Kanagawa Psychiatric Center

Yokohama-shi, Japan

Kanagawa Psychiatric Center

Yokohama-shi, Japan
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Nakamura M.,Kanagawa Psychiatric Center | Nakamura M.,Showa University | Nakamura M.,Advanced Telecommunications Research Institute
Brain and Nerve | Year: 2017

The neurobiological mechanisms that regulate the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) remain unknown to date. An optimized rTMS protocol has not been established, partly due to the wide variability in its aftereffects among individuals who have undergone the treatment. Responder rates to rTMS for treating major depression have been reported to be modest (30 to 40 percent). Thus, optimization and personalization of an rTMS protocol is required for better treatment outcomes. To this end, it is necessary to identify brain biomarkers for predicting responsiveness to rTMS treatment and the aftereffects and for personalizing rTMS. In this review, we introduced potential biomarkers of rTMS response for treating major depression by employing two modalities of resting-state functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG) from a perspective of neural network dynamics.


Hashimoto R.,Showa University | Hashimoto R.,Tokyo Metroplitan University | Itahashi T.,Showa University | Ohta H.,Showa University | And 7 more authors.
Social Neuroscience | Year: 2016

In interactive social situations, it is often crucial to be able to take another person’s perspective when evaluating one’s own or another person’s specific trait; individuals with autism spectrum disorder (ASD) critically lack this social skill. To examine how perspective-dependent self- and other-evaluation processes modulate functional connectivity in ASD, we conducted a functional magnetic resonance imaging study in which 26 high-functioning adults with ASD and 24 typically developed (TD) controls were asked to decide whether an adjective describing a personality trait correctly described the participant himself/herself (“self”) or the participant’s mother (“other”) by taking either the first (1P) or third person (3P) perspective. We observed that functional connectivity between the left sensorimotor cortex and the left middle cingulate cortex was enhanced in TD control individuals taking the 3P perspective, this enhancement was significantly reduced in ASD, and the degree of reduction was significantly correlated with the severity of autistic traits. Furthermore, the self-reference effect on functional connectivity between the left inferior frontal cortex and frontopolar cortices was significantly enhanced in TD control individuals taking the 3P perspective, whereas such effect was reversed in ASD. These findings indicate altered effects of perspective on the functional connectivity, which may underlie the deficits in social interaction and communication observed in individuals with ASD. © 2016 Informa UK Limited, trading as Taylor & Francis Group


Umino A.,Tokyo Medical and Dental University | Ishiwata S.,Tokyo Medical and Dental University | Iwama H.,Tokyo Medical and Dental University | Iwama H.,Kanagawa Psychiatric Center | Nishikawa T.,Tokyo Medical and Dental University
Frontiers in Molecular Neuroscience | Year: 2017

Endogenous D-serine is a putative dominant co-agonist for the N-methyl-D-aspartate glutamate receptor (NMDAR) in the mammalian forebrain. Although the NMDAR regulates the higher order brain functions by interacting with various neurotransmitter systems, the possible interactions between D-serine and an extra-glutamatergic system largely remain elusive. For the first time, we show in the rat and mouse using an in vivo microdialysis technique that the extracellular D-serine concentrations are under tonic increasing control by a major inhibitory transmitter, GABA, via the GABAA (GABAAR) in the medial prefrontal cortex (mPFC). Thus, an intra-mPFC infusion of a selective GABAAR antagonist, bicuculline (BIC), caused a concentration-dependent and reversible decrease in the extracellular levels of D-serine in the rat mPFC without affecting those of another intrinsic NMDAR coagonist, glycine and an NMDAR agonist, L-glutamate. The decreasing effects of BIC were eliminated by co-infusion of a selective GABAA agonist, muscimol (MUS) and were mimicked by a GABAA antagonist, gabazine (GBZ). In contrast, selective blockade of the GABAB or homomeric ρGABAA (formerly GABAC) receptor by saclofen or (1,2,5,6-tetrahydropyridin-4-yl)-methylphosphinic acid (TPMPA), respectively, failed to downregulate the prefrontal extracellular D-serine levels. Moreover, the local BIC application attenuated the ability of NMDA given to the mPFC to increase the cortical extracellular concentrations of taurine, indicating the hypofunction of the NMDAR. Finally, in the mouse mPFC, the reduction of the extracellular D-serine levels by a local injection of BIC into the prefrontal portion was replicated, and was precluded by inhibition of the neuronal or glial activity by co-local injection with tetrodotoxin (TTX) or fluorocitrate (Fluo), respectively. These findings suggest that the GABAA R-mediated regulation of the D-serine signaling may exert fine-tuning of the NMDAR function and require both neuronal and glial activities in the mammalian mPFC. © 2017 Umino, Ishiwata, Iwama and Nishikawa.


Nishimura K.,Tokyo Women's Medical University | Omori M.,Kanagawa Psychiatric Center | Katsumata Y.,Tokyo Women's Medical University | Sato E.,Keio University | And 6 more authors.
Journal of Rheumatology | Year: 2015

Objective. Neurocognitive impairment (NCI) has been intensively studied in patients with systemic lupus erythematosus (SLE). However, those studies have mostly included patients who were treated with corticosteroids, which may itself induce NCI. We investigated NCI in corticosteroid-naive people with SLE who did not exhibit any overt neuropsychiatric manifestations. Methods. Forty-three inpatients with SLE who had no current or past neuropsychiatric history participated in the study. Patients and 30 healthy control subjects with similar demographic characteristics were given a 1-h battery of neuropsychological tests. NCI was defined as scores at least 2 SD below the mean of the healthy control group on at least 2 of the 7 neurocognitive domains. Results of clinical, laboratory, and neurologic tests were compared regarding the presence of NCI. Results. NCI was identified in 12 patients (27.9%) with SLE and in 2 control subjects (6.7%). Patients with SLE showed a significant impairment compared with controls on tasks assessing immediate recall, complex attention/executive function, and psychomotor speed. We identified psychomotor speed (Digit Symbol Substitution Test) as the factor that best differentiated the 2 groups. Further, we identified the score of the SLE Disease Activity Index 2000 as an independent risk factor for NCI in patients with SLE. Conclusion. We conclude that reduced psychomotor speed is an SLE-specific pattern of NCI. Verbal-memory deficits that have been reported in patients with SLE were not evident among patients who were corticosteroid-naive. Our results indicate that impaired psychomotor speed may be added to the symptoms of early SLE. The Journal of Rheumatology Copyright © 2015. All rights reserved.


Nishimura K.,Tokyo Women's Medical University | Omori M.,Kanagawa Psychiatric Center | Sato E.,Tokyo Women's Medical University | Katsumata Y.,Tokyo Women's Medical University | And 5 more authors.
Journal of Neurology | Year: 2014

The objective of this study was to clarify the incidence, clinical characteristics, and courses of new-onset psychiatric manifestations after corticosteroid therapy in patients with systemic lupus erythematosus (SLE), including possible ways of differentiating between corticosteroid-induced psychiatric disorders (CIPDs) and central nervous system manifestations of SLE (CNS-SLE). We prospectively followed for 8 weeks 139 consecutive episodes in 135 in-patients who had a non-CNS-SLE flare treated with corticosteroids. Psychiatric events were evaluated once a week using DSM-IV criteria. We then conducted a post hoc etiological analysis of any newly developed psychiatric events during this follow-up period. In the 8 weeks of corticosteroid administration, new psychiatric events occurred in 20 (14.4 %) of the 139 episodes. The mean dosage of corticosteroids administered was prednisolone at 0.98 (range 0.24-1.39) mg/kg/day. Of the 20 psychiatric events, 14 (10.1 %) were suitable for the strict definition of CIPDs, accompanied by mood disorders in 13 (depressive in 2, manic in 9, and mixed in 2) and psychotic disorder in one. Two (1.4 %), both presenting delirium, were diagnosed as CNS-SLE on the basis of evidence of abnormal CNS findings even before psychiatric manifestations, all of which improved in parallel with these patients' recoveries through augmentation of immunosuppressive therapy. The other four events (2.9 %) could not be etiologically identified. This study suggests that corticosteroid therapy triggers CIPDs and CNS-SLE in patients with SLE. Delirium may be suggestive of CNS-SLE, while mood disorders may be more suggestive of CIPDs. Electroencephalographic abnormalities may possibly be predictive of CNS-SLE. © 2014 Springer-Verlag Berlin Heidelberg.


PubMed | Tokyo Women's Medical University and Kanagawa Psychiatric Center
Type: Journal Article | Journal: Lupus | Year: 2016

Psychological distress, such as depression and anxiety, has been intensively studied in patients with systemic lupus erythematosus (SLE). However, those studies have mostly included patients who were treated with corticosteroids, which might themselves induce mood disturbances. We investigated psychological distress in corticosteroid-naive patients with SLE who did not exhibit any overt neuropsychiatric manifestations.Forty-three SLE in-patients with no current or past abnormal neuropsychiatric history participated in the study. Patients and 30 healthy control subjects with similar demographic and personality characteristics were administered a comprehensive battery of psychological/neuropsychological tests. The Profile of Mood States (POMS) was used to assess depression and anxiety. Results of clinical, laboratory, and neurological tests were compared with regard to their presence.Prevalence of depression was higher in patients (n=11, 25.6%) than in controls (n=2, 6.7%; p=0.035), although prevalence of anxiety did not differ across groups (patients: 34.9%, n=15; controls: 16.7%, n=5; p=0.147). Using multiple logistic regression analysis, we identified avoidance coping methods (OR, 1.3; 95% CI 1.030-1.644; p=0.027) as an independent risk factor for depression.Our results indicate that depression presents more frequently in corticosteroid-naive patients with early-stage, active SLE than in the normal population, but anxiety does not. Depression may be related to psychological reactions to suffering from the disease.


Matsumoto T.,National Institute of Mental Health | Ozaki S.,Tokyo metropolitan Toshima Hospital | Kobayashi O.,Kanagawa Psychiatric Center | Wada K.,National Institute of Mental Health
Activitas Nervosa Superior | Year: 2015

The purpose of the present study is to examine the current situation of sedative-related disorders (mainly benzodiazepines) in Japan and the clinical characteristics of Japanese patients with this disorder. Subjects were 671 drug-related disorder patients diagnosed according to the ICD-IO classification as "Fl: mental and behavioural disorders due to psychoactive substance use/7 who abused psychoactive substances other than alcohol. Of all the psychiatric hospitals in Japan between September and October 2010, these drug-related disorder patients had consecutively consulted or were admitted to 153 psychiatric hospitals. The present study was conducted by means of a mail survey. Subjects7 clinical information, including history of psychoactive substance use, means of access to the primary drug of abuse, other ICD-10 diagnoses including Fl subcategory and comorbid psychiatric disorders, and recent history of self-destructive behavior, were collected from the attending psychiatrists of each subject. The data thus gathered concerning sedative-related disorder patients were compared with those patients with methamphetamine-related disorder, which has been the most serious drug-related problem in Japan since the 1950s. Out of the 671 subjects, 119 patients mainly abusing sedatives (the SRD group) were identified, while 361 patients were identified as mainly abusing methamphetamine (the MRD group). The MRD group was the largest population (53.8% of the total subjects), followed by the SRD group (17.7%), the inhalant-related disorder group with 56 patients (8.3%), and so on. Compared with the MRD group, the SRD group was younger, contained more female patients, and had a lower incidence of history of involvement with anti-social societies and anti-social behavior. Patients of the SRD group were more likely to have started abusing drugs with the intention of reducing the unpleasant symptoms of insomnia (42.9%), anxiety (26.1%), and depression (16.0%), and to acquire the drugs they abused from medical institutions such as psychiatric or primary care clinics (82.1%), while patients of the MRD group were more likely to have started out of curiosity (35.1%) or in response to peer pressure (47.1%), and to acquire their drugs from a "pusher77 (32.8%). Additionally, in the SRD group, the ICD-10 [Translated with permission from Seishinshinkeigaku-zasshi (Psychiatria et Neurologia Japonica), vol. 113, 1184- 1198, 2011] Fl subcategory diagnoses that were clinically most important were "dependence syndrome" (64.0%), "harmful use" (16.2%) and "acute intoxication" (16.2%), while the most important subcategory diagnosis in the MRD group was "psychotic disorder" (34.3%) and "residual disorder and late-onset psychotic disorder" (32.9%). Further, comorbid psychiatric disorders were more frequently found in the SRD group than in the MRD group; notably, co-occurrence of mood disorder was found in 45.0% of the SRD group in contrast to the MRD group (11.9%). Recent episodes of deliberate self-harm behavior were also more frequently found in the SRD group than the MRD group (33.6% vs. 10.5%); the major means by which these patients harmed themselves was by overdosing on prescribed drugs (23.5% vs. 4.7%). The present study suggests that sedative-related disorder is an important clinical issue in the field of drug-related disorders in Japan today, and that SRD patients may represent a distinct type of drug abusers whose clinical characteristics are different from those of MRD patients. The development and spread of treatment programs for "dependence syndrome" and "harmful use" will help SRD patients, and educating psychiatrists about SRD will help prevent future sedative abuse. © 2015, Neuroscientia o.s. All Rights Reserved.


Honma M.,National Institute of Mental Health | Honma M.,Showa University | Yoshiike T.,National Institute of Mental Health | Yoshiike T.,Kanagawa Psychiatric Center | And 3 more authors.
Scientific Reports | Year: 2015

Appropriate inhibitory response control is associated with goal-directed behavior. Sleep accelerates the offline consolidation of acquired motor skills that are explicitly predictable; however, the effect of sleep on implicit (unpredictable) motor skills remains controversial. We speculated that a key component of response inhibition skill differentiates between these skill consolidation properties because explicit prediction can minimize the inhibitory efforts in a motor skill. We explored the offline skill learning properties of response inhibition during sleep and wakefulness using auditory Go and Go/Nogo tasks. We attempted to discriminate the possible effects of time elapsed after training (12 or 24h), post-training sleep/wake state (sleep or wakefulness), and time of day (nighttime or daytime) in 79 healthy human subjects divided into 6 groups that underwent various sleep regimens prior to training and retesting. We found that delayed response inhibition skill improvement was achieved via a simple passage of daytime, regardless of the participants alertness level. Our results suggest that sleep-independent neuroplasticity occurs during the daytime and facilitates a delayed learning of response inhibition skill.


PubMed | University of Toronto, Kanagawa Psychiatric Center and Kiiko Matsumoto Acupuncture Clinic
Type: Clinical Trial | Journal: Complementary therapies in clinical practice | Year: 2015

To study the biological effects of acupuncture on depression, we hypothesized that acupuncture will exert its antidepressant effect through a bottom-up neuromodulation of the autonomic dysfunction in depression. The participants received press needle (PN) acupuncture for 72h continuously in a sham-controlled design. Psychological assessments and Holter electrocardiography were performed before and after PN acupuncture. We evaluated their autonomic functions through the heart rate variability (HRV). As a result, following PN acupuncture participants showed significant improvement in the Becks Depression Inventory scores (P=0.031), systolic/diastolic blood pressures (P=0.002/P=0.011), and coefficient of variation of the R-R interval (P<0.0001), compared to sham PN. The present findings showed PN acupuncture induced alterations in vagal function, blood pressure, and Becks Depression Inventory scores. It was suggested that vagal stabilization effect by acupuncture may be associated with the therapeutic mechanism in depression.


Nishimura K.,Tokyo Medical University | Omori M.,Kanagawa Psychiatric Center | Sato E.,Tokyo Medical University | Katsumata Y.,Tokyo Medical University | And 5 more authors.
Journal of Neurology | Year: 2014

The objective of this study was to clarify the incidence, clinical characteristics, and courses of new-onset psychiatric manifestations after corticosteroid therapy in patients with systemic lupus erythematosus (SLE), including possible ways of differentiating between corticosteroid-induced psychiatric disorders (CIPDs) and central nervous system manifestations of SLE (CNS-SLE). We prospectively followed for 8 weeks 139 consecutive episodes in 135 in-patients who had a non–CNS-SLE flare treated with corticosteroids. Psychiatric events were evaluated once a week using DSM-IV criteria. We then conducted a post hoc etiological analysis of any newly developed psychiatric events during this follow-up period. In the 8 weeks of corticosteroid administration, new psychiatric events occurred in 20 (14.4 %) of the 139 episodes. The mean dosage of corticosteroids administered was prednisolone at 0.98 (range 0.24–1.39) mg/kg/day. Of the 20 psychiatric events, 14 (10.1 %) were suitable for the strict definition of CIPDs, accompanied by mood disorders in 13 (depressive in 2, manic in 9, and mixed in 2) and psychotic disorder in one. Two (1.4 %), both presenting delirium, were diagnosed as CNS-SLE on the basis of evidence of abnormal CNS findings even before psychiatric manifestations, all of which improved in parallel with these patients’ recoveries through augmentation of immunosuppressive therapy. The other four events (2.9 %) could not be etiologically identified. This study suggests that corticosteroid therapy triggers CIPDs and CNS-SLE in patients with SLE. Delirium may be suggestive of CNS-SLE, while mood disorders may be more suggestive of CIPDs. Electroencephalographic abnormalities may possibly be predictive of CNS-SLE. © 2014, Springer-Verlag Berlin Heidelberg.

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