Grant: Operating Grant

Bipolar disorder (BD) is a complex and severe mood disorder that affects approximately 1% of the Canadian population. The current diagnostic criteria for psychiatric illnesses are based purely on self-reported or behavioural observation and they lack substantial biological validation. This contrasts sharply with several other areas of medicine where biological tests aid in diagnostic and treatment decisions. As a result, there is a pressing need to identify novel biological treatment targets reflecting the underlying pathophysiological processes for the majority of psychiatric disorders. Ultimately, these targets will optimize treatment choice, inform rational design of new treatments, reduce the overall health cost associated with these disorders and ultimately prevent the progression of illnesses. One such potential treatment target is oxidative stress, which is increased in the brain and peripheral blood cells of patients with BD. In fact, recent results from our group demonstrated a relationship between peripheral levels of oxidative damage to lipids and brain white matter integrity evaluated by neuroimaging in patients with BD, uncovering the potential for serum lipid oxidation to reflect central nervous system (CNS) damage in BD. Therefore, the overall goal of this proposal is to study the role of oxidative damage to lipids in BD. Specifically, we will: (1) investigate the levels of lipid oxidation in the myelin fraction of postmortem brain from patients with BD; (2) evaluate whether serum lipid oxidation correlates with white matter integrity in patients with BD and healthy controls; and (3) examine the relationship between central and peripheral levels of oxidative stress across patients with BD and healthy controls using paired cerebrospinal fluid (CSF) and serum samples. These data hold promise for the development of novel and effective treatments that will markedly improve the illness outcome.