Neurochemistry of major depression: a study using magnetic resonance spectroscopy.

Beata R Godlewska,Jamie Near,Philip J Cowen

doi:10.1007/s00213-014-3687-y

Beata R Godlewska, Jamie Near + Show 1 more

Open Access

https://doi.org/10.1007/s00213-014-3687-y

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Abstract

RationaleMagnetic resonance spectroscopy (MRS) is an acceptable non-invasive means of studying brain neurochemistry in depression. Previous studies in depressed patients have focused on measurement of the amino acid neurotransmitters, γ-aminobutyric acid (GABA) and glutamate.ObjectivesThe aim of this study is to use MRS in conjunction with the ultrashort echo time ‘SPECIAL’ technique to measure cortical levels of GABA, glutamate and glutathione (GSH) levels in unmedicated patients with major depression. We also examined the effect of 6-week treatment with the selective serotonin re-uptake inhibitor, escitalopram.MethodsWe studied patients with DSM-IV major depression and healthy age-matched controls using proton MRS. GABA, glutamate and GSH were measured relative to creatine in a voxel placed in occipital cortex.ResultsThere was no difference in GABA or glutamate levels between depressed participants and controls; however, depressed patients had lower GSH levels. Six-week escitalopram treatment, which resulted in significant clinical responses in some patients, did not alter concentrations of GABA, glutamate or GSH.ConclusionsThe sources of variability of GABA and glutamate measures in different studies of depressed patients require further study. Our results suggest that concomitant treatment with selective serotonin re-uptake inhibitors (SSRIs) is unlikely to be an important confounding factor. If lowered GSH levels can be confirmed, they may represent the presence of oxidative stress in some depressed patients.

Highlights

Magnetic resonance spectroscopy (MRS) provides an acceptable and non-invasive means of assessing aspects of brain neurochemistry in depressed patients in vivo
Particular attention has focused on levels of the amino acid neurotransmitters, glutamate and γ-aminobutyric acid (GABA) because of their postulated role in the pathophysiology of depression (Taylor et al 2003; Sanacora et al 2008; Sanacora 2010)
GABA concentrations are reported to be lowered in depression, in occipital cortex where GABA is easier to measure with current MRS methodology (Sanacora et al 1999, 2004; Hasler et al 2007)

Summary

Introduction

Magnetic resonance spectroscopy (MRS) provides an acceptable and non-invasive means of assessing aspects of brain neurochemistry in depressed patients in vivo. Findings to date in MRS studies in patients with major depression have not been consistent, probably related to methodological factors and likely patient heterogeneity. GABA concentrations are reported to be lowered in depression, in occipital cortex where GABA is easier to measure with current MRS methodology (Sanacora et al 1999, 2004; Hasler et al 2007). There is evidence that patients with depression have decreased antioxidant capacity in plasma as shown by lowered levels of glutathione peroxidase (GPX) (Maes et al 2011). A post-mortem study of prefrontal cortex in brain tissue, derived from the Stanley Foundation Consortium, found lowered levels of both GSH and GPX in patients diagnosed with major depression

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