Brain glutamate in medication-free depressed patients: a proton MRS study at 7 Tesla.

Beata R Godlewska,Charles Masaki,Ann L Sharpley,Philip J Cowen,Uzay E Emir

doi:10.1017/s0033291717003373

Abstract

The possible role of glutamate in the pathophysiology and treatment of depression is of intense current interest. Proton magnetic resonance spectroscopy (MRS) enables the detection of glutamate in the living human brain and meta-analyses of previous MRS studies in depressed patients have suggested that glutamate levels are decreased in anterior brain regions. Nevertheless, at conventional magnetic field strengths [1.5-3 Tesla (T)], it is difficult to separate glutamate from its metabolite and precursor, glutamine, with the two often being measured together as Glx. In contrast, MRS at 7 T allows clear spectral resolution of glutamate and glutamine. We studied 55 un-medicated depressed patients and 50 healthy controls who underwent MRS scanning at 7 T with voxels placed in anterior cingulate cortex, occipital cortex and putamen (PUT). Neurometabolites were calculated using the unsuppressed water signal as a reference. Compared with controls, depressed patients showed no significant difference in glutamate in any of the three voxels studied; however, glutamine concentrations in the patients were elevated by about 12% in the PUT (p < 0.001). The increase in glutamine in PUT is of interest in view of the postulated role of the basal ganglia in the neuropsychology of depression and is consistent with elevated activity in the descending cortical glutamatergic innervation to the PUT. The basal ganglia have rarely been the subject of MRS investigations in depressed patients and further MRS studies of these structures in depression are warranted.

Highlights

Glutamate is the major excitatory neurotransmitter in the human brain and recent years have seen growing interest in the role of altered glutamate activity in the pathophysiology of depression and bipolar disorder (Sanacora et al 2012; Taylor, 2014)
There is the probability of clinical heterogeneity, as demonstrated by a study by Haroon et al (2016) who found that glutamate levels in basal ganglia were significantly higher in depressed patients with raised levels of C-reactive protein (CRP), a peripheral marker of inflammation
In anterior cingulate cortex (ACC) and occipital cortex (OCC), there were no significant differences in concentrations of glutamate and glutamine between depressed patients and controls (Table 2)

Summary

Introduction

Glutamate is the major excitatory neurotransmitter in the human brain and recent years have seen growing interest in the role of altered glutamate activity in the pathophysiology of depression and bipolar disorder (Sanacora et al 2012; Taylor, 2014). This interest has been greatly stimulated by the striking antidepressant effects of the N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine, in depressed patients resistant to monoamine-potentiating agents (McGirr et al 2015). The basal ganglia have rarely been the subject of MRS investigations in depressed patients and further MRS studies of these structures in depression are warranted

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Conclusion