Glutamatergic dysregulation in pediatric psychiatric disorders: a systematic review of the magnetic resonance spectroscopy literature.

Abstract

As the major excitatory neurotransmitter in the brain, glutamate plays a critical role in normal brain function; thus, its dysregulation could lead to psychopathology in youth. A growing body of literature has investigated the role of glutamate in the pathophysiology of childhood psychiatric disorders through magnetic resonance spectroscopy (MRS). The aim of this study was to review the existing literature to gauge the specificity of such findings. PubMed was searched for all scientific, peer-reviewed articles published in English that included MRS measurements of glutamatergic metabolites in pediatric psychiatric populations through August 14, 2013. 50 articles were included in this review. These studies included measurements of glutamate or related metabolites with MRS in children with psychiatric disorders. All relevant data (eg, population; number, sex, and age of subjects; method of comparison; treatment history; MRS Tesla; brain regions of interest; glutamatergic findings; other findings; and comorbidities) were extracted from the included articles. The direction and significance of glutamate dysregulation and brain region(s) examined were used to compare the studies. Most consistently, increases in glutamatergic metabolites were found in the anterior cingulate cortex (ACC) and other regions in youth with attention-deficit/hyperactivity disorder (ADHD). Limited data suggested increases in glutamatergic metabolites in youth with autism spectrum disorders, emotional dysregulation, and high risk for schizophrenia and decreases in youth with major depression, bipolar disorder, and obsessive-compulsive disorder. There was limited but consistent evidence for normalization of glutamatergic levels with treatment, particularly in bipolar disorder and ADHD. A relatively small number of studies have examined the role of glutamatergic dysregulation in pediatric psychiatric disorders. Some consistencies can be found, but interpretation of the data is limited by differences in methodology, including age of subjects, severity of current symptoms, treatment, and scanning parameters.