Publications by authors named "Naohiro Okada"

Previous studies on metabolic profiling have shown decreased plasma levels of betaine in schizophrenia. Betaine serves as a substrate of betaine-homocysteine methyltransferase, which converts homocysteine to methionine. A decrease in betaine may lead to the elevation of homocysteine and an insufficient supply of methyl donors, which may affect DNA methylation.

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Resting-state functional connectivity (rsFC) is increasingly used to develop biomarkers for psychiatric disorders. Despite progress, development of the reliable and practical FC biomarker remains an unmet goal, particularly one that is clinically predictive at the individual level with generalizability, robustness, and accuracy. In this study, we propose a new approach to profile each connectivity from diverse perspective, encompassing not only disorder-related differences but also disorder-unrelated variations attributed to individual difference, within-subject across-runs, imaging protocol, and scanner factors.

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Bipolar disorder (BD) is often associated with extensive changes in white matter (WM) microstructure. While diffusion tensor imaging (DTI) has been used in BD studies, diffusion kurtosis imaging (DKI) has rarely been explored, particularly concerning the different subtypes of BD. This cross-sectional study compared DTI and DKI metrics of the brain WM in participants with BD type I (BD-I) and II (BD-II) and in healthy controls (HC).

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Dendritic cells (DCs) transduced with replication-deficient, wild-type human p53-expressing adenovirus Ad-p53 (Ad-p53 DCs) induce p53-targeting cytotoxic T lymphocytes (CTLs). However, the antitumor efficacy of Ad-p53 DCs is diminished by weak p53 immunogenicity in tumor cells and poor immune responses. We developed a p53-armed oncolytic adenovirus, OBP-702, to induce tumor-specific p53 expression and antitumor immune response, suggesting a role for OBP-702 in enhancing the antitumor efficacy of Ad-p53 DCs.

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Immunotherapy resistance in pancreatic ductal adenocarcinoma(PDAC)limits treatment outcomes; therefore, improving the immunosuppressive microenvironment is important for PDAC treatment. We developed an oncolytic adenovirus, OBP-702, carrying the tumor suppressor gene p53, and report its therapeutic potential to induce cytopathic effects and activate antitumor immunity via p53 induction. In the present study, we investigated the therapeutic potential of epigenetic modulators in oncolytic viral immunotherapy combined with a dendritic cell vaccine.

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Importance: Although individual prosociality, defined as voluntary behavior intended to benefit another, is known to promote help-seeking behaviors among adolescents, it remains unclear whether a prosocial community, such as the classroom, also facilitates these behaviors.

Objective: To investigate the associations of classroom-level and individual-level prosociality with help-seeking behaviors, considering age and gender, and to examine moderation effects of being bullied.

Design, Setting, And Participants: In this cross-sectional study, annual surveys were conducted via questionnaire among students in Japanese junior and senior high schools from 2020 to 2023.

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Introduction: The mega-analysis conducted by the ENIGMA Bipolar Disorder Working Group revealed significant volume increment effects of lithium on the hippocampus in individual with bipolar disorder. However, the study did not assess other medications and other subcortical regions.

Methods: Data of 235 individuals with bipolar disorder were taken from a mega-analysis conducted by the COCORO consortium in Japan.

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Objective classification biomarkers that are developed using resting-state functional magnetic resonance imaging (rs-fMRI) data are expected to contribute to more effective treatment for psychiatric disorders. Unfortunately, no widely accepted biomarkers are available at present, partially because of the large variety of analysis pipelines for their development. In this study, we comprehensively evaluated analysis pipelines using a large-scale, multi-site fMRI dataset for major depressive disorder (MDD).

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One of the challenges in diagnosing psychiatric disorders is that the results of biological and neuroscience research are not reflected in the diagnostic criteria. Thus, data-driven analyses incorporating biological and cross-disease perspectives, regardless of the diagnostic category, have recently been proposed. A data-driven clustering study based on subcortical volumes in 5604 subjects classified into four brain biotypes associated with cognitive/social functioning.

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An anomalous pattern of structural covariance has been reported in schizophrenia, which has been suggested to represent connectome changes during brain maturation and neuroprogressive processes. It remains unclear whether similar differences exist in a clinical high-risk state for psychosis, and if they are associated with a prodromal phenotype and/or later psychosis onset. This multicenter magnetic resonance imaging study cross-sectionally examined structural covariance in a large at-risk mental state (ARMS) sample with different outcomes.

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Dendritic cell(DC)vaccine therapy has been widely studied as cancer immunotherapy that potently induces cytotoxic T lymphocytes. However, their efficacy in clinical practice has not yet been established. We have developed an oncolytic adenovirus OBP-702 carrying the tumor suppressor gene p53 and have demonstrated its therapeutic potential to induce cytopathic effect and activate antitumor immunity via p53 induction.

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Article Synopsis
  • Autism spectrum disorder (ASD) is a complex lifelong condition, and this study aimed to create a classifier using resting-state fMRI from a large group of 730 Japanese adults to identify its neural and biological features.
  • The developed classifier showed effectiveness in differentiating individuals with ASD from neurotypical controls across various countries, including the US and Belgium, and it also applied to children and adolescents.
  • Importantly, the study found that the classifier identified crucial functional connections related to social interaction difficulties and neurotransmitter activity, and it linked ASD with similar neurobiological factors seen in ADHD and schizophrenia, enhancing understanding of related mental health disorders.
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  • Neuroimaging databases for neuro-psychiatric disorders provide valuable data for researchers to explore diseases, develop machine learning models, and redefine understanding of these conditions.* ! -
  • A review identified 42 global MRI datasets totaling 23,293 samples from patients with various disorders, including mood, developmental, schizophrenia, Parkinson's, and dementia.* ! -
  • Improved governance and addressing technical issues of these databases are essential for sharing data across borders, aiding in understanding, diagnosing, and creating early interventions for neuro-psychiatric disorders.* !
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  • A study examined the clinical outcomes of patients with blunt splenic injuries who received transarterial embolization (TAE), focusing on their hemodynamic status (stable vs unstable).
  • The research analyzed data from 38 adult patients treated at two centers from 2011 to 2022, comparing the survival rates, rebleeding incidents, and need for splenectomy between hemodynamically stable (HDS) and unstable (HDU) groups.
  • Results showed a high survival discharge rate for both groups (88.2% in HDU and 100% in HDS), but highlighted the need for more studies to assess the effectiveness of TAE compared to traditional surgery for HDU patients.
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  • Duplication of chromosome 15q11-13 is linked to autism spectrum disorder (ASD) and was studied in a mouse model known as 15q dup mice.
  • The study involved behavioral tests for anxiety and social interactions, alongside MRI scans, to explore the connection between brain structure and behavior in these mice.
  • Findings showed that 15q dup mice exhibited higher anxiety levels and varied social behaviors, with a correlation found between lower sociability and reduced gray matter in a specific brain region, highlighting the complexities of ASD's behavioral diversity.
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Discrepancies in self-rated and observer-rated depression severity may underlie the basis for biological heterogeneity in depressive disorders and be an important predictor of outcomes and indicators to optimize intervention strategies. However, the neural mechanisms underlying this discrepancy have been understudied. This study aimed to examine the brain networks that represent the neural basis of the discrepancy between self-rated and observer-rated depression severity using resting-state functional MRI.

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  • Near-infrared spectroscopy (NIRS) is a noninvasive method that measures brain blood oxygenation to understand neural activity.
  • Researchers studied resting-state brain activity in 24 individuals with schizophrenia and 90 healthy controls, discovering higher functional connectivity in specific brain areas of schizophrenia patients.
  • The findings link increased brain connectivity to the severity of negative symptoms and dosage of antipsychotic medication, indicating NIRS could have useful clinical applications.
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Introduction: Macronutrient intake can be one of the most influential factors in cognitive and neural development in adolescents. Adolescence is a specific period of cognitive and neural development, and nutritional effects during this period could be life-long. Therefore, understanding the effects of macronutrient intake on cognitive and neural development in adolescents is crucially important.

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  • The gamma-band auditory steady-state response (ASSR) is a brain signal related to hearing and attention, which is found to be weaker in people with schizophrenia.
  • The study looked at how this weaker signal connects to changes in brain white matter, especially in areas on the right side of the brain.
  • Results showed that healthy people had a good connection between the gamma-band ASSR and white matter, but people with schizophrenia didn't show the same connection, suggesting that their brain networks might not work as well.
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Importance: Few studies have used a large-sample, longitudinal, population-based cohort study to examine whether the COVID-19 pandemic as a global major life event is associated with structural plasticity of the adolescent hippocampus.

Objective: To examine whether Japan's first state of emergency (SoE) during the COVID-19 pandemic was associated with alterations in the macrostructures and microstructures of the hippocampus during its development.

Design, Setting, And Participants: The population-neuroscience Tokyo TEEN Cohort study is a prospective cohort study with 4 consecutive waves in Tokyo, Japan.

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Previous studies reported decreased glutamate levels in the anterior cingulate cortex (ACC) in non-treatment-resistant schizophrenia and first-episode psychosis. However, ACC glutamatergic changes in subjects at high-risk for psychosis, and the effects of commonly experienced environmental emotional/social stressors on glutamatergic function in adolescents remain unclear. In this study, adolescents recruited from the general population underwent proton magnetic resonance spectroscopy (MRS) of the pregenual ACC using a 3-Tesla scanner.

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  • A study conducted in Japan during the first three years of the COVID-19 pandemic examined long-term emotional and behavioral issues in adolescents, highlighting trends in help-seeking behavior and sociodemographic inequalities.
  • Results showed that emotional and behavioral difficulties peaked in 2021, with increased rates of hyperactivity/inattention and poor help-seeking persisting into 2022.
  • The findings indicate that disparities existed based on sociodemographic factors like gender and family structure, suggesting that targeted support is necessary to address the needs of disadvantaged youth during and after the pandemic.
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According to the operational diagnostic criteria, psychiatric disorders such as schizophrenia (SZ), bipolar disorder (BD), major depressive disorder (MDD), and autism spectrum disorder (ASD) are classified based on symptoms. While its cluster of symptoms defines each of these psychiatric disorders, there is also an overlap in symptoms between the disorders. We hypothesized that there are also similarities and differences in cortical structural neuroimaging features among these psychiatric disorders.

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Differential diagnosis is sometimes difficult in practical psychiatric settings, in terms of using the current diagnostic system based on presenting symptoms and signs. The creation of a novel diagnostic system using objective biomarkers is expected to take place. Neuroimaging studies and others reported that subcortical brain structures are the hubs for various psycho-behavioral functions, while there are so far no neuroimaging data-driven clinical criteria overcoming limitations of the current diagnostic system, which would reflect cognitive/social functioning.

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