Les télomères sont des structures associant l’extrémité de la molécule d’ADN de chaque bras chromosomique et plus d’une dizaine de protéines régulatrices. La séquence de l’ADN télomèrique est constituée par la répétition de l’hexanucléotide TTAGGG. En raison des modalités de réplication de l’ADN, les télomères se raccourcissent progressivement à chaque cycle cellulaire, et ce phénomène est accéléré par les stress oxydatifs. Une taille critique des télomères active les programmes génétiques de sénescence et/ou de mort cellulaire. La taille des télomères leucocytaires est actuellement considérée comme un marqueur de l’âge biologique, du risque morbide (pathologies cardiovasculaires, métaboliques, démence) et de la mortalité. Un raccourcissement accéléré a été observé dans la schizophrénie, les troubles de l’humeur et l’exposition au stress psychique, suggérant un vieillissement prématuré. Aucune donnée n’est disponible sur le statut des télomères dans le cortex de sujets déprimés. Nous avons étudié la taille des télomères dans l’ADN du cortex occipital de 24 patients déprimés et 12 témoins (don du Stanley Research Institute). Aucune différence significative n’a été mise en évidence. Ces résultats sont discutés à partir des données qui suggèrent un rôle de l’inflammation et du stress oxydatif dans la dépression, ainsi que l’existence d’un mécanisme de protection spécifique des télomères dans les neurones.

Telomeres are complex structures formed by the end of the DNA molecule at the tip of chromosomal arms. The telomeric sequence, which results from the repetition of the hexanucleotide TTAGGG, is partly single strand and is associated with more than ten proteins, including the enzyme telomerase. Because of the characteristics of the DNA replication process, only telomerase is able to elongate the telomeric sequence. Since the telomerase gene is repressed in virtually all the somatic cells, telomeres progressively shorten at each S phase of the cell cycle, and this shortening is accelerated by oxidative stress. A critically shortened telomere activates 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).

The mean telomere length has been evaluated by a real time quantitative PCR technique, which amplified the telomere sequence and a reference single copy sequence. Results have been expressed by the ratios of Ct obtained for the two amplification curves.

The mean Ct values were strictly identical (0.79±0.001) and the 36 PCR curves were coincident.

This study demonstrates for the first time that there is no shortening of telomeres in the cortex of patients with depressive disorder. Previous results have shown that in normal tissues telomeres length is inversely correlated to age, even in non proliferating tissues, but that the change is minimal in the brain. Thus, although consistent evidence for the role of a systemic and brain inflammation associated oxidative stress in depression has been provided, it must be concluded that the cerebral state of telomeres is not affected by the mechanism operating in the leucocytes. This observation raises the issue of the relation between the psychiatric pathological process and the peripheral telomere marker. It suggests the existence of specific telomere stabilizing factors in the cortex cells.