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Tomoko Suzuki,1 Koji Wada,1,2 Michiko Nakazato,3 Toshiyuki Ohtani,4 Michiko Yamazaki,2 Shunya Ikeda1,2 1Department of Public Health, School of Medicine, International University of Health and Welfare, Narita, Japan; 2Department of Social Medical Sciences, Graduate School of Medicine, International University of Health and Welfare, Tokyo, Japan; 3Department of Psychiatry, School of Medicine, International University of Health and Welfare, Narita, Japan; 4Safety and Health Organization, Chiba University, Chiba, JapanCorrespondence: Tomoko Suzuki, Department of Public Health, School of Medicine, International University of Health and Welfare, 4-3 Kozunomori, Narita, Chiba, 286-8686, Japan, Tel +81-476-20-7701, Fax +81-476- 28-1188, Email tsuzuki7@iuhw.ac.jp; tsuzuki2992@gmail.comPurpose: Most previous studies that described associations between adult attention-deficit/hyperactivity disorder (ADHD) and sociodemographic characteristics were focused on individuals diagnosed with ADHD, and few studies investigated ADHD traits in the general population. Additionally, some workers, who experienced no problems while at university and successfully graduated from university, developed ADHD traits after finding employment. This study described associations between ADHD traits and sociodemographic characteristics among Japanese workers who were university graduates.Patients and Methods: Participants were randomly selected workers (n=1240) from across Japan who completed a self-administered online survey. ADHD traits were measured using an adult ADHD Self-report Scale, with scoring rules applied to reflect the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Information was collected on sociodemographic characteristics including sex, age, socioeconomic status, working time, and health-related behaviors. We performed partial correlation analysis to estimate trend associations and used analysis of covariance to compare adjusted averages. This model was adjusted for all variables.Results: Males had higher levels of ADHD traits than females (p = 0.001), and younger age was associated with higher levels of ADHD traits (p < 0.001). Workers with low incomes had higher levels of ADHD traits than workers with high incomes (p = 0.009). More frequent consumption of midnight meals was associated with higher levels of ADHD traits (p < 0.001), although there were no differences for breakfast, lunch, and dinner. Those who did not get enough rest from sleep had higher levels of ADHD traits (p = 0.007).Conclusion: Results for high levels of ADHD traits among workers were consistent with previous studies for adults diagnosed with ADHD, even though all participants had successfully graduated from university. Assessment of these ADHD traits may support prevention of health deterioration related to these ADHD traits.Keywords: ADHD traits, eating habits, income, lifestyle habits, sleep, socioeconomic status

Individuals with high levels of autistic traits are at a high risk of experiencing depressive symptoms, and are also vulnerable to job stress. This study aimed to identify which combination of autistic traits and type of job stress are related to depressive symptoms. Participants comprised 992 workers from different regions of Japan. Autistic traits, depressive symptoms, and job stress were measured using the Autism-Spectrum Quotient, K6 scale, and Job Content Questionnaire, respectively. Logistic regression was performed to estimate the odds ratio and 95% confidence interval. Workers with high autistic traits scores reported significantly more depressive symptoms for all job stress types, especially high job demand. Depressive symptoms differed according to autistic traits and job stress. In workers with high autistic trait subscale scores, those with active job stress reported more depressive symptoms than those with high strain job stress, except for the "poor imagination" trait. This is contrary to previous reports that the active stress type is generally less associated with depressive symptoms than the high-strain stress type. To prevent depressive symptoms in workers with high autistic trait scores, it is important to understand which combination of autistic traits and type of job stress contribute to depressive symptoms.

Toshiyuki Ohtani,1– 3 Koji Matsuo,4 Chihiro Sutoh,5 Fumiyo Oshima,2,3 Yoshiyuki Hirano,2,3 Akio Wakabayashi,6 Eiji Shimizu2,3,5 1Safety and Health Organization, Chiba University, Chiba, Japan; 2Research Center for Child Mental Development, Chiba University, Chiba, Japan; 3United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Suita, Japan; 4Department of Psychiatry, Faculty of Medicine, Saitama Medical University, Saitama, Japan; 5Department of Cognitive Behavioral Physiology, Graduate School of Medicine and School of Medicine, Chiba University, Chiba University, Chiba, Japan; 6Department of Psychology,Graduate School of Humanities, Chiba University, Chiba, JapanCorrespondence: Toshiyuki OhtaniSafety and Health Organization, Chiba University, 1-33 Yayoicho, Inage-ku, Chiba, 263-8522, JapanTel/Fax +81 43 290 2216Email otanit@Chiba-u.jpPurpose: In clinical settings, diagnosing comorbid depression in individuals with autism spectrum disorder (ASD) is often difficult. Neuroimaging studies have reported reduced activation of frontal and temporal regions during emotional face recognition task (EFRT) in ASD and depression. However, to the best of our knowledge, no study has examined differences in frontotemporal activation during EFRT between ASD with and without comorbid depression. We aimed to compare the frontotemporal hemodynamic responses to the EFRT in ASD with and without depression and to find clues to help in discriminating the characteristics between them.Patients and Methods: In 24 drug-naïve young adults with ASD (12 with depression [ASD-Dep(+)] and 12 without depression [ASD-Dep(-)]) and 12 with typical development (TD), frontotemporal hemodynamic responses during an EFRT were measured using functional near-infrared spectroscopy (fNIRS).Results: The ASD groups showed reduced activation during EFRT than the TD group in the right ventrolateral prefrontal cortex (VLPFC). Moreover, the ASD-Dep(+) group showed reduced activation during EFRT than the ASD-Dep(-) group in the right anterior temporal cortex (aTC), and reduced activation than the TD group in the left VLPFC.Conclusion: The observed results might reflect reduced regional activation in ASD and ASD with comorbid depression.Keywords: autism spectrum disorder, depression comorbidity, functional near-infrared spectroscopy, emotional face recognition, social cognition, frontotemporal activation

Background: This study examined whether a combination of the Awareness and Care for my Autistic Traits (ACAT) program and treatment-as-usual (TAU) is more effective than only TAU in increasing the understanding of autistic attributes, reducing treatment stigma, and improving mental health and social adaptation among adolescents with autism spectrum disorder (ASD) and their parents/guardians. Methods: Forty-nine adolescents and their parents/guardians were randomly assigned to either a combination of ACAT and TAU (COMB) group or only TAU group. The COMB group received six weekly 100-min ACAT sessions while the TAU group received no additional intervention. The primary outcome was the change in the understanding of autistic attributes (Autism Knowledge Quiz-Child: AKQ-C), administered to autistic adolescents from pre-to post-intervention. The secondary outcomes included the change in AKQ-parent version (AKQ-P) administered to their parents/guardians, treatment stigma, improving mental health, and social adaptation among autistic adolescents and their parents/guardians. All measures except for the self-rating scales were scored by asessors blind to the group assignment. Results: The individuals (both autistic adolescents and their parents/guardians) in the COMB group, showed an increased score of the AKQ-C and AKQ-P than did those in the TAU group. Autistic adolescents in the COMB group also demonstrated reduced treatment-related stigma and behavioral problems than those in the TAU group, while there were no group differences in the change in social adaptation. For parents/guardians, there were no group differences in the change in treatment-related stigma, mental health, adaptive skills, or attitudes toward their children. Conclusions: The results suggest that the ACAT could be an effective treatment modality for both autistic adolescents and their parents/guardians to increase the understanding of autistic attributes. The ACAT may positively affect self-understanding, reduce treatment stigma, and stabilize behavioral issues for autistic adolescents, but it may not effectively reduce treatment barriers or improve mental health for parents/guardians. Further research should consider whether additional support for parents/guardians could be beneficial. Trial registration: Registration number - UMIN000029851 and date of registration - 06/01/2018.

Purpose: To examine the reliability and validity of the Camouflaging Autistic Traits Questionnaire–Japanese version (CAT-Q-J). Methods: Self-report questionnaires were administered to 204 adults with and 410 adults without autism. Test–retest reliability was confirmed via another survey administered after two weeks.Results: The overall CAT-Q-J showed good reliability, correlating approximately with other scales, supporting its convergent validity. However, a few subscales had insufficient reliability and validity. Exploratory factor analyses showed three factors similar to the original in non-autistic sample (plus a factor comprising reversed items). For the autistic sample, three factors partially differed from the original. Conclusion: Despite acceptable consistency, reliability, and validity at an overall level, the CAT-Q-J should be used with caution.

Objective It is challenging to safely treat blood blister–like aneurysms (BBAs) of the internal carotid artery. Endovascular surgery has been reported, but the optimal strategy is yet to be established. We report our endovascular treatment strategy using the Low-profile Visualized Intraluminal Support (LVIS) stent. Methods Twelve patients with ruptured BBAs including 1 patient with 2 separate aneurysmal bulges were treated from December 2017 to January 2020. Single LVIS stent-assisted coil embolization was performed as the initial treatment. If the coil could not be placed in the aneurysm, or follow-up angiography showed persistent filling or regrowth of the aneurysm, a second LVIS stent was deployed as an overlapping stent. Clinical characteristics, treatment details, and clinical outcomes were retrospectively examined. Results Single stent-assisted coiling was performed in 8 patients (69%), 2 overlapping stents with coiling in 1 (8%), a single stent in 2 (15%), and 2 overlapping stents in 2 (15%). Three patients with persistent filling or regrowth of the aneurysm were re-treated with overlapping stents. Follow-up angiography confirmed complete occlusion in 12 aneurysms (92%). No re-rupture occurred. Postoperative symptomatic ischemia was confirmed in 4 patients (33%), and all 4 patients suffered severe subarachnoid hemorrhage. Modified Rankin scale was 0–2 in 8 patients (67%). Conclusions LVIS stent-assisted coil embolization is effective in preventing re-rupture of BBAs. However, the morphology of the aneurysm may change within a short period, so careful angiographic follow-up is needed. Appropriate preoperative antiplatelet administration and optimal timing of the treatment may reduce the risk of postoperative ischemic complication.

ObjectiveThis study aimed to validate the Sick, Control, One stone, Fat, and Food (SCOFF) questionnaire in relation to the Eating Disorders Examination Questionnaire (EDE-Q) and to examine the appropriateness of a question concerning weight loss among Japanese university students. The psychometric properties of the two Japanese versions were determined among 649 Japanese college students. The original version (SCOFF-O) employed the original item 3, whereas the revised version (SCOFF-2.5) modified the item to “Have you recently lost more than 2.5 kg within three months?” Validity was tested relative to EDE-Q.ResultsThe test–retest reliabilities of SCOFF-O and SCOFF-2.5 were 0.52 and 0.57, while the correlations of SCOFF-O and SCOFF-2.5 with EDE-Q werer = 0.53 andr = 0.56. The sensitivity and specificity of SCOFF-O were 65.2 and 89.7, and those of SCOFF-2.5 were 69.5 and 86.5, respectively. There were significant correlations between the question concerning losing 2.5 kg and the EDE-Q subscales. The Japanese version of SCOFF-2.5 is an appropriate tool for the early screening of eating disorders among Japanese university students.

Objective Psychological problems associated with isolation and mistrust are common among young adults with autism spectrum disorder (ASD). Schema therapy (ST) has recently been shown to be effective against chronic personality problems of various mental disorders, including personality disorders. This pilot clinical trial aimed to explore the feasibility and acceptability of ST in young adults with high-functioning ASD. Results Following the intervention, a significant reduction in early maladaptive schemas and improvements in quality of life and social adjustment were observed. ST may be feasible and is applicable to young adults with HF-ASD. Trial registration UMIN000014535; registered on July 11, 2014

Background One aim of an autism spectrum disorder (ASD) diagnosis is to obtain special support for the disorder, though this does not guarantee practical support. We developed a psychoeducational program using cognitive-behavioral therapy (CBT) and Aware and Care for my Autistic Traits (ACAT) for Japanese adolescents with high-functioning ASD and their parents. Methods This multisite study is a randomized controlled trial. In total, 24 participants will be assigned to the ACAT group and 24 to the treatment-as-usual (TAU) group. The ACAT group will receive a weekly 100-min session for 6 weeks, regular medical care, and one follow-up session. In this ongoing clinical trial, we will compare the scores of the measures recorded in the pre- and post-intervention stages between the ACAT and TAU groups. A total of 41 patients out of a target of 48 have participated in the trial to date. The primary outcome measure is the Autism Knowledge Questionnaire. Secondary outcome measures include Barriers to Access to Care Evaluation 3rd Edition, the Strengths and Difficulties Questionnaire, the Vineland Adaptive Behavior Scales second edition, the Parenting Resilience Elements Questionnaire, the General Health Questionnaire 12, and the Depression Self-Rating Scale for Children assessments, as well as an electroencephalographic recording. Discussion It is expected that participants in the ACAT group will significantly increase their self-understanding and awareness of ASD symptoms compared to those in the TAU group. Additionally, the ACAT group is expected to exhibit improved social adaptation and mental health if children and parents are able to better understand the ASD characteristics through sessions. This intervention will contribute to the establishment of an effective evidence-based treatment strategy for adolescents with ASD. Trial registration UMIN Register 000029851. Registered on January 06, 2018

In 1908, Bleuler proposed a unitary theory of schizophrenia, hypothesizing a “loosening of associations” as the central mechanism underlying disturbances in thinking, motivation, and affective expression. Here, we test Bleuler’s model in an archival sample of 79 healthy controls and 76 patients with chronic schizophrenia who had completed neuropsychological tests, including a measure of learning of novel word pairs, which was specifically selected to probe the structure and formation of new verbal associations. The patients also had positive and negative symptoms ratings, including measures of flat affect, anhedonia, and thought disorder. A subset of patients and controls (n = 39) had available prior archival 3-T magnetic resonance imaging (MRI) measures of prefrontal cortex (PFC) gray matter volumes. In relation to controls, patients showed evidence of a selective impairment in associative learning, independent of their overall reduced neuropsychological functioning. This neuropsychological impairment, in turn, correlated significantly with overall levels of negative but not positive symptoms, with the data showing an especially strong contribution of flattened emotional expression to verbal associate learning deficits in this patient sample. Moreover, the archival MRI data were consistent with prior research pointing to an important role of the PFC in supporting verbal associate learning and memory in patients and controls. Taken together, the current results provided evidence of a selective impairment in schizophrenia on a PFC-supported verbal associate learning and memory task, which was accompanied by negative symptoms in general, and flattened emotional expression, in particular.

We hypothesized that neuropsychological disturbance in schizophrenia (SZ) may reflect faulty interactions of executive attention and episodic memory, emanating, in part, from reduced prefrontal cortex (PFC) gray matter volume. Participants with SZ (n = 84) and age-matched (n = 77) controls completed both the Wisconsin Card Sorting Test (WCST) and the Wechsler Memory Scale–Third Edition (WMS-III), used, respectively, as measures of executive attention and episodic memory. A subset of SZ (n = 27) and control (n = 17) groups also had available 3-T magnetic resonance imaging (MRI) studies of the PFC. For SZ, but not control groups, neuropsychological results indicated that executive attention interacted significantly with episodic memory, with failures of executive attention, as reflected by increased WCST perseverative errors, directly linked to poor performance on the WMS-III measure of delayed visual recall of action scenes. MRI results indicated reduced left PFC gray matter volume for SZ group, which in turn correlated significantly with their deficits in visual memory but not in executive attention. Results showed that 61% of the variance in neuropsychological performance in the SZ group was attributed to gray matter volume of left inferior prefrontal gyrus gray matter volume. PFC-mediated failure of executive attention-episodic memory interactions may represent an important mechanism in neuropsychological disturbance in SZ.

Background There is a good deal of evidence that cognitive behavioural therapy is effective for children and adolescents with anxiety-related problems. In Japan, an anxiety prevention programme based on cognitive behavioural therapy called ‘Journey of the Brave’ has been developed, and it has been demonstrated to be effective for elementary school students (aged 10–11 years). The purpose of this study was to have classroom teachers deliver the programme to junior high school students (aged 12–13 years) and to test the feasibility and efficacy of the programme in this setting. Methods This study was a prospective observational study and was approved by the Chiba University Review Board. An intervention group consisting of six classes of students in their first year of junior high school at two different schools (n = 149; 81 boys, 68 girls) received seven 50-min programme sessions. Participants in the control group were recruited from four classes of students in their second year of junior high school at one school (n = 89; 51 boys, 38 girls). All participants completed the Spence Children’s Anxiety Scale at pre-test, post-test, and 2–3 month follow-up. Statistical analysis was conducted using a mixed-effects model for repeated measures model. Results Mean total anxiety scores indicated a non-significant decrease at the 2–3 month follow-up for the intervention group compared to the control group. The group differences on the SCAS from baseline to post-test was − .71 (95% CI − 2.48 to 1.06, p = .43), and the 2–3 month follow-up was − .49 (95% CI − 2.60 to 1.61, p = .64). Conclusions In this pilot study, implementation of the programme confirmed the partial feasibility of the programme but did not elicit a significant reduction in anxiety scores. In addition, there are several methodological limitations to this study. In the future, we propose to test the feasibility and efficacy of the programme with the required sample size and by comparing groups with equal characteristics as well as by carrying out additional follow-up assessments. Trial registration UMIN000032517.

Objective: Schema therapy (ST) has recently been shown to be effective for the treatment of various mental disorders, including personality disorders. This pilot clinical trial aimed to explore the feasibility, acceptability, and effectiveness of ST for adults with high-functioning autism spectrum disorder (HF-ASD)Results: From pre- to post-treatment, we found significant improvements in social functions (GAF and WHO-QOL), early maladaptive schema (YSQ), and depression and anxiety (BDI-II and STAI).Trial registration: UMIN000014535; registered on July 11, 2014.

Background Idarucizumab is a specific antidote for the anticoagulant dabigatran. Although its efficacy has been recently reported, the drug is still in postmarketing surveillance and requires case data in different emergency settings. A newer intravenous thrombolytic therapy with recombinant tissue plasminogen activator has been proposed after injection of idarucizumab in patients receiving dabigatran; however, the safety and efficacy of this therapy are equivocal because of the limited number of reported cases. We describe a case of a patient with acute lacunar stroke causing dysarthria and hemiparesis successfully treated with intravenous thrombolytic therapy with recombinant tissue plasminogen activator after reversal of dabigatran with idarucizumab. Case presentation A 67-year-old Asian woman was transferred to our emergency center 200 minutes after sudden onset of dysarthria and right-sided hemiparesis. She had been taking dabigatran for prevention of stroke recurrence caused by atrial fibrillation. Diffusion-weighted magnetic resonance imaging revealed a new lacunar infarction near old putamen infarctions. We treated her with intravenous thrombolytic therapy with recombinant tissue plasminogen activator after administering idarucizumab. The time to recombinant tissue plasminogen activator administration was 5 minutes from idarucizumab injection and 269 minutes from symptom onset. The patient’s activated partial thromboplastin times were 68.0 and 43.2 seconds before and after the therapy, respectively. The patient’s neurological symptoms improved significantly after the treatment, and she experienced no adverse events. Conclusions Intravenous thrombolytic therapy with recombinant tissue plasminogen activator after reversal of dabigatran with idarucizumab may be safe and feasible in patients with acute ischemic stroke with lacunar infarct. Furthermore, intravenous thrombolytic therapy with recombinant tissue plasminogen activator could be used in patients in emergency settings until just before the end of the recommended time limit within which it needs to be administered because of the immediate effect of idarucizumab.

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.

In clinical settings, autism spectrum disorder (ASD) with comorbid depression is often difficult to diagnose, and should be considered in treatment. However, to our knowledge, no functional imaging study has examined the difference between ASD adolescents with and without comorbid depression. We aimed to compare the characteristics and prefrontal brain function of ASD with and without depression in order to identify a biological marker that can be used to detect the difference. Twenty-eight drug-naïve adolescents with ASD (14 ASD with and 14 ASD without depression) and 14 age- and gender-matched adolescents with typical development were evaluated using several variables. These included intelligence quotient, autism quotient, depression severity using the Beck Depression Inventory 2nd edition (BDI-II), and level of social functioning using the Social Adaptation Self-evaluation Scale (SASS). In addition, frontotemporal hemodynamic responses during a verbal fluency task (VFT) were measured using functional near-infrared spectroscopy (fNIRS). The ASD group, including both of the ASD with and ASD without depression groups, showed smaller hemodynamic responses than the typical development group in portions of the left dorsolateral prefrontal cortex (DLPFC), bilateral ventrolateral prefrontal cortex (VLPFC) and anterior part of the temporal cortex (aTC) during the VFT. Moreover, the smaller hemodynamic responses in the right VLPFC during the VFT in the ASD group were associated with the worse BDI-II and SASS scores. Furthermore, the ASD with depression group showed smaller hemodynamic responses in the right VLPFC during the VFT than the ASD without depression group in a direct comparison. Adolescents with ASD showed reduced activation in broad frontotemporal regions during a cognitive task compared with those with typical development. More specifically, the right VLPFC activation reflected the level of self-estimated depression and social functioning in the ASD subjects, and could be used to discriminate between ASD adolescents with and without depression.

The postoperative metabolic states of subarachnoid hemorrhage (SAH) patients were investigated using indirect calorimetry (IDC) and various nutritional evaluations to establish any difference in perioperative metabolic and nutritional states between microsurgical and endovascular treatment. This study included 30 acute aneurysmal SAH patients with ruptured intracranial aneurysms treated by surgical clipping (n = 16) or coil embolization (n = 14) at a single institute. The resting energy expenditure (REE) and respiratory quotient were measured using IDC on days 1, 4, 7, 10, 14, and 17–21 after the operation. Various blood tests, including C-reactive protein (CRP) and prealbumin, were evaluated on the same days. The clipping group showed a significant increase in REE/basal energy expenditure (BEE) compared with the coiling group on days 1 and 4 (p = 0.04 and 0.03, respectively). No significant differences were found on days 7, 10, 14, and 17–21. The mean REE/BEE on days 1–14 and 1–21 showed no significant differences between the groups with repeated measures analysis of variance. The clipping group showed a significant decrease of prealbumin on day 4 and significant increase in CRP on days 1, 4, and 7. The clipping group was in the hypermetabolic state compared with the coiling group during the very early postoperative period. However, the difference associated with the treatment modality was relatively small compared to the effects of the SAH and of the sequelae.

We combined diffusion tension imaging (DTI) of prefrontal white matter integrity and neuropsychological measures to examine the functional neuroanatomy of human intelligence. Healthy participants completed the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) along with neuropsychological tests of attention and executive control, as measured by Trail Making Test (TMT) and Wisconsin Card Sorting Test (WCST). Stochastic tractography, considered the most effective DTI method, quantified white matter integrity of the medial orbital frontal cortex (mOFC) and rostral anterior cingulate cortex (rACC) circuitry. Based on prior studies, we hypothesized that posterior mOFC-rACC connections may play a key structural role linking attentional control processes and intelligence. Behavioral results provided strong support for this hypothesis, specifically linking attentional control processes, measured by Trails B and WCST perseverative errors, to intelligent quotient (IQ). Hierarchical regression results indicated left posterior mOFC-rACC fractional anisotropy (FA) and Trails B performance time, but not WCST perseverative errors, each contributed significantly to IQ, accounting for approximately 33.95-51.60% of the variance in IQ scores. These findings suggested that left posterior mOFC-rACC white matter connections may play a key role in supporting the relationship of executive functions of attentional control and general intelligence in healthy cognition.

The present report describes a patient with pseudo-occlusion of the left internal carotid artery accompanied by aortic anomalies consisting of right-sided aortic arch with aberrant left subclavian artery arising from Kommerell’s diverticulum. Initial attempt of carotid artery stenting via the trans-femoral approach was unsuccessful because of low origin of the left common carotid artery. Therefore, carotid artery stenting (CAS) via the trans-brachial approach was successfully performed with distal balloon protection. Eight months later, the patient presented with restenosis of the left internal carotid artery, and CAS via the trans-brachial approach was performed again. CAS via the trans-brachial approach should be considered when standard femoral access is relatively contraindicated due to aortic anomalies consisting of a right-sided aortic arch.

Objective: We combined neuropsychological and structural magnetic resonance imaging (MRI) measures to examine the neural and informational processes underlying episodic memory in healthy participants. Method: The Doors-and-People Test (DPT) provided a detailed assessment of episodic memory, including recall and recognition tasks of matched difficulty for social (e.g., people) and non-social (e.g., shape) content. The Wisconsin Card Sorting (WCS) test provided a measure of category learning that relies heavily on executive control and inhibition. A subset of participants also had available high-resolution, 3-T MRI gray matter volume studies of prefrontal cortex (PFC) parcellated into four regions: 1) frontal pole; 2) superior frontal gyrus; 3) middle frontal gyrus; and 4) inferior frontal gyrus. Results: Bivariate neuropsychological correlations revealed a highly statistically significant relationship of reduced WCS perseverative errors and stronger recall for people but not for shapes. By contrast, WCS perseveration did not correlate with any recognition measures. Hierarchical regression revealed that perseverative errors and people recall test scores combined to account for approximately 29.98% to 57.78% of the variance in left PFC gray matter volume. Conclusions: These results may point to an important role of the PFC in mnemonic process of retrieval inhibition in episodic memory for recall of social content in healthy participants.

A 68-year-old woman presented with segmental aplasia of bilateral internal carotid arteries accompanied by unruptured intracranial aneurysms. The abnormality was discovered incidentally at the age of 44 years. Cerebral angiography showed occlusion of bilateral internal carotid arteries, and the carotid territory was supplied by each posterior communicating artery with small intracranial aneurysms. Endovascular treatment for the intracranial aneurysms was planned. However, the patient did not want to undergo the endovascular procedure because of the increased risk due to the associated bilateral carotid abnormalities. Cerebral angiography was performed again at the age of 66 years, and the size of the aneurysms had not changed. Based on their segmental identity, aplasia of segment 6 of the internal carotid artery (ICA) including the first portion of the ophthalmic artery was observed bilaterally.

Methamphetamine abuse and dependence, frequently accompanied by schizophrenia-like psychotic symptoms [methamphetamine-associated psychosis (MAP)], is a serious public health problem worldwide. Few studies, however, have characterized brain dysfunction associated with MAP, nor investigated similarities and differences in brain dysfunction between MAP and schizophrenia. We compared prefrontal cortical activity associated with stop-signal inhibitory task in 21 patients with MAP, 14 patients with schizophrenia and 21 age- and gender-matched healthy controls using a 52-channel near-infrared spectroscopy (NIRS) system. Both the MAP and the schizophrenia groups showed significantly reduced activation in the bilateral ventrolateral prefrontal cortex compared with controls; however, only the MAP group showed reduced activation in the frontopolar prefrontal cortex. The MAP group demonstrated significant positive correlations between task performance and hemodynamic responses in the bilateral ventrolateral, polar and left dorsolateral regions of the prefrontal cortex. The MAP and schizophrenia groups demonstrated a significant difference in the relationship of impulsivity to hemodynamic changes in the bilateral premotor cortex. These findings characterize similarities and differences in prefrontal cortical dysfunction between psychosis associated with methamphetamine and schizophrenia. The reduced hemodynamic changes in the bilateral ventrolateral prefrontal cortex suggest a common underlying pathophysiology of MAP and schizophrenia, whereas those in the frontopolar prefrontal cortex point to an impaired state that is either inherent or caused specifically by methamphetamine use.

Objectives Neuroimaging studies have suggested prefrontal dysfunction in response to cognitive activation in bipolar disorder (BD). However, its characteristics in manic states have not been well understood. Thus, we compared prefrontal hemodynamic responses during a cognitive task between hypomanic and depressive states in BD. We then longitudinally compared hypomanic and subsequent euthymic states. Methods The prefrontal function of 27 patients with BD (11 hypomanic and 16 depressed) and 12 age- and gender-matched healthy controls (HCs) was evaluated using near-infrared spectroscopy (NIRS) during a verbal fluency task (VFT). Hypomanic symptoms were assessed using the Young Mania Rating Scale. Among the 11 hypomanic patients, eight participated in the second NIRS measurement after their hypomanic symptoms resolved. Results VFT performance did not differ among hypomanic, depressed, and HC groups. Both BD groups exhibited significantly lower activation during the VFT than HCs in the broader bilateral prefrontal cortex. Hemodynamic changes in the left dorsolateral prefrontal cortex (DLPFC) in the hypomanic patients with BD were significantly larger than those in the depressed patients. In addition, hypomanic symptom severity was positively correlated with activation in the left DLPFC and frontopolar cortex in patients with BD. Follow-up measurement of the hypomanic patients revealed that prefrontal activation was decreased after hypomanic symptoms resolved. Conclusions Combining cross-sectional and longitudinal assessments, the present results suggest that prefrontal hemodynamic responses associated with cognitive activation differ between hypomanic and depressive states in BD. NIRS measurement could be a useful tool for objectively evaluating state-dependent characteristics of prefrontal hemodynamics in BD.

Aim The present study examined the effect of irritable bowel syndrome (IBS), cognitive appraisal of IBS, and anxiety sensitivity on anticipatory anxiety (AA) and agoraphobia (AG) in patients with panic disorder (PD). Methods We examined 244 PD patients who completed a set of questionnaires that included the Rome II Modular Questionnaire to assess the presence of IBS, the Anxiety Sensitivity Index (ASI), the Cognitive Appraisal Rating Scale (CARS; assessing the cognitive appraisal of abdominal symptoms in four dimensions: commitment, appraisal of effect, appraisal of threat, and controllability), and items about the severity of AA and AG. The Mini International Neuropsychiatric Interview was used to diagnose AG and PD. Results After excluding individuals with possible organic gastrointestinal diseases by using ‘red flag items,’ valid data were obtained from 174 participants, including 110 PD patients without IBS (PD/IBS[–]) and 64 with IBS (PD/IBS[+]). The PD/IBS[+] group had higher AA and higher comorbidity with AG than the PD/IBS[–] group. In the PD/IBS[+] group, the controllability score of CARS was significantly correlated with AA and ASI. Multiple regression analysis showed a significant effect of ASI but not of controllability on AA in PD/IBS[+] subjects. Conclusion This study suggested that the presence of IBS may be related to agoraphobia and anticipatory anxiety in PD patients. Cognitive appraisal could be partly related to anticipatory anxiety in PD patients with IBS with anxiety sensitivity mediating this correlation.

Object Blockade of Ca++-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPAR) inhibits the proliferation of human glioblastoma by inhibiting Akt phosphorylation, which is independent of the phosphatidylinositol 3-kinase pathway. Inhibiting platelet-derived growth factor receptor (PDGFR)–mediated phosphorylation causes growth inhibition in glioblastoma cells. The authors of this study investigated the effects of YM872 and AG1296, singly and in combination and targeting different pathways upstream of Akt, on Akt-mediated tumor growth in glioblastoma cells in vivo and in vitro. Methods The expression of AMPAR, PDGFR, and c-kit in glioblastoma cells was analyzed via immunofluorescence. Glioblastoma cells, both in culture and in xenografts grown in mice, were treated with YM872 and AG1296, singly or in combination. Inhibition of tumor growth was observed after treatment in the xenograft model. Cell proliferation assays were performed using anti–Ki 67 antibody in vivo and in vitro. The CD34-positive tumor vessel counts within the vascular hot spots of tumor specimens were evaluated. Phosphorylation of Akt was studied using Western blot analysis. Results Combined administration of YM872 and AG1296 had a significant enhanced effect on the inhibition of cell proliferation and reduction of tumor vascularity in the xenograft model. These agents singly and in combination demonstrated a significant reduction of Akt phosphorylation at Ser473 and inhibition of tumor proliferation in vitro, although combined administration had no enhanced antitumor effects. Conclusions The strongly enhanced antitumor effect of this combination therapy in vivo rather than in vitro may be attributable to disruption of the aberrant vascular niche. This combination therapy might provide substantial benefits to patients with glioblastoma.

Background: As the proportion of teens in the onset ages has increased, it has become important to detect eating disorder (ED) students early in school and clarify the way of support. Though epidemiological surveys of Yogo teachers have been conducted to inquire the number of ED students, none of these were based on DSM-5. Thus, we conducted a wide area survey in Japan for proposing a better framework of support for Yogo teachers in the early detection/support of ED students. Methods: A questionnaire survey organized by ED type (based on DSM-5) was administered to Yogo teachers working at elementary/junior high/senior high/special needs schools in four prefectures of Japan in 2015, and 1886 responses were obtained. Based on the results, the encounter rates (the proportions of Yogo teachers who had met ED students) were calculated, and factors affecting them were examined by logistic regression analysis. Results: The order of the encounter rates of the ED type was Anorexia Nervosa (AN)>Bulimia Nervosa (BN)>Avoidant/Restrictive Food Intake Disorder (ARFID)>Binge Eating Disorder (BED)>others. The factors significantly affecting the rates were location, school type, number of students, experience years, and AN knowledge for AN, school type, experience years, BN knowledge for BN, location, school type, experience years, BED knowledge for BED, location, experience years, ARFID knowledge for ARFID and school type, experience years, Others knowledge for Others. Conclusions: Since the encounter rate of AN was highest, providing support for AN would be effective. Moreover, a factor affecting the rate of all ED types was the ED knowledge. Senior high schools had the highest rates for AN, BN and BED, and special needs schools had the highest for others. These findings imply that for detecting/supporting ED students early, it is necessary to offer knowledge of the corresponding ED type to Yogo teachers at the corresponding school type.

Although post-traumatic stress disorder (PTSD) may be seen to represent a failure to extinguish learned fear, significant aspects of the pathophysiology relevant to this hypothesis remain unknown. Both the amygdala and hippocampus are necessary for fear extinction occur, and thus both regions may be abnormal in PTSD. Twenty-five people who experienced the Tokyo subway sarin attack in 1995, nine who later developed PTSD and 16 who did not, underwent magnetic resonance imaging (MRI) with manual tracing to determine bilateral amygdala and hippocampus volumes. At the time of scanning, one had PTSD and eight had a history of PTSD. Results indicated that the group with a history of PTSD had significantly smaller mean bilateral amygdala volume than did the group that did not develop PTSD. Furthermore, left amygdala volume showed a significant negative correlation with severity of PTSD symptomatology as well as reduced gray matter density in the left anterior cingulate cortex. To our knowledge, this is the first observation of an association between PTSD and amygdala volume. Furthermore the apparent interplay between amygdala and anterior cingulate cortex represents support at the level of gross brain morphology for the theory of PTSD as a failure of fear extinction.

Eye movement desensitization and reprocessing (EMDR) is an effective psychological intervention for posttraumatic stress disorder (PTSD). Trauma-related recall (Recall) with eye movements (EMs) is thought to reduce distress. However, the neural mechanisms underlying this process remain unknown. Thirteen patients with PTSD received EMDR treatment over the course of 2-10 weeks. We assessed the change in hemoglobin concentration in the lateral prefrontal cortex (PFC) during Recall with and without EM using multi-channel near-infrared spectroscopy (NIRS). Clinical diagnosis and improvement were evaluated using the Clinician-Administered PTSD Scale. Recall with EM was associated with a significant decrease in oxygenated hemoglobin concentration ([oxy-Hb]) in the lateral PFC as compared with Recall without EM. Longitudinally, [oxy-Hb] during Recall significantly decreased and the amount of decrease was significantly correlated with clinical improvement when the post-treatment data was compared with that of the pre-treatment. Our results suggest that performing EM during Recall reduces the over-activity of the lateral PFC, which may be part of the biological basis for the efficacy of EMDR in PTSD. NIRS may be a useful tool for objective assessment of psychological intervention in PTSD.

Background Birth months have been shown to affect susceptibility to schizophrenia and other mental disorders, thus this factor could also affect predisposition to delinquency through biological effects on brain development and personality and/or through relative age effects at school. This study aimed to examine the relationship between birth-season and relative age at school on the risk of delinquency. Methods We investigated the ratio of observed and expected births in winter/summer and that in the first/last months of the Japanese school year in 5008 young male Japanese delinquents. Results No significant difference was found between observed and expected numbers of births in winter/summer or those in the first/last months of the school year. Conclusions The present study did not provide evidence for any effect from season of birth or a relative age effect within the school year on the risk of delinquency in Japanese male teenagers.

Objectives: There is evidence of prefrontal cortex (PFC) dysfunction in patients with bipolar disorder (BP). Magnetic resonance and neuropathological studies show abnormalities of the brain microvasculature in patients with BP. However, the underlying biological mechanisms are not well understood. We investigated the relationship between activation of the PFC during a cognitive task and the vascular function in response to a physiological task in patients with BP. Methods: Fourteen euthymic patients with BP and 14 control subjects matched for age, sex, and education were recruited. We examined the response of the PFC during a verbal fluency task and during 5% CO2 inhalation using a 24-channel near-infrared spectroscopy imaging system to measure alteration of oxygenated and deoxygenated hemoglobin. Results: The BP patients showed a significantly lower level of PFC activation during the cognitive task compared to the healthy controls, but the task-performance of the BP patients was not significantly different from that of the controls. The vascular response of the BP patients to CO2 was not significantly different from that of controls. Conclusions: This study suggests functional hypoactivation of the PFC during a cognitive load in patients with BP while they are in a euthymic state. The mechanism of this hypoactivation is different from that of vascular regulation in response to a physiological stimulus.

Methamphetamine abuse and dependence, frequently accompanied by schizophrenia-like psychotic symptoms [methamphetamine-associated psychosis (MAP)], is a serious public health problem worldwide. Few studies, however, have characterized brain dysfunction associated with MAP, nor investigated similarities and differences in brain dysfunction between MAP and schizophrenia. We compared prefrontal cortical activity associated with stop-signal inhibitory task in 21 patients with MAP, 14 patients with schizophrenia and 21 age- and gender-matched healthy controls using a 52-channel near-infrared spectroscopy (NIRS) system. Both the MAP and the schizophrenia groups showed significantly reduced activation in the bilateral ventrolateral prefrontal cortex compared with controls; however, only the MAP group showed reduced activation in the frontopolar prefrontal cortex. The MAP group demonstrated significant positive correlations between task performance and hemodynamic responses in the bilateral ventrolateral, polar and left dorsolateral regions of the prefrontal cortex. The MAP and schizophrenia groups demonstrated a significant difference in the relationship of impulsivity to hemodynamic changes in the bilateral premotor cortex. These findings characterize similarities and differences in prefrontal cortical dysfunction between psychosis associated with methamphetamine and schizophrenia. The reduced hemodynamic changes in the bilateral ventrolateral prefrontal cortex suggest a common underlying pathophysiology of MAP and schizophrenia, whereas those in the frontopolar prefrontal cortex point to an impaired state that is either inherent or caused specifically by methamphetamine use.

The medial orbitofrontal cortex (mOFC) and rostral part of anterior cingulate cortex (rACC) have been suggested to be involved in the neural network of salience and emotional processing, and associated with specific clinical symptoms in schizophrenia. Considering the schizophrenia dysconnectivity hypothesis, the connectivity abnormalities between mOFC and rACC might be associated with clinical characteristics in first episode schizophrenia patients (FESZ).After parcellating mOFC into the anterior and posterior part, diffusion properties of the mOFC-rACC white matter connections for 21 patients with FESZ and 21 healthy controls (HCs) were examined using stochastic tractography, one of the most effective Diffusion Tensor Imaging (DTI) methods for examining tracts between adjacent gray matter (GM) regions.Fractional anisotropy (FA) reductions were observed in bilateral posterior, but not anterior mOFC-rACC connections (left: p .0001; right: p .0001) in FESZ compared to HCs. In addition, reduced FA in the left posterior mOFC-rACC connection was associated with more severe anhedonia-asociality (rho = -.633, p = .006) and total score (rho = -.520, p = .032) in the Scale for the Assessment of Negative Symptoms (SANS); reduced FA in the right posterior mOFC-rACC connection was associated with more severe affective flattening (rho = -.644, p = .005), total score (rho = -.535, p = .027) in SANS, hallucinations (rho = -.551, p = .018), delusions (rho = -.632, p = .005) and total score (rho = -.721, p = .001) in the Scale for the Assessment of Positive Symptoms (SAPS) in FESZ.The observed white matter abnormalities within the connections between mOFC and rACC might be associated with the psychopathology of the early stage of schizophrenia.

Background Patients with affective disorders exhibit changes in regional brain function and show abnormal social adaptation. However, to our knowledge, no near-infrared spectroscopy (NIRS) study has examined the relationship between these two phenomena longitudinally. This study examined the region-specific functional abnormality associated with bipolar disorder (BD) and major depressive disorder (MDD), and the association between particular longitudinal changes in regional activation and social adaptation. Methods We evaluated frontotemporal functioning during a verbal fluency test (VFT) for patients with BD ( N =18), those with MDD ( N =10), and healthy controls (HCs; N =14) using NIRS. NIRS measurements and the Social Adaptation Self-evaluation Scale (SASS) were administered twice with an interval of approximately 6 months. Results The BD and MDD groups showed lesser activation than the HCs in the bilateral ventro-lateral prefrontal cortex and the anterior part of the temporal cortex (VLPFC/aTC). Longitudinal changes in SASS scores were positively associated with the extent of change in left VLPFC/aTC activation in the BD group and with right VLPFC/aTC activation in the MDD group. Limitations Our small sample size limited statistical power, and the effect of medication and multiple comparisons cannot be excluded, although these effects were considered in the interpretation of the present results. Conclusion Longitudinal increases of VLPFC/aTC activation were associated with improvement in social adaptation in patients with BD and those with MDD. NIRS measurement could be a useful tool for objective evaluation of changes in social adaptation in BD and MDD.

Recent functional neuroimaging work has suggested that interregional functional connectivity between the anterior cingulate cortex (ACC), other limbic, and prefrontal regions may be involved in the pathophysiology of posttraumatic stress disorder (PTSD). However, less attention has been paid to the white matter network. Voxel-based analysis enables an exploration of morphological or functional changes throughout the entire brain. Here we undertook the first application of this technology to diffusion tensor data in patients with PTSD. Participants were 9 victims of the Tokyo subway sarin attack with PTSD and 16 matched victims of the same traumatic event without PTSD. The voxel-based analysis showed a significant fractional anisotropy increase in the left anterior cingulum, subjacent to the left ACC gray matter where we previously found a volume decrement, in PTSD subjects. Moreover, the severity was positively, but not significantly associated with the fractional anisotropy of the left anterior cingulum in the victims with PTSD, using the region of interest defined in the native space with the inverse normalization technique. The present study demonstrated further evidence of abnormalities of both the ACC, a structure that is pivotally involved in attention, emotional regulation, and fear conditioning, and of subjacent white matter in the pathology of PTSD.

We examined intelligence and memory in 25 healthy participants who had both prior magnetic resonance imaging (MRI) of gray matter volumes of medial orbital frontal cortex (mOFC) and rostral anterior cingulate cortex (rACC), along with diffusion tensor imaging (DTI) of posterior and anterior mOFC-rACC white matter microstructure, as assessed by fractional anisotropy (FA). Results showed distinct relationships between these basic structural brain parameters and higher cognition, highlighted by a highly significant correlation of left rACC gray matter volume with memory, and to a lesser extent, though still statistically significant, correlation of left posterior mOFC-rACC FA with intelligence. Regression analyses showed that left posterior mOFC-rACC connections and left rACC gray matter volume each contributed to intelligence, with left posterior mOFC-rACC FA uniquely accounting for between 20.43 and 24.99 % of the variance in intelligence, in comparison to 13.54 to 17.98 % uniquely explained by left rACC gray matter volume. For memory, only left rACC gray matter volume explained neuropsychological performance, uniquely accounting for a remarkably high portion of individual variation, ranging from 73.61 to 79.21 %. These results pointed to differential contributions of white mater microstructure connections and gray matter volumes to individual differences in intelligence and memory, respectively.

Previous investigations of auditory P300 event-related potentials have provided electrophysiological evidence for attentional problems in patients with posttraumatic stress disorder (PTSD). The present study sought to evaluate the relationship between P300 deficits and underlying brain morphological abnormalities in never-treated, comorbidity-free patients with PTSD following the Tokyo subway sarin attack. Out of 47 victims recruited, 8 victims with PTSD and 13 victims without PTSD were identified. Correlational analyses were performed between auditory P300 amplitude at Pz electrode site elicited in an oddball task and anterior cingulate gray matter volume that was shown to be reduced in our previous study using voxel-based morphometry on magnetic resonance imaging. Victims with PTSD showed significantly lower amplitudes of P300 compared with victims without PTSD, and the lower P300 amplitudes at Pz were significantly associated with higher avoidance/numbing scores in the PTSD group. Furthermore, in the PTSD group only, the P300 amplitudes showed a trend toward significant positive correlation with voxel densities of the anterior cingulate cortex gray matter. These results provide the first evidence that electrophysiological deficits of controlled attention observed in patients with PTSD may be linked to underlying brain morphological abnormalities.