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

Abstract

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.The lifetime prevalence of bipolar disorder is between 1% and 3% and may be present in children and adolescents (1, 2). Attention deficit hyperactivity disorder (ADHD) has been reported in 70% to 98% of children with bipolar disorder (2). The ability to distinguish bipolar disorder, ADHD, and ADHD with comorbid bipolar disorder is important in terms of treatment management because bipolar disorder and ADHD require different treatment strategies (3,4 Proton magnetic resonance spectroscopy ( 1 H MRS) can measure a number of cerebral metabolites, including creatine plus phosphocreatine (Cr), myo-inositol-containing compounds (Ino: myo-inositol with small contributions from inositol-1-phosphate [5]), and glutamate plus glutamine (Glx). 1 H MRS has shown a higher Ino-to-Cr ratio in the anterior cingulate cortex and frontal cortex gray matter of children with bipolar disorder than in healthy comparison subjects (6-8). In contrast, 1 H MRS has shown a higher Glx-to-Cr ratio in the prefrontal cortex and frontal lobe of children with ADHD than in healthy comparison subjects (9, 10).We used 1 H MRS to investigate anterior cingulate cortex metabolite levels in children and adolescents with ADHD alone, ADHD plus bipolar disorder, and no psychiatric diagnosis. Some of the healthy comparison subjects were siblings of the children with ADHD. Siblings were chosen in an effort to distinguish state differences between children with ADHD, those with ADHD plus bipolar disorder, and healthy comparison subjects. Using 1 H MRS, Chang et al. (11) measured trait differences in the prefrontal cortex of children genetically at risk for bipolar disorder. On the basis of the literature, we hypothesized that a higher Glxto-Cr ratio would be associated with ADHD and a higher Ino-to-Cr ratio would be associated with ADHD plus bipolar disorder; thus the Glx-to-Ino ratio could distinguish ADHD from ADHD plus bipolar disorder. MethodThis study was approved by the Institutional Review Boards of Massach...

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