A research group led by Director Ryota Hashimoto of the Department of Pathology of Mental Diseases at the National Institute of Mental Health of the National Center of Neurology and Psychiatry (NCNP), Project Associate Professor Naohiro Okada of the International Research Center for Neurointelligence (IRCN) at the University of Tokyo Institutes for Advanced Study (UTIAS), and Professor Kiyoto Kasai of the Graduate School of Medicine at the University of Tokyo collected structural brain magnetic resonance images (MRI images) of 5604 participants (patients with four major psychiatric disorders: schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder as well as healthy controls) in collaboration with 14 research institutions across Japan. A data-driven mega-analysis of subcortical regional structures revealed that these structures can be classified into four types (brain biotypes).
A clustering analysis of the subcortical regional volumes demonstrated that the brain biotypes are associated with cognitive and social functioning. The findings are expected to contribute to progress in research on psychiatric disorders and the development of novel diagnostic and therapeutic approaches and were published on August 4, 2023, in the international scientific journal Molecular Psychiatry.
Currently, the diagnoses of psychiatric disorders are made based on the psychiatrist's experience with patients' symptoms and prognosis, without finding the underlying cause and the mechanism of disease onset. Therefore, these may differ, and only 30−50% of patients benefit from medication and psychotherapy. Developing a more objective diagnostic approach is necessary.
Within the framework of the Cognitive Genetics Collaborative Research Organization (COCORO), which consists of 43 institutions conducting research on psychiatric disorders, the research group has been engaged in research aimed at unraveling the etiology and pathology of psychiatric disorders as well as the molecular mechanisms of brain functions.
In the current study, the research group collected structural brain MRI data of 1,500 patients with schizophrenia, 235 patients with bipolar disorder, 598 patients with major depressive disorder, 193 patients with autism spectrum disorder, and 3,078 healthy controls from 14 COCORO research institutions. Volumetric features of the subcortical regional structures, including the hippocampus, amygdala, and thalamus, which play central roles in psychobehavioral functioning, were analyzed (using FreeSurfer).
As a result, they succeeded in demonstrating larger lateral ventricle volumes in patient groups with schizophrenia, bipolar disorder, and major depressive disorder, and smaller hippocampal volume in patients with schizophrenia and those with bipolar disorder than in healthy controls. These results are in concordance with the results from a large-scale multi-center study in the US (Enhancing NeuroImaging Genetics through Meta Analysis: ENIGMA).
Moreover, a clustering analysis was performed based on the data of the volumes of subcortical regional structures from 5,604 participants. After the exclusion of data from two participants, seven clusters emerged in this analysis, which could be classified into four brain biotypes.
Associations of the brain biotypes with intelligence (assessed using the Wechsler Adult Intelligence Scale: WAIS), social functioning (assessed using the University of California San Diego Performance-Based Skills Assessment-Brief Version: UPSA) and working hours per week were investigated, and the results showed that the four brain biotypes were associated with cognitive and social functioning. This study is the first to reveal these associations, given that previous studies outside Japan had only involved examination of associations between MRI images and psychiatric disorders.
Limitations of this study include its cross-sectional nature, owing to which all the MRI images were acquired at a single point of time. The research group stated that alterations in the brain biotypes along with the disease course must be investigated in future studies. The creation of animal models for neurological disorders has not been achieved so far because distinct biological indicators for these disorders had not been found. The findings from this study will allow researchers to create animal models to replicate these brain biotypes.
Hashimoto said, "Our findings may lead to the development of a novel diagnostic approach that is different from the current diagnostic framework. We continue research to advance clinical practice in psychiatry to help patients by predicting their prognosis and by providing them with therapeutic options."
Journal Information
Publication: Molecular Psychiatry
Title: Subcortical volumetric alterations in four major psychiatric disorders: a mega-analysis study of 5604 subjects and a volumetric data-driven approach for classification
DOI: 10.1038/s41380-023-02141-9
This article has been translated by JST with permission from The Science News Ltd. (https://sci-news.co.jp/). Unauthorized reproduction of the article and photographs is prohibited.