Abstract
Abstract Telomeres are complex structures formed by the end of the DNA molecule at the tip of each chromosomal arm. The repeated (TTAGGG) telomeric sequence progressively shortens during lifespan because it cannot be replicated as somatic cells divide, and is highly susceptible to breakage by free radicals. Critically shortened telomeres activate the genetic program of cell senescence and/or apoptosis. The telomere length measured in peripheral blood leucocytes is considered a reliable marker of biological age, mortality risk and exposure to various pathological conditions, including cardiovascular disease, dementia, and metabolic syndrome. Telomere erosion has been observed in psychiatric disorders including schizophrenia and mood disorders, suggesting an accelerated aging of 10 to 20 years. Whether this peripheral dynamic is reflected by a similar pattern in the brain remains unknown. To address this issue we have measured the telomere length in the occipital DNA cortex of 24 patients with major depressive disorder and 12 controls (donated by the Stanley Research Institute) by a real time quantitative PCR technique. The mean telomere lengths were identical in the depressed and control groups. Thus, although there is consistent evidence for the role of systemic inflammation and oxidative stress in depression, it must be concluded that the cerebral status of telomeres is not affected. This observation raises the issue of the relation between the psychiatric pathological process, and peripheral and central biomarkers.
Highlights
Telomeres are complex nucleoprotein structures, capping the linear DNA end at the tip of each chromosome arm (Aubert & Landsdorp, 2008)
The Ct ratios of telomeres varied from 0.78 to 0.80 and their means were strictly identical in all tested groups: 0.79 (± 0.001), indicating for the first time that there was no telomere erosion in the cortex of patients with depressive disorder, even in case of long lasting recurring symptoms, psychotic characteristics or suicidal behavior
Four studies including 251 depressed individuals have reported that there was a significant shortening of mean telomere length (MTL) in the leucocytes of patients with long lifetime MDD duration, equivalent to approximately 7 to 10 years of accelerated aging (Wolkowitz et al, 2011; Simon et al, 2006; Hartmann et al, 2010; Wikgren et al, 2012)
Summary
Received September 21, 2012; accepted November 14, 2012; Act Nerv Super 56(3), 89-94; ISSN-1802-9698. There is evidence that oxidative stress associated with chronic inflammatory disease and low-grade systemic inflammation, plays a major role in this ROSmediated telomere shortening (O’Donovan et al, 2011).The reduction of telomere sequences to a critical length activates interlinked cellular safeguard systems, at crossroads of genome stability surveillance, cell cycle progression, cell death, and tissue renewal, leading to activation of the cell senescence program (Sahin & DePinho, 2010). Together with the well-recognized medical comorbidities (metabolic and cardiovascular) observed in MDD (Moussavi et al, 2007), these findings have led to the hypothesis that depression should be recognized as a somatic disease in its own right, which causes premature aging (Wolkowitz et al, 2011) In this context, it has been suggested that the shortening of telomeres in neurons of the cerebral cortex by cumulative oxidative stress, might contribute to the physiopathology of MDD and influence brain aging.
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