Increased Glutamate Levels in the Medial Prefrontal Cortex in Patients with Postpartum Depression

Abstract

The medial prefrontal cortex (MPFC) is a key brain area in depressive symptomatology; specifically, glutamate (Glu) has been reported to play a significant role in major depression (MD) in this area. MPFC Glu levels are sensitive to ovarian hormone fluctuations and pregnancy and the postpartum period are associated with the most substantial physiological alterations of female hormones. It is therefore logical to measure MPFC Glu levels in women with postpartum depression (PPD). Using in vivo magnetic resonance spectroscopy (MRS) at a field strength of 3 T, we acquired single-voxel spectra from the MPFC of 12 women with PPD and 12 healthy controls (HCs) matched for postpartum scan timing. Water-referenced MPFC Glu levels were measured using a MRS technique that allowed us to be specific for Glu with very little glutamine contamination. The concentrations of other water-quantified brain metabolites such as glycerophosphorylcholine plus phosphorylcholine, N-acetylaspartate (NAA), and creatine plus phosphocreatine were measured in the same MR spectra. MPFC Glu levels were higher in women with PPD (7.21±1.20) compared to matched HCs (6.04±1.21). There were no differences between groups for other brain metabolites measured. These findings suggest an association between Glu dysregulation in the MPFC and PPD. Whether the pathophysiology of PPD differs from the pathophysiology of MD remains to be determined. Further investigations are needed to determine the chronological associations between the occurrence of symptoms of PPD and the onset of changes in MPFC Glu levels.

Chronic Gestational Stress Leads to Depressive-Like Behavior and Compromises Medial Prefrontal Cortex Structure and Function during the Postpartum Period

“…Another factor that could contribute to the adverse outcomes associated with gestational stress is glutamate [59]–[62]. A recent study has found that women with PPD have increased glutamate levels in the mPFC [19]. Repeated stress is also associated with increased glutamate neurotransmission in the mPFC [63] and excessive glutamate can lead to dendritic spine loss [64].…”

GABAergic neuroactive steroids and resting-state functional connectivity in postpartum depression: A preliminary study

“…Additional studies have shown abnormalities in ventral striatal response to reward (Moses-Kolko, EL et al, 2011), increased glutamate levels in the medial prefrontal cortex (McEwen, AM et al, 2012) and reduced postsynaptic serotonin-1A receptor binding, in particular in the ACC and mesiotemporal cortices (Moses-Kolko, EL et al, 2008). A single study (Epperson, CN et al, 2006) measured NAS.…”

Glycine site N-methyl-D-aspartate receptor antagonist 7-CTKA produces rapid antidepressant-like effects in male rats

“…[3][4][5] Ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, has been widely reported to have rapid antidepressant effects in both preclinical and clinical studies. 6,7 A single dose of ketamine exerted fast antidepressant effects within a few hours in patients with treatment-resistant major depression.…”