Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

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

DOI： 10.1038/s41380-024-02785-1

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Other Link： https://www.nature.com/articles/s41380-024-02785-1

Language：Japanese   Publisher：(一社)日本認知症学会  

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In panic disorder (PD), functional disturbance of the hypothalamus-pituitary-adrenal (HPA) axis has been considered. However, in neuroimaging studies of PD, the hypothalamus and pituitary gland are poorly studied.We investigated the volume of PD patients' hypothalamus and pituitary gland, enrolling 38 PD patients and 38 healthy controls. Severity of PD was mild to moderate according to the Panic Disorder Severity Scale, and the illness duration was relatively short (median = 2.8 years). The hypothalamus' gray matter was automatically extracted and segmented, whereas the pituitary gland was manually traced. Regarding the hypothalamus, the paraventricular nucleus (PVH), which produces the corticotropin-releasing hormone, was of interest.The volumes of the pituitary and the bilateral anterior-superior hypothalamic subunits, where the PVH would be located, were compared by the multiple regression analyses controlling for age and intracranial content volume. To compensate for limitation in the abovementioned segmentation and analyses, the voxel-based morphometry with small volume correction (VBM-SVC) targeting the whole hypothalamus was also performed.The multiple regression analyses did not find significant effect of PD diagnosis on the volumes. However, in the VBM-SVC analysis, volume reduction of the PVH was suggested in PD even when patients who experienced PD for ≥ 3 years were excluded [peak coordinate (x, y, z = -2, 3, -8), FWE-corrected P = .022 (cluster-level) and 0.003 (peak-level), voxel size = 63]. Our results suggested structural alteration of the PVH in PD patients for the first time, indicating importance of the HPA-axis in PD pathology.

DOI： 10.1007/s11682-023-00834-x

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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

AIM: Live two-way video, easily accessible from home via smartphones and other devices, is becoming a new way of providing psychiatric treatment. However, lack of evidence for real-world clinical setting effectiveness hampers its approval by medical insurance in some countries. Here, we conducted the first large-scale pragmatic, randomized controlled trial to determine the effectiveness of long-term treatment for multiple psychiatric disorders via two-way video using smartphones and other devices, which are currently the primary means of telecommunication. METHODS: This randomized controlled trial compared two-way video versus face-to-face treatment for depressive disorder, anxiety disorder, and obsessive-compulsive disorder in the subacute/maintenance phase during a 24-week period. Adult patients with the above-mentioned disorders were allocated to either a two-way video group (≥50% video sessions) or a face-to-face group (100% in-person sessions) and received standard treatment covered by public medical insurance. The primary outcome was the 36-Item Short-Form Health Survey Mental Component Summary (SF-36 MCS) score. Secondary outcomes included all-cause discontinuation, working alliance, adverse events, and the severity rating scales for each disorder. RESULTS: A total of 199 patients participated in this study. After 24 weeks of treatment, two-way video treatment was found to be noninferior to face-to-face treatment regarding SF-36 MCS score (48.50 vs 46.68, respectively; p < 0.001). There were no significant differences between the groups regarding most secondary end points, including all-cause discontinuation, treatment efficacy, and satisfaction. CONCLUSION: Two-way video treatment using smartphones and other devices, was noninferior to face-to-face treatment in real-world clinical settings. Modern telemedicine, easily accessible from home, can be used as a form of health care.

DOI： 10.1111/pcn.13618

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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

BACKGROUND: Distinct oral atypical antipsychotics have different effects on autonomic nervous system (ANS) activity. Among them, oral aripiprazole has been linked to dysfunction of the ANS in schizophrenia. Long-acting injectable aripiprazole is a major treatment option for schizophrenia, but the effect of the aripiprazole formulation on ANS activity remains unclear. In this study, we compared ANS activity between oral aripiprazole and aripiprazole once-monthly (AOM) in schizophrenia. METHODS: Of the 122 patients with schizophrenia who participated in this study, 72 received oral aripiprazole and 50 received AOM as monotherapy. We used power spectral analysis of heart rate variability to assess ANS activity. RESULTS: Patients who received oral aripiprazole showed significantly diminished sympathetic nervous activity compared with those who received AOM. Multiple regression analysis revealed that the aripiprazole formulation significantly influenced sympathetic nervous activity. CONCLUSION: Compared with oral aripiprazole, AOM appears to have fewer adverse effects, such as sympathetic nervous dysfunction.

DOI： 10.1186/s12888-023-04617-y

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AIM: Treatment guidelines are designed to assist patients and health care providers and are used as tools for making treatment decisions in clinical situations. The treatment guidelines of the Japanese Society of Mood Disorders establish treatment recommendations for each severity of depression. The individual fitness score (IFS) was developed as a simple and objective indicator to assess whether individual patients are practicing treatment by the recommendations of the depression treatment guidelines of the Japanese Society of Mood Disorders. METHODS: The EGUIDE project members determined the IFS through the modified Delphi method. In this article, the IFS was calculated based on the treatment of depressed patients treated and discharged between 2016 and 2020 at facilities participating in the EGUIDE project. In addition, we compared scores at admission and discharge. RESULTS: The study included 428 depressed patients (mild n = 22, moderate/severe n = 331, psychotic n = 75) at 57 facilities. The mean IFS scores by severity were statistically significantly higher at discharge than at admission with moderate/severe depression (mild 36.1 ± 34.2 vs. 41.6 ± 36.9, p = 0.49; moderate/severe 50.2 ± 33.6 vs. 55.7 ± 32.6, p = 2.1 × 10-3; psychotic 47.4 ± 32.9 versus 52.9 ± 36.0, p = 0.23). CONCLUSION: We developed the IFS based on the depression treatment guideline, which enables us to objectively determine how close the treatment is to the guideline at the time of evaluation in individual cases. Therefore, the IFS may influence guideline-oriented treatment behavior and lead to the equalization of depression treatment in Japan, including pharmacotherapy.

DOI： 10.1002/npr2.12301

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Language：Japanese   Publisher：(有)科学評論社  

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DOI： 10.1111/psyg.12895

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AIM: The aim of this study was to conduct a 5-h training programme on anger-focused emotional management for nurses and verify its effectiveness. DESIGN: The study used a one-group pretest-posttest design. METHODS: Participants (N = 283) attended a programme comprising lectures and exercises. The Japanese version of the Buss-Perry Aggression Questionnaire was administered pre-, post- and 3-month posttraining. Regression analyses were used to assess the effects of the programme by gender. RESULTS: For the total aggression score, the difference between the pre- and posttraining scores was -2.827 points and remained at -1.602 points 3-month posttraining. Physical aggression scores decreased posttraining, but the scores increased after 3 months. There were statistically significant gender differences in hostility scores; pre-training scores were slightly higher for men than for women and lower for men after 3 months. Total and physical aggression scores were higher for men than for women. The training programme decreased aggression, and the effect persisted after 3 months.

DOI： 10.1002/nop2.1367

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Language：Japanese   Publisher：(株)アークメディア  

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

PURPOSE: In the treatment guidelines for major depressive disorder (MDD), the recommended treatment differs based on the severity. However, the type of treatment provided based on the severity of MDD in real-world clinical practice has not been investigated. In this study, we clarified the actual situation of MDD treatment in clinical practice and compared the treatment based on the severity of MDD. METHODS: We used data from 1484 patients with MDD at discharge from October 2016 to March 2020. RESULTS: The number of psychotropic prescriptions tended to be lower in those diagnosed with MDD in the severe group compared to in the non-severe group. There were significant differences among the three groups (mild, moderate/severe, and psychotic) in the percentage of patients who were not prescribed antipsychotics (p = 1.9 ×10-6), a combination of antipsychotics and antidepressants (p = 5.0 ×10-4), and the implementation rate of modified electroconvulsive therapy (m-ECT) (p = 3.4 ×10-9). The percentage of patients with a severe diagnosis who underwent m-ECT was higher, which corresponded to the severity. CONCLUSION: Our findings showed that the use of psychotropics decreased when the severity of MDD was diagnosed, and the rate of a combination of antipsychotics and antidepressants and the implementation rate of m-ECT increased with the severity. However, this study suggests that there is still an evidence-practice gap in the treatment of MDD in Japan, and guidelines are only partially adhered to in the treatment of depression.

DOI： 10.1016/j.ajp.2022.103174

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Previous cross-sectional studies have reported that adolescent patients with anorexia nervosa (AN) showed global gray matter volume (GMV) reductions at the acute phase which were restored at the weight-recovered phase, compared with healthy controls (HC). However, few studies have investigated white matter volume (WMV) or cortical thickness in the context of AN, and results have been inconsistent. Voxel-based morphometry analyses for GM and WM, and cortical thickness analyses for GM were conducted in 31 adolescent patients with AN (vs. 18 HC) in the acute phase, and 16 patients with AN (vs. 13 HC) in the follow-up weight-recovered phase, over an approximately 1-year follow-up interval. At the acute phase, the AN patients showed significant reductions of GMVs and cortical thickness in widespread brain regions, compared with HC. Significant WMV reductions were identified in the bilateral superior longitudinal fascicle, superior thalamic radiation, corona radiata, and fornix, pons, and medulla in the patients. At the weight-recovered phase, the AN patients showed a significant GMV reduction in the left hippocampus, and a WMV reduction in the pons, compared with the HC. There was no difference in cortical thickness between two groups at the weight-recovered phase. In conclusion, the widespread volumetric reductions in GM and WM, and reduced cortical thickness observed in AN patients in the acute phase were not evident in the follow-up weight-recovered phase. The volume reductions observed in the hippocampus and pons in the weight-recovered phase could potentially reflect delayed neurogenesis or recovery from starvation in the AN patients.

DOI： 10.1007/s11682-021-00622-5

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STUDY OBJECTIVES: To investigate the proportion of inpatients with schizophrenia and major depressive disorder prescribed hypnotic medication, and the association between such medication and the use of other antipsychotic agents. METHODS: This was a nationwide cross-sectional study performed as part of the 'Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment' (EGUIDE) project. Data from 2146 inpatients with schizophrenia and 1031 inpatients with major depressive disorder were analyzed. All types and dosages of psychotropic drugs were recorded and the data at the time of discharge were analyzed. Associations between the use of hypnotic medication and other antipsychotic agents were evaluated using multivariate logistic regression analyses. RESULTS: The proportions of schizophrenia patients who were prescribed any and two or more hypnotic agents were 55.7% and 17.6%, respectively, and the corresponding proportions for patients with major depressive disorder were 63.6% and 22.6%, respectively. In schizophrenia patients, multivariate logistic regression analyses showed that two or more antipsychotics, anticholinergic drugs, anxiolytics, and mood stabilizers/antiepileptic drugs were positively associated with the use of any hypnotic agent. In patients with major depressive disorder, multivariate logistic regression analyses revealed that two or more antidepressants, two or more antipsychotics, anxiolytics, and mood stabilizers/antiepileptic drugs were positively associated with the use of any hypnotic agent. CONCLUSIONS: Prescription of hypnotic agents was found to be highly frequent among inpatients with psychiatric disorders. Prescription of two or more main antipsychotic agents was commonly associated with the use of hypnotic medication for both schizophrenia and major depressive disorder.

DOI： 10.1016/j.sleep.2021.11.005

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BACKGROUND: Matrix metalloproteinase 9 (MMP-9) has been reported to be correlated with declines in hippocampal volume and cognitive function in ApoE4-positive MCI patients. OBJECTIVES: The present study was aimed to investigate the effects of plasma matrix MMP-9 on the conversion risk between mild cognitive impairment (MCI) patients with and without ApoE4. DESIGN AND SETTING: Retrospective observational study using the data extracted from the Alzheimer's Disease Neuroimaging Initiative database. PARTICIPANTS: We included 211 ApoE4-positive MCI subjects (ApoE4+ MCI) and 184 ApoE4-negative MCI subjects (ApoE4- MCI). MEASUREMENTS: We obtained demographic and data including plasma MMP-9 levels at baseline and longitudinal changes in Clinical Dementia Rating (CDR) up to 15 years. We compared conversion rates between ApoE4+ MCI and ApoE4- MCI by the Log-rank test and calculated the hazard ratio (HR) for covariates including age, sex, educational attainment, drinking and smoking histories, medications, and plasma MMP-9 levels using a multiple Cox regression analysis of ApoE4+ MCI and ApoE4- MCI. RESULTS: No significant differences were observed in baseline plasma MMP-9 levels between ApoE4+ MCI and ApoE4- MCI. High plasma MMP-9 levels increased the conversion risk significantly more than low plasma MMP-9 levels (HR, 2.46 [95% CI, 1.31-4.48]) and middle plasma MMP-9 levels (HR, 1.67 [95% CI, 1.04-2.65]) in ApoE4+ MCI, but not in ApoE4- MCI. CONCLUSION: Plasma MMP-9 would be the risk of the future conversion to dementia in ApoE4+ MCI.

DOI： 10.14283/jpad.2022.19

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The COVID-19 pandemic has been affecting the mental health of hospital workers. During the prolonged pandemic, hospital workers may experience much more severe psychological distress, leading to an increased risk of suicide. This study aimed to investigate changes in psychological effects on hospital workers over 12 months from the beginning of the pandemic and clarify factors associated with psychological distress and suicide-related ideation 1-year after the pandemic's beginning. These repeated, cross-sectional surveys collected demographic, mental health, and stress-related data from workers in 2 hospitals in Yokohama, Japan. The first survey, conducted in March-April 2020, contained the 12-item General Health Questionnaire (GHQ-12) assessing general distress and the Impact of Event Scale-Revised (IES-R) assessing event-related distress. In the second survey in March 2021, hospital workers at the same two hospitals were reassessed using the same questionnaire, and Item 9 of the Patient Health Questionnaire (PHQ-9) was added to assess their suicide-related ideation. The findings of the first and second surveys revealed that the average score of GHQ-12 (3.08 and 3.73, respectively), the IES-R total score (6.8 and 12.12, respectively), and the prevalence rates of severe general distress (35.0% and 44.0%, respectively) and severe event-related distress (7.0% and 17.1%, respectively) deteriorated. The second survey showed that 8.6% of the hospital workers were experiencing suicide-related ideation. Both the general and event-related distress were associated with suicide-related ideation. In these surveys, mental health outcomes among the hospital workers deteriorated over one year from the pandemic's beginning, and their severe psychological distress was the risk factor for the suicide-related ideation. Further studies are needed to compare the psychological effects on hospital workers during and after the prolonged pandemic and to explore appropriate measures to support hospital workers' mental health.

DOI： 10.1371/journal.pone.0277174

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INTRODUCTION: The COVID-19 pandemic has had a profound impact on the mental health of people around the world. Anxiety related to infection, stress and stigma caused by the forced changes in daily life have reportedly increased the incidence and symptoms of depression, anxiety disorder and obsessive-compulsive disorder. Under such circumstances, telepsychiatry is gaining importance and attracting a great deal of attention. However, few large pragmatic clinical trials on the use of telepsychiatry targeting multiple psychiatric disorders have been conducted to date. METHODS: The targeted study cohort will consist of adults (>18 years) who meet the DSM-5 diagnostic criteria for either (1) depressive disorders, (2) anxiety disorders, or (3) obsessive-compulsive and related disorders. Patients will be assigned in a 1:1 ratio to either a "telepsychiatry group" (at least 50% of treatments to be conducted using telemedicine, with at least one face-to-face treatment [FTF] within six months) or an "FTF group" (all treatments to be conducted FTF, with no telemedicine). Both groups will receive the usual treatment covered by public medical insurance. The study will utilize a master protocol design in that there will be primary and secondary outcomes for the entire group regardless of diagnosis, as well as the outcomes for each individual disorder group. DISCUSSION: This study will be a non-inferiority trial to test that the treatment effect of telepsychiatry is not inferior to that of FTF alone. This study will provide useful insights into the effect of the COVID-19 pandemic on the practice of psychiatry. TRIAL REGISTRATION: jRCT1030210037, Japan Registry of Clinical Trials (jRCT).

DOI： 10.1016/j.cct.2021.106596

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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DOI： 10.1016/j.schres.2020.08.028

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.neulet.2020.135588

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Language：Japanese   Publisher：神奈川県医師会  

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Language：Japanese   Publisher：神奈川県医師会  

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The aim of the present study was to investigate the psychological effects of the COVID-19 outbreak and associated factors on hospital workers at the beginning of the outbreak with a large disease cluster on the Diamond Princess cruise ship. This cross-sectional, survey-based study collected demographic data, mental health measurements, and stress-related questionnaires from workers in 2 hospitals in Yokohama, Japan, from March 23, 2020, to April 6, 2020. The prevalence rates of general psychological distress and event-related distress were assessed using the 12-item General Health Questionnaire (GHQ-12) and the 22-item Impact of Event Scale-Revised (IES-R), respectively. Exploratory factor analysis was conducted on the 26-item stress-related questionnaires. Multivariable logistic regression analysis was performed to identify factors associated with mental health outcomes for workers both at high- and low-risk for infection of COVID-19. A questionnaire was distributed to 4133 hospital workers, and 2697 (65.3%) valid questionnaires were used for analyses. Overall, 536 (20.0%) were high-risk workers, 944 (35.0%) of all hospital workers showed general distress, and 189 (7.0%) demonstrated event-related distress. Multivariable logistic regression analyses revealed that 'Feeling of being isolated and discriminated' was associated with both the general and event-related distress for both the high- and low-risk workers. In this survey, not only high-risk workers but also low-risk workers in the hospitals admitting COVID-19 patients reported experiencing psychological distress at the beginning of the outbreak.

DOI： 10.1371/journal.pone.0245294

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Language：English   Publisher：(一社)日本認知症学会  

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Language：English   Publisher：(一社)日本認知症学会  

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

OBJECTIVE: The present study investigated the effects of plasma matrix metalloproteinases (MMPs) on longitudinal changes in Alzheimer's disease (AD)-related biomarkers in cerebrospinal fluid (CSF), brain atrophy, and cognitive function in patients with mild cognitive impairment due to AD (MCI-AD). METHODS: We used data from the Alzheimer's Disease Neuroimaging Initiative database. We included 95 ApoE4-positive patients with MCI-AD who were confirmed to have low Aβ42 and/or high phosphorylated-tau (p-tau) in CSF. We obtained baseline demographic data, plasma MMP levels, including MMP-1, -2, -7, -9, -10, and tissue inhibitor of MMP-1 (TIMP-1), longitudinal annual data on Aβ42, total tau, and p-tau in CSF, MRI-measured hippocampal volumes, and cognitive function evaluated by the Mini-Mental State Examination (MMSE) and AD Assessment Scale-11 (ADAS-11) over 4 years. We examined the effects of baseline MMP levels on longitudinal changes in CSF AD biomarkers, hippocampal volumes, and cognitive function using a linear mixed regression analysis. RESULTS: No significant differences were observed in baseline plasma MMP levels between MCI-AD patients and control subjects, except for MMP-10, which was significantly lower in MCI-AD than in controls. The baseline levels of MMPs did not correlate with longitudinal changes in CSF biomarkers. Declines in hippocampal volumes and cognitive function evaluated by MMSE and ADAS-11 were significantly faster in MCI-AD patients with high-MMP-9 levels at baseline than in those with middle and low MMP-9 levels at baseline. CONCLUSION: High plasma MMP-9 levels in MCI-AD patients might enhance neurodegeneration and cognitive decline.

DOI： 10.1016/j.jns.2020.116989

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BACKGROUND: Although the pathogenesis of panic attacks has been well studied in patients with panic disorder (PD), the neurobiological basis of the long-term fear memories and avoidance behavior that are often observed in PD have not been well investigated. Recent animal studies have suggested that nucleus accumbens (NAcc) plays an important role in neurobiological basis of long-term fear memories and avoidance behavior. METHODS: Thirty-eight patients with PD and 38 matched healthy control subjects (HC) participated in this study. Differences in relative volumes and shape deformations of NAcc were evaluated between groups. Correlation analyses were conducted to quantify the association between structural abnormalities in the NAcc and trait, state anxiety measured by the State-Trait Anxiety Inventory (STAI). RESULTS: Significant volume reductions were observed in the bilateral NAcc in the patients with PD, relative to the HC. In terms of shape differences, the PD patients demonstrated significant inward deformation of the NAcc bilaterally, compared to the HC. Degree of shape deformation in the right NAcc was associated with higher scores of the STAI-Trait, and STAI-State measures in the PD patients. LIMITATIONS: All the patients received medication such as Psychotropic drug. CONCLUSION: Patients with PD showed reduced volumes in the NAcc, especially in lateral regions, compared with HC. Furthermore, shape deformation in the right NAcc was associated with trait anxiety and state anxiety, which has been associated with avoidance behavior.

DOI： 10.1016/j.jad.2020.03.172

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Language：Japanese   Publisher：(有)科学評論社  

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AIMS: In this study, we implemented the Illness Management and Recovery (IMR) program for middle-aged and older patients with schizophrenia hospitalized for long periods and assessed the effect of the IMR program on psychiatric symptoms and psychosocial function. The effects of the IMR program on brain structure were also evaluated. METHODS: The IMR program was implemented for 19 patients with schizophrenia; 17 patients with schizophrenia receiving treatment as usual (TAU) were also recruited as controls. In all patients, mean age was 61.4 years (range, 50-77 years) and mean hospitalization duration was 13.1 years (range, 1-31 years) at enrollment. Structural magnetic resonance images and Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) scores as clinical variables were obtained at the beginning and end of the IMR program. Longitudinal analyses were performed to compare the effects of the IMR program on clinical symptoms and cortical thickness in the superior temporal gyrus (STG) between the IMR and TAU groups. RESULTS: Significant improvements in GAF scores and the total, Insight and Judgment, and Positive components of the PANSS were found in the IMR group compared with the TAU group. Cortical thickness in the left STG was preserved in the IMR group compared with the TAU group. CONCLUSIONS: This is the first report demonstrating the effectiveness of the IMR program for improving psychotic symptoms and psychosocial function and protecting brain structure in middle-aged and older inpatients with schizophrenia hospitalized for long periods.

DOI： 10.1111/pcn.12919

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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BACKGROUND: Panic disorder (PD), an anxiety disorder characterized by the recurrence of panic attacks, has been reported to be associated with volumetric changes in several brain regions. There are, however, very few studies investigating abnormalities in cortical thickness, and little is known about the relationship between cortical thickness and social dysfunction in PD. METHODS: Thirty-eight patients with PD and 38 healthy control participants (HC) were recruited for this study. A whole-brain analysis was performed to evaluate groupwise differences in cortical thickness using the FreeSurfer software. Symptom severity and social functioning were evaluated with the Panic Disorder Severity Scale (PDSS) and the Global Assessment of Functioning (GAF) scale. RESULTS: The patients with PD demonstrated a significant reduction in cortical thickness in the left rostral middle frontal cortex (MFC), compared with the HC. Correlational analyses revealed that cortical thickness in the left rostral MFC showed a significant negative relationship with PDSS score and a significant positive relationship with GAF scores in the PD patients. LIMITATIONS: All the patients received medication. CONCLUSION: PD patients showed reduced cortical thickness in the left rostral MFC compared with HC. Furthermore, cortical thickness in this region was associated with patients' symptom severity and degree of social dysfunction.

DOI： 10.1016/j.jad.2018.07.064

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Verlag  

Although smaller gray matter volumes (GMV) in the prefrontal cortex (PFC) in schizophrenia and bipolar disorder have been reported cross-sectionally, there are, to our knowledge, no reports of longitudinal comparisons using manually drawn, gyrally based ROI, and their associations with symptoms. The object of this study was to determine whether first-episode schizophrenia (FESZ) and first-episode affective psychosis (FEAFF) patients show initial and progressive PFC GMV reduction in bilateral frontal pole, superior frontal gyrus (SFG), middle frontal gyrus (MFG), and inferior frontal gyrus (IFG) and examine their symptom associations. Twenty-one FESZ, 24 FEAFF and 23 healthy control subjects (HC) underwent 1.5T MRI with follow-up imaging on the same scanner ~ 1.5 years later. Groups were strikingly different in progressive GMV loss. FESZ showed significant progressive GMV loss in the left SFG, bilateral MFG, and bilateral IFG. In addition, left MFG and/or IFG GMV loss was associated with worsening of withdrawal–retardation and total BPRS symptoms scores. In contrast, FEAFF showed no significant difference in GMV compared with HC, either cross-sectionally or longitudinally. Of note, FreeSurfer run on the same images showed no significant changes longitudinally.

DOI： 10.1007/s00429-018-1634-0

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer New York LLC  

In schizophrenia, abnormalities in structural connectivity between brain regions known to contain mirror neurons and their relationship to negative symptoms related to a domain of social cognition are not well understood. Diffusion tensor imaging (DTI) scans were acquired in 16 patients with first episode schizophrenia and 16 matched healthy controls. FA and Trace of the tracts interconnecting regions known to be rich in mirror neurons, i.e., anterior cingulate cortex (ACC), inferior parietal lobe (IPL) and premotor cortex (PMC) were evaluated. A significant group effect for Trace was observed in IPL-PMC white matter fiber tract (F (1, 28) = 7.13, p = .012), as well as in the PMC-ACC white matter fiber tract (F (1, 28) = 4.64, p = .040). There were no group differences in FA. In addition, patients with schizophrenia showed a significant positive correlation between the Trace of the left IPL-PMC white matter fiber tract, and the Ability to Feel Intimacy and Closeness score (rho = .57, p = 0.034), and a negative correlation between the Trace of the left PMC-ACC and the Relationships with Friends and Peers score (rho = remove -.54, p = 0.049). We have demonstrated disrupted white mater microstructure within the white matter tracts subserving brain regions containing mirror neurons. We further showed that such structural disruptions might impact negative symptoms and, more specifically, contribute to the inability to feel intimacy (a measure conceptually related to theory of mind) in first episode schizophrenia. Further studies are needed to understand the potential of our results for diagnosis, prognosis and therapeutic interventions.

DOI： 10.1007/s11682-017-9685-z

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The thalamus is believed to play crucial role in processing viscero-sensory information, and regulating the activity of amygdala in patients with panic disorder (PD). Previous functional neuroimaging studies have detected abnormal activation in the thalamus in patients with PD compared with healthy control subjects (HC). Very few studies, however, have investigated for volumetric abnormalities in the thalamus in patients with PD. Furthermore, to the best of our knowledge, no previous study has investigated for shape abnormalities in the thalamus in patients with PD. Twenty-five patients with PD and 25 HC participants (all female) were recruited for the study. A voxel-wise volume comparison analysis and a vertex-wise shape analysis were conducted to evaluate structural abnormalities in the PD patients compared to HC. The patients with PD demonstrated significant gray matter volume reductions in the thalamus bilaterally, relative to the HC. The shape analysis detected significant inward deformation in some thalamic regions in the PD patients, including the anterior nucleus, mediodorsal nucleus, and pulvinar nucleus. PD patients showed shape deformations in key thalamic regions that are believed to play a role in regulating emotional and cognitive functions.

DOI： 10.1371/journal.pone.0208152

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The amygdala plays an important functional role in fear and anxiety. Abnormalities in the amygdala are believed to be involved in the neurobiological basis of panic disorder (PD). Previous structural neuroimaging studies have found global volumetric and morphological abnormalities in the amygdala in patients with PD. Very few studies, however, have explored for structural abnormalities in various amygdala sub-regions, which consist of various sub-nuclei, each with different functions. This study aimed to evaluate for volumetric abnormalities in the amygdala sub-nuclei, in order to provide a better understanding neurobiological basis of PD. Thirty-eight patients with PD and 38 matched healthy control (HC) participants underwent structural MRI scanning. The volume of the whole amygdala, as well as its consistent sub-nuclei, were calculated using FreeSurfer software. Relative volumes of these amygdala sub-regions were compared between the two groups. Results showed significantly smaller volumes in the right lateral and basal nuclei in the patients with PD compared with the HC. Lateral and basal nuclei are thought to play crucial role for processing sensory information related with anxiety and fear. Our results suggest that these particular amygdala sub-regions play a role in the development of PD symptoms.

DOI： 10.1371/journal.pone.0207163

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

AimNumerous reports have described differences in the distribution of orbitofrontal cortex (OFC) sulcogyral patterns between patients with schizophrenia (SZ patients) and healthy controls (HC). Alterations in OFC morphology are also observed in those at high risk for developing SZ and in first-episode SZ, suggesting that genetic associations may be extant in determining OFC sulcogyral patterns. We investigated the association between single nucleotide polymorphisms (SNP) in NRG1 and OFC sulcogyral patterns.
MethodsA total of 59 Japanese patients diagnosed with SZ and 60 HC were scanned on a 1.5-T magnet. Patients were also assessed clinically. OFC sulcogyral patterns were evaluated for each participant, and genotyping was performed for four SNP in NRG1(SNP8NRG243177, SNP8NRG221533, SNP8NRG241930, and rs1081062).
ResultsThere were significant differences in the distribution of OFC sulcogyral patterns between SZ patients and HC ((2) = 6.52, P = 0.038). SZ patients showed an increase in the frequency of Type III expression, which was associated with an earlier age of disease onset ( = -0.302, F = 4.948, P = 0.030). Although no difference was found in genotype frequencies between SZ patients and HC, an NRG1SNP, SNP8NRG243177, was associated with Type II expression in SZ patients ( = 0.237, F = 4.120, P = 0.047).
ConclusionOur results suggest that OFC sulcogyral pattern formation in schizophrenia may be associated with NRG1 allele frequency, which is closely related to neurodevelopment.

DOI： 10.1111/pcn.12384

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Although the insula and temporal pole (TP) of paralimbic regions are important in both affective and cognitive processing, it is not well known whether gray matter volume (GMV) abnormalities in these regions show post-onset progression and differentially affect first-episode schizophrenia (FESZ) and first-episode affective psychosis (FEAFF) patients. To determine whether there are initial and progressive GMV deficits in insula and TP in FESZ and FEAFF (mainly manic) patients, their relative specificity to FESZ or FEAFF, and relationship to symptoms, we conducted a naturalistic study at first hospitalization for psychosis and follow-up similar to 1.5 years later. Initial 1.5T magnetic resonance imaging (MRI) scans and follow-up scans were on the same scanner. Twenty-two FESZ, 23 FEAFF, and 23 healthy control (HC) subjects were group matched for age, gender, parental socioeconomic status, and handedness. At first hospitalization, FESZ showed significantly smaller bilateral insular GMV compared with FEAFF, and smaller left TP GMV compared with FEAFF and HC. Moreover, on 1.5 years follow-up, FESZ showed progressive GMV decreases in bilateral insula compared with FEAFF and HC, and in TP GMV compared with HC. In contrast, FEAFF showed no progression. Progression of FESZ GMV in both insula and TP was inversely associated with changes in the overall Brief Psychiatric Rating Scale symptom score, indicating less improvement or worsening of symptoms.

DOI： 10.1093/schbul/sbv177

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Language：Japanese   Publisher：神奈川県精神医学会  

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Language：Japanese   Publisher：神奈川県精神医学会  

77歳男性。日中の傾眠や無気力で発症し、近医にてアルツハイマー型認知症と診断された。しかし病状は急激に進行し、2ヵ月間のうちに歩行障害や着衣失行、失禁も認められるようになったため、精査目的で当科に入院となった。チャドック反射など病的な神経学的所見が確認されるとともに、頭部MRI検査では大脳、小脳、脳幹に無数の粟粒性小結節影が確認された。胸部CT検査では右肺下葉に4cm大の腫瘤性病変が認められ、原発性肺癌・粟粒状脳転移(終末期)と診断された。その際には本人の意識レベルは低下し、疎通も不良となっていた。家族と頻回の面接を行い、病前の本人の意思、家族の希望から在宅医療を導入したが、退院5日後に永眠した。粟粒状脳転移という非常に稀な病態を経験するとともに、早期診断に対する身体診察の重要性を再認識させられた。急激な病状進行のため、診断後には早急に終末期医療の方針を決めなくてはならず、その難しさを実感した。(著者抄録)

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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DOI： 10.1016/j.pscychresns.2014.02.007

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Although diffusion tensor imaging (DTI) studies have reported fractional anisotropy (FA) abnormalities in multiple white matter (WM) regions in schizophrenia, relationship between abnormal FA and negative symptoms has not been fully explored. DTI data were acquired from twenty-four patients with chronic schizophrenia and twenty-five healthy controls. Regional brain abnormalities were evaluated by conducting FA comparisons in the cerebral and each lobar WMs between groups. Focal abnormalities were also evaluated with a voxel-wise tract specific method. Associations between structural WM changes and negative symptoms were assessed using the Scale for the Assessment of Negative Symptoms (SANS). The patient group showed decreased FA in the cerebrum, especially in the frontal lobe, compared with controls. A voxel-wise analysis showed FA decreases in almost all WM tracts in schizophrenia. Correlation analyses demonstrated negative relationships between FA in the cerebrum, particularly in the left hemisphere, and SANS global and global rating scores (Anhedonia-Asociality, Attention, and Affective-Flattening), and also associations between FA of left frontal lobe and SANS global score, Anhedonia-Asociality, and Attention. This study demonstrates that patients with chronic schizophrenia evince widespread cerebral FA abnormalities and that these abnormalities, especially in the left hemisphere, are associated with negative symptoms. Published by Elsevier Ireland Ltd.

DOI： 10.1016/j.pscychresns.2014.02.007

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PUBLIC LIBRARY SCIENCE  

Numerous brain regions are believed to be involved in the neuropathology of panic disorder (PD) including fronto-limbic regions, thalamus, brain stem, and cerebellum. However, while several previous studies have demonstrated volumetric gray matter reductions in these brain regions, there have been no studies evaluating volumetric white matter changes in the fiber bundles connecting these regions. In addition, although patients with PD typically exhibit social, interpersonal and occupational dysfunction, the neuropathologies underlying these dysfunctions remain unclear. A voxel-based morphometry study was conducted to evaluate differences in regional white matter volume between 40 patients with PD and 40 healthy control subjects (HC). Correlation analyses were performed between the regional white matter volumes and patients' scores on the Panic Disorder Severity Scale (PDSS) and the Global Assessment of Functioning (GAF). Patients with PD demonstrated significant volumetric reductions in widespread white matter regions including fronto-limbic, thalamo-cortical and cerebellar pathways (p&lt;0.05, FDR corrected). Furthermore, there was a significant negative relationship between right orbitofrontal gyrus (OFG) white matter volume and the severity of patients' clinical symptoms, as assessed with the PDSS. A significant positive relationship was also observed between patients' right OFG volumes and their scores on the GAF. Our results suggest that volumetric reductions in widespread white matter regions may play an important role in the pathology of PD. In particular, our results suggest that structural white matter abnormalities in the right OFG may contribute to the social, personal and occupational dysfunction typically experienced by patients with PD.

DOI： 10.1371/journal.pone.0092862

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

In this study we use high resolution Magnetic Resonance imaging (MRI) and apply rigorous manual tracing criteria in order to assess volumetrically the prefrontal cortex (PFC) in schizophrenia. Previous MRI studies suggested PFC is included in neural systems necessary for emotional processing and cognition, and regional PFC abnormalities might, thus, lead to specific negative symptoms, as well as a frequent association of poorer performance in category switching. The aim of this study was to use 3 T imaging and reliable manual parcellation to determine if, as hypothesized, this higher precision would reveal additional MRI abnormalities in PFC in schizophrenia, and an association between PFC abnormalities and specific negative symptoms, as well as in category switching. Using 3-T MRI, 27 schizophrenia patients and 27 healthy controls were examined. PFC was manually parcellated into frontal pole, superior frontal gyrus (SFG), middle frontal gyrus (MFG), and inferior frontal gyrus (IFG). Left SFG (p = 0.004), bilateral MFG (left: p = 0.007; right: p = 0.007), and bilateral IFG (left: p &lt; 0.001; right: p = 0.002) showed volume reduction. There were symptom associations between smaller left MFG volumes and more affective flattening (R = -0.465, p = 0.015), and smaller left IFG volumes and poorer performance on the alternating semantic category test (R = 0.440, p = 0.025). In summary, 3-T imaging revealed widespread gyral volume deficits in PFC gyri, and specific associations with selective negative symptoms, such as affective flattening, and with deficits in cognitive switching. (C) 2013 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.schres.2013.10.026

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DOI： 10.1001/jamapsychiatry.2013.665

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Introduction: The middle longitudinal fascicle (MdLF) is a long association fiber connecting the superior temporal gyrus (STG) and temporal pole with the angular gyrus through the white matter of the STG, structures which are known to play a crucial role in the pathology of schizophrenia. Functions of MdLF are thought to be related to language and thought processing in the left hemisphere, and with attention in the right hemisphere. While deficits of these functions are core clinical features of schizophrenia, no study has investigated the structural abnormalities of MdLF in schizophrenia.
Method: 3 T diffusion tensor data was acquired from twenty-six patients with schizophrenia and twenty-five healthy control subjects. Streamline tractography technique was used to extract MdLF. Fractional anisotropy (FA) was compared between the two groups. In addition, relationships were investigated between FA in the left MdLF and the Disorganized Thoughts Factor derived from the Positive and Negative Symptom Scale five factor model, and between FA in the right MdLF and the Poor Attention.
Result: Relative to control subjects, the patients with chronic schizophrenia showed significant mean FA reductions in the bilateral MdLF. The FA of the left MdLF demonstrated a significant negative association with the Disorganized Thoughts Factor, and the FA of the right MdLF showed a significant negative relationship with the Poor Attention.
Conclusions: This study provides new evidence for structural deficits in the bilateral MdLF in patients with chronic schizophrenia. It further demonstrates the contribution of these abnormalities to the core clinical features - especially to disorganization and attention deficit. (C) 2012 Elsevier B. V. All rights reserved.

DOI： 10.1016/j.schres.2012.11.030

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Background: Previous voxelwise Diffusion Tensor Imaging (DTI) investigations of white matter in first-episode schizophrenia (FESZ) have been limited to the analysis of Fractional Anisotropy (FA) and mean diffusivity (MD), with their findings inconsistent in terms of the anatomical locations and extent of abnormalities. This study examines white matter abnormalities in FESZ, compared with healthy controls, using a tract-based spatial statistics (TBSS) approach applied to multiple measures of tract integrity, and correlates these findings with symptom severity.
Methods: Seventeen first-episode patients with schizophrenia and seventeen age-and gender-matched healthy controls (HC) participated in this imaging study where FA, MD, and axial and radial diffusivities were compared between the two groups using TBSS.
Results: First-episode patients with schizophrenia showed lower FA values in the genu and body of corpus callosum, the internal capsule, the external capsule, the fornix, the superior, inferior fronto-occipital fasciculus, the cingulum, and the uncinate fasciculus compared with HC. Increased MD and radial diffusivity were shown in virtually all white matter regions. There was no significant difference, however, observed for axial diffusivity between the two groups. Pearson correlation analysis showed that the FA values of the right inferior fronto-occipital fasciculus were positively correlated with positive symptoms, negative symptoms, and total correct items of the Wisconsin Card Sorting Test. FA values of right external capsule also showed significant positive correlation with category completed scores of the WCST.
Conclusions: These data suggest extensive, possibly myelin related white matter disruptions in FESZ. (C) 2012 Elsevier B. V. All rights reserved.

DOI： 10.1016/j.schres.2012.11.029

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Region of Interest (ROI) longitudinal studies have detected progressive gray matter (GM) volume reductions in patients with first-episode schizophrenia (FESZ). However, there are only a few longitudinal voxel-based morphometry (VBM) studies, and these have been limited in ability to detect relationships between volume loss and symptoms, perhaps because of methodologic issues. Nor have previous studies compared and validated VBM results with manual Region of Interest (ROI) analysis.
In the present VBM study, high-dimensional warping and individualized baseline-rescan templates were used to evaluate longitudinal volume changes within subjects and compared with longitudinal manual ROI analysis on the same subjects. VBM evaluated thirty-three FESZ and thirty-six matched healthy control subjects (HC) at baseline (cross-sectionally) and longitudinally evaluated 21 FESZ and 23 HC after an average of 1.5 years from baseline scans. Correlation analyses detected the relationship between changes in regional GM volumes in FESZ and clinical symptoms derived from the Brief Psychiatric Rating Scale, as well as cognitive function as assessed by the Mini-Mental State Examination.
At baseline, patients with FESZ had significantly smaller GM volume compared to HC in some regions including the left superior temporal gyrus (STG). On rescan after 1.5 years, patients showed significant GM volume reductions compared with HC in the left STG including Heschl's gyrus, and in widespread brain neocortical regions of frontal, parietal, and limbic regions including the cingulate gyrus. FESZ showed an association of positive symptoms and volume loss in temporal (especially STG) and frontal regions, and negative symptoms and volume loss in STG and frontal regions. Worse cognitive function was linked to widespread volume reduction, in frontal, temporal and parietal regions. The validation VBM analyses showed results similar to our previous ROI findings for STG and cingulate gyrus. We conclude FESZ show widespread, progressive GM volume reductions in many brain regions. Importantly, these reductions are directly associated with a worse clinical course. Congruence with ROI analyses suggests the promise of this longitudinal VBM methodology. Published by Elsevier Inc.

DOI： 10.1016/j.neuroimage.2011.08.066

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Language：Japanese   Publisher：(有)科学評論社  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Aim: Although recent studies suggest abnormalities of the cerebral cortex, limbic structures, and brain stem regions in panic disorder (PD), the extent to which the midbrain is associated with PD pathophysiology is unclear. The aim of this study was to investigate structural abnormalities of the midbrain using magnetic resonance imaging and to determine if there is a clinical correlation between midbrain volume and clinical measurements in patients with PD.
Methods: Thirty-eight patients with PD (PD group) and 38 healthy controls (HC group) participated in this study. The midbrain was measured with a manual tracing method with high spatial resolution magnetic resonance imaging. The Panic Disorder Severity Scale and Global Assessment of Functioning were used to examine the correlation between volume abnormality and clinical symptoms and functioning in the PD group.
Results: Relative midbrain volume was larger in the PD group than in the HC group. The relative volume of the dorsal midbrain was larger in the PD group, while the volume of the ventral midbrain was not. We found a significant positive correlation between relative dorsal midbrain volume and total Panic Disorder Severity Scale score, and a significant negative correlation between relative dorsal midbrain volume and Global Assessment of Functioning score in the PD group.

DOI： 10.1111/j.1440-1819.2011.02219.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Aim: The sulcogyral pattern of the orbitofrontal cortex (OFC) is characterized by a remarkable inter-individual variability that likely reflects neurobehavioral traits and genetic aspects of neurodevelopment. The aim of the present study was to evaluate the OFC sulcogyral pattern of patients with schizophrenia (SZ) and healthy controls (HC) to determine group differences in OFC sulcogyral pattern as well as gender differences between groups.
Methods: Forty-seven SZ patients (M/F, 23/24) and forty-seven HC (M/F, 17/30), matched on age and gender, were analyzed using magnetic resonance imaging. The sulcogyral pattern was classified into type I, II, or III based on the guidelines set by Chiavaras and Petrides in a previous paper. Chi-squared analysis was used to investigate group and gender differences in the sulcogyral pattern distribution, and categorical regression was used to explore clinical correlations.
Results: The distribution of OFC sulcogyral pattern in HC replicated the results found in the previous study (left, chi(2) = 0.02, P = 0.989; right, chi(2) = 0.97, P = 0.616), in that there were no gender differences. Moreover, the distribution in SZ-M was in accordance with that in the previous study (left, chi(2) = 1.59, P = 0.451; right, chi(2) = 0.14, P = 0.933). Additionally, within SZ-M, patients with the type III pattern had a higher total positive and negative syndrome scale score (beta = 0.902, F = 14.75, P = 0.001). In contrast, the distribution in the right hemisphere in the SZ-F group differed significantly from that observed in SZ-M (chi(2) = 6.017, P = 0.046), but did not differ from HC (chi(2) = 2.557, P = 0.110).
Conclusion: OFC sulcogyral pattern is altered in SZ-M but not in SZ-F, possibly reflecting gender differences in early neurodevelopment.

DOI： 10.1111/j.1440-1819.2011.02229.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Aims: The posterior region of the orbitofrontal cortex (OFC), which forms its sulcogyral pattern during neurodevelopment, receives multisensory inputs. The purpose of the present study was to assess the relationship between posterior OFC sulcogyral pattern and OFC volume difference in patients with panic disorder.
Methods: The anatomical pattern of the posterior orbital sulcus (POS) was classified into three subtypes (absent POS, single POS, double POS) using 3-D high-spatial resolution magnetic resonance images obtained from 28 patients with panic disorder and 28 age-and gender-matched healthy controls. Optimized voxel-based morphometry (VBM) was performed to assess OFC volume differences between the two groups by subtype. Categorical regression analysis was applied to examine the association of POS subtypes with State-Trait Anxiety Inventory and Revised Neuroticism-Extraversion-Openness Personality Inventory scores.
Results: No significant difference was found in POS subtype distribution between control subjects and patients with panic disorder. VBM, however, indicated volume reduction in the right posterior-medial OFC region in panic disorder patients with absent POS and single POS. Single POS was positively associated with Trait-Anxiety (beta = 0.446, F = 6.409, P = 0.020), and absent POS was negatively associated with Trait-Anxiety (beta = -0.394, F = 5.341, P = 0.032) and Neuroticism trait (beta = -0.492, F = 6.989, P = 0.017).
Conclusions: POS subtypes may be relevant to volume reduction in OFC and the anxiety trait in patients with panic disorder. These findings suggest that volume reduction in OFC in panic disorder may be associated with neurodevelopment.

DOI： 10.1111/j.1440-1819.2010.02085.x

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DOI： 10.1016/j.pscychresns.2008.10.004

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While clinical features of panic disorder show significant sexual dimorphism, previous structural MRI studies have not sufficiently controlled for sex when looking at regional brain abnormalities in panic disorder. Using optimized voxel-based morphometry (VBM), regional gray matter volume was compared between 24 patients (male/female: 9/15) with panic disorder and 24 healthy subjects matched for age and sex. Significant gray matter volume reductions were found in the bilateral dorsomedial and right ventromedial prefrontal cortices, right amygdala, anterior cingulate cortex, bilateral insular cortex, occipitotemporal gyrus and left cerebellar vermis in the patients compared with the controls. Among these regions, the VBM revealed significant sexual dimorphism: volume reduction in the right amygdala and the bilateral insular cortex was significantly greater in the males, while reduction in the right superior temporal gyrus was greater in females. Furthermore, a significant reduction in the dorsolateral and ventrolateral prefrontal cortices, thalamus, and parietal cortex was specific to the female patients. The present study demonstrated the morphological changes in extensive brain regions of patients with panic disorder compared with the sex-matched controls. The current results further suggested that the sexually dimorphic clinical phenotypes of panic disorder might have a neurobiological background even at the structural level of the brain.

DOI： 10.1016/j.pscychresns.2008.10.004

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Language：Japanese   Publisher：日本不安症学会  

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Language：English   Publisher：WILEY-BLACKWELL PUBLISHING, INC  

Aims: Anxiety a core feature of panic disorder, is linked to function of the amygdala. Volume alterations in the brain of patients with panic disorder have previously been reported, but there has been no report of amygdala volume association with anxiety.
Methods: Volumes of hippocampus and amygdala were manually measured using magnetic resonance imaging obtained from 27 patients with panic disorder and 30 healthy comparison subjects. In addition the amygdala was focused on, applying small volume correction to optimized voxel-based morphometry (VBM). State-Trait Anxiety Inventory and the NEO Personality Inventory Revised were also used to evaluate anxiety.
Results: Amygdala volumes in both hemispheres were significantly smaller in patients with panic disorder compared with control subjects (left: t = -2.248, d.f. = 55, P = 0.029; right: t = -2.892, d.f. = 55, P = 0.005). VBM showed that structural alteration in the panic disorder group occurred on the corticomedial nuclear group within the right amygdala (coordinates [x, y, z (mm)]: [26,-6,-16], Z score = 3.92, family-wise error-corrected P = 0.002). The state anxiety was negatively correlated with the left amygdala volume in patients with panic disorder (r = -0.545, P = 0.016).
Conclusions: These findings suggested that the smaller volume of the amygdala may be associated with anxiety in panic disorder. Of note, the smaller subregion in the amygdala estimated on VBM could correspond to the corticomedial nuclear group including the central nucleus, which may play a crucial role in panic attack.

DOI： 10.1111/j.1440-1819.2009.01960.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Aim: Recent neuroimaging studies have suggested that the anterior cingulate cortex (ACC) has an important role in the pathology of panic disorder. Despite numerous functional neuroimaging studies that have elucidated the strong relationship between functional abnormalities of the ACC and panic disorder and its symptoms and response to emotional tasks associated with panic disorder, there has been no study showing volumetric changes of the ACC or its subregions.
Methods: To clarify the structural abnormalities of ACC and its subregions, the combination of region of interest (ROI) and optimized voxel-based morphometry (VBM) methods were performed on 26 patients with panic disorder, and 26 age and sex-matched healthy subjects. In the ROI study, ACC was divided into four subregions: dorsal, rostral, subcallosal and subgenual ACC.
Results: The results of the manually traced ROI volume comparison showed significant volume reduction in the right dorsal ACC. VBM also showed a volume reduction in the right dorsal as well as a part of the rostral ACC as a compound mass.
Conclusions: Both manual ROI tracing and optimized VBM suggest a subregion-specific pattern of ACC volume deficit in panic disorder. In addition to functional abnormalities, these results suggest that structural abnormalities of the ACC contribute to the pathophysiology of panic disorder.

DOI： 10.1111/j.1440-1819.2008.01800.x

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Language：Japanese   Publisher：日本生物学的精神医学会  

統合失調症症例32名を対象に包括システムによるロールシャッハ・テストを実施し、現実検討力を反映するといわれる認知的媒介スコアが比較的保たれている群と著しく障害されている群について、各群の臨床的特徴や脳容積、脳容積変化について比較検討した。その結果、認知的媒介の比較的保たれている群と比べ、著しく障害されている群には入院歴のある者が有意に多く、脳容積に関しては、左側上側頭回前部に容積減少が認められた。健常者との比較では、同部位の容積減少は認知的媒介の著しく障害されている群のみで認められた。以上より、統合失調症において左側上側頭回前部の容積減少と認知機能との関連性が示唆された。

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2008&ichushi_jid=J02508&link_issn=&doc_id=20080501070006&doc_link_id=%2Fcy8brsci%2F2008%2F001901%2F006%2F0041-0049%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcy8brsci%2F2008%2F001901%2F006%2F0041-0049%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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Language：English   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Huntington's disease (HD) is a hereditary disorder clinically characterized by involuntary movements, cognitive decline and psychiatric symptoms. We report on a patient with HD, whose involuntary movements and psychiatric symptoms were clinically improved with perospirone, a second-generation antipsychotic agent with antagonistic effects on serotonin 5-HT2A and dopamine D-2 (D2) receptors, as well as a unique agonistic effect on serotonin 5-HT1A (5-HT1A) receptors. The fact that perospirone antagonizes D-2 receptors could explain its effects on the hyperkinetic syndrome, while its agonistic effects on 5-HT1A receptors may explain the amelioration of psychiatric symptoms (fear and anxiety) in this patient. Future studies would be valuable to elucidate the utility of perospirone for the treatment of involuntary movements and psychiatric symptoms in HD. (c) 2006 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.pnpbp.2006.06.021

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Language：Japanese   Publisher：日本神経心理学会  

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Language：Japanese   Publisher：日本神経心理学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING ASIA  

The purpose of this study is to clarify the relationship between childhood tendencies of attention deficit/hyperactivity disorder (AD/HD) and illicit drug abuse in Japanese prisoners, and to clarify whether drug abusers with AD/HD prefer methamphetamine (MAP) more than other illicit drugs. The Japanese version of the Wender Utah Rating Scale (WURS), which is a self-reporting instrument to retrospectively identify childhood tendencies of AD/HD tendencies, was carried given to 413 prisoners without a drug addiction and 282 prisoners with a drug addiction (192, MAP; 53, toluene; and 37, cannabis). WURS scores were compared between prisoners with and without a drug addiction, and between MAP, toluene, and cannabis abusers. Consequently, prisoners with a drug addiction showed significantly higher WURS scores than those without the addiction (P &LT; 0.001). Toluene abusers showed significantly higher WURS scores than cannabis abusers (P &LT; 0.001), and included a higher proportion with scores over cut-off than MAP or cannabis abusers (P = 0.005). In conclusion, a close relationship existed between illicit drug abuse and childhood AD/HD tendencies. Drug-abusing prisoners with AD/HD tendencies were not prone to choose MAP over other illicit drugs.

DOI： 10.1111/j.1440-1819.2005.01376.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING ASIA  

It was examined whether bulimia and dissociation are common in male self-cutters, as has been found in female self-cutters. The subjects were 796 male inmates of a juvenile prison. A self-reporting questionnaire was used to assess self-cutting, histories of psychoactive substance use, problem behaviors, and traumatic life events in the subjects. The Adolescent Dissociative Experience Scale and the Bulimia Investigatory Test of Edinburgh were also used. Subjects were divided into two groups: self-cutting and non-cutting. Questionnaire responses and dissociation and bulimia assessments were compared between the groups. Self-cutters began smoking (P &LT; 0.001) and drinking (P &LT; 0.001) earlier, and more frequently used illicit psychoactive drugs (P &LT; 0.001), experienced childhood physical abuse (P &LT; 0.001), and reported suicide attempts (P &LT; 0.001), suicidal ideation (P &LT; 0.001), and outward violence toward a person (P &LT; 0.001) or object (P &LT; 0.001) than non-cutters. Self-cutters also scored significantly higher on the bulimia (P &LT; 0.001) and dissociation tests (P &LT; 0.001). Logistic regression analysis demonstrated that suicide attempt (odds ratio, 4.311) and suicidal ideation (odds ratio, 2.336) could discriminate between male inmates with and without self-cutting. Male self-cutters showed 'multi-impulsive bulimic' tendencies resembling those of female self-cutters, although to a lesser extent. Clinical features of male as opposed to female self-cutters were influenced by gender differences.

DOI： 10.1111/j.1440-1819.2005.01377.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING ASIA  

The purpose of the present paper was to examine the differences in clinical features between self-cutters and self-burners, to clarify clinical implications of self-mutilating behaviors other than self-cutting. Subjects were 201 delinquent adolescents consecutively entering a Japanese juvenile detention center from February 2003 to March 2003. The subjects were assessed using a self-reporting questionnaire to evaluate self-mutilation, traumatic events, and problematic behaviors. Beck Depression Inventory-2 (BDI-2) and Adolescent Dissociative Experience Scale (A-DES) were also tested. Subjects were classified into four groups according to self-mutilating behaviors: non-self-cutting or -burning (NSCB), self-cutting (SC), self-burning (SB), and self-cutting and self-burning (SCB). The questionnaire answers and scores of the BDI-2 and A-DES were compared between the four groups. Of 201 subjects, 33 (16.4%) had cut their wrists or forearms at least once, and 72 of 201 (35.8%) had burned themselves at least once. The SC and SCB group had traumatic events, problematic behavior, and various types of self-mutilating behavior more frequently than the other two groups. The SCB group reported additional types of self-mutilating behavior more than the SC group. The SCB group also experienced multiple body customizations compared to the SC group, and exhibited higher scores on the BDI-2 and A-DES than the other three groups. The self-burning without self-cutting may have limited clinical implications. However, the self-burning with self-cutting may suggest depression and dissociation, as well as possible indication of self-mutilating behavior.

DOI： 10.1111/j.1440-1819.2005.01333.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING ASIA  

The present study was aimed to clarify the differences in clinical implications between wrist- and arm-cutting. Subjects were 201 delinquent adolescents (178 males and 23 females) who had been admitted to a detention center from February to March 2003. A self-reporting questionnaire and the Adolescent Dissociative Experience Scale (ADES) were given. Traumatic events and other self-injurious behavior were compared among four groups. In total, 33 (16.4%) subjects reported wrist- and/or arm-cutting. Of the females, 60.9% (n = 14) had experienced self cutting behaviors compared to 10.7% of males (n = 19). Subjects were divided into four groups; 'non-cutting' (NC: n = 168, 83.6%), 'wrist-cutting' (WC: n = 5, 2.5%), 'arm-cutting' (AC: n = 19, 9.5%), and 'wrist- and arm-cutting' (WAC: n = 9, 4.5%). WC, AC, and WAC groups reported early separation, bulling in school, and histories of sexual/physical abuse more frequently than NC group. WC and WAC groups reported suicidal ideation and suicide attempts more frequently than NC and AC groups. The ADES scores in AC and WAC groups were significantly higher than in those in NC group (P &lt; 0.001), while the scores in WC were not different from NC groups. WC and WAC groups self-cut due to suicide idea more frequently than the AC group, while AC group self-cut due to anger expression more frequently than WC or WAC groups. Self-cutters experienced early separation, bullying in school, and sexual/physical abuse more frequently than-non-self-cutters. Arm-cutting behavior may predict dissociation, while wrist-cutting may involve with suicidality.

DOI： 10.1111/j.1440-1819.2004.01271.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING ASIA  

The purpose of the present study was to clarify the relationship between bulimic behavior, dissociative phenomenon and sexual/physical abuse histories in Japanese subjects with habitual self-mutilation. Subjects consisted of 34 female outpatients who had cut their wrists or arms on more than 10 occasions. Two age-matched groups, which consisted of 31 general psychiatric outpatients and 26 non-clinical volunteers, served as controls. They were assessed with the Beck Depression Inventory-II, Bulimia Investigatory Test of Edinburgh, Adolescent Dissociative Experience Scale, and an original self-reporting questionnaire concerning various problematic behaviors and sexual/physical abuse histories. The habitual self-mutilation and the two control groups were compared. The habitual self-mutilation group had significantly higher scores on the Beck Depression Inventory-II, Bulimia Investigatory Test of Edinburgh, and Adolescent Dissociative Experience Scale than either of the two control groups (P&lt;0.001). Furthermore, the habitual self-mutilation group more frequently had a history of illicit psychoactive drug use (P=0.001), shoplifting (P&lt;0.001), suicide attempts (P&lt;0.001), overdosing with medicine (P&lt;0.001), sexual abuse (P=0.011), and childhood physical abuse (P=0.001) than the general psychiatric controls. These results are consistent with those in Western studies. Habitual self-mutilation is likely to coexist with depression, bulimia, and dissociation. Such patients frequently have clinical features similar to those of 'multi-impulsive bulimia'. Evidence supports the association between habitual self-mutilation and sexual/childhood physical abuse in Japan.

DOI： 10.1111/j.1440-1819.2003.01216.x

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A case of AFP-producing gastric cancer successfully treated with CPT-11 and cisplatin combined therapy is reported together with a review of the literature. A 52-year-old male was admitted with complaints of upper abdominal pain and body weight loss. Gastric cancer with multiple liver metastases was diagnosed based on endoscopy and computed tomography findings. The patient&#039;s serum AFP level was 697,100 ng/ml and a biopsy specimen showed AFP-positive tumor cells immunohistochemically. He was treated with a combination chemotherapy consisting of CPT-11 (70 mg/m2) on day 1 and 15, and cisplatin (80 mg/m2) on day 1, repeated every 4 weeks. The primary lesion of the stomach and the liver metastases were remarkably reduced, and the serum level of AFP decreased to 18 ng/ml after 5 cycles of this treatment. No severe side effects were seen during this treatment. This result suggests that combination chemotherapy consisting of CPT-11 and cisplatin may be effective and safe for patients with AFP-producing gastric cancer with multiple liver metastases.

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J-GLOBAL

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J-GLOBAL

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(株)アークメディア  

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Language：Japanese   Publisher：科学評論社  

CiNii Books

CiNii Research

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Other Link： https://search.jamas.or.jp/link/ui/2022046009

Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：日本うつ病学会・日本認知療法・認知行動療法学会  

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Language：Japanese   Publisher：科学評論社  

CiNii Books

CiNii Research

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Language：Japanese   Publisher：(株)先端医学社  

CiNii Research

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Language：Japanese   Publisher：(一社)日本総合病院精神医学会  

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Language：Japanese   Publisher：(株)ワールドプランニング  

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J-GLOBAL

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J-GLOBAL

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER SCIENCE INC  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER SCIENCE INC  

Web of Science

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER SCIENCE INC  

Web of Science

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER SCIENCE INC  

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J-GLOBAL

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Language：Japanese   Publisher：(株)医学書院  

12歳時の交通外傷による前頭葉眼窩面損傷後、経時的に様々な精神症状を呈した1例(40歳男性)を経験したので、前頭葉損傷と精神症状の関連について考察を加えて報告した。本例においてみられた発動性減退、易刺激性、易怒性などの症状は、いずれも前頭葉眼窩面損傷後にみられる症状として記載されてきたものである。本例ではさらに強迫傾向や他飲水がみられたが、これらは眼窩脳損傷群の情動障害でみられる「脱抑制的多動」と解することができた。WCSTやStroopテストの成績低下がみられたが、これは画像上明らかであった眼窩部の脳損傷の影響が前頭葉外側穹窿部にも及んで入る可能性が考えられた。強迫傾向と多飲水を前頭葉外側穹窿部の障害との関連で考えると、これらの症状が行動の中止困難、保続、固着の症状の表れととらえることができるかもしれない。

DOI： 10.11477/mf.1405100392

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J-GLOBAL

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J-GLOBAL

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Language：Japanese   Publisher：神奈川県精神医学会  

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Language：Japanese   Publisher：神奈川県医師会  

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Language：Japanese   Publisher：神奈川県医師会  

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