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Smaller Cornu Ammonis 2–3/Dentate Gyrus Volumes and Elevated Cortisol in Multiple Sclerosis Patients with Depressive Symptoms

  • Stefan M. Gold
    Affiliations
    Multiple Sclerosis Program, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, California
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  • Kyle C. Kern
    Affiliations
    Department of Neurology, Division of Brain Mapping, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, California
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  • Mary-Frances O'Connor
    Affiliations
    Cousins Center, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, California
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  • Michael J. Montag
    Affiliations
    Department of Neurology, Division of Brain Mapping, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, California
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  • Aileen Kim
    Affiliations
    Department of Neurology, Division of Brain Mapping, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, California
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  • Ye S. Yoo
    Affiliations
    Department of Neurology, Division of Brain Mapping, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, California
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  • Barbara S. Giesser
    Affiliations
    Multiple Sclerosis Program, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, California
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  • Nancy L. Sicotte
    Correspondence
    Address correspondence to Nancy L. Sicotte, M.D., 710 Westwood Boulevard, Room 4-238, Los Angeles, CA 90095
    Affiliations
    Multiple Sclerosis Program, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, California

    Department of Neurology, Division of Brain Mapping, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, California
    Search for articles by this author

      Background

      The hippocampus is likely involved in mood disorders, but in vivo evidence for the role of anatomically distinct hippocampal subregions is lacking. Multiple sclerosis, an inflammatory disease of the central nervous system, is linked to a high prevalence of depression as well as hippocampal damage and may thus provide important insight into the pathologic correlates of medical depression. We examined the role of subregional hippocampal volume for depression in relapsing-remitting multiple sclerosis.

      Methods

      Anatomically defined hippocampal subregional volumes (cornu ammonis 1–3 [CA1–CA3] and the dentate gyrus [CA23DG], subiculum, entorhinal cortex) were measured using a high-resolution T2-weighted magnetic resonance imaging sequence in 29 relapsing-remitting multiple sclerosis patients and 20 matched healthy control subjects. Diurnal salivary cortisol was assessed at awakening, 4 pm, and 9 pm on 2 consecutive days. Subjects also completed the Beck Depression Inventory.

      Results

      Multiple sclerosis patients showed smaller hippocampal volumes compared with control subjects, particularly in the CA1 and subiculum subregions. In addition, multiple sclerosis patients with depressive symptoms (Beck Depression Inventory score >13) also showed smaller CA23DG volumes and higher cortisol levels. Within the multiple sclerosis group, CA23DG volume was correlated with depressive symptoms and cortisol levels. There were no associations with number of previous steroid treatments, global atrophy, or disease duration.

      Conclusions

      This report provides in vivo evidence for selective association of smaller CA23DG subregional volumes in the hippocampus with cortisol hypersecretion and depressive symptoms in multiple sclerosis.

      Key Words

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