Vitamin D₃ Supplemental Treatment for Mania in Youth with Bipolar Spectrum Disorders

Objective: We aimed to determine the effect of an open-label 8 week Vitamin D₃ supplementation on manic symptoms, anterior cingulate cortex (ACC) glutamate, and γ-aminobutyric acid (GABA) in youth exhibiting symptoms of mania; that is, patients with bipolar spectrum disorders (BSD). We hypothesized that an 8 week Vitamin D₃ supplementation would improve symptoms of mania, decrease ACC glutamate, and increase ACC GABA in BSD patients. Single time point metabolite levels were also evaluated in typically developing children (TD). Methods: The BSD group included patients not only diagnosed with BD but also those exhibiting bipolar symptomology, including BD not otherwise specified (BD-NOS) and subthreshold mood ratings (Young Mania Rating Scale [YMRS] ≥8 and Clinical Global Impressions - Severity [CGI-S] ≥3). Inclusion criteria were: male or female participants, 6-17 years old. Sixteen youth with BSD exhibiting manic symptoms and 19 TD were included. BSD patients were asked to a take daily dose (2000 IU) of Vitamin D₃ (for 8 weeks) as a supplement. Neuroimaging data were acquired in both groups at baseline, and also for the BSD group at the end of 8 week Vitamin D₃ supplementation. Results: Baseline ACC GABA/creatine (Cr) was lower in BSD than in TD (F[1,31]=8.91, p=0.007). Following an 8 week Vitamin D₃ supplementation, in BSD patients, there was a significant decrease in YMRS scores (t=-3.66, p=0.002, df=15) and Children's Depression Rating Scale (CDRS) scores (t=-2.93, p=0.01, df=15); and a significant increase in ACC GABA (t=3.18, p=0.007, df=14). Conclusions: Following an 8 week open label trial with Vitamin D₃, BSD patients exhibited improvement in their mood symptoms in conjunction with their brain neurochemistry.