Telomere length and telomerase in a well-characterized sample of individuals with major depressive disorder compared to controls.
BACKGROUND
Leukocyte telomere length (LTL) is a marker of cellular turnover and oxidative stress. Studies suggest major depressive disorder (MDD) is associated with oxidative stress, but examinations of MDD and LTL have yielded mixed results, likely because of differences in measurement methods and unmeasured confounding. This study examined LTL and telomerase activity in 166 individuals with MDD compared to 166 age- and gender-matched matched controls free of any psychiatric disorder, using well-validated assays and clinical assessment methods, and controlling for a range of potential confounders.


METHODS
Subjects aged 18 to 70 were evaluated by trained raters and provided blood for LTL and telomerase activity measurement. LTL was assayed using Southern blot and replicated with qPCR, and telomerase activity was assayed with a repeat amplification protocol using a commercial kit.


RESULTS
There was no significant difference in telomere length for individuals with MDD [mean (SD)=9.1 (3.0)kbp] compared to controls [mean(SD)=8.9(2.5)kbp] measured by Southern blot (p=0.65) or by confirmatory qPCR (p=0.91) assays. Controlling for potential confounders did not alter the results. Telomerase activity did not differ by MDD diagnosis overall (p=0.40), but the effect of MDD was significantly modified by gender (t(299)=2.67, p=0.0079) even after controlling for potential confounders, with telomerase activity significantly greater only in males with MDD versus controls.


CONCLUSIONS
Our well-characterized, well-powered examination of concurrently assessed telomere length and telomerase activity in individuals with clinically significant, chronic MDD and matched controls failed to provide strong evidence of an association of MDD with shorter LTL, while telomerase activity was higher in men with MDD [corrected].
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, United States; Harvard Medical School, Boston, MA, United States. Electronic address: nsimon@mgh.harvard.edu.
Naomi M
NM
Simon
Dana-Farber Cancer Institute, Boston, MA, United States.
Zandra E
ZE
Walton
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, United States; Harvard Medical School, Boston, MA, United States.
Eric
E
Bui
Dana-Farber Cancer Institute, Boston, MA, United States; Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, MA, United States.
Jennifer
J
Prescott
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, United States; Harvard Medical School, Boston, MA, United States.
Elizabeth
E
Hoge
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, United States.
Aparna
A
Keshaviah
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, United States.
Noah
N
Schwarz
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, United States.
Taylor
T
Dryman
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, United States.
Rebecca A
RA
Ojserkis
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, United States.
Benjamin
B
Kovachy
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, United States; Harvard Medical School, Boston, MA, United States.
David
D
Mischoulon
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, United States; Harvard Medical School, Boston, MA, United States.
John
J
Worthington
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States; Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, MA, United States.
Immaculata
I
De Vivo
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, United States; Harvard Medical School, Boston, MA, United States.
Maurizio
M
Fava
Harvard Medical School, Boston, MA, United States; Dana-Farber Cancer Institute, Boston, MA, United States.
Kwok-Kin
KK
Wong
D000293:Adolescent; D000328:Adult; D000368:Aged; D003865:Major Depressive Disorder / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019098:Telomerase / Q000097:blood*; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D059505:Telomere Homeostasis; D055815:Young Adult
D019098:Telomerase
Major depressive disorder; Telomerase; Telomere length