Effect of Divalproex on Brain Morphometry, Chemistry, and Function in Youth at High-Risk for Bipolar Disorder: A Pilot Study

Objective: Divalproex has been found efficacious in treating adolescents with and at high risk for bipolar disorder (BD), but little is known about the effects of mood stabilizers on the brain itself. We sought to examine the effects of divalproex on the structure, chemistry, and function of specific brain regions in children at high-risk for BD. Methods: A total of 24 children with mood dysregulation but not full BD, all offspring of a parent with BD, were treated with divalproex monotherapy for 12 weeks. A subset of 11 subjects and 6 healthy controls were scanned with magnetic resonance imaging (MRI, magnetic resonance spectroscopy [MRS], and functional MRI [fMRI]) at baseline and after 12 weeks. Results: There were no significant changes in amygdalar or cortical volume found over 12 weeks. Furthermore, no changes in neurometabolite ratios were found. However, we found the degree of decrease in prefrontal brain activation to correlate with degree of decrease in depressive symptom severity. Conclusions: Bipolar offspring at high risk for BD did not show gross morphometric, neurometabolite, or functional changes after 12 weeks of treatment with divalproex. Potential reasons include small sample size, short exposure to medications, or lack of significant neurobiological impact of divalproex in this particular population.