Publications by authors named "Toshiya Murai"

184 Publications

Novel 3-D action video game mechanics reveal differentiable cognitive constructs in young players, but not in old.

Sci Rep 2022 Jul 21;12(1):11751. Epub 2022 Jul 21.

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

Video game research predominantly uses a "one game-one function" approach-researchers deploy a constellation of task-like minigames to span multiple domains or consider a complex video game to essentially represent one cognitive construct. To profile cognitive functioning in a more ecologically valid setting, we developed a novel 3-D action shooter video game explicitly designed to engage multiple cognitive domains. We compared gameplay data with results from a web-based cognitive battery (WebCNP) for 158 participants (aged 18-74). There were significant negative main effects on game performance from age and gender, even when controlling for prior video game exposure. Among younger players, game mechanics displayed significant and unique correlations to cognitive constructs such as aim accuracy with attention and stealth with abstract thinking within the same session. Among older players the relation between game components and cognitive domains was unclear. Findings suggest that while game mechanics within a single game can be deconstructed to correspond to existing cognitive metrics, how game mechanics are understood and utilized likely differs between the young and old. We argue that while complex games can be utilized to measure distinct cognitive functions, the translation scheme of gameplay to cognitive function should not be one-size-fits-all across all demographics.
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http://dx.doi.org/10.1038/s41598-022-15679-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304325PMC
July 2022

Altered white matter microstructure and neurocognitive function of HIV-infected patients with low nadir CD4.

J Neurovirol 2022 Jul 1. Epub 2022 Jul 1.

Department of Psychiatry, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan.

Altered white matter microstructure has been reported repeatedly using diffusion tensor imaging (DTI) in HIV-associated neurocognitive disorders. However, the associations between neurocognitive deficits and impaired white matter remains obscure due to frequent physical and psychiatric comorbidities in the patients. Severe immune suppression, reflected by low nadir CD4 T-cell counts, is reported to be associated with the neurocognitive deficits in the patients. In the present study, we examined white matter integrity using DTI and tract-based spatial statistics (TBSS), and neurocognitive functions using a battery of tests, in 15 HIV-infected patients with low nadir CD4, 16 HIV-infected patients with high nadir CD4, and 33 age- and sex-matched healthy controls. As DTI measures, we analyzed fractional anisotropy (FA) and mean diffusivity (MD). In addition, we investigated the correlation between white matter impairments and neurocognitive deficits. Among the three participant groups, the patients with low nadir CD4 showed significantly lower performance in processing speed and motor skills, and had significantly increased MD in widespread regions of white matter in both hemispheres. In the patients with low nadir CD4, there was a significant negative correlation between motor skills and MD in the right motor tracts, as well as in the corpus callosum. In summary, this study may provide white matter correlates of neurocognitive deficits in HIV-infected patients with past severe immune suppression as legacy effects.
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http://dx.doi.org/10.1007/s13365-022-01053-8DOI Listing
July 2022

Cortical changes in patients with schizophrenia across two ethnic backgrounds.

Sci Rep 2022 Jun 25;12(1):10810. Epub 2022 Jun 25.

LVR-Hospital Essen, Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Duisburg-Essen, Virchowstr. 174, 45147, Essen, Germany.

While it is known that cultural background influences the healthy brain, less is known about how it affects cortical changes in schizophrenia. Here, we tested whether schizophrenia differentially affected the brain in Japanese and German patients. In a sample of 155 patients with a diagnosis of schizophrenia and 191 healthy controls from Japan and Germany, we acquired 3 T-MRI of the brain. We subsequently compared cortical thickness and cortical surface area to identify whether differences between healthy controls and patients might be influenced by ethnicity. Additional analyses were performed to account for effects of duration of illness and medication. We found pronounced interactions between schizophrenia and cultural background in the cortical thickness of several areas, including the left inferior and middle temporal gyrus, as well as the right lateral occipital cortex. Regarding cortical surface area, interaction effects appeared in the insula and the occipital cortex, among others. Some of these brain areas are related to the expression of psychotic symptoms, which are known to differ across cultures. Our results indicate that cultural background impacts cortical structures in different ways, probably resulting in varying clinical manifestations, and call for the inclusion of more diverse samples in schizophrenia research.
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http://dx.doi.org/10.1038/s41598-022-14914-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233668PMC
June 2022

Cross-Disorder Analysis of Genic and Regulatory Copy Number Variations in Bipolar Disorder, Schizophrenia, and Autism Spectrum Disorder.

Biol Psychiatry 2022 Apr 22. Epub 2022 Apr 22.

Department of Pathology of Mental Diseases, National Institute of Mental Health National Center of Neurology and Psychiatry, Tokyo, Japan; Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan; Japan Community Health Care Organization Osaka Hospital, Osaka, Japan.

Background: We aimed to determine the similarities and differences in the roles of genic and regulatory copy number variations (CNVs) in bipolar disorder (BD), schizophrenia (SCZ), and autism spectrum disorder (ASD).

Methods: Based on high-resolution CNV data from 8708 Japanese samples, we performed to our knowledge the largest cross-disorder analysis of genic and regulatory CNVs in BD, SCZ, and ASD.

Results: In genic CNVs, we found an increased burden of smaller (<100 kb) exonic deletions in BD, which contrasted with the highest burden of larger (>500 kb) exonic CNVs in SCZ/ASD. Pathogenic CNVs linked to neurodevelopmental disorders were significantly associated with the risk for each disorder, but BD and SCZ/ASD differed in terms of the effect size (smaller in BD) and subtype distribution of CNVs linked to neurodevelopmental disorders. We identified 3 synaptic genes (DLG2, PCDH15, and ASTN2) as risk factors for BD. Whereas gene set analysis showed that BD-associated pathways were restricted to chromatin biology, SCZ and ASD involved more extensive and similar pathways. Nevertheless, a correlation analysis of gene set results indicated weak but significant pathway similarities between BD and SCZ or ASD (r = 0.25-0.31). In SCZ and ASD, but not BD, CNVs were significantly enriched in enhancers and promoters in brain tissue.

Conclusions: BD and SCZ/ASD differ in terms of CNV burden, characteristics of CNVs linked to neurodevelopmental disorders, and regulatory CNVs. On the other hand, they have shared molecular mechanisms, including chromatin biology. The BD risk genes identified here could provide insight into the pathogenesis of BD.
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http://dx.doi.org/10.1016/j.biopsych.2022.04.003DOI Listing
April 2022

Neuroimaging at 7 Tesla: a pictorial narrative review.

Quant Imaging Med Surg 2022 Jun;12(6):3406-3435

Human Brain Research Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Neuroimaging using the 7-Tesla (7T) human magnetic resonance (MR) system is rapidly gaining popularity after being approved for clinical use in the European Union and the USA. This trend is the same for functional MR imaging (MRI). The primary advantages of 7T over lower magnetic fields are its higher signal-to-noise and contrast-to-noise ratios, which provide high-resolution acquisitions and better contrast, making it easier to detect lesions and structural changes in brain disorders. Another advantage is the capability to measure a greater number of neurochemicals by virtue of the increased spectral resolution. Many structural and functional studies using 7T have been conducted to visualize details in the white matter and layers of the cortex and hippocampus, the subnucleus or regions of the putamen, the globus pallidus, thalamus and substantia nigra, and in small structures, such as the subthalamic nucleus, habenula, perforating arteries, and the perivascular space, that are difficult to observe at lower magnetic field strengths. The target disorders for 7T neuroimaging range from tumoral diseases to vascular, neurodegenerative, and psychiatric disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy, major depressive disorder, and schizophrenia. MR spectroscopy has also been used for research because of its increased chemical shift that separates overlapping peaks and resolves neurochemicals more effectively at 7T than a lower magnetic field. This paper presents a narrative review of these topics and an illustrative presentation of images obtained at 7T. We expect 7T neuroimaging to provide a new imaging biomarker of various brain disorders.
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http://dx.doi.org/10.21037/qims-21-969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9131333PMC
June 2022

Lurasidone-induced hyperosmolar hyperglycemic syndrome: A case report.

Neuropsychopharmacol Rep 2022 May 24. Epub 2022 May 24.

Department of Psychiatry, Kyoto University Hospital, Kyoto, Japan.

Introduction: Lurasidone has few metabolic adverse effects and is recommended as an alternative when other antipsychotic drugs considerably increase body weight or blood sugar concentrations.

Case Presentation: An 81-year-old man with bipolar disorder developed hyperosmolar hyperglycemic syndrome as a side effect of lurasidone. Routine monitoring of blood glucose concentrations led to the early detection and treatment of this disease, preventing life-threatening complications.

Discussion And Conclusion: We describe a rare case of lurasidone-induced hyperosmolar hyperglycemic syndrome. The mortality rate of this syndrome is estimated to be up to 20%. This rate is significantly higher than that of diabetic ketoacidosis (currently <2%). Although lurasidone is considered to have a low risk of raising blood glucose concentrations, symptoms of hyperglycemia must be evaluated and blood glucose concentrations should be monitored regularly.
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http://dx.doi.org/10.1002/npr2.12259DOI Listing
May 2022

Assessment of Suvorexant and Eszopiclone as Alternatives to Benzodiazepines for Treating Insomnia in Patients With Major Depressive Disorder.

Clin Neuropharmacol 2022 May-Jun 01;45(3):52-60. Epub 2022 Apr 14.

Departments of Clinical Pharmacology and Therapeutics.

Objectives: We investigated the utility of switching from benzodiazepines to suvorexant or eszopiclone to manage benzodiazepine-unresponsive insomnia in patients with major depressive disorder (MDD) in a randomized, open-label study.

Methods: Patients with MDD who have insomnia symptoms (a score of >7 on the Insomnia Severity Index Japanese version [ISI-J]), who had received benzodiazepine treatment for more than 2 weeks (n = 18) were randomized to 4 weeks of suvorexant (20 or 15 mg/d) or eszopiclone (3 or 2 mg/d) treatment. The primary endpoint was an improvement in insomnia severity from baseline assessed by the ISI-J score at 2 and 4 weeks after switching from benzodiazepines. The secondary endpoints included changes in the scores of the Pittsburgh Sleep Quality Index Japanese version, the Beck Depression Inventory II, Generalized Anxiety Disorder 7, the digit span test, and the digit symbol substitution test from baseline. Adverse events were recorded throughout the study.

Results: Patients taking suvorexant or eszopiclone had improved ISI-J scores (-4.3 for suvorexant and -4.1 for eszopiclone at week 4; P = 0.04 for eszopiclone). Both drugs tended to improve the Beck Depression Inventory II and Generalized Anxiety Disorder 7 scores 2 and 4 weeks after switching. The Pittsburgh Sleep Quality Index Japanese version, digit symbol substitution test, and digit span test scores and the incidence of adverse events did not change from baseline.

Conclusions: Switching to suvorexant or eszopiclone was well tolerated and improved the severity of benzodiazepine-unresponsive insomnia in MDD patients. Both drugs could be beneficial alternatives to benzodiazepines for treating insomnia in MDD patients.
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http://dx.doi.org/10.1097/WNF.0000000000000499DOI Listing
May 2022

Epigenetic aging in Williams syndrome.

J Child Psychol Psychiatry 2022 Apr 13. Epub 2022 Apr 13.

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

Background: Williams syndrome (WS) is a rare genetic disorder caused by a microdeletion at the 7q11.23 region and is characterized by diverse symptoms encompassing physical and cognitive features. WS was reported to be associated to altered DNA methylation (DNAm) patterns. However, due to the limited information from long-term studies, it remains unclear whether WS accelerates aging. Genome-wide DNAm profiles can serve as "epigenetic clocks" to help estimate biological aging along with age-related markers, such as plasma proteins and telomere length.

Methods: We investigated GrimAge, DNAm-based telomere length (DNAmTL), and other epigenetic clocks in blood samples of 32 patients with WS and 32 healthy controls.

Results: We observed a significant acceleration in GrimAge, DNAmTL, and other epigenetic clocks in patients with WS as compared with those of controls. In addition, several GrimAge components, such as adrenomedullin, growth differentiation factor-15, leptin and plasminogen activator inhibitor-1, were altered in patients with WS.

Conclusions: This study provides novel evidence supporting the hypothesis that WS may be associated to accelerated biological aging. A better understanding of the overall underlying biological effects of WS can provide new foundations for improved patient care; thus, long-term follow-up studies are still warranted.
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http://dx.doi.org/10.1111/jcpp.13613DOI Listing
April 2022

Development of a classifier for gambling disorder based on functional connections between brain regions.

Psychiatry Clin Neurosci 2022 Jun 14;76(6):260-267. Epub 2022 Apr 14.

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

Aim: Recently, a machine-learning (ML) technique has been used to create generalizable classifiers for psychiatric disorders based on information of functional connections (FCs) between brain regions at resting state. These classifiers predict diagnostic labels by a weighted linear sum (WLS) of the correlation values of a small number of selected FCs. We aimed to develop a generalizable classifier for gambling disorder (GD) from the information of FCs using the ML technique and examine relationships between WLS and clinical data.

Methods: As a training dataset for ML, data from 71 GD patients and 90 healthy controls (HCs) were obtained from two magnetic resonance imaging sites. We used an ML algorithm consisting of a cascade of an L1-regularized sparse canonical correlation analysis and a sparse logistic regression to create the classifier. The generalizability of the classifier was verified using an external dataset. This external dataset consisted of six GD patients and 14 HCs, and was collected at a different site from the sites of the training dataset. Correlations between WLS and South Oaks Gambling Screen (SOGS) and duration of illness were examined.

Results: The classifier distinguished between the GD patients and HCs with high accuracy in leave-one-out cross-validation (area under curve (AUC = 0.89)). This performance was confirmed in the external dataset (AUC = 0.81). There was no correlation between WLS, and SOGS and duration of illness in the GD patients.

Conclusion: We developed a generalizable classifier for GD based on information of functional connections between brain regions at resting state.
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http://dx.doi.org/10.1111/pcn.13350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322453PMC
June 2022

Depressive symptoms reduce when dorsolateral prefrontal cortex-precuneus connectivity normalizes after functional connectivity neurofeedback.

Sci Rep 2022 02 16;12(1):2581. Epub 2022 Feb 16.

Department of Decoded Neurofeedback (DecNef), Computational Neuroscience Laboratories, Advanced Telecommunications Research Institute International (ATR), Hikaridai 2-2-2. Seika-cho, Soraku, Kyoto, 619-0237, Japan.

Depressive disorders contribute heavily to global disease burden; This is possibly because patients are often treated homogeneously, despite having heterogeneous symptoms with differing underlying neural mechanisms. A novel treatment that can directly influence the neural circuit relevant to an individual patient's subset of symptoms might more precisely and thus effectively aid in the alleviation of their specific symptoms. We tested this hypothesis in a proof-of-concept study using fMRI functional connectivity neurofeedback. We targeted connectivity between the left dorsolateral prefrontal cortex/middle frontal gyrus and the left precuneus/posterior cingulate cortex, because this connection has been well-established as relating to a specific subset of depressive symptoms. Specifically, this connectivity has been shown in a data-driven manner to be less anticorrelated in patients with melancholic depression than in healthy controls. Furthermore, a posterior cingulate dominant state-which results in a loss of this anticorrelation-is expected to specifically relate to an increase in rumination symptoms such as brooding. In line with predictions, we found that, with neurofeedback training, the more a participant normalized this connectivity (restored the anticorrelation), the more related (depressive and brooding symptoms), but not unrelated (trait anxiety), symptoms were reduced. Because these results look promising, this paradigm next needs to be examined with a greater sample size and with better controls. Nonetheless, here we provide preliminary evidence for a correlation between the normalization of a neural network and a reduction in related symptoms. Showing their reproducibility, these results were found in two experiments that took place several years apart by different experimenters. Indicative of its potential clinical utility, effects of this treatment remained one-two months later.Clinical trial registration: Both experiments reported here were registered clinical trials (UMIN000015249, jRCTs052180169).
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http://dx.doi.org/10.1038/s41598-022-05860-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8850610PMC
February 2022

Life Habits and Mental Health: Behavioural Addiction, Health Benefits of Daily Habits, and the Reward System.

Front Psychiatry 2022 27;13:813507. Epub 2022 Jan 27.

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

In this review, the underlying mechanisms of health benefits and the risk of habitual behaviours such as internet use and media multitasking were explored, considering their associations with the reward/motivation system. The review highlights that several routines that are beneficial when undertaken normally may evolve into excessive behaviour and have a negative impact, as represented by "the inverted U-curve model". This is especially critical in the current era, where technology like the internet has become mainstream despite the enormous addictive risk. The understanding of underlying mechanisms of behavioural addiction and optimal level of habitual behaviours for mental health benefits are deepened by shedding light on some findings of neuroimaging studies to have hints to facilitate better management and prevention strategies of addictive problems. With the evolution of the world, and the inevitable use of some technologies that carry the risk of addiction, more effective strategies for preventing and managing addiction are in more demand than before, and the insights of this study are also valuable foundations for future research.
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http://dx.doi.org/10.3389/fpsyt.2022.813507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829329PMC
January 2022

Epigenetic clock analysis and increased plasminogen activator inhibitor-1 in high-functioning autism spectrum disorder.

PLoS One 2022 3;17(2):e0263478. Epub 2022 Feb 3.

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

Background: Autism spectrum disorder (ASD) is characterized by impaired social communication and behavioral problems. An increased risk of premature mortality has been observed in individuals with ASD. Therefore, we hypothesized that biological aging is accelerated in individuals with ASD. Recently, several studies have established genome-wide DNA methylation (DNAm) profiles as 'epigenetic clocks' that can estimate biological aging. In addition, ASD has been associated with differential DNAm patterns.

Methods: We used two independent datasets from blood samples consisting of adult patients with high-functioning ASD and controls: the 1st cohort (38 ASD cases and 31 controls) and the 2nd cohort (6 ASD cases and 10 controls). We explored well-studied epigenetic clocks such as HorvathAge, HannumAge, SkinBloodAge, PhenoAge, GrimAge, and DNAm-based telomere length (DNAmTL). In addition, we investigated seven DNAm-based age-related plasma proteins, including plasminogen activator inhibitor-1 (PAI-1), and smoking status, which are the components of GrimAge.

Results: Compared to controls, individuals with ASD in the 1st cohort, but not in the 2nd cohort, exhibited a trend for increased GrimAge acceleration and a significant increase of PAI-1 levels. A meta-analysis showed significantly increased PAI-1 levels in individuals with ASD compared to controls.

Conclusion: Our findings suggest there is no epigenetic age acceleration in the blood of individuals with ASD. However, this study provides novel evidence regarding increased plasma PAI-1 levels in individuals with high-functioning ASD. These findings suggest PAI-1 may be a biomarker for high-functioning ASD, however, larger studies based on epigenetic clocks and PAI-1 will be necessary to confirm these findings.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0263478PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8812940PMC
March 2022

Extracting Apathy From Depression Syndrome in Traumatic Brain Injury by Using a Clustering Method.

J Neuropsychiatry Clin Neurosci 2022 19;34(2):158-167. Epub 2021 Nov 19.

Medical Innovation Center (Ubukata, Oishi) and Department of Psychiatry (Ueda, Fujimoto, Ueno, Murai), Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Objective: Depression and apathy are common after traumatic brain injury (TBI), and different intervention strategies are recommended for each. However, a differential diagnosis can be difficult in clinical settings, especially given that apathy is considered to be a symptom of depression. In this study, the investigators aimed to isolate apathy from depression among patients with TBI and to examine whether apathy is exclusively associated with the amount of daily activity, as previously reported in the literature.

Methods: Eighty-eight patients with chronic TBI completed the Japanese versions of the 21-item Beck Depression Inventory-II (BDI-II) and the Starkstein Apathy Scale (AS). Daily activity was measured with a 24-hour life log. A hierarchical cluster analysis was applied to divide the BDI-II data into separable components, and components' correlations with results of the AS and 24-hour life log scale were evaluated.

Results: The BDI-II and AS revealed that 37 patients (42.0%) had both depression and apathy. BDI-II data were classified into four separate clusters (somatic symptoms, loss of self-worth, affective symptoms, and apathy symptoms). Loss of self-worth and apathy symptoms subscores were significantly positively correlated with total AS score (r=0.32, p=0.002, and r=0.52, p<0.001, respectively). The apathy symptoms subscore was significantly correlated with the amount of daily activity (r=-0.29, p=0.009).

Conclusions: The findings suggest that the BDI-II can differentiate between apathy and depression among patients with TBI, which is essential when selecting intervention options. Moreover, apathy symptoms predicted patients' real-life daily activity.
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http://dx.doi.org/10.1176/appi.neuropsych.21020046DOI Listing
May 2022

A Call for a Rational Polypharmacy Policy: International Insights From Psychiatrists.

Psychiatry Investig 2021 Nov 5;18(11):1058-1067. Epub 2021 Nov 5.

Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Objective: Recently, rational polypharmacy approaches have been proposed, regardless of the lower risk and cost of monotherapy. Considering monotherapy as first-line treatment and polypharmacy as rational treatment, a balanced attitude toward polypharmacy is recommended. However, the high prevalence of polypharmacy led the Japanese government to establish a polypharmacy reduction policy. Based on this, the association between the policy and psychiatrists' attitude toward polypharmacy has been under debate.

Methods: We developed an original questionnaire about Psychiatrists' attitudes toward polypharmacy (PAP). We compared the PAP scores with the treatment decision-making in clinical case vignettes. Multiple regression analyses were performed to quantify associations of explanatory variables including policy factors and PAP scores. The anonymous questionnaires were administered to psychiatrists worldwide.

Results: The study included 347 psychiatrists from 34 countries. Decision-making toward polypharmacy was associated with high PAP scores. Multiple regression analysis revealed that low PAP scores were associated with the policy factor (β=-0.20, p=0.004). The culture in Korea was associated with high PAP scores (β=0.34, p<0.001), whereas the culture in India and Nepal were associated with low scores (β=-0.15, p=0.01, and β=-0.17, p=0.006, respectively).

Conclusion: Policy on polypharmacy may influence psychiatrists' decision-making. Thus, policies considering rational polypharmacy should be established.
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http://dx.doi.org/10.30773/pi.2021.0169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600221PMC
November 2021

Structural brain changes in severe and enduring anorexia nervosa: A multimodal magnetic resonance imaging study of gray matter volume, cortical thickness, and white matter integrity.

Psychiatry Res Neuroimaging 2021 12 2;318:111393. Epub 2021 Oct 2.

Department of Psychiatry, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawaracho, Sakyo-ku, Kyoto, Japan.

Whole-brain T1-weighted imaging and diffusion tensor imaging was performed in 35 adult women with anorexia nervosa (AN) and 35 healthy controls. We conducted voxel-based group comparisons for gray matter volume (GMV), cortical thickness (CT), and fractional anisotropy (FA) values, using age and total intracranial volume as nuisance covariates. We then conducted the same group comparisons for these three measures, but this time also controlled for the following global pathological measures: total GMV, mean CT across the whole brain, and mean FA across the entire white matter skeleton. Compared with the healthy controls, AN patients had lower GMV and CT in widespread cortical regions, and smaller FA values in widespread white matter regions. After controlling for global parameters, almost all of the differences between the two groups disappeared, except for higher CT in the medial orbital gyrus and parietal operculum in the AN group. Structural brain changes in AN are likely to be composed of both global and region-specific changes. The former changes are likely to have a dominant impact, while the latter changes might in part explain the disease-specific pathophysiology of AN.
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http://dx.doi.org/10.1016/j.pscychresns.2021.111393DOI Listing
December 2021

Structural brain changes in severe and enduring anorexia nervosa: A multimodal magnetic resonance imaging study of gray matter volume, cortical thickness, and white matter integrity.

Psychiatry Res Neuroimaging 2021 12 2;318:111393. Epub 2021 Oct 2.

Department of Psychiatry, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawaracho, Sakyo-ku, Kyoto, Japan.

Whole-brain T1-weighted imaging and diffusion tensor imaging was performed in 35 adult women with anorexia nervosa (AN) and 35 healthy controls. We conducted voxel-based group comparisons for gray matter volume (GMV), cortical thickness (CT), and fractional anisotropy (FA) values, using age and total intracranial volume as nuisance covariates. We then conducted the same group comparisons for these three measures, but this time also controlled for the following global pathological measures: total GMV, mean CT across the whole brain, and mean FA across the entire white matter skeleton. Compared with the healthy controls, AN patients had lower GMV and CT in widespread cortical regions, and smaller FA values in widespread white matter regions. After controlling for global parameters, almost all of the differences between the two groups disappeared, except for higher CT in the medial orbital gyrus and parietal operculum in the AN group. Structural brain changes in AN are likely to be composed of both global and region-specific changes. The former changes are likely to have a dominant impact, while the latter changes might in part explain the disease-specific pathophysiology of AN.
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http://dx.doi.org/10.1016/j.pscychresns.2021.111393DOI Listing
December 2021

Utility of a novel tablet computer software for memory impairment in participants with brain injuries: A randomized control trial.

Neuropsychol Rehabil 2021 Oct 12:1-18. Epub 2021 Oct 12.

Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences, Hyogo, Japan.

This study examined the effectiveness of a novel information and communication technology (ICT) tool developed for external memory compensation to improve memory function in participants with brain injuries. In this 3-month randomized control study, participants with memory impairment secondary to brain injury were randomly assigned on a 1:1 basis to either intervention (the ICT tool [ARATA]) or 3-month waitlist control groups. This study's primary outcome measure was memory-related difficulties in everyday life, assessed using the Everyday Memory Checklist (EMC). Secondary outcomes included tests for memory function and psychosocial status, all of which were administered by blinded assessors. Seventy-eight participants (53 males, 25 females; mean age, 43.5 ± 12.7 [SD] years) were enrolled and 39 participants were allocated to each group (intervention and control). There was no significant difference in EMC scores between the two groups throughout the study (mean 0.26; 95% CI: -2.55-3.07; =0.853); however, the intervention group scored significantly higher on the Rivermead Behavioural Memory and General Self-Efficacy tests compared to the control group. While the ICT tool did not improve the primary study outcome, evidence suggests that the ICT tool can improve memory functions related to activities of daily living.
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http://dx.doi.org/10.1080/09602011.2021.1987276DOI Listing
October 2021

Establishment of induced pluripotent stem cells from schizophrenia discordant fraternal twins.

Stem Cell Res 2021 08 14;55:102504. Epub 2021 Aug 14.

iPSC-based Drug-Discovery and Development Team, RIKEN BioResource Research Center, Kyoto, Japan; Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan; Medical-risk Avoidance Based on iPS Cells Team, RIKEN Center for Advanced Intelligence Project (AIP), Kyoto, Japan. Electronic address:

Schizophrenia (SCZ) is one of the major psychiatric disorders. The genetic factor is certainly influential in the onset of the disease but is not decisive. There is no identified molecular/cellular marker of the disease, and the pathomechanism is still unknown. In this study, we generated human induced pluripotent stem cells (iPSCs) derived from SCZ-discordant fraternal twins, and they could contribute to elucidation of the pathomechanism of SCZ.
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http://dx.doi.org/10.1016/j.scr.2021.102504DOI 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

Exploring the Relationship Between Mental Well-Being, Exercise Routines, and the Intake of Image and Performance Enhancing Drugs During the Coronavirus Disease 2019 Pandemic: A Comparison Across Sport Disciplines.

Front Psychol 2021 6;12:689058. Epub 2021 Jul 6.

Organization for Promotion of Neurodevelopmental Disorder Research, Kyoto, Japan.

Physical distancing under the coronavirus disease 2019 (COVID-19) pandemic had a significant impact on lifestyles, including exercise routines. In this study, we examined the relationship between mental health and addictive behaviors, such as excessive exercise and the use of image and performance enhancing drugs (IPEDs) across 12 sport disciplines. A large cross-sectional sample of the adult population ( = 2,295) was surveyed. The mean age was 33.09 ( = 11.40). The number of male participants was 668 (30.0%). The use of IPEDs was assessed in conjunction with psychometric measures such as the Exercise Addiction Inventory (EAI) and the Appearance Anxiety Inventory (AAI). The participants were grouped into activity group (AG) and non-activity group (NAG) according to the presence or absence of their exercise habits. The results were compared between these groups, as well as across sport disciplines, while taking into account the relationship between different psychological measures and IPEDs consumption. The frequency of IPEDs use was higher among AG (34.6%) than NAG (14.6%), although AG participants reported less history of addictions (7.1%) than NAG (11.8%). The logistic regression analysis revealed that scores equal to or above cutoff points, in both the EAI and AAI, predicted the IPEDs use. Regarding the differences across the various sport disciplines, those who were involved in practicing Weight Lifting and Cross Fit were found to be more at risk of excessive exercising and more inclined to use a wide range of IPEDs. Although exercise could help to increase well-being and prevent addictions during the COVID-19 pandemic, our results show that those in the AG are particularly vulnerable to excessive IPEDs use. Sport disciplines associated with higher EAI and AAI scores have also shown a higher tendency to excessive IPEDs use. Furthermore, the factor of having above the cutoff scores in EAI or AAI in each sport could indicate larger IPEDs consumption regardless of the discipline. In light of the current findings, it is necessary to better define the "non-excessive" levels of exercise in various sport disciplines and an adequate intake of IPEDs to ensure the safety and well-being of people during a pandemic.
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http://dx.doi.org/10.3389/fpsyg.2021.689058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290335PMC
July 2021

The Molecular Basis of Depression: Implications of Sex-Related Differences in Epigenetic Regulation.

Front Mol Neurosci 2021 1;14:708004. Epub 2021 Jul 1.

SK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Major depressive disorder (MDD) is a leading cause of disability worldwide. Although the etiology and pathophysiology of MDD remain poorly understood, aberrant neuroplasticity mediated by the epigenetic dysregulation of gene expression within the brain, which may occur due to genetic and environmental factors, may increase the risk of this disorder. Evidence has also been reported for sex-related differences in the pathophysiology of MDD, with female patients showing a greater severity of symptoms, higher degree of functional impairment, and more atypical depressive symptoms. Males and females also differ in their responsiveness to antidepressants. These clinical findings suggest that sex-dependent molecular and neural mechanisms may underlie the development of depression and the actions of antidepressant medications. This review discusses recent advances regarding the role of epigenetics in stress and depression. The first section presents a brief introduction of the basic mechanisms of epigenetic regulation, including histone modifications, DNA methylation, and non-coding RNAs. The second section reviews their contributions to neural plasticity, the risk of depression, and resilience against depression, with a particular focus on epigenetic modulators that have causal relationships with stress and depression in both clinical and animal studies. The third section highlights studies exploring sex-dependent epigenetic alterations associated with susceptibility to stress and depression. Finally, we discuss future directions to understand the etiology and pathophysiology of MDD, which would contribute to optimized and personalized therapy.
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http://dx.doi.org/10.3389/fnmol.2021.708004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282210PMC
July 2021

The relationship between attention and avoidance coping in anorexia nervosa: functional magnetic resonance imaging study.

BJPsych Open 2021 Jul 13;7(4):e130. Epub 2021 Jul 13.

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

Background: Numerous studies have demonstrated attentional control difficulties and high avoidance coping in patients with anorexia nervosa. Attention is a critical coping resource because it enables individuals to demonstrate self-control and complete goal-directed behaviours.

Aims: We aimed to examine whether attentional control difficulty is related to high avoidance coping, and investigate the neural underpinnings of attentional control difficulties in individuals with anorexia nervosa.

Method: Twenty-three patients with anorexia nervosa and 17 healthy controls completed questionnaires that assessed attention and coping, and underwent functional magnetic resonance imaging while performing a go/no-go task.

Results: Patients with anorexia nervosa showed weaker attentional control, higher omission error rates and higher avoidance coping compared with healthy controls. Attentional control difficulty was associated with higher avoidance coping in both groups. Functional magnetic resonance imaging analysis showed less deactivation in regions representing internal mental processing, such as the praecuneus, cuneus and left lingual gyrus, during the no-go condition. Moreover, weakened deactivation of the left lingual gyrus was associated with higher commission error rate in the anorexia nervosa group.

Conclusions: Our results suggest that patients with anorexia nervosa may have difficulty in maintaining attention to external ongoing events because of disturbance from internal self-related thought, and support the notion that attentional control difficulties underlie the frequent use of avoidance coping in anorexia nervosa.
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http://dx.doi.org/10.1192/bjo.2021.963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281280PMC
July 2021

Sevoflurane in electroconvulsive therapy: A systematic review and meta-analysis of randomised trials.

J Psychiatr Res 2021 09 16;141:16-25. Epub 2021 Jun 16.

Department of Neuropsychiatry, Kansai Medical University, Moriguchi-shi, Osaka, 570-8506, Japan. Electronic address:

Sevoflurane is the most commonly used inhaled anaesthetic in electroconvulsive therapy (ECT). The objective of this study was to provide an up-to-date and comprehensive review on how the use of sevoflurane affects seizure adequacy (seizure duration and postictal suppression index [PSI]) and circulatory dynamics in ECT. We performed a meta-analysis of RCTs that investigated seizure adequacy and circulatory dynamics in patients treated with ECT using sevoflurane (sevoflurane group) and intravenous anaesthetics (non-sevoflurane group). A total of 12 RCTs (377 patients and 1339 ECT sessions) were included. Sevoflurane significantly decreased the electroencephalogram (EEG) seizure durations in comparison with intravenous anaesthetics, whereas no significant difference was observed in PSI (EEG: 9 studies, standardized mean difference (SMD) = 0.74, 95% confidence interval (CI) = -1.11 to -0.38, p = 0.0002; PSI: 4 studies, SMD = -0.06, CI -0.13 to 0.25, p = 0.59). The use of sevoflurane in ECT significantly increased heart rate (HR) compared with intravenous anaesthetics (9 studies, SMD = 0.31, CI 012-0.51, p = 0.004). In the pre-planned subgroup analysis, sevoflurane significantly reduced seizure duration compared with other types of anaesthetics, including propofol, barbiturates and ketamine. Furthermore, it was found that the risk of adverse events in ECT with sevoflurane were not significantly different from intravenous anaesthetics (6 studies, risk ratio = 1.33, CI 0.95-1.86, p = 0.09), with agitaion being the most common adverse effects. The results of our study suggest that using sevoflurane for ECT significantly reduces seizure duration, increases maximum HR and brings about no difference in the adverse event risk compared with those using intravenous anaesthetics for ECT. Therefore, there may not be compelling evidence favouring sevoflurane use for ECT, except in cases where intravenous access is difficult.
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http://dx.doi.org/10.1016/j.jpsychires.2021.06.030DOI Listing
September 2021

Gene-environment interactions mediate stress susceptibility and resilience through the CaMKIIβ/TARPγ-8/AMPAR pathway.

iScience 2021 May 2;24(5):102504. Epub 2021 May 2.

SK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.

Although stressful events predispose individuals to psychiatric disorders, such as depression, not all people who undergo a stressful life experience become depressed, suggesting that gene-environment interactions (GxE) determine depression risk. The ventral hippocampus (vHPC) plays key roles in motivation, sociability, anhedonia, despair-like behaviors, anxiety, sleep, and feeding, pointing to the involvement of this brain region in depression. However, the molecular mechanisms underlying the cross talk between the vHPC and GxE in shaping behavioral susceptibility and resilience to chronic stress remain elusive. Here, we show that Ca/calmodulin-dependent protein kinase IIβ (CaMKIIβ) activity in the vHPC is differentially modulated in GxE mouse models of depression susceptibility and resilience, and that CaMKIIβ-mediated TARPγ-8 phosphorylation enhances the expression of AMPA receptor subunit GluA1 in the postsynaptic sites to enable stress resilience. We present previously missing molecular mechanisms underlying chronic stress-elicited behavioral changes, providing strategies for preventing and treating stress-related psychiatric disorders.
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http://dx.doi.org/10.1016/j.isci.2021.102504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170005PMC
May 2021

Salient Properties in Bimanual Haptic Volume Perception: Influence of Object Shape, Finger Pair, and Schizotypal Personality Traits.

IEEE Trans Haptics 2021 Oct-Dec;14(4):816-824. Epub 2021 Dec 16.

Bimanual haptic volume perception refers to somatosensory access to volume information through both hands, and the characteristics that influence this perception remain unclear. This article investigated the influence of target object shapes and finger pairs on bimanual haptic perception; in addition, associations of bimanual haptic impairment and schizotypal features in nonpsychotic individuals were investigated. Twenty blindfolded participants bimanually discriminated volume variations in regular solid objects under different shape (tetrahedron, cube, or sphere) and finger pair (high- or low-sensitivity pairs) conditions using a newly developed bimanual haptic volume presentation device. Discrimination thresholds were then associated with schizotypal traits using the Chinese version of the Schizotypal Personality Questionnaire. Target object shape and finger pairs significantly influenced bimanual haptic volume perception. Volume discrimination thresholds were significantly higher with the tetrahedron stimuli than the cubic or spherical stimuli in high-sensitivity pair conditions, but no significant differences among shapes were found in low-sensitivity pair conditions. Moreover, volume discrimination thresholds with high-sensitivity pairs were correlated with the paranoid score of the schizotypal personality questionnaire. The findings provide initial evidence toward understanding the nature of bimanual haptic volume perception, including the properties of objects, individuals, and object-individual interfaces.
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http://dx.doi.org/10.1109/TOH.2021.3077882DOI Listing
January 2022

Treatment-resistant schizophrenia characterised by dopamine supersensitivity psychosis and efficacy of asenapine.

BMJ Case Rep 2021 Apr 13;14(4). Epub 2021 Apr 13.

Psychiatry, Kyoto University Hospital, Kyoto, Japan.

Dopamine supersensitivity psychosis (DSP) frequently arises with long-term antipsychotic treatment and accounts for a significant proportion of treatment-resistant schizophrenia. The mechanism underlying DSP is thought to be a compensatory increase in dopamine receptor density in the striatum caused by long-term antipsychotic treatment. Previous animal studies have reported that antipsychotics increase serotonin 5-HT2A receptor density in the striatum and that 5-HT2A receptor blockers suppress dopamine-sensitive psychomotor activity, which may be linked to the pathophysiology of DSP. In this paper, we describe a patient who was hospitalised with treatment-resistant schizophrenia. Following treatment with high-dose antipsychotic polypharmacy for 10 weeks, the patient experienced worsening of psychotic and extrapyramidal symptoms. The patient was then started on second-generation antipsychotic asenapine while other antipsychotics were tapered off, resulting in improvement of these symptoms. Retrospectively, we presumed that the high-dose antipsychotic polypharmacy caused DSP, which was effectively treated by the potent 5-HT2A receptor antagonism of asenapine.
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http://dx.doi.org/10.1136/bcr-2021-242495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051386PMC
April 2021

Cognitive underpinnings of multidimensional Japanese literacy and its impact on higher-level language skills.

Sci Rep 2021 01 26;11(1):2190. Epub 2021 Jan 26.

Department of Psychiatry, Graduate School of Medicine, Kyoto University, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.

This study aimed to identify the cognitive underpinnings of Japanese kanji abilities and clarify the contributions of kanji acquisition to the development of higher-level language skills based on a three-dimensional view of kanji abilities encompassing reading accuracy, writing accuracy, and semantic comprehension. First, a series of regression analyses was used to identify the multifactorial models of each dimension of Japanese kanji acquisition. These models suggest that, among basic cognitive skills, naming speed, visuospatial processing, and syntactic processing underpin kanji abilities in a dimension-specific manner, whereas phonological processing is a common factor. Second, although all the dimensions of kanji abilities predicted acquired verbal knowledge equally, writing skills on the text level, measured as idea density, were only predicted by the writing dimension (indirectly via acquired knowledge). Our findings represent the first evidence of the dimension-specific relationships of the three dimensions of Japanese kanji abilities with their cognitive predictors, as well as with higher-level language skills. They suggest the importance of handwriting acquisition during school years for the development of language skills through to adulthood. Finally, taking the seminal "Nun study," which suggests that higher idea density is protective against dementia, into account, we propose a theoretical framework for the lifelong trajectory of literacy acquisition.
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http://dx.doi.org/10.1038/s41598-021-81909-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838263PMC
January 2021

Combined pattern of childhood psycho-behavioral characteristics in patients with schizophrenia: a retrospective study in Japan.

BMC Psychiatry 2021 01 26;21(1):57. Epub 2021 Jan 26.

Department of Psychiatry, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan.

Background: Although epidemiological and genetic studies have provided scientific evidence that places schizophrenia into the framework of early neurodevelopmental disorders, the psycho-behavioral characteristics of children that later go on to develop schizophrenia have not been sufficiently clarified. This study aimed to retrospectively identify characteristics specific to patients with schizophrenia during childhood via their guardians' reporting of these characteristics.

Methods: Participants included 54 outpatients with schizophrenia in their twenties who fulfilled DSM-IV-TR criteria. Additionally, 192 normal healthy subjects participated as sex- and age-matched controls. The guardians of all participants were recruited to rate participants' childhood characteristics from 6 to 8 years of age on a modified version of the Child Behavior Checklist (CBCL), which was used as a retrospective assessment questionnaire. Using t-tests, logistic regression, and Receiver Operating Characteristic (ROC) curve analysis, we estimated the psycho-behavioral characteristics specific to schizophrenia during childhood. Using the obtained logistic regression model, we prototyped a risk-predicting algorithm based on the CBCL scores.

Results: Among the eight CBCL subscale t-scores, "withdrawn" (p = 0.002), "thought problems" (p = 0.001), and "lack of aggressive behavior" (p = 0.002) were each significantly associated with the later diagnosis of schizophrenia, although none of these mean scores were in the clinical range at the time of childhood. The algorithm of the logistic regression model, based on eight CBCL subscales, had an area under the ROC curve of 82.8% (95% CI: 76-89%), which indicated that this algorithm's prediction of late development of schizophrenia has moderate accuracy.

Conclusions: The results suggest that according to guardian reports, participants showed psycho-behavioral characteristics during childhood, different to those of healthy controls, which could be predictive of the later development of schizophrenia. Our newly developed algorithm is available to use in future studies to further test its validity.
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http://dx.doi.org/10.1186/s12888-021-03049-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836163PMC
January 2021

Autistic traits are associated with the functional connectivity of between-but not within-attention systems in the general population.

BMC Neurosci 2020 11 23;21(1):49. Epub 2020 Nov 23.

Department of Neuropsychiatry, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaharacho, Sakyo-Ku, Kyoto, 606-8507, Japan.

Background: Previous studies have demonstrated that individuals with autism spectrum disorder (ASD) exhibit dysfunction in the three attention systems (i.e., alerting, orienting, and executive control) as well as atypical relationships among these systems. Additionally, other studies have reported that individuals with subclinical but high levels of autistic traits show similar attentional tendencies to those observed in ASD. Based on these findings, it was hypothesized that autistic traits would affect the functions and relationships of the three attention systems in a general population. Resting-state functional magnetic resonance imaging (fMRI) was performed in 119 healthy adults to investigate relationships between autistic traits and within- and between-system functional connectivity (FC) among the three attention systems. Twenty-six regions of interest that were defined as components of the three attention systems by a previous task-based fMRI study were examined in terms of within- and between-system FC. We assessed autistic traits using the Autism-Spectrum Quotient.

Results: Correlational analyses revealed that autistic traits were significantly correlated with between-system FC, but not with within-system FC.

Conclusions: Our results imply that a high autistic trait level, even when subclinical, is associated with the way the three attention systems interact.
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http://dx.doi.org/10.1186/s12868-020-00603-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686764PMC
November 2020

Spatial Patterns of Amyloid Deposition in Patients with Chronic Focal or Diffuse Traumatic Brain Injury Using F-FPYBF-2 PET.

Neuropsychiatr Dis Treat 2020 12;16:2719-2732. Epub 2020 Nov 12.

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

Aim: Amyloid-β (Aβ) accumulation, accelerated by traumatic brain injury (TBI), may play a crucial role in neurodegeneration in chronic-stage TBI. The injury type could influence Aβ dynamics because of TBI's complex, heterogeneous nature. We, therefore, investigated spatial patterns of amyloid deposition according to injury type after TBI using 5-(5-(2-(2-(2-[F]-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)--methylpyridin-2-amine (F-FPYBF-2) positron emission tomography (PET).

Methods: Altogether, 20 patients with chronic TBI [12 with focal injury, 8 with diffuse axonal injury (DAI)] underwent F-FPYBF-2 PET, structural magnetic resonance imaging (MRI), and neuropsychological examination. Additionally, 50 healthy controls underwent either F-FPYBF-2 PET (n=30) or structural MRI (n=20).

Results: Standardized uptake value ratio (SUVR) on PET images and regional brain volumes were measured in four cortical (frontal, parietal, occipital, temporal) and subcortical (combined caudate, putamen, pallidum, thalamus) regions. Patients with DAI showed significantly increased (compared with controls) SUVR in occipital and temporal cortices and decreased brain volume in occipital cortex (corrected p < 0.05). Although patients with focal injury showed decreased SUVR in all regions except occipital cortex, there were no significant differences (compared with controls) in the SUVR in any regions. There were no significant correlations between increased SUVR and neuropsychological impairments in patients with DAI.

Conclusion: Varying spatial patterns of amyloid deposition suggest amyloid pathology diversity depending on the injury type in chronic-TBI patients.
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http://dx.doi.org/10.2147/NDT.S268504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669502PMC
November 2020
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