Sodium valproate (VPA) decreased amygdala volume over a 6-week treatment period in children with bipolar disorder, according to structural magnetic resonance imaging (MRI) results from a study published in Psychiatry Research: Neuroimaging.

Bipolar disorder is present in approximately 4% of the population. Better understanding of pediatric bipolar disorder has shown that early onset may involve a particularly severe form of the disease. Furthermore, mania in pediatric bipolar disorder is significantly more likely to involve mixed states and risk for suicidal behaviors. Although lithium for the acute treatment and prophylaxis of mania has demonstrated efficacy in pediatric bipolar disorder, VPA is often more effective as therapy for mixed states. Studies conducted in animals and adults have indicated that VPA may have neuroprotective and neurotrophic effects, but the effects of VPA on brain structure in pediatric bipolar disorder are not known.

Fadwa Cazala, PhD, of the School of Medicine at The University of Texas Health Science Center in Houston, Texas, and colleagues examined the effects of VPA on fronto-limbic brain structures in 14 patients with pediatric bipolar disorder. Patients underwent a structural MRI before and after 6 weeks of VPA treatment. Of the 14 patients, 10 were male, and the mean age was 13.4 years. The investigators used Bayesian linear mixed modeling to examine 7 brain region volumes as a function of dichotomous pre/post time.

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The mixed modeling results showed that the amygdala experienced a -2.44% change over the 6-week period, and the lateral orbito-frontal region decreased by -1.41%, the medial orbitofrontal by -1.32%, the caudal anterior cingulate by -1.89%, and the posterior cingulate region by -0.99%. The hippocampus and rostral cingulate regions showed no change.

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The authors noted that their results do not indicate a neuroprotective effect for VPA in pediatric bipolar disorder but suggested that the short treatment period may have affected the results. This is in contrast to prior research, which has shown neuroprotective effects for VPA. The authors call for future large-scale, placebo-controlled, randomized studies with longer VPA treatment periods to explore their results.


Cazala F, Suchting R, Zeni CP, et al. Effects of valproate on brain volumes in pediatric bipolar disorder: a preliminary study. Psychiatry Res Neuroimaging. 2018;278:65-68.