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Hippocampal Neuroinflammation and Depression: Relevance to Multiple Sclerosis and Other Neuropsychiatric Illnesses

  • Kevin J. Manning
    Correspondence
    Address correspondence to: Kevin J. Manning, Ph.D., Department of Psychiatry, University of Connecticut Health Center, 263 Farmington Avenue (MC 2103), Farmington CT, 06030; .
    Affiliations
    Department of Psychiatry, University of Connecticut Health Center, Farmington, Connecticut
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      The high prevalence of depression in multiple sclerosis (MS) is well established. The lifetime prevalence of major depression in MS is 50% compared with an estimated prevalence of 10–15% in the general population (
      • Siegert R.J.
      • Abernethy D.A.
      Depression in multiple sclerosis: A review.
      ). Neuroinflammation is one potential mechanism that could be the cause of the increased rate of depression. MS is an inflammatory autoimmune disorder resulting in chronic microglial activation and subsequent neurodegeneration (
      • Weiner H.L.
      Multiple sclerosis is an inflammatory T-cell-mediated autoimmune disease.
      ), and evidence suggests that major depression independent of comorbid medical illness is associated with the presence of peripheral inflammatory markers (
      • Dowlati Y.
      • Herrmann N.
      • Swardfager W.
      • Liu H.
      • Sham L.
      • Reim E.K.
      • et al.
      A meta-analysis of cytokines in major depression.
      ). Colasanti et al. (
      • Colasanti A.
      • Guo Q.
      • Giannetti P.
      • Wall M.B.
      • Newbould R.D.
      • Bishop C.
      • et al.
      Hippocampal neuroinflammation, functional connectivity, and depressive symptoms in multiple sclerosis.
      ), in Biological Psychiatry, draw on these converging lines of research to address the question of whether the high prevalence of depression in patients with MS is associated with neuroinflammation in specific brain regions. The authors select the hippocampus as their region of interest, considering the following: 1) the hippocampus may be particularly sensitive to neuroinflammation, 2) the hippocampus is functionally connected to the medial prefrontal cortex, amygdala, and subgenual cingulate responsible for emotional processing, and 3) some but not all evidence suggests that hippocampal pathology features prominently in both MS and major depression (
      • Colasanti A.
      • Guo Q.
      • Giannetti P.
      • Wall M.B.
      • Newbould R.D.
      • Bishop C.
      • et al.
      Hippocampal neuroinflammation, functional connectivity, and depressive symptoms in multiple sclerosis.
      ). Understanding whether hippocampal neuroinflammation is associated with depression has clinical implications for MS that would generalize to the study of other neuropsychiatric illnesses.
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