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Resilience Is Associated With Larger Dentate Gyrus, While Suicide Decedents With Major Depressive Disorder Have Fewer Granule Neurons

  • Maura Boldrini
    Correspondence
    Address correspondence to Maura Boldrini, M.D., Ph.D., Department of Psychiatry, Columbia University, Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, 1051 Riverside Drive, Box 42, New York NY 10032.
    Affiliations
    Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, New York

    Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, New York
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  • Hanga Galfalvy
    Affiliations
    Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, New York

    Department of Biostatistics, Columbia University, New York State Psychiatric Institute, New York, New York
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  • Andrew J. Dwork
    Affiliations
    Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, New York

    Department of Pathology and Cell Biology, Columbia University, New York State Psychiatric Institute, New York, New York

    Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, New York

    Division of Integrative Neuroscience, New York State Psychiatric Institute, New York, New York
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  • Gorazd B. Rosoklija
    Affiliations
    Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, New York

    Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, New York

    Division of Integrative Neuroscience, New York State Psychiatric Institute, New York, New York

    Macedonian Academy of Sciences and Arts, Ss. Cyril and Methodius University, Skopje, Macedonia
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  • Iskra Trencevska-Ivanovska
    Affiliations
    Skopje Psychiatric Hospital, Ss. Cyril and Methodius University, Skopje, Macedonia
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  • Goran Pavlovski
    Affiliations
    Institute for Forensic Medicine, Ss. Cyril and Methodius University, Skopje, Macedonia
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  • René Hen
    Affiliations
    Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, New York

    Department of Neuroscience, Columbia University, New York State Psychiatric Institute, New York, New York

    Department of Pharmacology, Columbia University, New York State Psychiatric Institute, New York, New York

    Division of Integrative Neuroscience, New York State Psychiatric Institute, New York, New York
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  • Victoria Arango
    Affiliations
    Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, New York

    Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, New York
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  • J. John Mann
    Affiliations
    Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, New York

    Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, New York
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      Abstract

      Background

      Early life adversity (ELA) increases major depressive disorder (MDD) and suicide risk and potentially affects dentate gyrus (DG) plasticity. We reported smaller DG and fewer granular neurons (GNs) in MDD. ELA effects on DG plasticity in suicide decedents with MDD (MDDSui) and resilient subjects (ELA history without MDD or suicide) are unknown.

      Methods

      We quantified neural progenitor cells (NPCs), GNs, glia, and DG volume in whole hippocampus postmortem in four groups of drug-free, neuropathology-free subjects (N = 52 total): psychological autopsy-defined MDDSui and control subjects with and without ELA (before 15 years of age).

      Results

      ELA was associated with larger DG (p < .0001) and trending fewer NPCs (p = .0190) only in control subjects in whole DG, showing no effect on NPCs and DG volume in MDDSui. ELA exposure was associated with more GNs (p = .0003) and a trend for more glia (p = .0160) in whole DG in MDDSui and control subjects. MDDSui without ELA had fewer anterior and mid DG GNs (p < .0001), fewer anterior DG NPCs (p < .0001), and smaller whole DG volume (p = .0005) compared with control subjects without ELA. In MDDSui, lower Global Assessment Scale score correlated with fewer GNs and smaller DG.

      Conclusions

      Resilience to ELA involves a larger DG, perhaps related to more neurogenesis depleting NPCs, and because mature GNs and glia numbers do not differ in the resilient group, perhaps there are effects on process extension and synaptic load that can be examined in future studies. In MDDSui without ELA, smaller DG volume, with fewer GNs and NPCs, suggests less neurogenesis and/or more apoptosis and dendrite changes.

      Keywords

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