Lateralized Caudate Metabolic Abnormalities in Adolescent Major Depressive Disorder: A Proton MR Spectroscopy Study

Abstract

Objective-Proton magnetic resonance spectroscopy ( 1 H-MRS) has been increasingly used to examine striatal neurochemistry in adult major depressive disorder. This study extends the use of this modality to pediatric major depression to test the hypothesis that adolescents with major depression have elevated concentrations of striatal choline and creatine and lower concentrations of N-acetylaspartate.Method-Fourteen adolescents (ages 12-19 years, eight female) who had major depressive disorder for at least 8 weeks and a severity score of 40 or higher on the Children's Depression Rating Scale -Revised and 10 healthy comparison adolescents (six female) group-matched for gender, age, and handedness were enrolled. All underwent three-dimensional 3-T 1 H-MRS at high spatial resolution (0.75-cm 3 voxels). Relative levels of choline, creatine, and N-acetylaspartate in the left and right caudate, putamen, and thalamus were scaled into concentrations using phantom replacement, and levels were compared for the two cohorts.Results-Relative to comparison subjects, adolescents with major depressive disorder had significantly elevated concentrations of choline (2.11 mM versus 1.56 mM) and creatine (6.65 mM versus 5.26 mM) in the left caudate. No other neurochemical differences were observed between the groups.Conclusions-These findings most likely reflect accelerated membrane turnover and impaired metabolism in the left caudate. The results are consistent with prior imaging reports of focal and lateralized abnormalities in the caudate in adult major depression.Rates of major depressive disorder rise dramatically in adolescence, with an estimated lifetime prevalence of 15% in adolescents by ages 15-18. Major depression is associated with significant morbidity, including deterioration in academic functioning, increased risk of substance use, and attempted and completed suicides (1,2). Furthermore, adolescent major depression is a strong predictor of major depression in adulthood, which carries its own burden of disadvantage (3). These findings highlight the need for specific neurobiological research in adolescent major depression.Converging lines of evidence suggest that the pathophysiology of depression entails impairment of cellular resilience and neuroplasticity in specific cortical, subcortical, and limbic brain regions. The relationship between the basal ganglia and depression has been inferred from the high comorbidity between depression and Parkinson's disease as well as Huntington's NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript disease, both basal ganglia-related disorders. In addition, morphometric studies (but not all) and functional neuroimaging studies have documented smaller caudate, putamen, and thalamus as well as impaired metabolism and blood flow in the striatum and thalamus in depression (4-10).Proton magnetic resonance spectroscopy ( 1 H-MRS) has provided additional evidence for the involvement of the striatum in adult major depression. 1 H-MRS provides metabolic assay of ne...

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Sex-specific antidepressant effects of dietary creatine with and without sub-acute fluoxetine in rats

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