Language：Japanese   Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

A functional MRI comparison of patients with obsessive-compulsive disorder and normal controls during a Chinese character Stroop task

DOI： 10.1016/j.pscychresns.2004.12.004

Language：English   Publishing type：Research paper (scientific journal)  

Brain activation of patients with obsessive-compulsive disorder during neuropsychological and symptom provocation tasks before and after symptom improvement

DOI： 10.1016/j.biopsycg.2004.12.039

Language：English   Publisher：Psychiatry and Clinical Neurosciences  

Aim: To investigate the association of olfactory identification ability with both the prevalence of mild cognitive impairment (MCI) and regional brain atrophy in a community-dwelling older population. Methods: A total of 1293 participants without dementia aged 65 years or older underwent a Japanese version of the 4-Item Pocket Smell Test, an assessment of cognitive function, and brain magnetic resonance imaging scanning in 2017–2018. Regional gray matter volumes (GMVs) and white matter lesions volume (WMLV) were estimated using FreeSurfer software. The association of impaired olfactory identification with the presence of MCI and regional GMVs or WMLV was estimated by logistic regression analysis and ANCOVA, respectively. We also assessed the association between impaired olfactory identification and GMVs without regions of interest, using a voxel-based morphometry (VBM) analysis. Results: Participants with impaired olfactory identification had a significantly higher likelihood of MCI than those without (odds ratio, 1.99 [95% confidence interval, 1.36–2.91]). In the FreeSurfer analysis, participants with impaired olfactory identification had significantly lower GMVs in the entorhinal cortex, inferior temporal gyrus, amygdala, thalamus, hippocampus, and cingulate gyrus, and higher WMLV than those without. The VBM analysis also showed that impaired olfactory identification was significantly associated with lower volume of the left entorhinal cortex, left amygdala, left hippocampus, bilateral thalami, and bilateral subcallosal areas. Conclusion: Our findings suggest that cognitive function and brain changes may need to be evaluated in older individuals with impaired olfactory identification, which may reflect the extent of neurodegeneration, WMLV, and subsequent cognitive impairment.

DOI： 10.1111/pcn.13813

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Language：English   Publisher：Psychiatry and Clinical Neurosciences Reports  

Background: Attention-deficit/hyperactivity disorder (ADHD) symptoms, including executive function, emotional regulation, and motivation, can persist into adulthood and are often associated with mental illnesses. Cognitive behavioral therapy (CBT) may help ADHD adults in Japan, but the lack of studies and the variability in group CBT approaches make its effects unclear. Japan lacks unified CBT programs and adult ADHD guidelines, making it difficult to implement international individual CBT recommendations due to cultural differences. This study will assess the feasibility of a novel CBT program for Japanese adult ADHD patients. Methods: This feasibility study will be open, nonrandomized, single-arm, multicenter study. Twelve ADHD patients aged 20–65 years who are currently receiving treatment will be included based on Conners' Adult ADHD Rating Scale (CAARS) clinical severity threshold. An intervention phase of 12–16 weeks and a 12-week follow-up will total 24–28 weeks for all participants. The intervention will use a new CBT program tailored to individual assessments. Results: The primary objective is to determine feasibility using dropout rates, adverse events, and CAARS score changes between Weeks 1 and 16. The secondary outcomes will assess long-term effects of treatment beyond the intervention period and provide descriptive statistics on sex, depression, quality of life, and autistic scores in relation to the intervention outcomes. The full analysis set and per protocol set will be used for statistical analysis. Conclusions: This study is essential for the development of CBT interventions in accordance with Japan's healthcare system that are tailored to the unique needs of its population.

DOI： 10.1002/pcn5.70036

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Language：English   Publisher：Scientific Reports  

We investigated the association of retinopathy with the risk of dementia in a general older Japanese population. A total of 1709 population-based residents aged 60 years or older without dementia were followed prospectively for 10 years (2007–2017). They underwent color fundus photography in 2007. Retinopathy was graded according to the Modified Airlie House Classification. Main outcome was the Incidence of dementia. A Cox proportional hazards model was used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) for the risk of dementia by the presence of retinopathy. During the follow-up period, 374 participants developed all-cause dementia. The cumulative incidence of dementia was significantly higher in those with retinopathy than those without (p < 0.05). Individuals with retinopathy had significantly higher risk of developing dementia than those without after adjustment for potential confounding factors (HR 1.64, 95% CI 1.19–2.25). Regarding the components of retinopathy, the presence of microaneurysms was significantly associated with a higher multivariable-adjusted HR for incident dementia (HR 1.94, 95% CI 1.37–2.74). Our findings suggest that, in addition to systemic risk factors, retinal microvascular signs from fundus photography provide valuable information for estimating the risk of developing dementia.

DOI： 10.1038/s41598-024-62688-7

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Language：English   Publisher：European Journal of Neuroscience  

Prominent pathological hypotheses for schizophrenia include auditory processing deficits and dysconnectivity within cerebral networks. However, most neuroimaging studies have focused on impairments in either resting-state or task-related functional connectivity in patients with schizophrenia. The aims of our study were to examine (1) blood oxygen level-dependent (BOLD) signals during auditory steady-state response (ASSR) tasks, (2) functional connectivity during the resting-state and ASSR tasks and (3) state shifts between the resting-state and ASSR tasks in patients with schizophrenia. To reduce the functional consequences of scanner noise, we employed resting-state and sparse sampling auditory fMRI paradigms in 25 schizophrenia patients and 25 healthy controls. Auditory stimuli were binaural click trains at frequencies of 20, 30, 40 and 80 Hz. Based on the detected ASSR-evoked BOLD signals, we examined the functional connectivity between the thalamus and bilateral auditory cortex during both the resting state and ASSR task state, as well as their alterations. The schizophrenia group exhibited significantly diminished BOLD signals in the bilateral auditory cortex and thalamus during the 80 Hz ASSR task (corrected p < 0.05). We observed a significant inverse relationship between the resting state and ASSR task state in altered functional connectivity within the thalamo-auditory network in schizophrenia patients. Specifically, our findings demonstrated stronger functional connectivity in the resting state (p < 0.004) and reduced functional connectivity during the ASSR task (p = 0.048), which was mediated by abnormal state shifts, within the schizophrenia group. These results highlight the presence of abnormal thalamocortical connectivity associated with deficits in the shift between resting and task states in patients with schizophrenia.

DOI： 10.1111/ejn.16298

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Language：English   Publisher：Frontiers in Neuroscience  

Introduction: Gamma-band oscillatory deficits have attracted considerable attention as promising biomarkers of schizophrenia (SZ). Notably, a reduced auditory steady-state response (ASSR) in the low gamma band (40 Hz) is widely recognized as a robust finding among SZ patients. However, a comprehensive investigation into the potential utility of the high-gamma-band ASSR in detecting altered neural oscillations in SZ has not yet been conducted. Methods: The present study aimed to assess the ASSR using magnetoencephalography (MEG) data obtained during steady-state stimuli at frequencies of 20, 30, 40, and 80 Hz from 23 SZ patients and 21 healthy controls (HCs). To evaluate the ASSR, we examined the evoked power and phase-locking factor (PLF) in the time-frequency domain for both the primary and secondary auditory cortices. Furthermore, we calculated the phase-locking angle (PLA) to examine oscillatory phase lead or delay in SZ patients. Taking advantage of the high spatial resolution of MEG, we also focused on the hemispheric laterality of low- and high-gamma-band ASSR deficits in SZ. Results: We found abnormal phase delay in the 40 Hz ASSR within the bilateral auditory cortex of SZ patients. Regarding the 80 Hz ASSR, our investigation identified an aberrant phase lead in the left secondary auditory cortex in SZ, accompanied by reduced evoked power in both auditory cortices. Discussion: Given that abnormal phase lead on 80 Hz ASSR exhibited the highest discriminative power between HC and SZ, we propose that the examination of PLA in the 80 Hz ASSR holds significant promise as a robust candidate for identifying neurophysiological endophenotypes associated with SZ. Furthermore, the left-hemisphere phase lead observed in the deficits of 80 Hz PLA aligns with numerous prior studies, which have consistently proposed that SZ is characterized by left-lateralized brain dysfunctions.

DOI： 10.3389/fnins.2023.1277733

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Language：English   Publisher：Scientific Reports  

Angiogenic factors associated with Moyamoya disease (MMD) are overexpressed in M2 polarized microglia in ischemic stroke, suggesting that microglia may be involved in the pathophysiology of MMD; however, existing approaches are not applicable to explore this hypothesis. Herein we applied blood induced microglial-like (iMG) cells. We recruited 25 adult patients with MMD and 24 healthy volunteers. Patients with MMD were subdivided into progressive (N = 7) or stable (N = 18) group whether novel symptoms or radiographic advancement of Suzuki stage within 1 year was observed or not. We produced 3 types of iMG cells; resting, M1-, and M2-induced cells from monocytes, then RNA sequencing followed by GO and KEGG pathway enrichment analysis and qPCR assay were performed. RNA sequencing of M2-induced iMG cells revealed that 600 genes were significantly upregulated (338) or downregulated (262) in patients with MMD. Inflammation and immune-related factors and angiogenesis-related factors were specifically associated with MMD in GO analysis. qPCR for MMP9, VEGFA, and TGFB1 expression validated these findings. This study is the first to demonstrate that M2 microglia may be involved in the angiogenic process of MMD. The iMG technique provides a promising approach to explore the bioactivity of microglia in cerebrovascular diseases.

DOI： 10.1038/s41598-023-41456-z

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Language：English   Publisher：Archives of Gerontology and Geriatrics  

Background: To investigate the association of gait speed with regional brain volumes and the risk of incident dementia. Methods: A total of 1112 dementia-free Japanese residents aged ≥65 years who underwent brain magnetic resonance imaging were followed for 5.0 years (median). The participants were classified into the age- and sex-specific quartile levels of maximum gait speed. Regional gray matter volumes (GMV) and white matter hyperintensities volumes (WMHV) were measured by applying voxel-based morphometry methods. The cross-sectional association of maximum gait speed with regional GMV was examined using an analysis of covariance. We also estimated the association between maximum gait speed level and the risk of developing dementia using a Cox proportional hazards model. Mediation analyses were conducted to determine the contribution of regional brain volumes to the association between maximum gait speed and dementia. Results: Lower maximum gait speed was significantly associated with lower GMV of the total brain, frontal lobe, temporal lobe, cingulate gyrus, insula, hippocampus, amygdala, basal ganglia, thalamus, and cerebellum, and increased WMHV at baseline. During the follow-up, 108 participants developed dementia. The incidence rate of all dementias increased significantly with decreasing maximum gait speed after adjusting for potential confounders (P for trend = 0.03). The mediating effects of the GMV of the hippocampus, GMV of the insula, and WMHV were significant. Conclusions: Lower maximum gait speed was significantly associated with an increased risk of dementia. Reduced GMV of the hippocampus or insula, and an increase in WMHV was likely to be involved in this association.

DOI： 10.1016/j.archger.2022.104883

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Language：English   Publisher：Psychiatry and Clinical Neurosciences  

DOI： 10.1111/pcn.13505

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Language：English   Publisher：Frontiers in Psychiatry  

Backgrounds: Hikikomori, pathological social withdrawal, is becoming a crucial mental health issue in Japan and worldwide. We have developed a 3-day family intervention program for hikikomori sufferers based on Mental Health First Aid (MHFA) and Community Reinforcement and Family Training (CRAFT). This study aims to confirm the effectiveness of the 3-day program by a randomized controlled trial. Methods: This study was registered on the UMIN Clinical Trials Registry (UMIN000037289). Fifteen parents were assigned to the treat as usual (TAU) group (TAU only; Age Mean, 65.6; SD, 7.8), and 14 to the Program group (program + TAU; Age Mean, 67.9; SD, 8.6). This study was discontinued due to the COVID-19 pandemic; the recruitment rate was 36.3% of our target sample size of 80. Results: Perceived skills improved temporally and stigma temporally worsened in the TAU group. Confidence decreased and attitude showed no change in both groups. Aggressive behaviors of hikikomori sufferers were significantly worsened in the Program group; however, no serious domestic violence was reported. In the TAU group, Avoidance and irregular life patterns were improved. Activity levels were worsened in both groups. Two participants (16.7%) in the Program group and one participant (7.7%) in the TAU group reported actual behavioral changes (e.g., utilizing support). Conclusion: We could not draw general conclusions on the effectiveness of the program due to the study discontinuation. Nevertheless, this study indicates the necessity for revision of the program to improve family members’ confidence in engaging with hikikomori sufferers, with safer approaching by families.

DOI： 10.3389/fpsyt.2022.1029653

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Language：English   Publisher：Progress in Neuro Psychopharmacology and Biological Psychiatry  

Background It is gradually becoming clear that obsessive-compulsive disorder (OCD) patients have aberrant resting-state large-scale intrinsic networks of cingulo-opercular salience (SN), default mode (DMN), and front-parietal network (FPN). However, it remains unknown whether unaffected first-degree relatives of OCD patients have these alterations as a vulnerability marker to the disorder. Methods We performed resting-state functional magnetic resonance imaging (rsfMRI) scans of 47 medication-free OCD patients, 21 unaffected healthy first-degree relatives of OCD patients, and 62 healthy control (HC) participants. We explored differences between the three groups in the functional connectivity from SN (seeds: anterior-insula (AI) and dorsal anterior cingulate cortex (dACC)), DMN (seeds: medial prefrontal cortex (MPFC) and posterior parietal cortex (PCC)), and FPN (seeds: dorsolateral prefrontal cortex (DLPFC)). Results Compared to HC, both OCD patients and first-degree relatives showed significantly greater functional connectivity between AI and PCC and between DLPFC and the thalamus. Compared to first-degree relatives and HC, OCD patients showed reduced functional connectivity between PCC and DLPFC, and this altered functional connectivity was negatively correlated with anxiety and depressive symptom within OCD group. Conclusions OCD patients and unaffected first-degree relatives of OCD patients showed overlapping alterations in resting state functional connectivity between the regions of SN and DMN and between DLPFC and the thalamus. Our results suggested that alterations between large-scale intrinsic networks and within the dorsal cognitive cortico-striato-thalamo-cortical (CSTC) circuit could represent endophenotype markers of OCD.

DOI： 10.1016/j.pnpbp.2022.110516

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Language：English   Publisher：Journal of Psychiatric Research  

Although preliminary neuroimaging research suggests that patients with hoarding disorder (HD) show widespread abnormal task-related activity in the brain, there has been no research on alterations in the white matter tracts in these patients. The aim of this study was to investigate the characteristics of the major white matter tracts in patients with HD. Tract-based spatial statistics were used to search for white matter tract abnormalities throughout the brain in 25 patients with HD and 36 healthy controls. Post hoc analysis of regions of interest was performed to detect correlations with clinical features. Compared with the controls, patients with HD showed decreased fractional anisotropy and increased radial diffusivity in anatomically widespread white matter tracts. Post hoc analysis of regions of interest revealed a significant negative correlation between the severity of hoarding symptoms and fractional anisotropy in the left anterior limb of the internal capsule and a positive correlation between the severity of these symptoms and radial diffusivity in the right anterior thalamic radiation. Patients with HD showed a broad range of alterations in the frontal white matter tracts, including the frontothalamic circuit, frontoparietal network, and frontolimbic pathway. The findings of this study indicate associations between frontal white matter abnormalities related to the severity of hoarding symptoms in HD and the cortical regions involved in cognitive dysfunction. The insights provided would be useful for understanding the neurobiological basis of HD.

DOI： 10.1016/j.jpsychires.2022.01.031

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Authorship：Last author  

Language：English   Publisher：Journal of the American Geriatrics Society  

Background: Little is known about the influence of serum level of soluble triggering receptor expressed on myeloid cells 2 (sTREM2), which is a soluble type of an innate immune receptor expressed on the microglia, on the association of the daily sleep duration with the risk of dementia. Methods: A total of 1230 Japanese community-residents aged 60 and older without dementia were followed prospectively for 10 years (2002–2012). Serum sTREM2 levels were divided into two groups using the median value (334.8 pg/ml). Self-reported daily sleep duration was grouped into three categories of <5.0, 5.0–7.9, and ≥8.0 h. A Cox proportional hazards model was used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) of daily sleep duration on the risk of dementia according to serum sTREM2 levels. Results: During the follow-up, 262 subjects developed dementia. In subjects with low serum sTREM2 levels, subjects with ≥8.0 h of daily sleep had a significantly greater risk of dementia (multivariable-adjusted HR 2.05 [95% CI 1.32–3.19]) than those with 5.0–7.9 h of daily sleep, but those with <5.0 h did not. In contrast, the risk of dementia increased significantly in subjects with both <5.0 (1.95 [1.03–3.68]) and ≥8.0 h of daily sleep (1.48 [1.06–2.07]) in the subjects with high serum sTREM2 levels. Conclusions: The influence of daily sleep duration on risk of dementia differed according to serum sTREM2 levels in the older Japanese population. Short daily sleep may be associated with greater risk of dementia only in subjects with a high serum sTREM2 level.

DOI： 10.1111/jgs.17634

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Language：English   Publishing type：Research paper (scientific journal)  

Previous studies have reported clinical characteristics of hoarding disorder (HD), such as early onset, a chronic course, familiality, high unmarried rate, and high rates of comorbidities. However, clinical research targeting Japanese HD patients has been very limited. As a result, there is a low recognition of HD in Japan, leading to insufficient evaluation and treatment of Japanese HD patients. The aim of the current study was to delineate the clinical characteristics of Japanese HD patients. Thirty HD patients, 20 obsessive-compulsive disorder (OCD) patients, and 21 normal controls (NC) were targeted in this study. The HD group had a tendency toward higher familiality, earlier onset, and longer disease duration compared to the OCD group. In addition, the HD group showed a significantly higher unmarried rate than the NC group. The top two comorbidities in the HD group were major depressive disorder (56.7%) and attention-deficit/hyperactivity disorder (26.7%). The HD group had significantly higher scores on hoarding rating scales and lower scores on the Global Assessment of Functioning Scale than the other two groups. The current study showed a clinical trend in Japanese HD patients similar to previous studies in various countries, suggesting that HD may be a universal disease with consistent clinical symptoms.

DOI： 10.1016/j.heliyon.2020.e03527

Language：English   Publishing type：Research paper (scientific journal)  

Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect common trajectories in brain development and maturation. Large-scale investigation of structural covariance networks in obsessive-compulsive disorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T₁-weighted MRI scans acquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCD Working Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33 cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to the similarity between two brain morphological features in terms of deviation from healthy controls (i.e. z-score transformed). Global networks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency), and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networks was undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measures were integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the network density range of K = 0.10–0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach. Compared with healthy controls, at a global level, the structural covariance networks of OCD showed lower clustering (P 5 0.0001), lower modularity (P 5 0.0001), and lower small-worldness (P = 0.017). Detection of community membership emphasized lower network segregation in OCD compared to healthy controls. At the regional level, there were lower (rank-transformed) centrality values in OCD for volume of caudate nucleus and thalamus, and surface area of paracentral cortex, indicative of altered distribution of brain hubs. Centrality of cingulate and orbito-frontal as well as other brain areas was associated with OCD illness duration, suggesting greater involvement of these brain areas with illness chronicity. In summary, the findings of this study, the largest brain structural covariance study of OCD to date, point to a less segregated organization of structural covariance networks in OCD, and reorganization of brain hubs. The segregation findings suggest a possible signature of altered brain morphometry in OCD, while the hub findings point to OCD-related alterations in trajectories of brain development and maturation, particularly in cingulate and orbitofrontal regions.

DOI： 10.1093/brain/awaa001

Language：English   Publishing type：Research paper (scientific journal)  

Hoarding disorder (HD) is a newly listed disease in the new category of Obsessive–Compulsive and Related Disorders in the DSM-5. Patients with HD find it difficult to discard possessions regardless of their actual value and to organize those things. As a result, the possessions overflow the living space and hinder living functions. Though the hoarding symptom had been regarded as a subtype of obsessive–compulsive disorder (OCD) to date, recent studies have revealed many differences in clinical characteristics, including onset, course, degree of insight, and treatment responses, between hoarding and other subtypes. Moreover, several neuroimaging studies have found specific changes of brain structure and function in OCD patients with hoarding symptoms compared to patients with non-hoarding OCD. Meanwhile, strategies for treatment of HD have not been standardized. At present, psychological treatment using cognitive behavioral therapy techniques has a certain effect. In this review, we outline the pathophysiology and treatment of HD.

DOI： 10.1111/pcn.12853

Language：English   Publishing type：Research paper (scientific journal)  

Background: Previous studies have shown that hoarding behavior usually starts at a subclinical level in early adolescence and gradually worsens; however, a limited number of studies have examined the prevalence of hoarding behavior and its association with developmental disorders in young adults. The aims of this study were to estimate the prevalence of hoarding behavior and to identify correlations between hoarding behavior and developmental disorder traits in university students. Methods: The study participants included 801 university students (616 men, 185 women) who completed questionnaires (ASRS: Adult ADHD Self-Report Scale version 1.1, AQ16: Autism-Spectrum Quotient with 16 items, and CIR: Clutter Image Rating). Results: Among 801 participants, 27 (3.4%) exceeded the CIR cut-off score. Moreover, the participants with hoarding behavior had a significantly higher percentage of ADHD traits compared to participants without hoarding behavior (HB(+) vs HB(-), 40.7% vs 21.7%). In addition, 7.4% of HB(+) participants had autism spectrum disorder (ASD) traits, compared to 4.1% of HB(-) participants. A correlation analysis revealed that the CIR composite score had a stronger correlation with the ASRS inattentive score than with the hyperactivity/impulsivity score (CIR composite vs ASRS IA, r = 0.283; CIR composite vs ASRS H/I, r = 0.147). Conclusions: The results showed a high prevalence of ADHD traits in the university students with hoarding behavior. Moreover, we found that the hoarding behavior was more strongly correlated with inattentive symptoms rather than with hyperactivity/impulsivity symptoms. Our results support the concept of a common pathophysiology behind hoarding behavior and ADHD in young adults.

DOI： 10.1186/s13030-019-0156-1

Language：English   Publishing type：Research paper (scientific journal)  

Background: Lateralized dysfunction has been suggested in obsessive-compulsive disorder (OCD). However, it is currently unclear whether OCD is characterized by abnormal patterns of brain structural asymmetry. Here we carried out what is by far the largest study of brain structural asymmetry in OCD. Methods: We studied a collection of 16 pediatric datasets (501 patients with OCD and 439 healthy control subjects), as well as 30 adult datasets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium. Asymmetries of the volumes of subcortical structures, and of measures of regional cortical thickness and surface areas, were assessed based on T1-weighted magnetic resonance imaging scans, using harmonized image analysis and quality control protocols. We investigated possible alterations of brain asymmetry in patients with OCD. We also explored potential associations of asymmetry with specific aspects of the disorder and medication status. Results: In the pediatric datasets, the largest case-control differences were observed for volume asymmetry of the thalamus (more leftward; Cohen's d = 0.19) and the pallidum (less leftward; d = −0.21). Additional analyses suggested putative links between these asymmetry patterns and medication status, OCD severity, or anxiety and depression comorbidities. No significant case-control differences were found in the adult datasets. Conclusions: The results suggest subtle changes of the average asymmetry of subcortical structures in pediatric OCD, which are not detectable in adults with the disorder. These findings may reflect altered neurodevelopmental processes in OCD.

DOI： 10.1016/j.biopsych.2019.04.022

Language：English   Publishing type：Research paper (scientific journal)  

Background: Impaired cognitive flexibility has been implicated in the genetic basis of obsessive-compulsive disorder (OCD). Recent endophenotype studies of OCD showed neural inefficiency in the cognitive control network and interference by the limbic network of the cognitive control network. Exploring the relationship between the functional brain network and impaired cognitive flexibility may provide novel information about the neurobiological basis of OCD. Methods: We obtained resting-state functional magnetic resonance imaging (rsfMRI) scans and measured the cognitive flexibility of 37 medication-free OCD patients and 40 healthy control (HC) participants using the Wisconsin Card Sorting Test (WCST). We explored the difference between OCD and HC groups in the functional brain network related to impaired cognitive flexibility from the amygdala and dorsal striatal regions of interest (ROIs) by using a seed-based approach. Results: Significant differences between the OCD and HC groups were identified in the resting state functional network from the dorsal caudate. Increased functional connectivity from the dorsal caudate to the dorsal anterior cingulate cortex (dACC) and anterior insula (AI) was associated with poorer cognitive flexibility in the OCD group, but better cognitive flexibility in the HC group. Conclusions: These results provide evidence that the impaired cognitive flexibility of OCD may be associated with dysfunctions of the brain network from the dorsal caudate (DC) to important nodes of the salience network. Our results extend the neuropsychological model of OCD by showing intrinsically different associations between OCD and HC in functional network and cognitive flexibility.

DOI： 10.1016/j.nicl.2019.102004

Language：English   Publishing type：Research paper (scientific journal)  

Background Hoarding disorder (HD) is a disease concept newly presented in DSM-5. As far as we know, no studies have examined the structural changes relevant to hoarding by applying the diagnostic criteria of HD in DSM-5. In the present study, we aimed to find abnormalities in gray matter (GM) structures of patients with HD. Methods Seventeen patients who met the DSM-5 criteria for HD, 17 obsessive-compulsive disorder (OCD) patients, and 17 healthy controls (HCs) participated in this study. All participants underwent MRI scanning of the brain by a 3.0-Tesla MRI scanner. In a voxel-based morphometric procedure, preprocessed GM structural images were used to compare the three groups. Thereafter we investigated the correlation between the clinical data (age of onset, symptomatic severity) and GM volume. Results The HD group showed a significantly increased GM volume compared to the OCD and healthy control groups (p<0.05) in both Brodmann area (BA)10 and BA11. There was no significant difference between OCD and healthy control groups. No significant correlation between the clinical data including age of onset, symptom severity score, and GM volume was observed in HD and OCD groups. Conclusions The results might help to explain the inconsistency of previous studies. As with OCD, HD is considered to have cognitive dysfunction as its basis. This result is convincing after considering the clinical features of HD and suggested that structural abnormalities in the prefrontal regions might relate to the pathophysiology of HD.

DOI： 10.1371/journal.pone.0200814

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Objective: Brain imaging studies of structural abnormalities in OCD have yielded inconsistent results, partly because of limited statistical power, clinical heterogeneity, and methodological differences. The authors conducted meta- and mega-analyses comprising the largest study of cortical morphometry in OCD ever undertaken. Method: T1-weighted MRI scans of 1,905 OCD patients and 1,760 healthy controls from 27 sites worldwide were processed locally using FreeSurfer to assess cortical thickness and surface area. Effect sizes for differences between patients and controls, and associations with clinical characteristics, were calculated using linear regression models controlling for age, sex, site, and intracranial volume. Results: In adult OCD patients versus controls, we found a significantly lower surface area for the transverse temporal cortexand a thinner inferiorparietalcortex.Medicated adult OCD patients also showed thinner cortices throughout the brain. In pediatric OCD patients compared with controls, we found significantly thinner inferior and superior parietal cortices, but none of the regions analyzed showedsignificant differences in surface area. However, medicated pediatric OCD patients had lower surface area in frontal regions. Cohen's d effect sizes varied from 20.10 to 20.33. Conclusions: The parietal cortex was consistently implicated in both adults and children with OCD. More widespread cortical thickness abnormalities were found in medicated adult OCD patients, and more pronounced surface area deficits (mainly in frontal regions) were found in medicated pediatric OCD patients. These cortical measures represent distinct morphological features and may be differentially affected during different stages of development and illness, and possibly moderated by disease profile and medication.

DOI： 10.1176/appi.ajp.2017.17050485

Language：English   Publishing type：Research paper (scientific journal)  

Though problematic hoarding is believed to be a universal human behavior, investigations of clinically-defined hoarding disorder (HD) have been confined almost exclusively to Western countries. The current investigation sought to describe and directly compare the features of individuals meeting diagnostic criteria for HD across four distinct cultural settings. Participants were 82 individuals meeting DSM-5 diagnostic criteria for HD, recruited and assessed by trained clinicians at one of four project sites: London, Barcelona, Fukuoka, and Rio de Janeiro. A series of semi-structured interviews and self-report scales were administered, including assessments of socio-demographic characteristics, psychiatric comorbidity, and severity of hoarding and related features. Results indicate that the severity and core features of HD, as well as the cognitions and behaviors commonly associated with this condition, are largely stable across cultures. However, some differences in patient demographics—in particular age, marital status, and clinical expression—as well as comorbid psychiatric features also emerged. These findings confirm that HD, as defined in DSM-5, exists and presents with similar phenomenology across the studied cultures. Future, more fine-grained, research will be needed to study the features of the disorder in additional cultures (e.g., non-industrialized nations) and to evaluate the impact of these cultural aspects on the design of interventions for the disorder.

DOI： 10.1177/1363461518759203

Language：English   Publishing type：Research paper (scientific journal)  

We regret that Table 1 and Fig. 2 need correction. As for Table 1, we found a few critical errors. The patients' age is not 18–64 years old, correctly 17–64 years old. The patients' age of onset is not 4–38 years old, correctly 6–54 years old. The patients' duration of illness is not 0.6–42 years, correctly 0.6–51 years. As for Fig.2, several readers pointed us that it was difficult to see. So we would like to make corrections. We coloured the lines to make it distinguishable, and enlarged letters to make it more visible. We explained in footnote which line colour corresponds to which group. We attached the modified files. We are sorry to trouble you, but we hope that you will correct and replace them by the following files. We would like to apologise for any inconvenience caused.

DOI： 10.1016/j.jocrd.2017.11.005

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Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Aim Although many neuroimaging studies of obsessive-compulsive disorder (OCD) have reported broad abnormalities in gray matter (GM), their results remain inconsistent. One reason for this inconsistency could be the heterogeneity of OCD. In the present study, we aimed to classify alterations in brain anatomy by OCD subtype. Methods Magnetic resonance imaging examinations of 37 OCD patients and 37 matched healthy controls were conducted using a 3.0-Tesla scanner. In the voxel-based morphometric procedure, preprocessed GM structural images were used to compare the two groups, and multiple regression analysis was used to investigate the correlation between regional GM volume in OCD patients and the OCD symptom dimension type assessed by using the Dimensional Yale-Brown Obsessive-Compulsive Scale. Results We found significant reductions in GM volume in broad areas of the left prefrontal, right orbitofrontal, right parietal, right temporal, and right posterior cingulate cortex in the OCD patients compared to healthy controls. In addition, we found specific negative correlations between symptomatic dimension scores and regional GM volumes, mainly as decreased right cerebellum in 'aggression/checking' and decreased right insula in 'contamination/washing'. Conclusion The pathophysiology of OCD may involve widely distributed neural systems. Moreover, there are distinct correlations among symptomatic dimensions and structural abnormalities.

DOI： 10.1111/pcn.12269

Language：English   Publishing type：Research paper (scientific journal)  

Behavioral activation (BA) has recently attracted marked attention. While cognitive therapy focuses on the cognitive distortion of patients with depression and asks them to change their behaviors as the process of altering the cognitive distortion, BA pays attention to behavior to avoid an unpleasant situation or social situation as a key symptom that leads to persistence of the depression. Avoidance behaviors are often seen during every process of depression, from onset to recurrence. Avoidance behaviors, a decrease in pleasant phenomena, or increase in unpleasant phenomena, result in reinforcing a depressive mood. If patients can set appropriate behavioral targets and achieve them, the beneficial behaviors will be further promoted with positive feed-back. The behavioral change, as-a consequence, will result in improvement of the mood, cognition, and depression itself. In this manuscript, the author presents two clinical cases, in which BA assisted the patients in recovering from their depression. The first case was a male in his thirties who repeatedly took sick leave from his work because of maladjustment, which resulted in persistent depression. The second case was a female in her thirties who suffered from OCD and then became maladjusted to her place of work, depressive, and emotionally unstable. In both cases, avoidant behaviors caused their conditions to persist. Appropriate activities formed by BA improved their moods, and their self-efficacies were gradually regained. It was suggested that BA is markedly effective, especially in patients whose avoidant behaviors mainly cause the persistence of their depressive symptoms.

Language：English   Publishing type：Research paper (scientific journal)  

Individuals with antisocial behavior place a great physical and economic burden on society. Deficits in emotional processing have been recognized as a fundamental cause of antisocial behavior. Emerging evidence also highlights a significant contribution of attention allocation deficits to such behavior. A comprehensive literature search identified 12 studies that were eligible for inclusion in the meta-analysis, which compared 291 individuals with antisocial problems and 247 controls. Signed Differential Mapping revealed that compared with controls, gray matter volume (GMV) in subjects with antisocial behavior was reduced in the right lentiform nucleus (P < 0.0001), left insula (P=0.0002) and left frontopolar cortex (FPC) (P=0.0006), and was increased in the right fusiform gyrus (P < 0.0001), right inferior parietal lobule (P=0.0003), right superior parietal lobule (P=0.0004), right cingulate gyrus (P=0.0004) and the right postcentral gyrus (P=0.0004). Given the well-known contributions of limbic and paralimbic areas to emotional processing, the observed reductions in GMV in these regions might represent neural correlates of disturbance in emotional processing underlying antisocial behavior. Previous studies have suggested an FPC role in attention allocation during emotional processing. Therefore, GMV deviations in this area may constitute a neural basis of deficits in attention allocation linked with antisocial behavior.

DOI： 10.1093/scan/nst104

Language：English   Publishing type：Research paper (scientific journal)  

Individuals with antisocial behavior place a great physical and economic burden on society. Deficits in emotional processing have been recognized as a fundamental cause of antisocial behavior. Emerging evidence also highlights a significant contribution of attention allocation deficits to such behavior. A comprehensive literature search identified 12 studies that were eligible for inclusion in the meta-analysis, which compared 291 individuals with antisocial problems and 247 controls. Signed Differential Mapping revealed that compared with controls, gray matter volume (GMV) in subjects with antisocial behavior was reduced in the right lentiform nucleus (P < 0.0001), left insula (P = 0.0002) and left frontopolar cortex (FPC) (P = 0.0006), and was increased in the right fusiform gyrus (P < 0.0001), right inferior parietal lobule (P = 0.0003), right superior parietal lobule (P = 0.0004), right cingulate gyrus (P = 0.0004) and the right postcentral gyrus (P = 0.0004). Given the well-known contributions of limbic and paralimbic areas to emotional processing, the observed reductions in GMV in these regions might represent neural correlates of disturbance in emotional processing underlying antisocial behavior. Previous studies have suggested an FPC role in attention allocation during emotional processing. Therefore, GMV deviations in this area may constitute a neural basis of deficits in attention allocation linked with antisocial behavior.

DOI： 10.1093/scan/nst104

Language：English   Publishing type：Research paper (scientific journal)  

Obsessive-compulsive disorder (OCD) was previously considered refractory to most types of therapeutic intervention. There is now, however, ample evidence that selective serotonin reuptake inhibitors and behavior therapy are highly effective methods for treatment of OCD. Furthermore, recent neurobiological studies of OCD have found a close correlation between clinical symptoms, cognitive function, and brain function. A large number of previous neuroimaging studies using positron emission tomography, single-photon emission computed tomography or functional magnetic resonance imaging (fMRI) have identified abnormally high activities throughout the frontal cortex and subcortical structures in patients with OCD. Most studies reported excessive activation of these areas during symptom provocation. Furthermore, these hyperactivities were decreased after successful treatment using either selective serotonin reuptake inhibitors or behavioral therapy. Based on these findings, an orbitofronto-striatal model has been postulated as an abnormal neural circuit that mediates symptomatic expression of OCD. On the other hand, previous neuropsychological studies of OCD have reported cognitive dysfunction in executive function, attention, nonverbal memory, and visuospatial skills. Moreover, recent fMRI studies have revealed a correlation between neuropsychological dysfunction and clinical symptoms in OCD by using neuropsychological tasks during fMRI. The evidence from fMRI studies suggests that broader regions, including dorsolateral prefrontal and posterior regions, might be involved in the pathophysiology of OCD. Further, we should consider that OCD is heterogeneous and might have several different neural systems related to clinical factors, such as symptom dimensions. This review outlines recent neuropsychological and neuroimaging studies of OCD. We will also describe several neurobiological models that have been developed recently. Advanced findings in these fields will update the conventional biological model of OCD.

DOI： 10.1111/pcn.12195

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.neures.2010.12.008

Language：English   Publishing type：Research paper (scientific journal)  

Recently, ample evidence has suggested that selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy are highly effective treatments for OCD. There are, however, certain patients who are refractory to almost all types of therapeutic intervention. In recent studies, atypical antipsychotic augmentation of SSRIs and deep brain stimulation have been suggested to be effective for these refractory-type patients. Dysfunction of neuro-circuits throughout the frontal cortex and associated subcortical structures is considered to be due to both serotonergic and dopaminergic nerve system impairment. A large number of previous neuroimaging studies identified abnormally high metabolic activities throughout the frontal cortex as well as subcortical and limbic structures. These over-activities are suggested to be biological markers of the treatment response. In addition, structural and nerve connective dysfunction of these regions may be associated with a severe, treatment-resistant, and treatment-refractory status. A treatment-refractory state may be attributable to the clinical subtypes of OCD. Associations between the symptom subtype and brain activity reveal the heterogeneity of OCD. Several correlative analyses have shown distinct neural correlations associated with specific OCD symptom dimensions such as aggression/checking, contamination/cleaning, and hoarding. Overlapping of these neural disturbances will cause treatment-refractory OCD. Another reason for a treatment-refractory state may be comorbid disorders such as major depression and tic disorders. Comorbid depression will aggravate metabolic impairments in the hippocampus and thalamus and cause more severe disturbance of neuro-circuits in OCD. Obsessive-compulsive symptom with Tourette syndrome or pervasive developmental disorders will become refractory because of fixation caused by developmental factors and a perceptual element called "just right feeling". There should be a close relationship between neuro-circuit disturbance and a treatment-refractory state. The pathophysiology becomes more complicated due to the symptom subtype and comorbidity. Further investigations are needed to develop effective treatment strategies based on biological evidence.

Language：English   Publishing type：Research paper (scientific journal)  

Obsessive-compulsive disorder (OCD) is clinically heterogeneous. The aim of this study was to investigate differential neural responses to a symptom provocation task in drug-free patients who have predominantly aggression/checking symptoms (Checkers) and patients with contamination/washing symptoms (Washers). We compared the Checkers (n = 10) and the Washers (n = 12) separately to normal controls during the symptom provocation tasks using fMRI (functional magnetic resonance imaging). Moreover, we performed correlative analysis in each OCD group between brain activation and symptom severity. The Checkers showed hypoactivation in the left caudate and left anterior cingulate cortex (ACC) compared to the normal controls and a positive correlation between activated brain areas and symptom severity in the left ACC. The Washers showed hyperactivation in several bilateral cortico-cerebellar regions and a positive correlation between symptom severity and the bilateral fronto-temporal gyrus. We suggest that the caudate and ACC are associated with checking rituals and that large cortical brain regions are related to washing rituals.

DOI： 10.1016/j.pnpbp.2012.09.002

Language：English   Publishing type：Research paper (scientific journal)  

Context: Functional magnetic resonance imaging studies in attention-deficit/hyperactivity disorder (ADHD) revealed fronto-striato-parietal dysfunctions during tasks of inhibition and attention. However, it is unclear whether task-dissociated dysfunctions exist and to what extent they may be influenced by age and by long-term stimulant medication use. Objective: To conduct a meta-analysis of functional magnetic resonance imaging studies in ADHD during inhibition and attention tasks, exploring age and long-term stimulant medication use effects. Data Sources: Pub-Med, Science-Direct, Web of Knowledge, Google Scholar, and Scopus databases were searched up to May 2012 for meta-analyses. Meta-regression methods explored age and long-term stimulant medication use effects. Study Selection: Twenty-one data sets were included for inhibition (287 patients with ADHD and 320 control subjects), and 13 data sets were included for attention (171 patients with ADHD and 178 control subjects). Data Extraction: Peak coordinates of clusters of significant group differences, as well as demographic, clinical, and methodological variables, were extracted for each study or were obtained from the authors. Data Synthesis: Patients with ADHD relative to controls showed reduced activation for inhibition in the right inferior frontal cortex, supplementary motor area, and anterior cingulate cortex, as well as striato-thalamic areas, and showed reduced activation for attention in the right dorsolateral prefrontal cortex, posterior basal ganglia, and thalamic and parietal regions. Furthermore, the meta-regression analysis for the attention domain showed that long-term stimulant medication use was associated with more similar right caudate activation relative to controls. Age effects could be analyzed only for the inhibition meta-analysis, showing that the supplementary motor area and basal ganglia were underactivated solely in children with ADHD relative to controls, while the inferior frontal cortex and thalamus were underactivated solely in adults with ADHD relative to controls. Conclusions: Patients with ADHD have consistent functional abnormalities in 2 distinct domain-dissociated right hemispheric fronto-basal ganglia networks, including the inferior frontal cortex, supplementary motor area, and anterior cingulate cortex for inhibition and dorsolateral prefrontal cortex, parietal, and cerebellar areas for attention. Furthermore, preliminary evidence suggests that long-term stimulant medication use may be associated with more normal activation in right caudate during the attention domain.

DOI： 10.1001/jamapsychiatry.2013.277

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Responsible for pages：強迫性障害の薬物療法（p204-227）   Language：Japanese   Book type：Scholarly book

Responsible for pages：OCDに対する行動療法の神経科学的基盤（p103-117）   Language：Japanese   Book type：Scholarly book

Responsible for pages：強迫性障害の外来治療．外来治療の進め方の基本（p85-113）   Language：Japanese   Book type：Scholarly book

Language：Japanese  

Language：Japanese   Book type：Scholarly book

Language：Japanese   Book type：Scholarly book

Responsible for pages：p567   Language：Japanese   Book type：General book, introductory book for general audience

Responsible for pages：pp161-170   Language：Japanese   Book type：Scholarly book

Responsible for pages：pp257-264   Language：Japanese   Book type：Scholarly book

Responsible for pages：pp103-117   Book type：General book, introductory book for general audience

Responsible for pages：pp204-227   Book type：General book, introductory book for general audience

Presentation type：Symposium, workshop panel (public)  

Venue：福岡   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：名古屋   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：神戸   Country：Japan  

Brain changes in patients with OCD brought by BT and SSRI: a cognitive and symptom provocation fMRI study

Presentation type：Symposium, workshop panel (public)  

Country：Thailand  

Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Country：Japan  

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：広島   Country：Japan  

Event date： 2024.6

Venue：イスタンブール   Country：Turkey  

Event date： 2021.5

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Country：Japan  

Event date： 2019.10 - 2020.6

Language：English   Presentation type：Symposium, workshop panel (public)  

Country：Japan  

Event date： 2019.9 - 2019.6

Language：English   Presentation type：Symposium, workshop panel (public)  

Country：Japan  

Event date： 2019.6

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Country：Japan  

Event date： 2018.6

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Country：Japan  

Event date： 2018.6

Language：English  

Country：Japan  

Event date： 2017.6

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：大分   Country：Japan  

Event date： 2017.6

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡   Country：Japan  

Event date： 2008.9

Country：Japan  

Presentation type：Oral presentation (invited, special)  

Venue：岡山   Country：Japan  

Language：Japanese   Presentation type：Oral presentation (invited, special)  

Venue：飯塚   Country：Japan  

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Repository Public URL： http://hdl.handle.net/2324/4479044

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Number of participants：5,000

女性の医学最前線「強迫性障害」

医療と健康面「パニック障害」