Mania, glutamate/glutamine and risperidone in pediatric bipolar disorder: a proton magnetic resonance spectroscopy study of the anterior cingulate cortex

Abstract

Background: The purpose of this study was to investigate the anterior cingulate cortex (ACC) glutamate/glutamine (Glx) to creatine ratio (Glx/Cr) in two groups of children with Bipolar Disorder (BPD): those exhibiting manic symptoms requiring treatment and those being stably treated with the atypical antipsychotic risperidone. Atypical antipsychotics have been shown to increase serum glutamate levels and ACC Glx/Cr in subjects with schizophrenia. In this study, we hypothesized that the children with BPD in need of treatment would have lower Glx/Cr compared with the children with BPD being stably treated with risperidone.

Methods: Proton MR spectra were acquired, at 1.5 T, from the ACC of eighteen subjects with a DSM-IV diagnosis of BPD: ten (11.10+/-3.48 years; five female) were manic and not medicated with any antipsychotic and eight (10.88+/-2.99 years; one female) were medicated with the atypical antipsychotic risperidone.

Results: Children with BPD exhibiting manic symptoms requiring treatment had lower Glx/Cr than children with BPD being stably treated with the atypical antipsychotic risperidone. The children treated with risperidone also had significantly lower YMRS and CGI-Mania scores than the children not treated with risperidone. Both YMRS and CGI-Mania scores correlated negatively with ACC Glx/Cr levels.

Limitations: The cross-sectional design, small sample size, the use of Glx rather than glutamate or glutamine and the use of Cr ratios rather than absolute concentrations are limitations of this study.

Conclusions: Children with mania have lower Glx/Cr levels than children with BPD being stably treated with the atypical antipsychotic risperidone. Mania may be associated with reduced glutamate/glutamine levels in the ACC: other imaging studies have shown mania associated with hypometabolism in the ACC. These reductions in glutamate/glutamine may be increased following successful treatment with glutamatergic agents.

Figure 1

(a) A 2 cm x 2 cm x 1.2 cm (superior inferior) voxel in the anterior cingulate cortex of a child with BPD; and (b) a proton spectrum (TE=30 ms; TR = 2s) from that voxel with an LCModel fit. NAA: N-acetyl aspartate. Glx: Glutamate/Glutamine Cho: Choline containing compounds. Ino: Inositol containing compounds.