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Alterations of Mitochondrial DNA Copy Number and Telomere Length With Early Adversity and Psychopathology

  • Audrey R. Tyrka
    Correspondence
    Address correspondence to Audrey R. Tyrka M.D., Ph.D., Warren Alpert Medical School of Brown University, Department of Psychiatry and Human Behavior, 345 Blackstone Blvd, Providence, RI 02906
    Affiliations
    Mood Disorders Research Program and Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Providence

    Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence
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  • Stephanie H. Parade
    Affiliations
    Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence

    Bradley/Hasbro Children’s Research Center, E. P. Bradley Hospital, East Providence
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  • Lawrence H. Price
    Affiliations
    Mood Disorders Research Program and Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Providence

    Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence
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  • Hung-Teh Kao
    Affiliations
    Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence

    Laboratory of Molecular Psychiatry, Butler Hospital, Providence, Rhode Island.
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  • Barbara Porton
    Affiliations
    Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence

    Laboratory of Molecular Psychiatry, Butler Hospital, Providence, Rhode Island.
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  • Noah S. Philip
    Affiliations
    Mood Disorders Research Program and Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Providence

    Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence
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  • Emma S. Welch
    Affiliations
    Mood Disorders Research Program and Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Providence
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  • Linda L. Carpenter
    Affiliations
    Mood Disorders Research Program and Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Providence

    Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence
    Search for articles by this author

      Abstract

      Background

      Telomere shortening and alterations of mitochondrial biogenesis are involved in cellular aging. Childhood adversity is associated with telomere shortening, and several investigations have shown short telomeres in psychiatric disorders. Recent studies have examined whether mitochondria might be involved in neuropsychiatric conditions; findings are limited and no prior work has examined this in relation to stress exposure.

      Methods

      Two-hundred ninety healthy adults provided information on childhood parental loss and maltreatment and completed diagnostic interviews. Participants were categorized into four groups based upon the presence or absence of childhood adversity and the presence or absence of lifetime psychopathology (depressive, anxiety, and substance use disorders). Telomere length and mitochondrial DNA (mtDNA) copy number were measured from leukocyte DNA by quantitative polymerase chain reaction.

      Results

      Childhood adversity and lifetime psychopathology were each associated with shorter telomeres (p < .01) and higher mtDNA copy numbers (p < .001). Significantly higher mtDNA copy numbers and shorter telomeres were seen in individuals with major depression, depressive disorders, and anxiety disorders, as well as those with parental loss and childhood maltreatment. A history of substance disorders was also associated with significantly higher mtDNA copy numbers.

      Conclusions

      This study provides the first evidence of an alteration of mitochondrial biogenesis with early life stress and with anxiety and substance use disorders. We replicate prior work on telomere length and psychopathology and show that this effect is not secondary to medication use or comorbid medical illness. Finally, we show that early life stress and psychopathology are each associated with these markers of cellular aging.

      Keywords

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