Brain Correlates of Vulnerability to Severe Mental Illness

Abstract

Severe mental illness (SMI) refers to major depressive disorder, bipolar disorder and schizophrenia. The early onset and prolonged course make SMI a leading cause of disability in the population. There is a growing need to identify biological markers of SMI to assist with early diagnosis and to inform treatment. Neuroimaging holds substantial promise in this regard. I sought to examine brain correlates of vulnerability to SMI. First, I examined SMI from a family history perspective and investigated structural changes in youth at familial risk for bipolar disorder (BD). I found that structural alterations in the inferior frontal gyrus were present not only in individuals in the early stages of BD but also in their unaffected relatives. I subsequently explored SMI from an early symptom perspective and demonstrated that attenuated psychotic symptoms during adolescence are associated with reduced cortical folding, even before the onset of psychotic illness. For biomarkers to be of clinical utility, they must be reliable. Thus, for my next project I established the scan-rescan reliability of nine commonly used structural MRI measures in our sample, including youth with anxiety and attention-deficit / hyperactivity disorder. Finally, I have compiled data from multiple developmental cohorts and built a machine learning model to quantify neuroanatomical maturity. This chapter shed light on how deviation in developmental trajectories relates to risk for SMI. The findings presented in my thesis contribute to a better understanding of early structural brain markers associated with risk for mental illness.