Alterations of Mitochondrial DNA Copy Number and Telomere Length With Early Adversity and Psychopathology.
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.
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. Electronic address: Audrey_Tyrka@brown.edu.
Audrey R
AR
Tyrka
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.
Stephanie H
SH
Parade
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.
Lawrence H
LH
Price
Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence; Laboratory of Molecular Psychiatry, Butler Hospital, Providence, Rhode Island.
Hung-Teh
HT
Kao
Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence; Laboratory of Molecular Psychiatry, Butler Hospital, Providence, Rhode Island.
Barbara
B
Porton
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.
Noah S
NS
Philip
Mood Disorders Research Program and Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Providence.
Emma S
ES
Welch
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.
Linda L
LL
Carpenter
D000293:Adolescent; D000328:Adult; D000375:Aging / Q000235:genetics; D001008:Anxiety Disorders / Q000453:epidemiology*; D015415:Biomarkers / Q000378:metabolism; D016922:Cellular Senescence / Q000235:genetics; D002649:Child Abuse; D056915:DNA Copy Number Variations / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D003865:Major Depressive Disorder / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D063129:Parental Death; D011569:Psychiatric Status Rating Scales; D013315:Stress, Psychological / Q000235:genetics*; D019966:Substance-Related Disorders / Q000453:epidemiology*; D059506:Telomere Shortening / Q000235:genetics*; D055815:Young Adult
D015415:Biomarkers; D004272:DNA, Mitochondrial
Anxiety disorder; Childhood; Depressive disorder; Early life stress; Mitochondria; Telomere