We have used both studies of vascular function and analyses of large datasets to understand relations between long-term course of illness and cardiovascular risk. Our work analyzes utilizes large datasets to answer questions relevant to causality. Two approaches to mitigate selection bias involved identifying a dose-response relationship with severity of illness and studying risk in a nationally representative sample. Our work is the first to document a dose-response relationship between persistence or chronicity of depressive and manic symptoms on measures of vascular function and cardiovascular mortality and that this may be moderated by sex.

We have assessed how course of illness influences suicide risk in mood disorders with a recent focus on mixed depressive and (hypo)manic symptoms. Individuals with bipolar disorder and a history of mixed states have been shown to have had more frequent prior suicide in attempts. Our work to date, encompassing four analyses, using three prospective samples, has shown that this risk is explained (confounded) by a more chronic course of depressive symptoms in those who experience mixed states. Depressive symptoms appear to be the primary syndromal driver of suicide risk.

We have been involved with knowledge synthesis studies and position papers looking at disparities cardiovascular and other medical treatment for those with mental disorders. Our work seeks to call attention to the excess cardiovascular and other medical morbidity and mortality in bipolar and related disorders in the hope that more attention is paid to this underappreciated at-risk group.

We have found an increased risk of depression with very low cholesterol although new depression did not result in meaningful changes of lipids in postmenopausal women. In separate analyses, improvements in cholesterol ratio and triglycerides, measures associated with insulin resistance, followed resolution of depression. In a follow-up analysis from the Women’s Health Initiative, the association between very low (bottom quintile) cholesterol and subsequent depression was moderated by use of lipid-lowering agents, such that very low cholesterol due to a lipid-lowering agent was not associated with any increase in risk. Lipid lowering medications are under-prescribed to those with mental disorders. Our results challenge under-prescribing due to concern of iatrogenic impacts of low cholesterol on mood and hopefully attack one rationale for the undertreatment of cardiovascular risk factors in those with mood disorders.