Anterior cingulate volume in pediatric bipolar disorder and autism.

BACKGROUND: An increasing number of studies indicate the anterior cingulate gyrus (ACG) may play a role in the attention deficits associated with pediatric bipolar disorder (BD). Age, medications, and intelligence quotient (IQ) may affect ACG volume; few studies have controlled for these effects. METHODS: We recruited 16 children with BD and 24 children with autism spectrum disorder (ASD); 15 children with no psychiatric diagnosis (NP) were also included. All participants were evaluated with the K-SADS and a DSM-IV Autism/Asperger's Checklist; the ADI-R was also administered to ASD participants shortly after the study began. The participants completed a brain MRI scan on a 1.5Tesla Signa GE scanner. We segmented the ACG and compared left and right ACG volumes between groups. The influence of medications on the ACG volume was assessed while controlling for the effects of age and IQ. RESULTS: The left ACG volume was significantly smaller in the BD group compared to the NP (p=0.004) and ASD (p=0.006) groups. No significant differences were found in the right ACG volume. These differences do not appear to be attributable to medication use or IQ. CONCLUSIONS: Pediatric BD patients have a smaller left ACG volume compared to NP children and children diagnosed with ASD. This replication and extension of previous studies suggest that the ACG volume abnormality may be a biomarker for BD.

Pilot study of the effect of methyl B12 treatment on behavioral and biomarker measures in children with autism.

OBJECTIVES: The study objectives were to determine whether methyl B12 treatment improves behavioral measures in children with autism and whether improvement is associated with increased plasma concentrations of glutathione (GSH) and an increased redox ratio of reduced glutathione to oxidized glutathione (GSH/GSSG), both of which have been previously identified to be low in children with autism. DESIGN: This was a 12-week, double-blind, placebo-controlled, cross-over clinical trial of injectable methyl B12. Following this 12-week study, subjects were given the option of entering a 6-month open-label trial of methyl B12. SETTINGS/LOCATION: All procedures took place at the UC Davis M.I.N.D. Institute. SUBJECTS: Subjects were 3 to 8 years old with autism. INTERVENTIONS: All subjects received 6 weeks of placebo and 6 weeks of methyl B12 at a dose of 64.5 mcg/kg every three days administered subcutaneously into the buttocks. OUTCOME MEASURES: Blood for GSH analysis and behavioral assessments were obtained at baseline, week 6, and week 12. RESULTS: Thirty (30) subjects completed the 12-week, double-blind study and 22 subjects completed the 6-month extension study. No statistically significant mean differences in behavior tests or in glutathione status were identified between active and placebo groups. Nine (9) subjects (30%) demonstrated clinically significant improvement on the Clinical Global Impression Scale and at least two additional behavioral measures. More notably, these responders exhibited significantly increased plasma concentrations of GSH and GSH/GSSG. CONCLUSIONS: Comparison of the overall means between groups suggests that methyl B12 is ineffective in treating behavioral symptoms of autism. However, detailed data analysis suggests that methyl B12 may alleviate symptoms of autism in a subgroup of children, possibly by reducing oxidative stress. An increase in glutathione redox status (GSH/GSSG) may provide a biomarker for treatment response to methyl B12. Additional research is needed to delineate a subgroup of potential responders and ascertain a biomarker for response to methyl B12.