On August 31, 2023, Professor Wang Kai’s team published a research paper entitled White matter dysfunction in psychiatric disorders is associated with neurotransmitter and genetic profiles in Nature Mental Health, a Nature sub-journal. The research paper, for the first time, applies new concepts and methods of white matter BOLD signaling to the study of common mechanisms in large-scale psychiatric disorders, and shows that the functional characteristics of white matter fiber tracts in the brain of patients with severe psychiatric disorders based on BOLD signaling can provide information on lesions that is not visible in structural studies. The study provides new research perspectives for comprehensively understanding the role of white matter fiber tracts in psychiatric disorders, and deeply decipher the neurotransmitter and gene expression mechanisms of functional changes of white matter. Associate Professor Gongjun Ji and Dr. Jinmei Sun are the co-authors of the paper, Professor Kai Wang is the corresponding author, and the First Affiliated Hospital of Anhui Medical University is the first author of the paper.
According to statistics from the World Health Organization (WHO), nearly 1 billion people suffer from mental disorders, which is one of the main drivers of the global increase in disability, bringing a heavy burden to patients, families and society. Studies have shown that there are obvious commonalities in clinical symptoms, treatment options, and gene mutations among different mental disorders, and clarifying the commonalities and differences in the brains of patients with mental disorders is of great significance for the future diagnosis and treatment of mental disorders. Previous studies have focused on the gray matter of the brain, which is considered to be crucial to the higher functions of the brain, while the white matter, which occupies most of the brain volume, has been relatively neglected. In fact, nerve fibers in the white matter are important components of brain networks, which are the structural basis for information transmission in different brain regions and are involved in the pathogenesis of many psychiatric disorders.
Magnetic resonance imaging (MRI) is a well-established method for studying the structure of cerebral white matter, but there is a lack of validated methods for evaluating the function of white matter. In 2017, Prof. Wang Kai's team verified for the first time in China that brain white matter BOLD can be used to characterize the functional state of white matter, contrary to the long-standing assumption in the academic community that it is merely noise.
On the basis of previous research, this study analyzed multimodal magnetic resonance images of hundreds of patients with severe mental illnesses and healthy controls using the WhiteMatterSF software developed by the team (free to share). It tracked the major white matter fiber tracts in the participants’ brains, delineated their structural and functional characteristics, and analyzed the transmitter and gene expression mechanisms of the altered white matter function using public repositories and validated the results in an independent dataset.
The findings suggest that structural white matter damage in psychiatric disorders is located in the bilateral inferior frontal occipital fasciculus while functional abnormalities are located in the bilateral anterior thalamic radiations, and that there is a significant complementarity of structural and functional outcomes. Of the four psychiatric disorders (schizophrenia, depression, obsessive-compulsive disorder, and bi-directional disorder), schizophrenia had the most pronounced white matter alterations. Differential alterations in the function of 18 fiber tracts in psychiatric disorders were associated with the white matter distribution characteristics of dopamine receptors/transporters and acetylcholine, as well as the risk gene expression patterns of mental disorders. All the above findings were validated in the validation dataset.
This study was supported by the National Natural Science Foundation of China, and several experts and professors from the Fourth People's Hospital of Hefei, University of Science and Technology of China, West China Hospital, University of Electronic Science and Technology, Anhui Medical University, and the First Affiliated Hospital of Anhui Medical University have also made important contributions to this project.
Link to paper: https://www.nature.com/articles/s44220-023-00111-2