The study participants included 13 psychotropic drug-naive, right-hand-dominant child and adolescent outpatients with MDD, along with 13 healthy comparison subjects matched for age, gender, weight, height, handedness, and parental socioeconomic status. Functional impairment in MDD patients was measured with the Clinical Global Impression-Severity scale. The childhood Depression Rating Scale-Revised measured severity of depressive symptoms. All patients with MDD had a score of at least 43, indicating significant dysfunction. The Hamilton Anxiety Rating Scale measured severity of anxiety. Integrated volumetric MRI and H-MRS studies were performed in the same scanning session on the same day. For each subject, H-MRS spectra were acquired on the 1.5-Tesla MRI scanner. Anterior cingulate and occipital metabolite concentrations were analyzed by using independent t tests to assess for differences between MDD patients and controls. The study found that anterior cingulate glutametergic (Glx) concentrations were significantly lower (19-percent decrease) in MDD patients compared with controls. Reduced anterior cingulate Glx in MDD patients was associated with increased severity of functional impairment. These results remained comparably significant after controlling for age and anterior cingulate volume. Occipital cortex Glx did not differ between MDD patients and controls. These preliminary findings provide new evidence of localized functional neurochemical marker alterations in Glx in anterior cingulate cortex in pediatric MDD. Thus, altered anterior cingulate Glx neurotransmission may be involved in the pathogenesis of MDD. 2 tables, 2 figures, and 65 references