Cortical Similarities in Psychiatric and Mood Disorders Identified in Federated VBM Analysis via COINSTAC

Psychiatric disorders such as schizophrenia, major depressive disorder, and bipolar disorder have areas of significant overlap across multiple domains including genetics, neurochemistry, symptom profiles, and regional gray matter alterations. Various structural neuroimaging studies have identified a combination of shared and disorder-specific patterns of gray matter (GM) deficits across these different disorders, though few direct comparisons have been conducted. Given the overlap in symptom presentations and GM alterations, these disorders may have a common etiology or neuroanatomical basis that may relate to a certain vulnerability for mental illness. Pooling large data or heterogeneous data can ensure representation of several participant factors, providing more accurate results. However, ensuring large enough datasets at any one site can be cumbersome, costly, and may take many years of data collection. Large scale collaborative research is already facilitated by current data repositories and neuroinformatics consortia such as the Enhacing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium, institutionally supported databases, and data archives. However, these data sharing methodologies can still suffer from significant barriers. Federated approaches can augment these approaches and mitigate some of these barriers by enabling access or more sophisticated, shareable and scaled up analyses of large-scale data which may not be shareable and can easily be scaled up with the number of sites. In the current study, we examined GM alterations using Collaborative Informatics and Neuroimaging Suite Toolkit for Anonymous Computation (COINSTAC). Briefly, COINSTAC () is an open-source decentralized analysis application that provides a venue for analyses of neuroimaging datasets without sharing individual level data, while maintaining granular control of privacy. Through federated analysis, we examined T1-weighted images (N = 3,287) from eight psychiatric diagnostic groups across seven sites. We identified significant overlap in the GM patterns of individuals with schizophrenia, major depressive disorder, and autism spectrum disorder. These results show cortical and subcortical regions, specifically the bilateral insula, that may indicate a possible shared vulnerability to psychiatric disorders. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by National Institutes of Health grants: R01DA040487 (VC) and R01MH121246 (VC). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes 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 All data produced in the present study are available upon reasonable request to the authors.