Major Depressive Disorder and Measures of Cellular Aging: An Integrative Review

Kinser, Patricia A.; Lyon, Debra E.

doi:10.1155/2013/469070

Cited by 24 publications

(26 citation statements)

References 54 publications

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“…SCID vs. CES-D), as well as ascertainment of clinical samples versus non-clinical populations (for review see Kinser and Lyon, 2013; Schutte and Malouff, 2015). However, both positive and negative findings have been reported in studies using validated, structured clinical interviews to diagnose depression.…”

Section: Discussionmentioning

confidence: 99%

Telomere length and telomerase in a well-characterized sample of individuals with major depressive disorder compared to controls

Simon

Walton

Bui

et al. 2015

Psychoneuroendocrinology

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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. Conclusion 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 lower in men with MDD.

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Section: Discussionmentioning

confidence: 99%

Telomere length and telomerase in a well-characterized sample of individuals with major depressive disorder compared to controls

Simon

Walton

Bui

et al. 2015

Psychoneuroendocrinology

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“…Major depressive disorder (MDD) has been considered a syndrome of “premature aging” (Heuser, 2002), and this notion has been reiterated in several recent reviews (Kinser and Lyon, 2013; Luca et al, 2013; Wolkowitz et al, 2011b). Further, MDD has been associated with neuroanatomic/neurodevelopmental as well as brain transcriptome evidence of accelerated brain aging (Douillard-Guilloux et al, 2013; Koutsouleris et al, 2014).…”

Section: Telomere Length In Psychiatric Illnessesmentioning

confidence: 99%

Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging

Lindqvist

Epel

Mellon³

et al. 2015

Neuroscience & Biobehavioral Reviews

268

231

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Many psychiatric illnesses are associated with early mortality and with an increased risk of developing physical diseases that are more typically seen in the elderly. Moreover, certain psychiatric illnesses may be associated with accelerated cellular aging, evidenced by shortened leukocyte telomere length (LTL), which could underlie this association. Shortened LTL reflects a cell's mitotic history and cumulative exposure to inflammation and oxidation as well as the availability of telomerase, a telomere-lengthening enzyme. Critically short telomeres can cause cells to undergo senescence, apoptosis or genomic instability, and shorter LTL correlates with poorer health and predicts mortality. Emerging data suggest that LTL may be reduced in certain psychiatric illnesses, perhaps in proportion to exposure to the psychiatric illnesses, although conflicting data exist. Telomerase has been less well characterized in psychiatric illnesses, but a role in depression and in antidepressant and neurotrophic effects has been suggested by preclinical and clinical studies. In this article, studies on LTL and telomerase activity in psychiatric illnesses are critically reviewed, potential mediators are discussed, and future directions are suggested. A deeper understanding of cellular aging in psychiatric illnesses could lead to re-conceptualizing Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. DISCLOSURESJL is a consultant to Telomere Diagnostics Inc., formerly Telome Health, and owns stock in the company. The company had no role in this research or in writing this review. The remaining authors report no current disclosures or conflicts of interest. HHS Public Access

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“…Interestingly, MDD is highly comorbid with many diseases associated with advanced age such as cardiovascular disease, stroke, diabetes, osteoporosis, diabetes, immune impairments and dementia (Wolkowitz et al, 2011b). In fact, evidence is mounting that indicates MDD is associated with advanced cellular aging (Douillard-Guilloux et al, 2013;Kinser and Lyon, 2013). Numerous studies report shorter telomere lengths in peripheral blood mononuclear cells from MDD patients (Simon et al, 2006;Wolkowitz et al, 2010;Wikgren et al, 2012;Verhoeven et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Shortened telomere length in white matter oligodendrocytes in major depression: potential role of oxidative stress

Szebeni

DiPeri

et al. 2014

Int. J. Neuropsychopharm.

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Telomere shortening is observed in peripheral mononuclear cells from patients with major depressive disorder (MDD). Whether this finding and its biological causes impact the health of the brain in MDD is unknown. Brain cells have differing vulnerabilities to biological mechanisms known to play a role in accelerating telomere shortening. Here, two glia cell populations (oligodendrocytes and astrocytes) known to have different vulnerabilities to a key mediator of telomere shortening, oxidative stress, were studied. The two cell populations were separately collected by laser capture micro-dissection of two white matter regions shown previously to demonstrate pathology in MDD patients. Cells were collected from brain donors with MDD at the time of death and age-matched psychiatrically normal control donors (N = 12 donor pairs). Relative telomere lengths in white matter oligodendrocytes, but not astrocytes, from both brain regions were significantly shorter for MDD donors as compared to matched control donors. Gene expression levels of telomerase reverse transcriptase were significantly lower in white matter oligodendrocytes from MDD as compared to control donors. Likewise, the gene expression of oxidative defence enzymes superoxide dismutases (SOD1 and SOD2), catalase (CAT) and glutathione peroxidase (GPX1) were significantly lower in oligodendrocytes from MDD as compared to control donors. No such gene expression changes were observed in astrocytes from MDD donors. These findings suggest that attenuated oxidative stress defence and deficient telomerase contribute to telomere shortening in oligodendrocytes in MDD, and suggest an aetiological link between telomere shortening and white matter abnormalities previously described in MDD.

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Major Depressive Disorder and Measures of Cellular Aging: An Integrative Review

Cited by 24 publications

References 54 publications

Telomere length and telomerase in a well-characterized sample of individuals with major depressive disorder compared to controls

Telomere length and telomerase in a well-characterized sample of individuals with major depressive disorder compared to controls

Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging

Shortened telomere length in white matter oligodendrocytes in major depression: potential role of oxidative stress

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