An Integrative Approach for Subtyping Mental Disorders Using Multimodal Data

ABSTRACT Integrating multimodal biological, cognitive, and clinical data is crucial for uncovering distinct psychiatric disease subgroups, enabling precision diagnosis, personalized treatment, and more targeted drug development. However, a significant gap remains between traditional clustering approaches and the growing need for advanced methods that can integrate and jointly analyze multimodal biological and clinical data to achieve more biologically meaningful subtyping. This study introduces the Mixed INtegrative Data Subtyping (MINDS) method, a Bayesian hierarchical joint model designed to identify subtypes of Attention-Deficit/Hyperactivity Disorder (ADHD) and Obsessive-Compulsive Disorder (OCD) in adolescents using multimodal data from the Adolescent Brain Cognitive Development (ABCD) Study. MINDS integrates clinical assessments, neuro-cognitive measures, and neuroimaging biomarkers while simultaneously performing clustering and dimension reduction. By leveraging Polya-Gamma augmentation, we propose an efficient Gibbs sampler to improve computational efficiency and provide subtype identification. Simulation studies demonstrate the superior robustness of MINDS compared to traditional clustering techniques. Application to the ABCD study reveals more reliable and clinically meaningful subtypes of ADHD and OCD with distinct cognitive and behavioral profiles. These findings show the potential of multimodal model-based clustering for advancing precision psychiatry in mental health. Competing Interest Statement The authors have declared no competing interest. Funding Statement https://abcdstudy.org/ Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study used only openly available human data that were originally located at https://abcdstudy.org/ I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes compare with more alternatives, iClusterBayes and two-step JIVE ; include subjects that have missing variables in the ABCD data analysis Data Availability Data used in the preparation of this manuscript were obtained from the Adolescent Brain Cognitive Development (ABCD) Study (DOI: 10.15154/z563-zd24), held in the National Institute of Mental Health (NIMH) Data Archive (NDA). NDA is a collaborative informatics system created by the National Institutes of Health to provide a national resource to support and accelerate research in mental health.