The etiology of psychiatric disorders remains elusive and while clearly multifactorial in origin, objective and measurable clinical markers are lacking in the assessment of psychiatric disease. Contemporary psychiatric diagnosis continues to be made based on the presence (or absence) of grouped symptoms and it is in this tradition that the Diagnostic Statistical Manual (DSM) has long been the standard bearer in the categorization and diagnosis of psychiatric disease. The most recent revision of the DSM (DSM-V, 2013) attempts to incorporate new advances related to our understanding of the biologic factors, psychopathology, and treatment outcomes in psychiatric illness; however, the DSM remains, at best, a sparse intellectual framework that guides our understanding of the broad spectrum of mental and behavioral disorders and lacks the accuracy and precision that is the hallmark of modern medical diagnostics. Given our newly emerging and rapidly evolving understanding of the molecular underpinnings of psychiatric disease, modern imaging and neuroscience can begin to realize a more sensitive and specific clinical assessment of psychiatric disease.
The overarching work in our laboratory is to unpack the molecular features of neuropsychiatric disease through the development of a novel, innovative, collaborative, and interdisciplinary systems neuroscience approach coupled with advanced neuroimaging techniques and methodologies with an emphasis on autism spectrum disorder (ASD) and schizophrenia (SCZ). Specifically, our research features the first truly cogent genetic animal models of psychiatric disease. These rat models are complete biallelic genetic knockouts of identified high-risk gene deletions in ASD and SCZ allowing us the opportunity to uniquely interrogate the effect of a single gene deletion on the neuropathogenesis of ASD and SCZ. These newly available models provide a stable, reproducible platform in which to pursue a comprehensive systems neuroscience research and imaging program directed towards uncovering the MR microstructural changes linked to psychiatric illness and subsequent corroboration of these findings to underlying transcriptomic, proteomic, metabolomic, and synaptogenic changes within the brain. The elucidation of the underlying molecular features of neuropsychiatric disease and how these changes manifest themselves on neuroimaging is the first step towards the development of an imaging-centric diagnostic paradigm with gene-specific neuroimaging biomarkers that will shape how we ultimately screen, treat, follow, and arrive at a more comprehensive understanding of psychiatric illness.