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.

Attention-deficit hyperactivity disorder (ADHD) is a heterogeneous psychiatric disorder affecting 5-10% of children. One of the suggested mechanisms underlying the pathophysiology of ADHD is insufficient energy supply to neurons. Here, we investigated the role of omega 3 fatty acids in altering neural energy metabolism and behavior of spontaneously hypertensive rats (SHR), which is an animal model of ADHD. To this end, we employed Proton Magnetic Resonance Spectroscopy ((1)H MRS) to evaluate changes in brain neurochemistry in the SHR following consumption of one of three experimental diets (starting PND 21): fish oil enriched (FOE), regular (RD) and animal fat enriched (AFE) diet. Behavioral tests were performed to evaluate differences in locomotor activity and risk-taking behavior (starting PND 44). Comparison of frontal lobe metabolites showed that increased amounts of omega 3 fatty acids decreased total Creatine levels (tCr), but did not change Glutamate (Glu), total N-Acetylaspartate (tNAA), Lactate (Lac), Choline (Cho) or Inositol (Ino) levels. Although behavior was not significantly affected by different diets, significant correlations were observed between brain metabolites and behavior in the open field and elevated plus maze. SHR with higher levels of brain tCr and Glu exhibited greater hyperactivity in a familiar environment. On the other hand, risk-taking exploration of the elevated plus maze's open arms correlated negatively with forebrain tNAA and Lac levels. These findings support the possible alteration in energy metabolites in ADHD, correlating with hyperactivity in the animal model. The data also suggest that omega 3 fatty acids alter brain energy and phospholipid metabolism.