論文 - 野田　賀大

Effectiveness of Standard Sequential Bilateral Repetitive Transcranial Magnetic Stimulation vs Bilateral Theta Burst Stimulation in Older Adults With Depression: The FOUR-D Randomized Noninferiority Clinical Trial.

Blumberger DM, Mulsant BH, Thorpe KE, McClintock SM, Konstantinou GN, Lee HH, Nestor SM, Noda Y, Rajji TK, Trevizol AP, Vila-Rodriguez F, Daskalakis ZJ, Downar J

JAMA psychiatry （JAMA Psychiatry）  79 （ 11 ） 1065 - 1073 2022年09月

査読有り,  ISSN  2168-622X

　概要を見る

Importance: Treatment-resistant depression (TRD) is common in older adults. Bilateral repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex for 48 minutes has demonstrated efficacy in TRD. Theta burst stimulation (TBS), a newer form of rTMS, can also be delivered bilaterally using left intermittent TBS and right continuous TBS for only 4 minutes. Objective: To establish the effectiveness and tolerability of TBS compared with standard rTMS in older adults with TRD. Design, Setting, and Participants: In this randomized noninferiority trial with open treatment and blinded assessors, recruitment occurred between December 2016 and March 2020. The trial was conducted at the Centre for Addiction and Mental Health in Toronto, Ontario, Canada and included outpatients 60 years and older with a diagnosis of depression, moderate severity, and nonresponse to 1 or more antidepressant trial of adequate dosage and duration or intolerance of 2 or more trials. Interventions: Participants were randomized to receive a course of 4 to 6 weeks of either bilateral standard rTMS or TBS. Main Outcomes and Measures: The primary outcome measure was change in Montgomery-Åsberg Depression Rating Scale; secondary outcome measures included the 17-item Hamilton Rating Scale for Depression, Quick Inventory of Depressive Symptomatology (16-item) (self-report), and dropout rates. A noninferiority margin of 2.75 points was used for the primary outcome. All participants who attained the primary completion point of 4 weeks were analyzed. Results: A total of 87 participants (mean [SD] age, 67.1 [6.7] years; 47 [54.0%] female) were randomized to standard bilateral rTMS and 85 (mean [SD] age, 66.3 [5.3] years; 45 [52.9%] female) to TBS, of whom 85 (98%) and 79 (93%) were assessed for the primary outcome, respectively, whereas tolerability was assessed in all randomized participants. In the rTMS group, 4 (4.6%) were American Indian, reported other, or preferred not to answer; 5 (5.8%) were Asian; and 78 (89.7%) were White. In the TBS group, 6 (7.1%) were Asian, 2 (2.4%) were Black or reported other, and 77 (90.3%) were White. Mean (SD) Montgomery-Åsberg Depression Rating Scale total scores improved from 25.6 (4.0) to 17.3 (8.9) for rTMS and 25.7 (4.7) to 15.8 (9.1) for TBS (adjusted difference, 1.55; lower 95% CI -0.67), establishing noninferiority for TBS. The all-cause dropout rates were relatively similar between groups (rTMS: 2 of 87 [2.3%]; TBS: 6 of 85 [7.1%]; P =.14; χ2= 2.2). Conclusions and Relevance: In older adults with TRD, bilateral TBS compared with standard bilateral rTMS achieved noninferior reduction in depression symptoms. Both treatments had low and similar dropout rates. Using TBS rather than rTMS could increase access to treatment several-fold for older adults with TRD. Trial Registration: ClinicalTrials.gov Identifier: NCT02998580.

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Autistic children and adolescents with frequent restricted interest and repetitive behavior showed more difficulty in social cognition during mask-wearing during the COVID-19 pandemic: a multisite survey

Tamon H., Itahashi T., Yamaguchi S., Tachibana Y., Fujino J., Igarashi M., Kawashima M., Takahashi R., Shinohara N.A., Noda Y., Nakajima S., Hirota T., Aoki Y.Y.

BMC psychiatry （BMC psychiatry）  22 （ 1 ） 608 - 608 2022年09月

査読有り

　概要を見る

BACKGROUND: The public health measures enacted in order to control the coronavirus disease (COVID-19) pandemic have caused considerable changes to daily life. For autistic children and adolescents, adapting to the "new normal," including mask-wearing, may be difficult because of their restricted interest and repetitive behavior (RRB) characteristics. We aimed to examine the relationships between RRB characteristics and the impact of mask-wearing on their social communications during the pandemic. METHODS: We recruited participants with a clinical diagnosis of autism spectrum disorder based on DSM-5 diagnostic criteria from two outpatient clinics in Tokyo, Japan, between November 2020 and April 2021 using a convenience sampling methodology. As a result, the participants consisted of 102 children and adolescents (mean (SD) age = 11.6 (5.3)). We collected data on RRB characteristics frequency before and during the pandemic using the CoRonavIruS Health Impact Survey (CRISIS) - Adapted for Autism and Related Neurodevelopmental conditions (AFAR). We then conducted factor analyses to compute the RRB severity composite scores, which are divided into lower- (e.g., sensory seeking), and higher-order (e.g., restricted interest). We also investigated mask-wearing culture using a bespoke questionnaire, and using Spearman's rank correlation analyses, we examined the relationships between before pandemic RRB characteristics, and the impact of mask-wearing on social communications during the pandemic. RESULTS: We found that children and adolescents who exhibited lower-order RRB before the pandemic had difficulties in going-out with mask-wearing (rho = -0.25, q = .031), more challenges with mask-wearing (rho =  - 0.34, q = .0018), and difficulty in referring to others' emotions while wearing masks (rho =  - 0.36, q = .0016). We also found an association between higher-order RRB before the pandemic and an uncomfortable sensation (rho =  - 0.42, q = .0002) and difficulties in referring to other's emotions while wearing masks (rho =  - 0.25, q = .031). CONCLUSIONS: We revealed that various behaviors, such as sensory seeking, repetitive motor mannerisms and movements, and rituals and routines, undertaken before the pandemic could be important predictors of difficulties with mask-wearing and social communication for autistic children and adolescents during the pandemic. Caregivers and teachers wearing masks may need to provide extra support for social communication to autistic children and adolescents showing RRB characteristics frequently.

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Reduced signal propagation elicited by frontal transcranial magnetic stimulation is associated with oligodendrocyte abnormalities in treatment-resistant depression

Wada M., Nakajima S., Honda S., Takano M., Taniguchi K., Tsugawa S., Mimura Y., Hattori N., Koike S., Zomorrodi R., Blumberger D.M., Daskalakis Z.J., Mimura M., Noda Y.

Journal of psychiatry & neuroscience : JPN （Journal of psychiatry & neuroscience : JPN）  47 （ 5 ） E325 - E335 2022年09月

最終著者, 責任著者, 査読有り,  ISSN  1180-4882

　概要を見る

BACKGROUND: The efficacy of repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (dlPFC) has been established in patients with treatment-resistant depression (TRD), suggesting that alterations in signal propagation from the left dlPFC to other brain regions may be linked to the pathophysiology of TRD. Alterations at the cellular level, including dysfunction of oligodendrocytes, may contribute to these network abnormalities. The objectives of the present study were to compare signal propagation from the left dlPFC to other neural networks in patients with TRD and healthy controls. We used TMS combined with electroencephalography to explore links between cell-specific gene expression and signal propagation in TRD using a virtual-histology approach. METHODS: We examined source-level estimated signal propagation from the left dlPFC to the 7 neural networks in 60 patients with TRD and 30 healthy controls. We also calculated correlations between the interregional profiles of altered signal propagation and gene expression for 9 neural cell types derived from the Allen Human Brain Atlas data set. RESULTS: Signal propagation from the left dlPFC to the salience network was reduced in the θ and α bands in patients with TRD (p = 0.0055). Furthermore, this decreased signal propagation was correlated with cellspecific gene expression of oligodendrocytes (p < 0.000001). LIMITATIONS: These results show only part of the pathophysiology of TRD, because stimulation was limited to the left dlPFC. CONCLUSION: Reduced signal propagation from the left dlPFC to the salience network may represent a pathophysiological endophenotype of TRD; this finding may be associated with reduced expression of oligodendrocytes.

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Dopaminergic dysfunction and excitatory/inhibitory imbalance in treatment-resistant schizophrenia and novel neuromodulatory treatment

Wada M., Noda Y., Iwata Y., Tsugawa S., Yoshida K., Tani H., Hirano Y., Koike S., Sasabayashi D., Katayama H., Plitman E., Ohi K., Ueno F., Caravaggio F., Koizumi T., Gerretsen P., Suzuki T., Uchida H., Müller D.J., Mimura M., Remington G., Grace A.A., Graff-Guerrero A., Nakajima S.

Molecular Psychiatry （Molecular Psychiatry）  27 （ 7 ） 2950 - 2967 2022年07月

査読有り,  ISSN  13594184

　概要を見る

Antipsychotic drugs are the mainstay in the treatment of schizophrenia. However, one-third of patients do not show adequate improvement in positive symptoms with non-clozapine antipsychotics. Additionally, approximately half of them show poor response to clozapine, electroconvulsive therapy, or other augmentation strategies. However, the development of novel treatment for these conditions is difficult due to the complex and heterogenous pathophysiology of treatment-resistant schizophrenia (TRS). Therefore, this review provides key findings, potential treatments, and a roadmap for future research in this area. First, we review the neurobiological pathophysiology of TRS, particularly the dopaminergic, glutamatergic, and GABAergic pathways. Next, the limitations of existing and promising treatments are presented. Specifically, this article focuses on the therapeutic potential of neuromodulation, including electroconvulsive therapy, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and deep brain stimulation. Finally, we propose multivariate analyses that integrate various perspectives of the pathogenesis, such as dopaminergic dysfunction and excitatory/inhibitory imbalance, thereby elucidating the heterogeneity of TRS that could not be obtained by conventional statistics. These analyses can in turn lead to a precision medicine approach with closed-loop neuromodulation targeting the detected pathophysiology of TRS.

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TMS Database Registry Consortium Research Project in Japan (TReC-J) for Future Personalized Psychiatry

Noda Y., Kizaki J., Takahashi S., Mimura M.

Journal of Personalized Medicine （Journal of Personalized Medicine）  12 （ 5 ） 844 - 844 2022年05月

筆頭著者, 責任著者, 査読有り,  ISSN  2075-4426

　概要を見る

The registry project led by the Japanese Society for Clinical Transcranial Magnetic Stimulation (TMS) Research aims to establish a centralized database of epidemiological, clinical, and biological data on TMS therapy for refractory psychiatric disorders, including treatment-resistant depression, as well as to contribute to the elucidation of the therapeutic mechanism of TMS therapy and to the validation of its efficacy by analyzing and evaluating these data in a systematic approach. The objective of this registry project is to collect a wide range of complex data linked to patients with various neuropsychiatric disorders who received TMS therapy throughout Japan, and to make effective use of these data to promote cross-sectional and longitudinal exploratory observational studies. Research utilizing this registry project will be conducted in a multicenter, non-invasive, retrospective, and prospective observational research study design, regardless of the framework of insurance medical care, private practice, or clinical research. Through the establishment of the registry, which aims to make use of data, we will advance the elucidation of treatment mechanisms and identification of predictors of therapeutic response to TMS therapy for refractory psychiatric disorders on a more real-world research basis. Furthermore, as a future vision, we aim to develop novel neuromodulation medical devices, algorithms for predicting treatment efficacy, and digital therapeutics based on the knowledge generated from this TMS registry database.

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The impact of mask-wearing influenced by restricted interest and repetitive behavior on the mental distress of individuals with autism spectrum disorder during the COVID-19 pandemic: a multisite survey

Hiroki Tamon, Takashi Itahashi, Sosei Yamaguchi, Yoshiyuki Tachibana, Junya Fujino, Miki Igarashi, Makiko Kawashima, Riina Takahashi, Nozomi Shinohara, Yoshihiro Noda, Shinichiro Nakajima, Tomoya Hirota, Yuta Aoki

（Research Square Platform LLC）  2022年04月

　概要を見る

Abstract

Background The coronavirus disease of 2019 pandemic has caused considerable changes in daily life. For children with autism spectrum disorder, adapting to the “new normal,” including mask-wearing, may be difficult because of their restricted interest and repetitive behaviors symptoms. We aimed to examine the relationships between restricted interest and repetitive behaviors symptoms and the impact of mask-wearing on their social communications during the pandemic.Methods We recruited 102 children with autism spectrum disorder and collected data on sleep and exercise and the restricted interest and repetitive behaviors symptom frequency before and during the pandemic using an international questionnaire. Then, we conducted factor analyses to compute the restricted interest and repetitive behaviors severity composite scores, which are divided into lower-, such as sensory seeking, and higher-order, such as restricted interest. We also asked about the mask-wearing culture using a bespoke questionnaire. Using Spearman’s rank correlation analyses, we examined the relationships between the before pandemic restricted interest and repetitive behaviors symptoms and the impact of mask-wearing on their social communications during the pandemic.Results The current participants spent significantly less time outdoors during the pandemic than before (rho = 0.75, p = 0.005). We also revealed children who exhibited lower-order restricted interest and repetitive behaviors before the pandemic had more challenges with mask-wearing. Mask-wearing was associated with an uncomfortable sensation (rho=-0.34, p = 0.0004) and difficulty in referring to others’ emotions while wearing masks (rho=-0.30, p = 0.0002). We also found an association between higher-order restricted interest and repetitive behaviors and an uncomfortable sensation (rho=-0.42, p = 0.00001).Conclusions These symptoms could be an important predictor for children with autism to adapt to the new normal.

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Influence of External Natural Environment Including Sunshine Exposure on Public Mental Health: A Systematic Review

K Taniguchi, M Takano, Y Tobari, M Hayano, S Nakajima, M Mimura, ...

Psychiatry International 3 (1), 91-113 （Psychiatry International）  3 （ 1 ） 91 - 113 2022年03月

最終著者, 責任著者, 査読有り

　概要を見る

The COVID-19 pandemic has been raging around the world and public health measures such as lockdowns have forced people to go out less often, reducing sunlight exposure time, green space use, and physical activity. It is well known that exercise has a positive impact on mental health, but the impact of external environmental factors such as sunlight exposure and green space use on mental health has not been systematically reviewed. In this review, we categorized the major factors that may affect people’s mental health into (1) external environmental factors such as exposure to sunlight and green spaces, (2) internal life factors such as physical activity and lifestyle, and (3) mixed external and internal factors, and systematically examined the relationship between each factor and people’s mental health. The results showed that exposure to sunlight, spending leisure time in green spaces, and physical activity each had a positive impact on people’s mental health, including depression, anxiety, and stress states. Specifically, moderate physical activity in an external environment with sunlight exposure or green space was found to be an important factor. The study found that exposure to the natural environment through sunbathing and exercise is important for people’s mental health.

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Investigating structural subdivisions of the anterior cingulate cortex in schizophrenia, with implications for treatment resistance and glutamatergic levels

Ochi R., Plitman E., Patel R., Tarumi R., Iwata Y., Tsugawa S., Kim J., Honda S., Noda Y., Uchida H., Devenyi G.A., Mimura M., Graff-Guerrero A., Chakravarty M.M., Nakajima S.

Journal of Psychiatry and Neuroscience （Journal of Psychiatry and Neuroscience）  47 （ 1 ） E1 - E10 2022年01月

査読有り,  ISSN  11804882

　概要を見る

Background: Abnormalities in the anterior cingulate cortex (ACC) are thought to play an important role in the pathophysiology of schizophrenia. Given regional variations in ACC structure, the present study aimed to examine ACC structural subdivisions and their relationships to treatment resistance and glutamatergic levels in schizophrenia. Methods: This study included 100 patients with schizophrenia and 52 healthy controls from 2 cohorts. We applied non-negative matrix factorization to identify accurate and stable spatial components of ACC structure. Between groups, we compared ACC structural indices in each spatial component based on treatment resistance or response and tested relationships with ACC glutamate + glutamine levels. Results: We detected reductions in cortical thickness and increases in mean diffusivity in the spatial components on the surface of the cingulate sulcus, especially in patients with treatment-resistant and clozapine-resistant schizophrenia. Notably, mean diffusivity in these components was higher in patients who did not respond to clozapine compared to those who did. Furthermore, these ACC structural alterations were related to elevated ACC glutamate + glutamine levels but not related to symptomatology or antipsychotic dose. Limitations: Sample sizes, cross-sectional findings and mixed antipsychotic status were limitations of this study. Conclusion: This study identified reproducible abnormalities in ACC structures in patients with treatment-resistant and clozapine-resistant schizophrenia. Given that these spatial components play a role in inhibitory control, the present study strengthens the notion that glutamate-related disinhibition is a common biological feature of treatment resistance in schizophrenia.

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Trends in big data analyses by multicenter collaborative translational research in psychiatry

Onitsuka T., Hirano Y., Nemoto K., Hashimoto N., Kushima I., Koshiyama D., Koeda M., Takahashi T., Noda Y., Matsumoto J., Miura K., Nakazawa T., Hikida T., Kasai K., Ozaki N., Hashimoto R.

Psychiatry and clinical neurosciences （Psychiatry and clinical neurosciences）  76 （ 1 ） 1 - 14 2022年01月

査読有り,  ISSN  1323-1316

　概要を見る

The underlying pathologies of psychiatric disorders, which cause substantial personal and social losses, remain unknown, and their elucidation is an urgent issue. To clarify the core pathological mechanisms underlying psychiatric disorders, in addition to laboratory-based research that incorporates the latest findings, it is necessary to conduct large-sample-size research and verify reproducibility. For this purpose, it is critical to conduct multicenter collaborative research across various fields, such as psychiatry, neuroscience, molecular biology, genomics, neuroimaging, cognitive science, neurophysiology, psychology, and pharmacology. Moreover, collaborative research plays an important role in the development of young researchers. In this respect, the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium and Cognitive Genetics Collaborative Research Organization (COCORO) have played important roles. In this review, we first overview the importance of multicenter collaborative research and our target psychiatric disorders. Then, we introduce research findings on the pathophysiology of psychiatric disorders from neurocognitive, neurophysiological, neuroimaging, genetic, and basic neuroscience perspectives, focusing mainly on the findings obtained by COCORO. It is our hope that multicenter collaborative research will contribute to the elucidation of the pathological basis of psychiatric disorders.

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Glutamatergic and GABAergic metabolite levels in schizophrenia-spectrum disorders: a meta-analysis of ¹H-magnetic resonance spectroscopy studies

Nakahara T., Tsugawa S., Noda Y., Ueno F., Honda S., Kinjo M., Segawa H., Hondo N., Mori Y., Watanabe H., Nakahara K., Yoshida K., Wada M., Tarumi R., Iwata Y., Plitman E., Moriguchi S., de la Fuente-Sandoval C., Uchida H., Mimura M., Graff-Guerrero A., Nakajima S.

Molecular Psychiatry （Molecular Psychiatry）  27 （ 1 ） 744 - 757 2022年01月

責任著者, 査読有り,  ISSN  13594184

　概要を見る

Background: The glutamate (Glu) and gamma aminobutyric acid (GABA) hypotheses of schizophrenia were proposed in the 1980s. However, current findings on those metabolite levels in schizophrenia have been inconsistent, and the relationship between their abnormalities and the pathophysiology of schizophrenia remains unclear. To summarize the nature of the alterations of glutamatergic and GABAergic systems in schizophrenia, we conducted meta-analyses of proton magnetic resonance spectroscopy (1H-MRS) studies examining these metabolite levels. Methods: A systematic literature search was conducted using Embase, Medline, PsycINFO, and PubMed. Original studies that compared four metabolite levels (Glu, glutamine [Gln], Glx [Glu+Gln], and GABA), as measured by 1H-MRS, between individuals at high risk for psychosis, patients with first-episode psychosis, or patients with schizophrenia and healthy controls (HC) were included. A random-effects model was used to calculate the effect sizes for group differences in these metabolite levels of 18 regions of interest between the whole group or schizophrenia group and HC. Subgroup analysis and meta-regression were performed based on the status of antipsychotic treatment, illness stage, treatment resistance, and magnetic field strength. Results: One-hundred-thirty-four studies met the eligibility criteria, totaling 7993 participants with SZ-spectrum disorders and 8744 HC. 14 out of 18 ROIs had enough numbers of studies to examine the group difference in the metabolite levels. In the whole group, Glx levels in the basal ganglia (g = 0.32; 95% CIs: 0.18–0.45) were elevated. Subgroup analyses showed elevated Glx levels in the hippocampus (g = 0.47; 95% CIs: 0.21–0.73) and dorsolateral prefrontal cortex (g = 0.25; 95% CIs: 0.05–0.44) in unmedicated patients than HC. GABA levels in the MCC were decreased in the first-episode psychosis group compared with HC (g = −0.40; 95% CIs: −0.62 to −0.17). Treatment-resistant schizophrenia (TRS) group had elevated Glx and Glu levels in the MCC (Glx: g = 0.7; 95% CIs: 0.38–1.01; Glu: g = 0.63; 95% CIs: 0.31–0.94) while MCC Glu levels were decreased in the patient group except TRS (g = −0.17; 95% CIs: −0.33 to −0.01). Conclusions: Increased glutamatergic metabolite levels and reduced GABA levels indicate that the disruption of excitatory/inhibitory balance may be related to the pathophysiology of schizophrenia-spectrum disorders.

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Neuromelanin accumulation in patients with schizophrenia: A systematic review and meta-analysis

Ueno F., Iwata Y., Nakajima S., Caravaggio F., Rubio J.M., Horga G., Cassidy C.M., Torres-Carmona E., de Luca V., Tsugawa S., Honda S., Moriguchi S., Noda Y., Gerretsen P., Graff-Guerrero A.

Neuroscience and Biobehavioral Reviews （Neuroscience and Biobehavioral Reviews）  132   1205 - 1213 2022年01月

査読有り,  ISSN  01497634

　概要を見る

Although schizophrenia is associated with increased presynaptic dopamine function in the striatum, it remains unclear if neuromelanin levels, which are thought to serve as a biomarker for midbrain dopamine neuron function, are increased in patients with schizophrenia. We conducted a systematic review and meta-analysis of magnetic resonance imaging (MRI) and postmortem studies comparing neuromelanin (NM) levels between patients with schizophrenia and healthy controls (HCs). Standard mean differences were calculated to assess group differences in NM accumulation levels between patients with schizophrenia and HCs. This study included 7 articles in total. Five studies employed NM-sensitive MRI (NM-MRI) and two were postmortem brain studies. The patient group (n = 163) showed higher NM levels in the substantia nigra (SN) than HCs (n = 228) in both the analysis of the seven studies and the subgroup analysis of the 5 NM-MRI studies. This analysis suggest increased NM levels in the SN may be a potential biomarker for stratifying schizophrenia, warranting further research that accounts for the heterogeneity of this disorder.

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Pharmacotherapeutic combinations for the treatment of Alzheimer’s disease

Nagata T., Shinagawa S., Nakajima S., Noda Y., Mimura M.

Expert Opinion on Pharmacotherapy （Expert Opinion on Pharmacotherapy）  23 （ 6 ） 727 - 737 2022年

査読有り,  ISSN  14656566

　概要を見る

Introduction: Alzheimer’s disease (AD) is the most common form of dementia, and four medications are currently available as symptomatic therapies: three cholinesterase inhibitors (ChEI) and memantine. In June 2021, aducanumab was approved in the United States under an accelerated approval pathway as the first novel putative disease-modifying therapy (p-DMT) targeting the β-amyloid (Aβ) cascade in the brain. The combination of several monotherapies to address the multifactorial pathogenesis of neurodegenerative diseases is an anticipated next step. Areas covered: The cholinergic hypothesis and the amyloid cascade hypothesis have been proposed as explanations for the pathogenesis of AD. Given the limited effectiveness of monotherapies based on these hypotheses, approaches using combination therapy are attempting to address the complexity of AD pathogenesis, including putative causative proteins-related neurodegeneration, neurotransmitters, and neuroinflammation, in a comprehensive manner. Expert opinion: The efficacy of an initial or add-on combination approach to counteracting neurodegenerative processes and functional deterioration has been investigated. The combination of symptomatic therapies with approved anti-dementia medicines (one ChEI and memantine) has been found to be functionally effective for a moderately severe disease stage. Furthermore, combination strategies involving p-DMTs, symptomatic therapies, and neuro-regeneration may be useful in the future.

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A preliminary study on predictors of treatment response to repetitive transcranial magnetic stimulation in patients with treatment-resistant depression in Japan

Ikawa H., Tochigi M., Noda Y., Oba H., Kaminaga T., Sakurai K., Ikebuchi E., Hayashi N., Kunugi H.

Neuropsychopharmacology Reports （Neuropsychopharmacology Reports）  42 （ 4 ） 478 - 484 2022年

査読有り,  ISSN  2574-173X

　概要を見る

Background: Brain imaging studies have reported that the effect of repetitive transcranial magnetic stimulation (rTMS) is associated with the activities of the dorsolateral prefrontal cortex (DLPFC) and ventral medial prefrontal cortex (VMPFC). However, few studies have been conducted in Japanese patients. Aim: We aimed to identify brain regions associated with depressive symptom changes by measuring regional cerebral blood flow (rCBF) in the DLPFC and VMPFC before and after the high-frequency rTMS to the left DLPFC in Japanese patients with treatment-resistant depression. Method: Fourteen patients participated in the rTMS study and were assessed with the 17-item Hamilton depression rating scale (HAM-D17). Among them, 13 participants underwent magnetic resonance imaging scan of the brain using the arterial spin labeling method. The rCBF was calculated using the fine stereotactic region of interest template (FineSRT) program for automated analysis. We focused on eight regions reported in previous studies. Results: Depression severity significantly decreased after 2 week (HAM-D17:11.4 ± 2.8, P = 0.00027) and 4 week (HAM-D17: 11.0 ± 3.7, P = 0.0023) of rTMS treatment. There was no significant change in rCBF at each region in the pre-post design. However, there was a significantly negative correlation between baseline rCBF in the right DLPFC and the improvement in HAM-D17 score (r = −0.559, P = 0.047). Conclusion: We obtained supportive evidence for the effectiveness of rTMS to the prefrontal cortex in treatment-resistant depression, which may be associated with reduced rCBF of the right DLPFC before initiation of rTMS.

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Gamma-aminobutyric acid (GABA) levels in the midcingulate cortex and clozapine response in patients with treatment-resistant schizophrenia: A proton magnetic resonance spectroscopy (¹H-MRS) study

Ueno F., Nakajima S., Iwata Y., Honda S., Torres-Carmona E., Mar W., Tsugawa S., Truong P., Plitman E., Noda Y., Mimura M., Sailasuta N., Mikkelsen M., Edden R.A.E., De Luca V., Remington G., Gerretsen P., Graff-Guerrero A.

Psychiatry and Clinical Neurosciences （Psychiatry and Clinical Neurosciences）  76 （ 11 ） 587 - 594 2022年

査読有り,  ISSN  13231316

　概要を見る

Background: Gamma-Aminobutyric Acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system. GABAergic dysfunction has been implicated in the pathophysiology of schizophrenia. Clozapine, the only approved drug for treatment-resistant schizophrenia (TRS), involves the GABAergic system as one of its targets. However, no studies have investigated the relationship between brain GABA levels, as measured by proton magnetic resonance spectroscopy (1H-MRS), and clozapine response in patients with TRS. Methods: This study enrolled patients with TRS who did not respond to clozapine (ultra-resistant schizophrenia: URS) and who responded to clozapine (non-URS), patients with schizophrenia who responded to first-line antipsychotics (first-line responders: FLR), and healthy controls (HCs). We measured GABA levels in the midcingulate cortex (MCC) using 3T 1H-MRS and compared these levels among the groups. The associations between GABA levels and symptom severity were also explored within the patient groups. Results: A total of 98 participants (URS: n = 22; non-URS: n = 25; FLR: n = 16; HCs: n = 35) completed the study. We found overall group differences in MCC GABA levels (F(3,86) = 3.25, P = 0.04). Specifically, patients with URS showed higher GABA levels compared to those with non-URS (F(1,52) = 8.40, P = 0.03, Cohen's d = 0.84). MCC GABA levels showed no associations with any of the symptom severity scores within each group or the entire patient group. Conclusion: Our study is the first to report elevated GABA levels in the MCC in patients with schizophrenia resistant to clozapine treatment compared with those responsive to clozapine. Longitudinal studies are required to evaluate if GABA levels are a suitable biomarker to predict clozapine resistance.

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CRISIS AFAR: An International Collaborative Study of the Impact of the COVID-19 Pandemic on Youth with Autism and Neurodevelopmental Conditions.

B Vibert, P Segura, L Gallagher, S Georgiades, P Pervanidou, A Thurm, ...

medRxiv 2022年

P550. GABA Alteration in Patients With Treatment-Resistant Schizophrenia: A 1H-MRS Study

F Ueno, S Nakajima, Y Iwata, S Honda, J Kim, F Caravaggio, E Brown, ...

Biological Psychiatry 91 (9), S311 2022年

P549. MRI Neuromelanin Accumulation in Patients with Treatment-Resistant Schizophrenia: A Cross-Sectional Pilot Study

F Ueno, Y Iwata, S Nakajima, S Chavez, F Caravaggio, G Horga, ...

Biological Psychiatry 91 (9), S311 2022年

P548. Glymphatic System in Schizophrenia: An H-MRS High-Molecular-Weight Macromolecules Study

A Abdolizadeh, ET Carmona, F Ueno, S Nakajima, R Tarumi, S Tsugawa, ...

Biological Psychiatry 91 (9), S310-S311 2022年

P291. Effects of Sleep on the Gut Microbiota and Metabolome in Patients With Depression and Anxiety: A Prospective Observational Study

A Tanaka, K Sanada, S Kurokawa, K Miyaho, T Tachibana, Y Noda, ...

Biological Psychiatry 91 (9), S205 2022年

Gamma‐aminobutyric acid (GABA) levels in the midcingulate cortex and clozapine response in patients with treatment‐resistant schizophrenia: A proton magnetic resonance …

F Ueno, S Nakajima, Y Iwata, S Honda, E Torres‐Carmona, W Mar, ...

Psychiatry and Clinical Neurosciences 76 (11), 587-594 2022年