2014 Theses Doctoral

Neurodevelopmental risks for bipolar disorder

Freedman, David

This dissertation aims to add to the growing literature on the risks and mechanisms in early life that may be associated with later bipolar disorder (BP), expanding the understanding of when and why divergences from typical developmental course occur in BP, if they do. To do so, it utilizes prospectively obtained, serologically documented prenatal biomarkers and clinically documented prenatal and perinatal risk factors, as well as premorbid measures of neurocognitive functioning, in a well-defined birth cohort followed up for BP. This offers a unique opportunity to test some of the evidence as to whether BP is a neurodevelopmental illness. The first paper is a systematic literature review of the neurodevelopmental hypothesis of BP. This review focuses on three developmental time points: prenatal and perinatal exposures, premorbid and prodromal symptom development, and neurocognitive functioning prior to onset. The second paper focuses on two specific putative prenatal and perinatal risk factors for BP: T. gondii and oxytocin to induce labor. The third paper assesses cognition, using both the BP case-control study and the full birth cohort to assess risks for BP and the potential that cognitive impairment reflects a mediator or endophenotype of later BP. Taken as a whole, the findings suggest support for the neurodevelopmental hypothesis of BP and indicate some potentially specific risks for BP.