Functional MRI applications for psychiatric disease subtyping: a review

Abstract: Psychiatric disorders have historically been classified using symptom information alone. With the advent of new technologies that allowed researchers to investigate brain mechanisms more directly, interest in the mechanistic rationale behind defined pathologies and aetiology redefinition has greatly increased. This is particularly appealing for the field of personalised medicine, which searches for data-driven approaches to improve individual diagnosis, prognosis and treatment selection. Here we intend to systematically analyse the usage of functional MRI on both the elucidation of psychiatric disease biotypes and the interpretation of subtypes obtained via unsupervised learning applied to symptom or biomarker data. We searched the existing literature for functional MRI applications to the obtention or interpretation of psychiatric disease subtypes. The PRISMA guidelines were applied to filter the retrieved studies, and the active learning framework ASReviews was applied for article prioritization. From the 20 studies that met the inclusion criteria, 5 used functional MRI data to interpret symptom-derived disease clusters, 4 used it for the interpretation of clusters derived from biomarker data other than fMRI itself, and 11 applied clustering to fMRI directly. Major depression disorder and schizophrenia were the two most studied pathologies, followed by ADHD, psychosis, autism disorder, and early violence. No trans-diagnostic studies were retrieved. While interest in personalised medicine and data-driven disease subtyping is on the rise and psychiatry is not the exception, unsupervised analyses of functional MRI data are inconsistent to date, and much remains to be done in terms of gathering and centralising data, standardising pipelines and model validation, and method refinement. The usage of fMRI in the field of trans-diagnostic psychiatry remains vastly unexplored.