1H MRS Measurement of Cortical GABA and Glutamate in Primary Insomnia and Major Depressive Disorder: Relationship to Sleep Quality and Depression Severity

•1H MRS was used to examine GABA+ and Glu relative to creatine (Cr) in the dorsal anterior cingulate cortex (dACC) and parieto-occipital cortex (POC) in those with Major Depressive Disorder (MDD), Primary Insomnia (PI), and Healthy Controls (HC).•Relative to HCs, subjects with MDD exhibited decreased Glu/Cr in the dACC.•In those with MDD, Glu/Cr levels in the dACC were inversely correlated with anhedonia ratings.•In those with MDD, sleep quality was not associated with Glu/Cr in the dACC.•Relative to HCs, subjects with PI exhibited no significant differences in GABA+/Cr or Glu/Cr. Both Major Depressive Disorder (MDD) and Primary Insomnia (PI) have been linked to deficiencies in cortical γ-aminobutyric acid (GABA) and glutamate (Glu) thus suggesting a shared neurobiological link between these two conditions. The extent to which comorbid insomnia contributes to GABAergic or glutamatergic deficiencies in MDD remains unclear. We used single-voxel proton magnetic resonance spectroscopy (1H MRS) at 4 Tesla to examine GABA+ and Glu relative to creatine (Cr) in the dorsal anterior cingulate cortex (dACC) and in the parieto-occipital cortex (POC) of 51 non-medicated adults with MDD, 24 adults with Primary Insomnia (PI), and 25 age- and sex-matched good sleeper controls (HC). Measures of depression severity and subjective and objective sleep quality were compared with 1H MRS metabolite measures. MDD subjects exhibited a 15% decrease in Glu/Cr in the dACC compared to HC. Within the MDD group, there was a trend inverse correlation between dACC Glu/Cr and anhedonia ratings. We observed no significant association between measures of sleep quality with dACC Glu/Cr in those with MDD. The protocol and data interpretation would have been enhanced by the recruitment of MDD subjects with a broader range of affect severity and a more comprehensive assessment of clinical features. These findings support the role of cortical glutamatergic mechanisms in the pathophysiology of MDD. Insomnia severity did not further contribute to the relative deficiency of glutamatergic measures in MDD.