Nicholas D. Mitchell

University of Alberta, Edmonton, Alberta, Canada

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Publications (4)12.65 Total impact

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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.
    Full-text · Article · Jul 2012 · Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology
  • Nicholas D. Mitchell · Jean-Michel Le Melledo · Melanie Banasch · Glen B. Baker
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    ABSTRACT: Neuroactive steroids (NASs) are rapid acting steroids that produce nongenomic effects through interactions with neurotransmitter receptors, Although research on NASs has focused on their actions as negative or positive allosteric modulators at GABA A receptors, there can also be interactions with other receptors, including glutamate receptors, 5-HT 3 receptors, nicotinic receptors, a1 receptors and voltage- or non-voltage-gated calcium channels. Recent studies in animal models and in humans have investigated the role of NASs, including pregnenolone, pregnenolone sulfate, dehydroepian-drosterone, dehydroepiandrosterone sulfate, progesterone, and a number of 3a-reduced NASs (e.g. allopregnanolone, 5-a-dihydroprogesterone, 3a,5a-tetrahydroprogesterone, 3a,5a-tetrahydrodeoxycorticosterone) in depressive disorders. Although inconsistencies exist, alterations in levels of these NASs have been reported to be associated with major depressive disorder, postpartum depression, and premenstrual dysphoric disorder. In some cases, the actions of the NASs may involve interactions with brain-derived neurotrophic factor (BDNF) and/or the hypothalamic-pituitary-adrenal (HPA) axis. Antidepressant drugs have been shown to have effects on the levels and/or metabolism of NASs, and some NASs have been reported to have antidepressant effects in their own right after administration to animal models or humans. Although interactions appear to be complex, increasing evidence substantiates the importance of NASs in the pathophysiology and treatment of depressive disorders, and research in this area is reviewed in this paper.
    No preview · Article · Apr 2012 · Current Psychiatry Reviews
  • Nicholas D Mitchell · G B Baker
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    ABSTRACT: To review the literature on the involvement of glutamate (Glu), including its interactions with other neurochemical systems, in the pathophysiology of depression. A MEDLINE search using the terms glutamate, depression and major depressive disorder, was performed. Alterations in proteins involved in glutamatergic signalling are implicated in variations in behaviour in animal models of depression. Drugs acting at Glu receptors appear to have antidepressant-like effects in these models, and traditional antidepressant pharmacotherapies act on the glutamatergic system. Recent evidence from genetic studies and in vivo spectroscopy also correlate glutamatergic dysfunction with depression. Trials of N-methyl-d-aspartate receptor antagonists in humans have provided mixed results. A growing body of evidence indicates that the glutamatergic system is involved in the pathophysiology of depression, and may represent a target for intervention.
    No preview · Article · Sep 2010 · Acta Psychiatrica Scandinavica
  • Glen B. Baker · Nicholas D. Mitchell

    No preview · Chapter · May 2008