Kathleen L Benson1, Ryan Bottary2, Laura Schoerning3, Lee Baer4, Atilla Gonenc1, J Eric Jensen1, John W Winkelman5. 1. McLean Imaging Center, McLean Hospital, Belmont, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA. 2. Cognitive and Affective Neuroscience Laboratory, Department of Psychology, Boston College, Chestnut Hill, MA, USA. 3. University of Massachusetts School of Medicine, Worcester, MA, USA. 4. Department of Psychiatry, Harvard Medical School, Boston, MA, USA. 5. Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Departments of Psychiatry and Neurology, Massachusetts General Hospital, Boston, MA, USA. Electronic address: jwwinkelman@partners.org.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. LIMITATIONS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: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 dACCGlu/Cr and anhedonia ratings. We observed no significant association between measures of sleep quality with dACCGlu/Cr in those with MDD. LIMITATIONS: 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. CONCLUSIONS: 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.
Authors: Matti Gärtner; Anne Weigand; Milan Scheidegger; Mick Lehmann; Patrik O Wyss; Andreas Wunder; Anke Henning; Simone Grimm Journal: Eur Arch Psychiatry Clin Neurosci Date: 2022-01-12 Impact factor: 5.760