Publications by authors named "Hidehiko Takahashi"

180 Publications

COVID-19 vaccination and mental health in hospital workers.

Brain Behav 2021 11 17;11(11):e2382. Epub 2021 Oct 17.

Department of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

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http://dx.doi.org/10.1002/brb3.2382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8613412PMC
November 2021

Natural and Artificial Intelligence: A brief introduction to the interplay between AI and neuroscience research.

Neural Netw 2021 Dec 28;144:603-613. Epub 2021 Sep 28.

Laboratory for Advanced Brain Functions, Institute for Protein Research, Osaka University, Osaka, Japan. Electronic address:

Neuroscience and artificial intelligence (AI) share a long history of collaboration. Advances in neuroscience, alongside huge leaps in computer processing power over the last few decades, have given rise to a new generation of in silico neural networks inspired by the architecture of the brain. These AI systems are now capable of many of the advanced perceptual and cognitive abilities of biological systems, including object recognition and decision making. Moreover, AI is now increasingly being employed as a tool for neuroscience research and is transforming our understanding of brain functions. In particular, deep learning has been used to model how convolutional layers and recurrent connections in the brain's cerebral cortex control important functions, including visual processing, memory, and motor control. Excitingly, the use of neuroscience-inspired AI also holds great promise for understanding how changes in brain networks result in psychopathologies, and could even be utilized in treatment regimes. Here we discuss recent advancements in four areas in which the relationship between neuroscience and AI has led to major advancements in the field; (1) AI models of working memory, (2) AI visual processing, (3) AI analysis of big neuroscience datasets, and (4) computational psychiatry.
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http://dx.doi.org/10.1016/j.neunet.2021.09.018DOI Listing
December 2021

A multi-site, multi-disorder resting-state magnetic resonance image database.

Sci Data 2021 08 30;8(1):227. Epub 2021 Aug 30.

Brain Information Communication Research Laboratory Group, Advanced Telecommunications Research Institutes International, Kyoto, Japan.

Machine learning classifiers for psychiatric disorders using resting-state functional magnetic resonance imaging (rs-fMRI) have recently attracted attention as a method for directly examining relationships between neural circuits and psychiatric disorders. To develop accurate and generalizable classifiers, we compiled a large-scale, multi-site, multi-disorder neuroimaging database. The database comprises resting-state fMRI and structural images of the brain from 993 patients and 1,421 healthy individuals, as well as demographic information such as age, sex, and clinical rating scales. To harmonize the multi-site data, nine healthy participants ("traveling subjects") visited the sites from which the above datasets were obtained and underwent neuroimaging with 12 scanners. All participants consented to having their data shared and analyzed at multiple medical and research institutions participating in the project, and 706 patients and 1,122 healthy individuals consented to having their data disclosed. Finally, we have published four datasets: 1) the SRPBS Multi-disorder Connectivity Dataset 2), the SRPBS Multi-disorder MRI Dataset (restricted), 3) the SRPBS Multi-disorder MRI Dataset (unrestricted), and 4) the SRPBS Traveling Subject MRI Dataset.
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http://dx.doi.org/10.1038/s41597-021-01004-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405782PMC
August 2021

Anti-rods/rings autoantibodies in a patient with pancreatic injury.

Autoimmun Rev 2021 Aug 18:102922. Epub 2021 Aug 18.

Department of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.autrev.2021.102922DOI Listing
August 2021

Three-Dimensional Convolutional Autoencoder Extracts Features of Structural Brain Images With a "Diagnostic Label-Free" Approach: Application to Schizophrenia Datasets.

Front Neurosci 2021 7;15:652987. Epub 2021 Jul 7.

Department of Information Medicine, National Center of Neurology and Psychiatry, National Institute of Neuroscience, Tokyo, Japan.

There has been increasing interest in performing psychiatric brain imaging studies using deep learning. However, most studies in this field disregard three-dimensional (3D) spatial information and targeted disease discrimination, without considering the genetic and clinical heterogeneity of psychiatric disorders. The purpose of this study was to investigate the efficacy of a 3D convolutional autoencoder (3D-CAE) for extracting features related to psychiatric disorders without diagnostic labels. The network was trained using a Kyoto University dataset including 82 patients with schizophrenia (SZ) and 90 healthy subjects (HS) and was evaluated using Center for Biomedical Research Excellence (COBRE) datasets, including 71 SZ patients and 71 HS. We created 16 3D-CAE models with different channels and convolutions to explore the effective range of hyperparameters for psychiatric brain imaging. The number of blocks containing two convolutional layers and one pooling layer was set, ranging from 1 block to 4 blocks. The number of channels in the extraction layer varied from 1, 4, 16, and 32 channels. The proposed 3D-CAEs were successfully reproduced into 3D structural magnetic resonance imaging (MRI) scans with sufficiently low errors. In addition, the features extracted using 3D-CAE retained the relation to clinical information. We explored the appropriate hyperparameter range of 3D-CAE, and it was suggested that a model with 3 blocks may be related to extracting features for predicting the dose of medication and symptom severity in schizophrenia.
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http://dx.doi.org/10.3389/fnins.2021.652987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294943PMC
July 2021

Common Brain Networks Between Major Depressive-Disorder Diagnosis and Symptoms of Depression That Are Validated for Independent Cohorts.

Front Psychiatry 2021 10;12:667881. Epub 2021 Jun 10.

Brain Information Communication Research Laboratory Group, Advanced Telecommunications Research Institutes International, Kyoto, Japan.

Large-scale neuroimaging data acquired and shared by multiple institutions are essential to advance neuroscientific understanding of pathophysiological mechanisms in psychiatric disorders, such as major depressive disorder (MDD). About 75% of studies that have applied machine learning technique to neuroimaging have been based on diagnoses by clinicians. However, an increasing number of studies have highlighted the difficulty in finding a clear association between existing clinical diagnostic categories and neurobiological abnormalities. Here, using resting-state functional magnetic resonance imaging, we determined and validated resting-state functional connectivity related to depression symptoms that were thought to be directly related to neurobiological abnormalities. We then compared the resting-state functional connectivity related to depression symptoms with that related to depression diagnosis that we recently identified. In particular, for the discovery dataset with 477 participants from 4 imaging sites, we removed site differences using our recently developed harmonization method and developed a brain network prediction model of depression symptoms (Beck Depression Inventory-II [BDI] score). The prediction model significantly predicted BDI score for an independent validation dataset with 439 participants from 4 different imaging sites. Finally, we found 3 common functional connections between those related to depression symptoms and those related to MDD diagnosis. These findings contribute to a deeper understanding of the neural circuitry of depressive symptoms in MDD, a hetero-symptomatic population, revealing the neural basis of MDD.
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http://dx.doi.org/10.3389/fpsyt.2021.667881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224760PMC
June 2021

Detailed analysis of social support and proactive coping with depressive symptoms in Japanese HIV-infected individuals.

AIDS Care 2021 Jun 4:1-9. Epub 2021 Jun 4.

Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo, Japan.

The aim of this study was to determine the association of the type of social support and proactive coping with depressive symptoms (DS) in Japanese people living with human immunodeficiency virus (PLHIV), in order to select effective psychosocial care or intervention. Questionnaires were anonymously collected from randomly recruited participants. The questionnaire included items on demographic characteristics, HIV treatment-related factors, DS, social support, and coping. Hierarchical binary logistic regression was used to identify factors associated with DS. A total of 564 patients completed the questionnaire and 207 (37%) patients reported DS. Demographic factors, such as drug-use-related disorders [adjusted odds ratio (AOR) 7.21, 95% confidence interval (95%CI) 1.95-26.70], unemployment (AOR 3.06, 95%CI 1.50-6.27) and younger age (AOR 0.96, 95%CI 0.94-0.99) were significantly associated with DS. With regard to coping, higher levels of instrumental support seeking (AOR 1.09, 95%CI 1.01-1.18), lower levels of proactive coping (AOR 0.91, 95%CI 0.87-0.96) and lower levels of emotional support seeking (AOR 0.82, 95%CI 0.72-0.92) were significantly associated with DS. Our results highlight the need for psychosocial care to enhance or compensate proactive coping and emotional support seeking abilities in DS. Healthcare workers should pay attention to the mental health of young unemployed PLHIV with drug-use-related disorders.
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http://dx.doi.org/10.1080/09540121.2021.1934382DOI Listing
June 2021

A single session of navigation-guided repetitive transcranial magnetic stimulation over the right anterior temporoparietal junction in autism spectrum disorder.

Brain Stimul 2021 May-Jun;14(3):682-684. Epub 2021 Apr 13.

Medical Institute of Developmental Disabilities Research, Showa University, 6-11-11 Kita-karasuyama, Setagaya-ku, Tokyo, Japan; Kanagawa Psychiatric Center, 2-5-1 Serigaya, Yokohama, Kanagawa, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.brs.2021.04.009DOI Listing
November 2021

Factors affecting mental illness and social stress in hospital workers treating COVID-19: Paradoxical distress during pandemic era.

J Psychiatr Res 2021 05 6;137:298-302. Epub 2021 Mar 6.

Department of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. Electronic address:

Background: The coronavirus disease 2019 (COVID-19) has affected all countries in the world. Hospital workers are at high risk of mental illness, such as anxiety and depression. Furthermore, they also face many social stresses, such as deterioration of human relations and income reduction. Apart from mental illness, these social stresses can reduce motivation and lead to voluntary absenteeism, which contribute to a collapse of medical systems. Thus, for maintaining medical systems, it is crucial to clarify risk factors for both mental illness and increased social stress among hospital workers. However, little attention has been paid to factors affecting social stress, and thus, we aimed to address this gap.

Methods: In this cross-sectional survey of 588 hospital workers, the levels of anxiety, depression, and social stress were assessed using the 7-item Generalized Anxiety Disorder scale (GAD-7), 9-item Patient Health Questionnaire (PHQ-9), and Tokyo Metropolitan Distress Scale for Pandemic (TMDP). Multiple regression analyses were conducted to identify the demographic variables affecting these problems.

Results: Older age and female sex were common risk factors for anxiety, depression, and social stress. Moreover, occupational exposure to COVID-19 and hospital staff other than doctors/fewer non-work days were risk factors for increased anxiety and depression, respectively. Furthermore, living with families/others was a risk factor for increased social stress during this pandemic.

Conclusion: Our findings could be useful for developing policies and practices to minimize the risk of mental illness and increased social stress among hospital workers, highlighting that attention should be paid to social factors, such as an individual's household situation.
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http://dx.doi.org/10.1016/j.jpsychires.2021.03.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936542PMC
May 2021

Potential involvement of DSCAML1 mutations in neurodevelopmental disorders.

Genes Cells 2021 Mar 18;26(3):136-151. Epub 2021 Feb 18.

Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Tokyo, Japan.

The molecular mechanisms underlying neurodevelopmental disorders (NDDs) remain unclear. We previously identified Down syndrome cell adhesion molecule like 1 (Dscaml1) as a responsible gene for Ihara epileptic rat (IER), a rat model for human NDDs with epilepsy. However, the relationship between NDDs and DSCAML1 in humans is still elusive. In this study, we screened databases of autism spectrum disorders (ASD), intellectual disability (ID)/developmental disorders (DD) and schizophrenia for genomic mutations in human DSCAML1. We then performed in silico analyses to estimate the potential damage to the mutated DSCAML1 proteins and chose three representative mutations (DSCAML1 , DSCAML1 and DSCAML1 ), which lacked a cysteine residue in the seventh Ig domain, the intracellular region and the C-terminal PDZ-binding motif, respectively. In overexpression experiments in a cell line, DSCAML1 lost its mature N-glycosylation, whereas DSCAML1 was abnormally degraded via proteasome-dependent protein degradation. Furthermore, in primary hippocampal neurons, the ability of the wild-type DSCAML1 to regulate the number of synapses was lost with all mutant proteins. These results provide insight into understanding the roles of the domains in the DSCAML1 protein and further suggest that these mutations cause functional changes, albeit through different mechanisms, that likely affect the pathophysiology of NDDs.
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http://dx.doi.org/10.1111/gtc.12831DOI Listing
March 2021

Risk factors for low adherence to methylphenidate treatment in pediatric patients with attention-deficit/hyperactivity disorder.

Sci Rep 2021 01 18;11(1):1707. Epub 2021 Jan 18.

Department of Neuropsychiatry, Akita University Graduate School of Medicine, Hondo 1-1-1, Akita-city, Akita, 010-8543, Japan.

Poor adherence is a major concern in the treatment of attention-deficit/hyperactivity disorder (ADHD). The objective of this study was to evaluate factors linked to early interruption of and low adherence to treatment with osmotic-release oral system methylphenidate hydrochloride (OROS-MPH) in pediatric patients with ADHD. A total of 1353 young people (age 6-17 years) with a diagnosis of ADHD who newly started OROS-MPH were extracted from the pharmacoepidemiological data of 3 million people in Japan. The cohort was retrospectively surveyed every month for 12 months. Ten possible risk factors were extracted from the data and analyzed by multivariable logistic regression. Sensitivity analysis was conducted to ensure the robustness of the analysis. The results revealed that treatment adherence was generally poor, with a tendency for discontinuation in the early stage. Multivariable logistic regression results showed that adherence is reduced by female sex, lower starting dose, and concomitant atomoxetine or hypnotics. These findings may help clinicians to predict the risk of poor adherence in the early stage of treatment and improve not only patients' symptoms, but also their quality of life.
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http://dx.doi.org/10.1038/s41598-021-81416-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814069PMC
January 2021

Generalizable brain network markers of major depressive disorder across multiple imaging sites.

PLoS Biol 2020 12 7;18(12):e3000966. Epub 2020 Dec 7.

Brain Information Communication Research Laboratory Group, Advanced Telecommunications Research Institutes International, Kyoto, Japan.

Many studies have highlighted the difficulty inherent to the clinical application of fundamental neuroscience knowledge based on machine learning techniques. It is difficult to generalize machine learning brain markers to the data acquired from independent imaging sites, mainly due to large site differences in functional magnetic resonance imaging. We address the difficulty of finding a generalizable marker of major depressive disorder (MDD) that would distinguish patients from healthy controls based on resting-state functional connectivity patterns. For the discovery dataset with 713 participants from 4 imaging sites, we removed site differences using our recently developed harmonization method and developed a machine learning MDD classifier. The classifier achieved an approximately 70% generalization accuracy for an independent validation dataset with 521 participants from 5 different imaging sites. The successful generalization to a perfectly independent dataset acquired from multiple imaging sites is novel and ensures scientific reproducibility and clinical applicability.
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http://dx.doi.org/10.1371/journal.pbio.3000966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721148PMC
December 2020

Cognition and interpersonal coordination of patients with schizophrenia who have sports habits.

PLoS One 2020 9;15(11):e0241863. Epub 2020 Nov 9.

Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Kyoto, Japan.

Team sports activities are effective for improving the negative symptoms and cognitive functions in patients with schizophrenia. However, the interpersonal coordination during the sports and visual cognition of patients with schizophrenia who have team sports habits are unknown. The main objectives of this study were to test two hypotheses: first, patients with schizophrenia perform the skill requiring ball passing and receiving worse than healthy controls; and second, the patients will be impaired in these functionings in accordance with the previous studies regarding schizophrenia in general. Twelve patients with schizophrenia and 15 healthy controls, who had habits in football, participated in this study. The participants performed three conventional cognitive tests and a 3-vs-1 ball possession task to evaluate their interpersonal coordination. The results showed that in the 3-vs-1 possession task, the displacement in the pass angle for the patients was significantly smaller than that for the control. The recall in the complex figure test, the performance in the trail making test, and that in the five-choice reaction task for the patients were worse than those for the control. Moreover, we found the significant partial correlations in the patients between the extradimensional shift error and the pass angle as well as between the time in the trail making test and the displacement in the pass angle, whereas there was no significant correlation in the control group. This study clarified the impaired interpersonal coordination during team sports and the visual cognition of patients with schizophrenia who have team sports habits.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241863PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652240PMC
January 2021

Heart rate response to orthostatic challenge in patients with dementia with Lewy bodies and Alzheimer's disease.

Psychogeriatrics 2021 Jan 22;21(1):62-70. Epub 2020 Oct 22.

Liaison Psychiatry and Psycho-Oncology Unit, Department of Psychiatry and Behavioural Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

Background: To elucidate the differences in autonomic dysfunction between dementia with Lewy bodies (DLB) and Alzheimer's disease using a simple and convenient method, we investigated the heart rate response to orthostatic challenge.

Methods: Ninety-seven people participated in this cross-sectional study, and data from 26 DLB patients, 29 Alzheimer's disease patients, and 25 healthy elderly individuals were analysed. Participants underwent postural changes, including 5 min in a supine position, 1 min in a sitting position, and 3 min in an orthostatic position. Their heart rates were continuously recorded. Two heart rate variables were analysed as main outcomes: (i) the difference between heart rate in the sitting position and the peak heart rate within 15 s of orthostasis, defined as the 'early heart rate increase'; and (ii) the difference between the peak heart rate and the negative peak heart rate after this, defined as 'early heart rate recovery.' An early heart rate increase has been considered to reflect parasympathetic and sympathetic functions. Early heart rate recovery is considered to reflect parasympathetic function. We also investigated the frequency domains of resting heart rate variability.

Results: A significant difference was observed across the three groups in early heart rate increase, and that of the DLB group was lower than that of the healthy control group. Early heart rate recovery also differed significantly across the three groups, and that of the DLB group was less than that of the healthy control group. In addition, the power of the low-frequency component, which represents both sympathetic and parasympathetic activity, was significantly decreased in the DLB group compared to the Alzheimer's disease group.

Conclusions: Impaired heart rate response to standing was detected in patients with DLB. Electrocardiogram is a convenient, non-invasive method that might be useful as a subsidiary marker for DLB diagnosis and differentiation from Alzheimer's disease.
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http://dx.doi.org/10.1111/psyg.12625DOI Listing
January 2021

Early and late effects of electroconvulsive therapy associated with different temporal lobe structures.

Transl Psychiatry 2020 10 13;10(1):344. Epub 2020 Oct 13.

Department of Psychiatry, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Recent studies examining electroconvulsive therapy (ECT) have reported that early sessions can induce rapid antidepressant and antipsychotic effects, and the early termination of ECT was reported to increase the risk of relapse. We hypothesized that different neural mechanisms associated with the therapeutic effects of ECT may be involved in the different responses observed during the early and late periods of ECT treatment. We investigated whether these antidepressant and antipsychotic effects were associated with temporally and spatially different regional gray matter volume (GMV) changes during ECT. Fourteen patients with major depressive disorder, with or without psychotic features, underwent 3-Tesla structural magnetic resonance imaging scans before (time point [Tp] 1), after the fifth or sixth ECT session (Tp2), and after ECT completion (Tp3). We investigated the regions in which GMV changed between Tp1 and Tp2, Tp2 and Tp3, and Tp1 and Tp3 using voxel-based morphometry. In addition, we investigated the association between regional GMV changes and improvement in depressive or psychotic symptoms. GMV increase in the left superior and inferior temporal gyrus during Tp1-Tp2 was associated with improvement in psychotic symptoms (P < 0.025). GMV increase in the left hippocampus was associated with improvement of depressive symptoms in Tp2-Tp3 (P < 0.05). Our findings suggest that different temporal lobe structures are associated with early antipsychotic and late antidepressant effects of ECT.
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http://dx.doi.org/10.1038/s41398-020-01025-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553938PMC
October 2020

Memory Impairment and Hippocampal Volume after Carbon Monoxide Poisoning.

Arch Clin Neuropsychol 2021 Jan;36(1):145-148

Department of Psychiatry and Behavioral Neurosciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.

Objective: We report longitudinal changes in neuroimaging and neuropsychological measurements in a case of carbon monoxide (CO) poisoning showing reversible changes in hippocampal volume, which was closely linked to the degree of memory impairment.

Methods: The current study presents a female in her early 20s, with a high school level of education. She became aware of headaches and drowsiness while working in a restaurant that operated charcoal braziers, and she was urgently transported to our hospital. Her high blood carboxyhemoglobin concentration led to a diagnosis of CO poisoning, but no obvious abnormalities were found by brain magnetic resonance imaging (MRI) and physical examinations. She underwent a series of hyperbaric oxygen therapies. One year after CO poisoning, she consulted a psychiatrist due to her own awareness of gradually worsening memory function. She was assessed by brain MRI and standard neuropsychological tests every 6 months for 1 year.

Results: Her neuropsychological profile showed the impairment of memory function according to a low score of Delayed Recall Index of Wechsler Memory Scale-Revised. At 320 days after CO poisoning, her hippocampal volume had decreased by 3%. Her memory function was found to have improved at 530 days after CO poisoning. Of note, during this period, her hippocampal volume had increased by approximately 7%.

Conclusions: This report suggests that a clinician should conduct careful neuropsychological examinations to avoid overlooking mild sequelae of CO poisoning, even if a general assessment of brain MRI is normal.
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http://dx.doi.org/10.1093/arclin/acaa050DOI Listing
January 2021

Binding of Dopamine D1 Receptor and Noradrenaline Transporter in Individuals with Autism Spectrum Disorder: A PET Study.

Cereb Cortex 2020 11;30(12):6458-6468

Department of Functional Brain Imaging, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Chiba 263-8555, Japan.

Although previous studies have suggested the involvement of dopamine (DA) and noradrenaline (NA) neurotransmissions in the autism spectrum disorder (ASD) pathophysiology, few studies have examined these neurotransmissions in individuals with ASD in vivo. Here, we investigated DA D1 receptor (D1R) and noradrenaline transporter (NAT) binding in adults with ASD (n = 18) and neurotypical controls (n = 20) by utilizing two different PET radioligands, [11C]SCH23390 and (S,S)-[18F]FMeNER-D2, respectively. We found no significant group differences in DA D1R (striatum, anterior cingulate cortex, and temporal cortex) or NAT (thalamus and pons) binding. However, in the ASD group, there were significant negative correlations between DA D1R binding (striatum, anterior cingulate cortex and temporal cortex) and the "attention to detail" subscale score of the Autism Spectrum Quotient. Further, there was a significant positive correlation between DA D1R binding (temporal cortex) and emotion perception ability assessed by the neurocognitive battery. Associations of NAT binding with empathic abilities and executive function were found in controls, but were absent in the ASD group. Although a lack of significant group differences in binding might be partly due to the heterogeneity of ASD, our results indicate that central DA and NA function might play certain roles in the clinical characteristics of ASD.
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http://dx.doi.org/10.1093/cercor/bhaa211DOI Listing
November 2020

Atypical spatial frequency dependence of visual metacognition among schizophrenia patients.

Neuroimage Clin 2020 26;27:102296. Epub 2020 May 26.

Center for Information and Neural Networks (CiNet), NICT, Japan; Japan Science and Technology Agency (JST), PRESTO, Japan.

Although altered early stages of visual processing have been reported among schizophrenia patients, how such atypical visual processing may affect higher-level cognition remains largely unknown. Here we tested the hypothesis that metacognitive performance may be atypically modulated by spatial frequency (SF) of visual stimuli among individuals with schizophrenia, given their altered magnocellular function. To study the effect of SF on metacognitive performance, we asked patients and controls to perform a visual detection task on gratings with different SFs and report confidence, and analyzed the data using the signal detection theoretic measure meta-d'. Control subjects showed better metacognitive performance after yes- (stimulus presence) than after no- (stimulus absence) responses ('yes-response advantage') for high SF (HSF) stimuli but not for low SF (LSF) stimuli. The patients, to the contrary, showed a 'yes-response advantage' not only for HSF but also for LSF stimuli, indicating atypical SF dependency of metacognition. An fMRI experiment using the same task revealed that the dorsolateral prefrontal cortex (DLPFC), known to be crucial for metacognition, shows activity mirroring the behavioral results: decoding accuracy of perceptual confidence in DLPFC was significantly higher for HSF than for LSF stimuli in controls, whereas this decoding accuracy was independent of SF in patients. Additionally, the functional connectivity of DLPFC with parietal and visual areas was modulated by SF and response type (yes/no) in a different manner between controls and patients. While individuals without schizophrenia may flexibly adapt metacognitive computations across SF ranges, patients may employ a different mechanism that is independent of SF. Because visual stimuli of low SF have been linked to predictive top-down processing, this may reflect atypical functioning in these processes in schizophrenia.
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http://dx.doi.org/10.1016/j.nicl.2020.102296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327871PMC
March 2021

Benzodiazepines Reduce Relapse and Recurrence Rates in Patients with Psychotic Depression.

J Clin Med 2020 Jun 21;9(6). Epub 2020 Jun 21.

Department of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.

The long-term use of benzodiazepines is not recommended for the treatment of major depressive disorder (MDD) due to the risk of adverse effects, including dependence, falls, dementia, mortality and the lack of evidence of effectiveness for symptoms other than anxiety. However, there are many patients with MDD for whom antidepressants are co-administrated with benzodiazepines. This study aimed to identify whether the use of benzodiazepines is associated with a lower risk of relapse or recurrence of MDD in some patients, and the characteristics of these patients. Kaplan-Meier survival analysis was used to quantify the relapse and recurrence of MDD in 108 patients with MDD who achieved remission during hospitalization. Among them, 26 patients had been diagnosed with severe MDD with psychotic features. There was no significant difference in the rate of relapse/recurrence between patients with and without benzodiazepines when all patients were analyzed together. However, among the 26 patients with psychotic depression, 21.2% in the benzodiazepine group and 75.0% in the non-benzodiazepine group experienced relapse (log rank = 0.0040). Kaplan-Meier survival analysis revealed that this effect was dose-dependent. The adjunctive use of benzodiazepines may reduce relapse/recurrence rates in patients with severe MDD with psychotic features.
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http://dx.doi.org/10.3390/jcm9061938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356546PMC
June 2020

Framing effects on financial and health problems in gambling disorder.

Addict Behav 2020 11 10;110:106502. Epub 2020 Jun 10.

Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; Department of Psychiatry, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address:

Gambling disorder (GD) patients show excessively risky decision-making in the financial domain. We aimed to clarify whether GD patients show risky decision-making in domain-general or in domain-specific. Furthermore, we also investigated the effect of the well-known cognitive bias, the framing effect on GD's decision-making under risk. Sixty-two male GD patients and 74 age-matched healthy male controls (HC) conducted a risky choice task in which they should choose solutions for difficult situations between a sure and a risky option that had the same expectations. Six situations were prepared for each financial and health domain. For each domain, three situations were presented with options using positive frames, and the other three situations were presented with options using negative frames. The results showed that GD chose more risky options in the financial domain with positive frames than HC, but chose comparably in the financial domain with negative frames, whereas GD and HC chose comparably in the health domain regardless of the frames. Thus, GD showed risky decision-making in domain-specific. In addition, the results indicate the importance of considering the influence of the framing effect for assessment of risky decision-making by GD. Domains and the influence of the framing effect should be considered when decision-making patterns of neuropsychiatric disorders are studied.
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http://dx.doi.org/10.1016/j.addbeh.2020.106502DOI Listing
November 2020

Overlapping but Asymmetrical Relationships Between Schizophrenia and Autism Revealed by Brain Connectivity.

Schizophr Bull 2020 Apr 17. Epub 2020 Apr 17.

Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

Although the relationship between schizophrenia spectrum disorder (SSD) and autism spectrum disorder (ASD) has long been debated, it has not yet been fully elucidated. The authors quantified and visualized the relationship between ASD and SSD using dual classifiers that discriminate patients from healthy controls (HCs) based on resting-state functional connectivity magnetic resonance imaging. To develop a reliable SSD classifier, sophisticated machine-learning algorithms that automatically selected SSD-specific functional connections were applied to Japanese datasets from Kyoto University Hospital (N = 170) including patients with chronic-stage SSD. The generalizability of the SSD classifier was tested by 2 independent validation cohorts, and 1 cohort including first-episode schizophrenia. The specificity of the SSD classifier was tested by 2 Japanese cohorts of ASD and major depressive disorder. The weighted linear summation of the classifier's functional connections constituted the biological dimensions representing neural classification certainty for the disorders. Our previously developed ASD classifier was used as ASD dimension. Distributions of individuals with SSD, ASD, and HCs s were examined on the SSD and ASD biological dimensions. We found that the SSD and ASD populations exhibited overlapping but asymmetrical patterns in the 2 biological dimensions. That is, the SSD population showed increased classification certainty for the ASD dimension but not vice versa. Furthermore, the 2 dimensions were correlated within the ASD population but not the SSD population. In conclusion, using the 2 biological dimensions based on resting-state functional connectivity enabled us to discover the quantified relationships between SSD and ASD.
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http://dx.doi.org/10.1093/schbul/sbaa021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505174PMC
April 2020

Primary functional brain connections associated with melancholic major depressive disorder and modulation by antidepressants.

Sci Rep 2020 02 26;10(1):3542. Epub 2020 Feb 26.

Department of Psychiatry and Neurosciences, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.

The limited efficacy of available antidepressant therapies may be due to how they affect the underlying brain network. The purpose of this study was to develop a melancholic MDD biomarker to identify critically important functional connections (FCs), and explore their association to treatments. Resting state fMRI data of 130 individuals (65 melancholic major depressive disorder (MDD) patients, 65 healthy controls) were included to build a melancholic MDD classifier, and 10 FCs were selected by our sparse machine learning algorithm. This biomarker generalized to a drug-free independent cohort of melancholic MDD, and did not generalize to other MDD subtypes or other psychiatric disorders. Moreover, we found that antidepressants had a heterogeneous effect on the identified FCs of 25 melancholic MDDs. In particular, it did impact the FC between left dorsolateral prefrontal cortex (DLPFC)/inferior frontal gyrus (IFG) and posterior cingulate cortex (PCC)/precuneus, ranked as the second 'most important' FC based on the biomarker weights, whilst other eight FCs were normalized. Given that left DLPFC has been proposed as an explicit target of depression treatments, this suggest that the limited efficacy of antidepressants might be compensated by combining therapies with targeted treatment as an optimized approach in the future.
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http://dx.doi.org/10.1038/s41598-020-60527-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044159PMC
February 2020

Brain and behavioral alterations in subjects with social anxiety dominated by empathic embarrassment.

Proc Natl Acad Sci U S A 2020 02 10;117(8):4385-4391. Epub 2020 Feb 10.

Department of Art, School of Arts, Design and Architecture, Aalto University, FI-00076 Espoo, Finland

Social-anxiety disorder involves a fear of embarrassing oneself in the presence of others. Taijin-kyofusho (TKS), a subtype common in East Asia, additionally includes a fear of embarrassing others. TKS individuals are hypersensitive to others' feelings and worry that their physical or behavioral defects humiliate others. To explore the underlying neurocognitive mechanisms, we compared TKS ratings with questionnaire-based empathic disposition, cognitive flexibility (set-shifting), and empathy-associated brain activity in 23 Japanese adults. During 3-tesla functional MRI, subjects watched video clips of badly singing people who expressed either authentic embarrassment (EMBAR) or hubristic pride (PRIDE). We expected the EMBAR singers to embarrass the viewers via emotion-sharing involving affective empathy (affEMP), and the PRIDE singers to embarrass via perspective-taking involving cognitive empathy (cogEMP). During affEMP (EMBAR > PRIDE), TKS scores correlated positively with dispositional affEMP (personal-distress dimension) and with amygdala activity. During cogEMP (EMBAR < PRIDE), TKS scores correlated negatively with cognitive flexibility and with activity of the posterior superior temporal sulcus/temporoparietal junction (pSTS/TPJ). Intersubject correlation analysis implied stronger involvement of the anterior insula, inferior frontal gyrus, and premotor cortex during affEMP than cogEMP and stronger involvement of the medial prefrontal cortex, posterior cingulate cortex, and pSTS/TPJ during cogEMP than affEMP. During cogEMP, the whole-brain functional connectivity was weaker the higher the TKS scores. The observed imbalance between affEMP and cogEMP, and the disruption of functional brain connectivity, likely deteriorate cognitive processing during embarrassing situations in persons who suffer from other-oriented social anxiety dominated by empathic embarrassment.
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http://dx.doi.org/10.1073/pnas.1918081117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049137PMC
February 2020

Role of the right temporoparietal junction in intergroup bias in trust decisions.

Hum Brain Mapp 2020 04 19;41(6):1677-1688. Epub 2019 Dec 19.

Medical Institute of Developmental Disabilities Research, Showa University, Setagaya-ku, Tokyo, Japan.

Intergroup bias, which is the tendency to behave more positively toward an in-group member than toward an out-group member, is pervasive in real life. In particular, intergroup bias in trust decisions substantially influences multiple areas of life and thus better understanding of this tendency can provide significant insights into human social behavior. Although previous functional magnetic resonance imaging studies showed the involvement of the right temporoparietal junction (TPJ) in intergroup trust bias, a causal relationship between the two has rarely been explored. By combining repetitive transcranial magnetic stimulation and a newly developed trust game task, we investigated the causal role of the right TPJ in intergroup bias in trust decisions. In the trust game task, the counterpart's group membership (in-group or out-group) and reciprocity were manipulated. We applied either neuronavigated inhibitory continuous theta burst stimulation (cTBS) or sham stimulation over the right TPJ before performing the trust game task in healthy volunteers. After the sham stimulation, the participants' degrees of investments with in-group members were significantly higher than those with out-group members. However, after cTBS to the right TPJ, this difference was not observed. The current results extend previous findings by showing that the causal roles of the right TPJ can be observed in intergroup bias in trust decisions. Our findings add to our understanding of the mechanisms of human social behavior.
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http://dx.doi.org/10.1002/hbm.24903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268017PMC
April 2020

Detection of autoantibodies against GABARα1 in patients with schizophrenia.

Schizophr Res 2020 Feb 2;216:543-546. Epub 2019 Dec 2.

Department of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.

Recent studies have identified autoantibodies against synaptic molecules in patients with encephalitis. Autoantibodies against the N-Methyl-d-Aspartate receptor have been reported in patients with schizophrenia; however, autoantibodies against other molecules are yet to be identified. This study used a cell-based assay to examine serum samples from individuals with schizophrenia and healthy controls. The results showed that 5 (8.6%) of 57 patients with schizophrenia harbor autoantibodies against the α1 subunit of the γ-aminobutyric acid A receptor (GABARα1), which are currently not know to be linked to the pathology of this disease. Some patients showed markedly high antibody titers (i.e., 1:10,000-100,000). None of the heathy control subjects were positive for GABARα1 antibodies. Therefore, these autoantibodies may form the basis of GABA-mediated pathology in a subgroup of patients with schizophrenia.
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http://dx.doi.org/10.1016/j.schres.2019.10.007DOI Listing
February 2020

Very early-onset of RBD with ADHD: a case report study.

Neurocase 2020 02 28;26(1):60-63. Epub 2019 Nov 28.

Department of sleep medicine, Ureshinogaoka Samariyabito Hospital, Okinawa, Japan.

We experienced a case of very early-onset REM sleep behavior disorder (RBD) with ADHD. This case showed typical RBD symptoms with REM sleep without atonia on polysomnography. Methylphenidate, which enhances the dopamine system, attenuated his ADHD symptoms but not RBD symptoms. We speculate that the dysfunction of the laterodorsal tegmental nucleus in the pontine was responsible for the symptoms of RBD and ADHD in this case. Very early-onset RBD is rare, and its profile is not well known. ADHD with dysfunction in the laterodorsal tegmental nucleus may form asubtype of ADHD that is commonly comorbid with very early-onset RBD.
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http://dx.doi.org/10.1080/13554794.2019.1697823DOI Listing
February 2020

A positive shift in resting-state functional connectivity between the insula and default mode network regions reflects the duration of illness in gambling disorder patients without lifetime substance abuse.

Psychiatry Res Neuroimaging 2020 01 14;295:111018. Epub 2019 Nov 14.

Department of Psychiatry, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahararacho, Sakyo-ku, Kyoto 606-8507, Japan; Medical Institute of Developmental Disabilities Research, Showa University Karasuyama Hospital, 6-11-11 Kitakarasuyama, Setagaya-ku, Tokyo 157-8577, Japan; Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. Electronic address:

The insula is considered an important structure involved in addiction and in the context of dynamic activity switching between large-scale brain networks, such as the default mode network (DMN) and the central executive network. Although insular-DMN resting-state functional connectivity (rsFC), which could affect such switching, has been examined in substance addiction populations, the results have been inconsistent, partly because of the confounding neural effects of the abused substances. To investigate this subject, using MRI, we examined insular-DMN rsFC in gambling disorder (GD) patients without a history of substance use. We examined rsFC between insular seeds and DMN regions of interest during rest in 23 GD patients and 27 age-, sex-, handedness-, and high education rate-matched healthy control (HC) subjects. We found a positive shift in insular-DMN rsFC in GD patients compared with HC subjects. Furthermore, the connectivity strength between insular seed regions and DMN regions was positively correlated with illness duration in GD patients. This alteration might affect switching between large-scale brain networks, potentially leading to a preoccupation with gambling as well as various types of cognitive impairments. Our results could clarify the controversial findings regarding substance addiction and enhance the system-level understanding of addiction.
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http://dx.doi.org/10.1016/j.pscychresns.2019.111018DOI Listing
January 2020

Impact of past experiences on decision-making in autism spectrum disorder.

Eur Arch Psychiatry Clin Neurosci 2020 Dec 26;270(8):1063-1071. Epub 2019 Sep 26.

Medical Institute of Developmental Disabilities Research, Showa University, 6-11-11 Kita-karasuyama, Setagaya-ku, Tokyo, 157-8577, Japan.

People are often influenced by past costs in their current decision-making, thus succumbing to a well-known bias recognized as the sunk cost effect. A recent study showed that the sunk cost effect is attenuated in individuals with autism spectrum disorder (ASD). However, the study only addressed one situation of utilization decision by focusing on the choice between similar attractive alternatives with different levels of sunk costs. Thus, it remains unclear how individuals with ASD behave under sunk costs in different types of decision situations, particularly progress decisions, in which the decision-maker allocates additional resources to an initially chosen alternative. The sunk cost effect in progress decisions was estimated using an economic task designed to assess the effect of the past investments on current decision-making. Twenty-four individuals with ASD and 21 age-, sex-, smoking status-, education-, and intelligence quotient-level-matched typical development (TD) subjects were evaluated. The TD participants were more willing to make the second incremental investment if a previous investment was made, indicating that their decisions were influenced by sunk costs. However, unlike the TD group, the rates of investments were not significantly increased after prior investments in the ASD group. The results agree with the previous evidence of a reduced sensitivity to context stimuli in individuals with ASD and help us obtain a broader picture of the impact of sunk costs on their decision-making. Our findings will contribute to a better understanding of ASD and may be useful in addressing practical implications of their socioeconomic behavior.
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http://dx.doi.org/10.1007/s00406-019-01071-4DOI Listing
December 2020
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