Original Article

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

  • Neuropsychopharmacology 37, 24282435 (2012)
  • doi:10.1038/npp.2012.101
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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.

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Acknowledgements

We thank the Misericordia Unit 3E and the Grey Nuns ante- and postpartum unit for their support. We would also like to thank the University of Alberta Hospital Foundation. This research was sponsored by a Canadian Institutes of Health Research (CIHR) grant to Dr Jean-Michel Le Melledo, Dr Peter Allen, Dr Glen Baker, Dr Chris Hanstock, and Dr Steve Newman, and by CIHR and a Wyeth Ayerst Research and Development Grant for a post-doctoral fellowship to Dr Panteha Khalili. JMLM received salary support from the Alberta Heritage Foundation for Medical Research (AHFMR) during this investigation.

Author information

Affiliations

  1. Department of Psychiatry, University of Alberta, Edmonton, AB, Canada

    • Alyssa M McEwen
    • , Denee T A Burgess
    • , Panteha Khalili
    • , Stephen C Newman
    • , Glen B Baker
    • , Nicholas D Mitchell
    • , Janisse Khudabux-Der
    •  & Jean-Michel LeMelledo
  2. Department of Biomedical Engineering, University of Alberta, Edmonton, AB, Canada

    • Christopher C Hanstock
    • , Peter Seres
    •  & Peter S Allen

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Competing interests

The authors report no competing interests. Over the past 3 years, GBB has had compensation from the following, although these funds are unrelated to the current manuscript: The CIHR (operating grants); Pfizer Pharmaceuticals (an educational grant and an operating grant), the manufacturer of ziprasidone and pregabalin; and SinoVeda Canada (operating grant), a company involved with natural products.

Corresponding author

Correspondence to Jean-Michel LeMelledo.