Abstract

BACKGROUND: Patients with major depressive disorder (MDD) show glutamatergic deficits in the ventral anterior cingulate cortex. The glutamine/glutamate (Gln/Glu) ratio was proposed to be connected to glutamatergic cycling, which is hypothesized to be dysregulated in MDD. As an indicator of regional metabolite status, this ratio might be a robust state marker sensitive to clinical heterogeneity. METHODS: Thirty-two MDD patients (mean age 40.88 ± 13.66 years, 19 women) and control subjects (mean age 33.09 ± 8.24 years, 19 women) were compared for pregenual anterior cingulate cortex levels of Gln/Glu, Gln/total creatine (tCr), Glu/tCr, and gamma-aminobutyric acid/tCr as determined by high-field magnetic resonance spectroscopy. We tested if symptom severity (Hamilton Depression Rating Scale) and anhedonia (Snaith-Hamilton Pleasure Scale) influence the relation of metabolites to clinical symptoms. RESULTS: MDD patients showed higher Gln/Glu. This was driven by marginally higher Gln/tCr and nonsignificantly lower Glu/tCr. Groups defined by severity moderated relationship between Gln/Glu and the Hamilton Depression Rating Scale. Moreover, severe cases differed from both control subjects and moderate cases. Groups defined by the Snaith-Hamilton Pleasure Scale also displayed differential relationship between Gln/Glu and levels of anhedonia, predominantly driven by Gln/tCr. CONCLUSIONS: We elaborate previous accounts of metabolite deficits in the anterior cingulate cortex toward increased Gln/Glu. There is a moderated relationship between severity and the ratio, which suggests consideration of different mechanisms or disease state for the respective subgroups in future studies.

Authors	Colic, Lejla; von Düring, Felicia; Denzel, Dominik; Demenescu, Liliana Ramona; Lord, Anton R; Martens, Louise; Lison, Sarah; Frommer, Joerg; Vogel, Mathias; Kaufmann, Joern; Speck, Oliver; Li, Meng; Walter, Martin
Journal	BIOLOGICAL PSYCHIATRY
Pages	1049-1058
Volume	4
Date	1/04/2019
Grant ID	SFB779/A06
Funding Body	German Research Foundation
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1016/j.bpsc.2019.04.003