Over the last decade, second generation antipsychotics have been increasingly utilized.
Since their introduction, however, atypical antipsychotics have been increasingly associated
with significant metabolic complications including hyperlipidemia, insulin
resistance/diabetes mellitus, and obesity. These metabolic complications increase the risk
for cardiovascular disease in populations with an already elevated risk.
The initial goal of the proposed study is to identify early signs of endothelial dysfunction
and vascular disease in those treated with atypical antipsychotics. The identification of
early signs of vascular disease may further link metabolic complications with any
cardiovascular risk. Demonstration of changes in vascular function associated with atypical
antipsychotics represents an important identifiable intermediate of more long-term
The second goal of the proposed study is to identify genetic factors that may be associated
with the development of cardiovascular disease, which can later serve as a guide to predict
risk. Accurate prediction of risk may facilitate the future development of an empirical,
risk-based, individualized selection process for antipsychotic medications.
Aim 1: To quantify the role of antipsychotic-induced metabolic complications on the
development of vascular disease using measures of endothelial function.
Hypothesis 1: Atypical antipsychotics will lead to greater impairments in endothelial
function, evidenced by decreased flow-mediated dilation from baseline measures and compared
with changes over time in controls. Medication-induced metabolic complications will be
temporally associated with these impairments in endothelial function.
Aim 2: To investigate the role of candidate pharmacogenetic polymorphisms with
cardiovascular and metabolic complications of atypical antipsychotics.
Hypothesis 2: Profiles of polymorphisms at receptors targeted by atypical antipsychotics
will be associated with impaired cardiovascular function and metabolic complications.
- 18-50 years of age
- Being started on a first-line, second-generation, antipsychotic associated with
weight gain (risperidone, olanzapine, or quetiapine) for the treatment of an
affective or psychotic disorder -OR- psychiatric controls not taking antipsychotic
medications will also be enrolled
- Exclusion criteria will include the presence of any of the following: neoplasm,
active thyroid disease (i.e. not euthyroid), pregnancy or planned pregnancy, diabetes
mellitus, Raynaud's disease, anticoagulant therapy, or inability to provide informed
consent. We will exclude participants who have started valproic acid derivatives in
the preceding 6 months, given its association with insulin resistance and weight
gain. Participants with active substance abuse or dependence will also be excluded.