Stephen H Chen1, Elissa S Epel2, Synthia H Mellon3, Jue Lin4, Victor I Reus2, Rebecca Rosser2, Eve Kupferman2, Heather Burke2, Laura Mahan2, Elizabeth H Blackburn4, Owen M Wolkowitz5. 1. Department of Psychology, Wellesley College, Wellesley, MA, USA. 2. Department of Psychiatry, University of California, San Francisco (UCSF), School of Medicine, 401 Parnassus Avenue, San Francisco, CA 94143, USA. 3. Department of OB-GYN and Reproductive Sciences, UCSF School of Medicine, San Francisco, CA, USA. 4. Department of Biochemistry and Biophysics, UCSF School of Medicine, San Francisco, CA, USA. 5. Department of Psychiatry, University of California, San Francisco (UCSF), School of Medicine, 401 Parnassus Avenue, San Francisco, CA 94143, USA. Electronic address: Owen.Wolkowitz@ucsf.edu.
Abstract
BACKGROUND: Adverse childhood experiences (ACEs) are associated with poor physical and mental health outcomes in adulthood. Adverse childhood experiences are also associated with shortened leukocyte telomere length (LTL) in adults, suggesting accelerated cell aging. No studies have yet assessed the relationship of ACEs to LTL in individuals with major depressive disorder (MDD), despite the high incidence of antecedent ACEs in individuals with MDD. Further, no studies in any population have assessed the relationship of ACEs to the activity of telomerase, the major enzyme responsible for maintaining LTL, or the relationship between telomerase and LTL in individuals with ACEs. METHODS: Twenty healthy, unmedicated adults with MDD and 20 healthy age-, sex- and ethnicity-matched controls had ACEs assessed and had blood drawn for LTL and peripheral blood mononuclear cell (PBMC) resting telomerase activity. RESULTS: In healthy controls, greater ACE exposure was associated with shorter LTL (p<.05) but was unassociated with telomerase activity. In MDD, however, the opposite pattern was seen: greater ACE exposure was unrelated to LTL but was associated with increased telomerase activity (p<.05) and with a higher telomerase:LTL ratio (p=.022). LIMITATIONS: Study limitations include the small sample size, a single timepoint assessment of telomerase activity, and the use of retrospective self-report to assess ACEs. CONCLUSIONS: These results replicate prior findings of shortened LTL in healthy adults with histories of multiple ACEs. However, in MDD, this relationship was substantially altered, raising the possibility that activation of telomerase in ACE-exposed individuals with MDD could represent a compensatory response to endangered telomeres.
BACKGROUND: Adverse childhood experiences (ACEs) are associated with poor physical and mental health outcomes in adulthood. Adverse childhood experiences are also associated with shortened leukocyte telomere length (LTL) in adults, suggesting accelerated cell aging. No studies have yet assessed the relationship of ACEs to LTL in individuals with major depressive disorder (MDD), despite the high incidence of antecedent ACEs in individuals with MDD. Further, no studies in any population have assessed the relationship of ACEs to the activity of telomerase, the major enzyme responsible for maintaining LTL, or the relationship between telomerase and LTL in individuals with ACEs. METHODS: Twenty healthy, unmedicated adults with MDD and 20 healthy age-, sex- and ethnicity-matched controls had ACEs assessed and had blood drawn for LTL and peripheral blood mononuclear cell (PBMC) resting telomerase activity. RESULTS: In healthy controls, greater ACE exposure was associated with shorter LTL (p<.05) but was unassociated with telomerase activity. In MDD, however, the opposite pattern was seen: greater ACE exposure was unrelated to LTL but was associated with increased telomerase activity (p<.05) and with a higher telomerase:LTL ratio (p=.022). LIMITATIONS: Study limitations include the small sample size, a single timepoint assessment of telomerase activity, and the use of retrospective self-report to assess ACEs. CONCLUSIONS: These results replicate prior findings of shortened LTL in healthy adults with histories of multiple ACEs. However, in MDD, this relationship was substantially altered, raising the possibility that activation of telomerase in ACE-exposed individuals with MDD could represent a compensatory response to endangered telomeres.
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