluate Long-interval Intracortical Inhibition (LICI) in the Dorsolateral Prefrontal Cortex (DLPFC) of individuals with Autism Spectrum Disorder (ASD) using transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) with source-based estimation analyses. Methods: We applied the LICI paradigm to the left DLPFC of 32 individuals with ASD and 34 healthy controls. First, sensor-level Local Mean Field Power (LMFP) was calculated from TMS-evoked potentials for all participants to detect the LICI effect. Subsequently, source-based analyses were performed using dynamic statistical parametric mapping to minimize the influence of volume conduction. Finally, time–frequency (TF) analyses at the source level were conducted to further characterize the LICI effects. Results: LMFP analysis revealed that cortical activity in the interval of 165–234 ms post-stimulation was suppressed by LICI (p = 0.024). Source-based analyses confirmed inhibitory effects within the same time range. Additionally, TF analyses indicated suppressive effects within 30–300 ms in the theta to alpha bands. However, no significant group differences in the LICI effects were detected. Conclusions: TMS-EEG combined with LICI alone may be insufficient to detect GABA(B) receptor dysfunction in ASD. Significance: This is the first TMS-EEG study to elucidate the LICI effect by applying source-estimation methods in ASD.

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【うつ病123のQ&A】(第VI部)うつ病の生物学的基盤と最新治療　Ketamineはなぜ,うつ病に効果があるのでしょうか?

内田裕之

精神科治療学（(株)星和書店） 40 （増刊） 214 - 215 2025年10月

ISSN 0912-1862

The association between amygdalar volume changes and depressive symptom improvements after repeated ketamine infusion in treatment-resistant depression: a double-blind, randomized, placebo-controlled trial with the following open-label study

Yonezawa K., Nakajima S., Hondo N., Ohtani Y., Nomoto-Takahashi K., Yatomi T., Tomiyama S., Nagai N., Kusudo K., Takahashi K., Honda S., Moriyama S., Yamada T., Koike S., Uchida H., Tani H.

Journal of Psychiatric Research 190 400 - 408 2025年10月

ISSN 00223956

Background: Ketamine is effective for treatment-resistant depression (TRD), where its mechanism remains unclear. Though the amygdala plays an important role in emotional processing and mood state, no study has explored the relationship between amygdalar subfield volumes and ketamine's effect in patients with TRD. We hypothesized that amygdalar subfield volume changes would correlate with clinical response to ketamine in patients with TRD. Methods: We used data from a double-blind, randomized, placebo-controlled trial (jRCTs031210124). Among 31 completers, 11 (35.5 %) participants in the ketamine group and 15 (48.4 %) participants in the placebo group underwent 0.8 mm-isotropic T1-and T2-weighted multimodal magnetic resonance imaging scans before and after the interventions. Depressive symptoms were assessed with the Montgomery Åsberg Depression Rating Scale (MADRS). We focused on the three amygdalar subfields: laterobasal (LB), centromedial, and superficial nuclei. Multivariable and post-hoc univariate regression analyses were conducted to explore the factors associated with the change in the MADRS total and subdomain scores. Results: There was a significant interaction between the volume changes in the right LB and group for the MADRS dysphoria score changes (F (3, 22) = 3.63, p = 0.029, R2 = 0.24, treatment by volume change interaction: β = 0.61, p = 0.028). Post-hoc analyses found that changes in MADRS dysphoria scores related to volume changes in the right LB in the ketamine group (β = 0.65, p = 0.028), but not in the placebo group. Conclusions: The reductions in right LB volumes correlate with better clinical responses to ketamine in patients with TRD, suggesting ketamine may exert its effect by attenuating amygdalar overactivity in this population.

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Glutamate plus glutamine to GABA ratio as a predictor of ketamine response in treatment-resistant depression: A double-blind, randomized, open-label extension study

Ohtani Y., Tani H., Honda S., Nomoto-Takahashi K., Yatomi T., Yonezawa K., Tomiyama S., Nagai N., Kusudo K., Moriyama S., Noda Y., Koike S., Edden R.A.E., Uchida H., Nakajima S.

Journal of Affective Disorders 383 354 - 362 2025年08月

ISSN 01650327

Background: Approximately 30 % of patients with treatment-resistant depression (TRD) respond to ketamine; however, no replicable predictors of response have been reported. The imbalance between excitatory and inhibitory neurotransmissions may be implicated in the mechanism of action of ketamine. This study aimed to evaluate whether the ratio of glutamate and glutamine (Glx) to GABA levels at baseline in the dorsal anterior cingulate cortex (dACC) could predict ketamine response in patients with TRD. Method: This exploratory study analyzed data from a double-blind randomized clinical trial with an open-label extension study (jRCTs031210124). Fifteen participants in the ketamine group and 15 of 16 participants in the placebo group received repeated intravenous ketamine during the double-blind and open-label extension periods, respectively. We measured Glx and GABA levels in the dACC before and after treatment during the double-blind period using proton magnetic resonance spectroscopy. The 17-item Hamilton Depression Rating Scale (HDRS-17) was measured for depressive symptomatology. General linear models were used to examine the relationship between baseline Glx/GABA ratio and HDRS-17 score changes. Result: Changes in HDRS-17 scores (mean (±SD)) following ketamine treatment were −4.9 (6.5) and −4.9 (5.2) in the double-blind and open-label periods, respectively. A higher baseline dACC Glx/GABA ratio was correlated with greater improvement in HDRS-17 (β = −0.42, p = 0.040). In the ketamine group, a reduction in the dACC Glx/GABA ratio was correlated with greater HDRS-17 improvement (β = 0.74, p = 0.009) with no such association in the placebo group. Conclusion: These results suggest that excitatory-inhibitory imbalance in the dACC may predict the efficacy of ketamine in TRD.

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Dynamic neural network modulation associated with rumination in major depressive disorder: a prospective observational comparative analysis of cognitive behavioral therapy and pharmacotherapy.

Katayama N, Shinagawa K, Hirano J, Kobayashi Y, Nakagawa A, Umeda S, Kamiya K, Tajima M, Amano M, Nogami W, Ihara S, Noda S, Terasawa Y, Kikuchi T, Mimura M, Uchida H

Translational psychiatry 15 （ 1 ） 267 2025年08月

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Risk factors for venous thromboembolism among psychiatric inpatients: a case control study.

Ishida T, Shimada M, Mizuno M, Suzuki T, Uchida H

Journal of psychiatric research 190 6 - 10 2025年07月

ISSN 0022-3956

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Impact of brain damage on moral judgment

Suganami M., Takahata K., Mimura Y., Yamamoto M., Uchida H., Muramatsu T., Mimura M.

Psychiatry and Clinical Neurosciences Reports 4 （ 2 ） e70126 2025年06月

Aim: This study aimed to determine the effects of damage to various brain regions on moral judgment using a novel third-party punishment task with fully manipulated conditions. Methods: We assessed 35 individuals with brain damage (26 with frontal lobe and nine with non-frontal lobe damage) and 30 healthy controls (HCs) using a moral judgment task consisting of 40 vignettes across five conditions, with varying degrees of intentionality and consequences. Participants rated the protagonist's “badness” and their aroused feelings. Cognitive impairments and empathetic traits were also assessed. Results: Compared to HCs, individuals with brain damage judged protagonists to be more blameworthy than did HCs in vignettes where harmful intentions were absent (No Negligence, p = 0.02; No Harm, p = 0.02). The order of moral judgment ratings across conditions was consistent between groups, indicating preserved knowledge of social/moral norms in brain-damaged individuals. Although these are preliminary results, there are no significant differences in moral judgment ratings between individuals with frontal and non-frontal lobe damage. Conclusion: This study revealed that individuals with damage to diverse brain regions show excessive punitive tendencies toward the actions of others without malicious intention. These effects cannot be fully explained by changes in empathy or emotional responses. Moral judgment ratings did not significantly differ between individuals with frontal and non-frontal lobe damage. However, given the small sample size of the non-frontal lesion group, these findings should be interpreted with caution, and further research is necessary to confirm this conclusion.

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Diverse tau pathologies in late-life mood disorders revealed by PET and autopsy assays

Kurose S., Moriguchi S., Kubota M., Tagai K., Momota Y., Ichihashi M., Sano Y., Endo H., Hirata K., Kataoka Y., Goto R., Mashima Y., Yamamoto Y., Suzuki H., Nakajima S., Mizutani M., Sano T., Kawamura K., Zhang M.R., Tatebe H., Tokuda T., Onaya M., Mimura M., Sahara N., Takahashi H., Uchida H., Takao M., Meyer J.H., Higuchi M., Takahata K.

Alzheimer S and Dementia 21 （ 6 ） e70195 2025年06月

ISSN 15525260

INTRODUCTION: Late-life mood disorders (LLMDs) may represent prodromal manifestations of neurodegenerative dementia; however, the neuropathological basis of LLMDs, including depression and bipolar disorder, remains unclear. We aimed to investigate the involvement of Alzheimer's disease (AD) and non-AD tau pathologies in LLMD participants. METHODS: Fifty-two LLMD participants and 47 age- and sex-matched healthy controls (HCs) underwent tau and amyloid beta (Aβ) positron emission tomography (PET) imaging using 18F-florzolotau and 11C-Pittsburgh compound B. Additionally, we conducted a clinicopathological correlation analysis in 208 autopsy cases, including various neurodegenerative diseases. RESULTS: LLMD participants were more likely to be tau PET and Aβ PET positive than HCs. The PET results were supported by the post mortem results that showed a higher likelihood of diverse tauopathies in patients with late-life mania or depression than those without. DISCUSSION: Our PET and autopsy assays suggest that AD and diverse non-AD tau pathologies might underlie the neuropathological basis of some LLMD cases. Highlights: Late-life mood disorders (LLMDs) may represent prodromal states of dementia. The neuropathological basis of LLMDs remains unclear. LLMD subjects were highly likely to be tau positron emission tomography (PET) positive. Brain bank data supported our PET results. Alzheimer's disease (AD) and diverse non-AD tau pathologies can contribute to LLMDs.

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Risk of falls associated with non-GABAergic hypnotics and benzodiazepines in hospitalized patients

Shishida K., Nishimura W., Shimomura Y., Murayama M., Yoshimura K., Uchida H., Mimura M., Takeuchi H.

General Hospital Psychiatry 94 10 - 15 2025年05月

ISSN 01638343

Objective: Non-GABAergic hypnotics introduced into clinical practice within the last two decades are pharmacologically presumed to have a lower risk of falls, but clinical investigations are scarce. We aimed to evaluate the risk of falls associated with different classes of hypnotics, namely benzodiazepines, ramelteon, suvorexant, and trazodone, in hospitalized individuals at a general hospital. Method: In this retrospective cohort study, data on the incidence of falls, hypnotic use, age, sex, body mass index (BMI), activities of daily living (ADL) score, presence of surgery, emergency admission, and ambulance use were collected for hospitalized patients aged 20 years or older who had been discharged from a tertiary general hospital in Japan between April 1, 2014, and March 31, 2019. The Cox proportional hazards model was used to examine factors associated with falls, adjusting for other demographics as covariates. Results: Among 28,029 patients, 383 falls occurred in 322 patients. Ramelteon or suvorexant was not associated with an elevated incidence of falls (adjusted hazard ratio [aHR], 0.78; 95 % CI, 0.34 to 1.81 and 0.44; 95 % CI, 0.13–1.46, respectively), in contrast to benzodiazepines (aHR, 2.17; 95 % CI 1.67–2.83) or trazodone (aHR, 1.96; 95 % CI 1.25–3.07). Advanced age, lower BMI, wheelchair dependency, non-surgical status, absence of emergency admissions, and ambulance use were also associated with the elevated incidence of falls. Conclusions: In hospitalized patients at general hospitals, ramelteon and suvorexant may not increase the risk of falls, while the use of benzodiazepines and trazodone requires careful attention to minimize this risk.

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Characterization of patients with major psychiatric disorders with AMPA receptor positron emission tomography

Hatano M., Nakajima W., Tani H., Uchida H., Miyazaki T., Arisawa T., Takada Y., Tsugawa S., Sano A., Nakano K., Eiro T., Abe H., Suda A., Asami T., Hishimoto A., Nagai N., Koizumi T., Nakajima S., Kurokawa S., Ohtani Y., Takahashi K., Kikuchi Y., Yatomi T., Honda S., Jinzaki M., Hirano Y., Mitoma R., Tamura S., Baba S., Togao O., Kosaka H., Okazawa H., Kimura Y., Mimura M., Takahashi T.

Molecular Psychiatry 30 （ 5 ） 1780 - 1790 2025年05月

ISSN 13594184

Synaptic phenotypes in living patients with psychiatric disorders are poorly characterized. Excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) is a fundamental component for neurotransmission. We recently developed a positron emission tomography (PET) tracer for AMPAR, [11C]K-2, the first technology to visualize and quantify AMPARs density in living human brain. In this study, we characterized patients with major psychiatric disorders with [11C]K-2. One hundred forty-nine patients with psychiatric disorders (schizophrenia, n = 42; bipolar disorder, n = 37; depression, n = 35; and autism spectrum disorder, n = 35) and 70 healthy participants underwent a PET scan with [11C]K-2 for measurement of AMPAR density. We detected brain regions that showed correlation between AMPAR density and symptomatology scores in each of four disorders. We also found brain areas with significant differences in AMPAR density between patients with each psychiatric disorder and healthy participants. Some of these areas were observed across diseases, indicating that these are commonly affected areas throughout psychiatric disorders. Schizophrenia, bipolar disorder, depression, and autism spectrum disorder are uniquely characterized by AMPAR distribution patterns. Our approach to psychiatric disorders using [11C]K-2 can elucidate the biological mechanisms across diseases and pave the way to develop novel diagnostics and therapeutics based on the synapse physiology.

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INTEGRATE: international guidelines for the algorithmic treatment of schizophrenia

McCutcheon R.A., Pillinger T., Varvari I., Halstead S., Ayinde O.O., Crossley N.A., Correll C.U., Hahn M., Howes O.D., Kane J.M., Kabir T., Konradsson-Geuken Å., Lennox B., Hui C.L.M., Rossell S.L., Solmi M., Sommer I.E., Taipale H., Uchida H., Venkatasubramanian G., Warren N., Agid O., Arango C., de Bartolomeis A., Bittner R.A., Bressan R.A., Buchanan R.W., Cecere G., Chen E.Y.H., Citrome L., Dollfus S., Dursun S.M., Ebdrup B.H., Elkis H., Emsley R., Fernandez-Egea E., Fleischhacker W., Freudenreich O., Gadelha A., Gangadin S.S., Gaughran F., Hallak J.E.C., Hasan A., Homan P., Jauhar S., Kaiser S., Kwon J.S., Lee J., Leucht S., Libiger J., Leweke M.F., MacCabe J.H., Marder S.R., Marques T.R., Melle I., Mucci A., Nakajima S., O'Donoghue B., Ojagbemi A., Perry B.I., Roos J.L., Rubio J.M., Rybakowski J.K., Sachs G., Siu C.O., Suzuki T., Taylor D.M., Takeuchi H., Thirthalli J., Thomas N., Üçok A., Varambally S., Vasiliu O., Wagner E., Siskind D.

The Lancet Psychiatry 12 （ 5 ） 384 - 394 2025年05月

ISSN 22150366

Schizophrenia is a mental illness involving multiple symptom domains and is often associated with substantial physical health comorbidities. Guidelines exist, but these tend to be country-specific and are often missing a concise yet comprehensive algorithmic approach. From May 1, 2023, to Jan 1, 2025, International Guidelines for Algorithmic Treatment (INTEGRATE) authors from all UN regions collaborated to develop a consensus guideline focused on the pharmacological treatment of schizophrenia. Following an umbrella review of the literature, input from expert workshops, a consensus survey, and lived experience focus groups, a consensus algorithmic guideline and associated digital tool were developed. Key recommendations include a focus on metabolic health from treatment initiation, timely assessment and management of non-response, symptom domain-specific interventions, mitigation of side-effects, and the prompt use of clozapine in cases of treatment resistance.

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Electroconvulsive Therapy Can Prevent a Worsening of Psychosis and Dystonic Voice in PRKN-associated Parkinson's Disease.

Tezuka T, Daida K, Nakajima S, Konishi M, Nihei Y, Funayama M, J Billingsley K, Blauwendraat C, Hattori N, Uchida H, Nakahara J, Seki M

Internal medicine (Tokyo, Japan) 2025年04月

ISSN 0918-2918

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Prediction of postoperative delirium by blood metabolome analysis

Arai N., Sugiura Y., Nakajima S., Wada M., Moriyama S., Mimura Y., Niinomi K., Takayama K., Maeda R., Kitada S., Fagarasan S., Tajima M., Boku S., Takebayashi M., Kato J., Kitago M., Kitagawa Y., Takahashi T., Shimizu H., Uchida H., Suematsu M., Mimura M., Noda Y.

Journal of Psychiatric Research 184 500 - 514 2025年04月

ISSN 00223956

No established blood markers can preoperatively predict postoperative delirium. Blood concentrations of amino acid catabolites and dipeptides, including those secreted extracellularly during T-lymphocyte activation, were investigated as predictors of postoperative delirium using metabolomic analyses to ascertain whether preoperative blood metabolites could predict postoperative delirium. Eighteen and 24 participants were included in the delirium and non-delirium groups, respectively. Higher preoperative levels of amino acid (tryptophan) catabolites, via the indoleamine 2,3-dioxygenase pathway, were observed in the delirium group and identified as potential predictors of postoperative delirium in this study. The delirium group had preoperatively elevated levels of tryptophan catabolites and only a limited increase postoperatively, suggesting that the tryptophan catabolic pathway may be activated preoperatively in patients at high risk of delirium. Non-targeted metabolomic analysis found a set of preoperatively elevated γ-glutamyl dipeptides as potential predictors of postoperative delirium. In vitro experiments showed that T-cell-receptor stimulation increases tryptophan metabolism and specific γ-glutamyl dipeptide secretion, offering a possible explanation for the increased levels of metabolites in postoperative delirium. This study showed that levels of amino acid metabolites associated with blood immune activity may have the potential to predict postoperative delirium.

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Identification of neurophysiological signatures of bipolar disorder by resting-state EEG microstate analysis

Taniguchi K., Kaneko N., Wada M., Takano M., Moriyama S., Mimura Y., Uchida H., Nakajima S., Noda Y.

Journal of Affective Disorders Reports 20 2025年04月

Background: This investigation probed the neurophysiological disparities between patients with bipolar disorder (BD) and healthy controls (HC) utilizing resting-state electroencephalography (rs-EEG) microstate (MS) analysis. The study, conducted at Keio University Hospital from 2017 to 2023, sought to differentiate BD from HC for early detection. Methods: The study included 36 BD (average age: 48.3 years) and 36 age- and sex-matched HC (average age: 47.8 years). Participants underwent a 5-min rs-EEG recording with eyes closed. MS analysis focused on the duration, occurrence, and coverage of MS (A − E) transitions. Comparisons were executed using Mann-Whitney U tests, and a logistic regression model distinguished the groups based on these MS indices. Results: Patients with BD exhibited a shorter MS-D duration (p < 0.001) and longer MS-C (p = 0.027) and MS-E (p = 0.020) durations compared to HC. The occurrence and coverage of MS-D were significantly lower in BD (p < 0.001 for both). The logistic regression model accurately classified 84.7% of cases (χ2(3)=42.03, p < 0.001). Limitations: Limitations include the potential influence of medication on MS dynamics and the cross-sectional design, which prevents causal conclusions. Longitudinal studies are required to comprehend the relationship between MS alterations and BD symptoms. Conclusion: Decreased MS-D indices, along with increased MS-C and MS-E indices in BD, imply dysfunction in the frontoparietal network and impairments in the default mode and salience networks. The altered temporal dynamics of rs-EEG MSs provide a unique neurophysiological profile of BD, suggesting that MS indices could potentially serve as neurophysiological markers for BD diagnosis.

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Electrodermal activity and skin temperature characteristics related to stress and depression: A 4-week observational study of office workers

Ishikawa Y., Sugio T., Shiga K., Izumi K., Minato K., Kitazawa M., Hanashiro S., Takemura R., Uchida H., Kishimoto T.

Journal of Affective Disorders Reports 20 2025年04月

Background: Mental health problems, particularly depression, significantly impact the working-age population and incur substantial socioeconomic costs. Electrodermal activity (EDA) and skin temperature, measurable through wearable devices, have emerged as potential biomarkers of depression. However, there is a lack of long-term observational studies in real-world settings. Methods: This 4-week observational study analyzed data from 147 office workers across 11 Japanese companies. Participants wore wearable devices during working hours for four weeks to collect EDA and skin temperature data. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), and stress was assessed using the 10-item version of the Perceived Stress Scale (PSS-10). The associations between electrodermal activity, skin temperature, and depressive/stress states were analyzed using the Mann–Whitney U test and logistic regression analysis. Results: Participants with PHQ-9 scores ≥5 showed higher median skin conductance and median tonic signal, although these differences lost statistical significance after Bonferroni correction. Logistic regression analysis revealed a negative correlation between age and both PHQ-9 and PSS-10 scores (OR=0.525, 0.646). The mean and standard deviation of skin temperature showed a positive association with depressive symptoms (OR=1.687, 1.733), while normalized EDASymp showed a negative association (OR=0.564). Conclusions: This study suggests that EDA and skin temperature, measured by wearable devices, may be associated with depressive symptoms among office workers. These physiological indicators could be utilized for mental health monitoring and early intervention in the workplace. Further validation with larger samples, and long-term follow-up studies, are warranted.

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Abnormal neuritic microstructures in the anterior limb of internal capsules in treatment-resistant depression - A cross-sectional NODDI study

Takahashi K., Noda Y., Hondo N., Shibukawa S., Kamagata K., Wada M., Honda S., Homma S., Tsukazaki A., Tsugawa S., Tobari Y., Moriyama S., Taniguchi K., Koike S., Cassidy C., Mimura M., Uchida H., Nakajima S.

Journal of Psychiatric Research 183 93 - 99 2025年03月

ISSN 00223956

Background: Microstructural deficits of brain tissue are implicated in the pathophysiology of major depressive disorder (MDD). Recent studies have highlighted the neurotrophic mechanisms underlying effective treatments such as ketamine for treatment-resistant depression (TRD). However, little is known about microstructural changes in TRD. Neurite orientation dispersion and density imaging (NODDI) has enabled in vivo investigation of gray matter (GM) and white matter (WM) microstructure. This study sought to examine microstructural abnormalities in gray and white matter in patients with TRD using NODDI. Methods: This study compared the neurite density index (NDI) and orientation dispersion index (ODI) of neurites in 70 patients with TRD and 35 healthy controls. We fitted separate optimal NODDI models for gray and white matter. The locations of microstructural deficit were identified using region-based and voxel-based analysis. The affected white matter fibers were tracked with correlational tractography analysis. Results: An increase of ODI at the middle to the ventral part of the right anterior limb of the internal capsule (ALIC) was observed in patients with TRD compared with healthy controls. The quantitative anisotropy of frontothalamic fibers passing through the ALIC negatively correlated with the ODI increase in the TRD group. Conclusion: The microstructural disorganization of the frontothalamic pathway could be linked to the pathophysiology and individual heterogeneity of TRD.

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Effects of short-term exposure to moderate amounts of alcohol on brain volume

Tsugawa S., Ueno F., Sakuma M., Tani H., Ochi R., Graff-Guerrero A., Noda Y., Uchida H., Mimura M., Oshima S., Matsushita S., Nakajima S.

Neuropsychopharmacology Reports 45 （ 1 ） e12500 2025年03月

Aim: Although numerous studies have reported that chronic alcohol consumption causes brain volume reduction and cerebrospinal fluid volume increase, few studies have examined the acute effects of alcohol on brain structure. This study aims to investigate the short-term brain volume changes following alcohol administration. Methods: Moderate doses of alcohol were administered intravenously to 18 healthy volunteers for a total of 90 min to achieve a blood alcohol concentration of 0.5 mg/mL. An alcohol clamp method combined with physiologically based pharmacokinetic modeling was used to achieve fine control over blood alcohol concentration. T1 images with 3T MRI were scanned at three time points: baseline, 0 min, and 90 min after the end of alcohol administration. Cortical, subcortical, and ventricular volumes were computed after segmentation with FreeSurfer. Repeated measures analysis of variance was used to evaluate longitudinal changes in brain volume at 96 regions. Results: Acute alcohol administration increased bilateral lateral ventricular volumes, which lasted until 90 min after the end of alcohol injection. On the other hand, the volumes of total gray matter, left precentral cortex, left caudal middle frontal cortex, and left superior frontal cortex decreased after alcohol administration, but these changes disappeared 90 min after the end of alcohol administration. Conclusion: Acute injection of moderate doses of alcohol may enlarge ventricle volumes and reduce gray matter volumes. The transient volume changes caused by acute administration of alcohol may be related to changes in CSF flow and water content of brain tissue, which warrants further study.

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Effects of Intravenous Hydroxyzine Versus Haloperidol Monotherapy for Delirium: A Retrospective Study

Kubo K., Takehara M., Hirata M., Huh S., Kawano S., Uchida H., Takeuchi H.

Journal of Clinical Psychiatry 86 （ 1 ） 2025年03月

ISSN 01606689

Objective: Although antipsychotics are used commonly for delirium, they increase the risk of mortality in elderly patients and those with dementia. As hydroxyzine has sedative and anxiolytic effects, it can be used in the treatment of delirium. We performed a retrospective study to compare the effects of intravenous hydroxyzine and haloperidol monotherapy on delirium. Methods: Patients who admitted to a university hospital from April 1, 2017, to September 30, 2022, and received either hydroxyzine or haloperidol intravenously as monotherapy for the treatment of delirium were included. The time to and rate of delirium improvement were compared. Improvement of delirium was defined as negative on the Confusion Assessment Method (CAM) or Confusion Assessment Method for the ICU (CAM-ICU) for 3 consecutive days. Results: Among 5,555 patients who developed delirium, 71 (1.3%) and 82 (1.5%) received intravenous hydroxyzine and haloperidol monotherapy, respectively. The time to delirium improvement was 7.0 days (95% CI, 5.7–8.3 days) for hydroxyzine and 8.2 days (95% CI, 7.6–8.8 days) for haloperidol, with no significant difference between the two groups (P= .059). On the other hand, the rate of delirium improvement was 23.9% for hydroxyzine and 8.5% for haloperidol, with a significant difference in favor of the hydroxyzine group (P = .009). Conclusions: We first showed that intravenous hydroxyzine monotherapy was not inferior for the time to delirium improvement and superior for the rate of delirium improvement to intravenous haloperidol monotherapy. Considering that hydroxyzine is relatively safe with few side effects, it can be a viable option for delirium as an alternative to antipsychotics.

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Establishment and clinical impacts of decision-support system for older patients with aortic valve stenosis: A retrospective observational study

Kawano S., Eguchi Y., Oosumi A., Takeuchi H., Takubo M., Kimura N., Nakano N., Ryuzaki T., Hayashida K., Ieda M., Uchida H., Mimura M., Fujisawa D.

General Hospital Psychiatry 92 106 - 111 2025年01月

ISSN 01638343

Objectives: Treatment decisions for severe aortic stenosis (AS) are complex, since there are two active and comparable options: transcatheter aortic valve implantation and surgical aortic valve replacement. The disease predominantly affects older individuals, who are frequently comorbid with from cognitive impairment. This study aimed to establish a screening-triggered system to assess the decision-making capacity of patients with AS, support their decision-making, and facilitate referrals to specialists when necessary. Methods: This is a retrospective pre-post observational study. Relevant healthcare professionals were trained to assess and support patients' decision-making capacities. Results: Subtotals of 203 and 244 patients were enrolled before and after the implementation of the system, respectively. The requests for decision-making support significantly increased (from 1.5 % to 14.8 % of the patients). 11.5 % of the patients were identified as with declined decision-making capacity. The proportion of patients who received active treatments for AS significantly decreased from 95.0 % to 83.0 %. The nurses' documentation of patients' decision-making capacities significantly increased. Conclusion: This screening-triggered system identified a substantial proportion of patients with declined decision-making capacity. A significant decrease in patients receiving active treatments for AS and increased documentation of patients' decision-making capacities in nursing records were observed. A future randomized controlled is warranted.

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論文 - 内田 裕之

内田　裕之

論文 - 内田　裕之