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

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.

Differences in brain chemistry in children and adolescents with attention deficit hyperactivity disorder with and without comorbid bipolar disorder: a proton magnetic resonance spectroscopy study.

OBJECTIVE: The authors' goal was to investigate phosphatidylinositol and glutamatergic metabolism in the anterior cingulate cortex of children and adolescents with attention deficit hyperactivity disorder (ADHD) alone, children with ADHD plus bipolar disorder, and children with no axis I diagnosis. METHOD: Proton spectra were acquired from a 4.8-ml voxel placed in the anterior cingulate cortex of 30 subjects who were 6 to 13 years old. Fifteen subjects had ADHD and no comorbid disorder, eight had ADHD plus bipolar disorder, and seven were healthy comparison subjects. RESULTS: Children with ADHD had a significantly higher ratio of glutamate plus glutamine to myo-inositol-containing compounds than children with ADHD plus bipolar disorder and healthy children. CONCLUSIONS: myo-Inositol-containing compounds may provide information on the action of antimanic treatments such as lithium, valproate, and carbamazepine. Glutamate and glutamine are measures of glutamatergic neurotransmission and thus may also reflect changes in serotonin and dopamine pathways.

Examining the association between pediatric bipolar disorder and anxiety disorders in psychiatrically referred children and adolescents.

BACKGROUND: To examine the association between anxiety (ANX) and bipolar disorders (BPD) in a clinically referred pediatric sample. METHODS: Subjects were consecutively referred youth aged <18 years, with a DSM-III-R/DSM-IV diagnosis of BPD (n=297) or a disruptive behavior disorder (DBD) (n=1100) on structured interview. RESULTS: Bipolar disorder in youth was associated with a significantly increased risk for most of the DSM-IV anxiety disorders and was not specifically linked to any one disorder in particular. CONCLUSIONS: Bipolar disorder in youth is a significant risk factor for anxiety comorbidity. Considering the morbidity and dysfunction as well as the differing therapeutic needs associated with bipolar and anxiety symptomatology, appropriate therapeutic approaches will be needed for the management of youth with this comorbidity.