Scientists and clinicians who are interested in the neurochemistry of depression and associated mood disorders.Over the past two decades, magnetic resonance spectroscopy (MRS) has been used to study the role of glutamate neurotransmission in the pathophysiology of depression. Unfortunately, due to inconsistent methodology and patient heterogeneity, results have been variable (1). Regardless, glutamatergic abnormalities in anterior cingulate cortex (ACC) (3) are believed to be associated with depression pathogenesis. Additionally, basal ganglia abnormalities have been shown to be involved in depression pathophysiology (4). One limitation of previous MRS studies on depression is that they have used field strengths of 3 T or below and therefore cannot spectrally differentiate between glutamate and glutamine. Therefore, to further probe the glutamatergic interactions associated with depression, we have acquired spectra at 7 T in the OCC, the ACC and the putamen (PUT). Subjects: Unmedicated depressed patients (n=40, 18 males, 22 females, average age = 32 ± 11) were studied after obtaining written informed consent. All patients were assessed for depression using the DSM-IV criteria for major depressive disorder with a Structured Clinical Interview (SCID-I). Healthy controls (n=28, 16 males, 12 females, average age = 33 ± 12) had no history of depression or other DSM-IV diagnoses. Magnetic Resonance Protocol: All subjects were scanned using a 7T whole body MR system (Siemens, Erlangen) with a Nova Medical 32-channel receive array head-coil. To aid in selecting the VOIs, structural 3D T1-weighted images were acquired with an MP-RAGE sequence (5) (FOV=192×192 mm²; TR=2.2 s; TE=2.82 ms; slice thickness = 1 mm; slices = 96; non- selective inversion; scan time 3 mins) for all subjects. Spectra were measured using semi-LASER (6), (TE=36 ms, TR = 7 s, nt = 64) with VAPOR water suppression and outer volume suppression (7). Signal was acquired from three separate volumes of interest (VOIs) – one in the OCC, one in the ACC and one in the PUT. Post-processing and Statistical Analysis: Metabolites were quantified with LCModel (8) using the unsuppressed water signal as reference. Only those measured reliably (Cramér-Rao lower bounds (CRLB) < 50%, cross correlation coefficients r > -0.5) were reported. Metabolite differences between groups and VOIs were assessed using a repeated measures ANOVA and post-hoc t-tests.Spectra with good SNR and spectral resolution were consistently obtained from all regions as illustrated in Figure 1. Average water linewidths were 13.5 ± 2.0 Hz for OCC, 15.3 Hz ± 2.6 Hz for ACC, 18.2 ± 2.5 Hz for PUT. Statistical testing identified lower Glu concentrations in the OCC (p-value < 0.05) of depressed subjects but no significant difference for Gln. No statistical difference for either metabolite was found in the ACC (p-value > 0.1). Significantly higher Gln (p-value < 0.05) but no difference in Glu was found in the PUT. Figure 2 illustrates metabolite concentration in healthy and depressed patients. This study provides one of the first examinations of the neurochemistry of depression at 7 T. We identified a significant decrease in Glu in occipital cortex but in contrast to other studies no change in ACC. A novel discovery is that that Gln concentrations increase in PUT in depressed subjects. This result requires further investigation and correlation with depressive symptomatology putatively linked to basal-ganglia, for example, retardation and anhedonia. Previous 3 T studies have generally found lowered levels of Glx (Gln and Glu) in ACC (1). As we determined no significant differences in the ACC but changes in OCC and putamen, our data suggest additional studies may be required in order to clarify the role of glutamate and glutamine in depression.