Effective Lithium (Li)-prophylaxis is the most important factor for a good prognosis in bipolar disorder (BD). However, 40-50% do not respond on Li-treatment and there is a lack of biomarkers for Li-response. We aim to develop biological markers for Li-response to use for a more targeted drug choice already at onset of BD. Based on previous findings we hypothesize that a high telomerase activity and/or epigenetic changes early after Li-introduction can be used as such biomarkers.
Different genetic variants can be associated with a good Li-response. We have assessed more than 700 patients for Lithium-response, which constitute a large part of the material in the international project ConLiGen. There are also other molecular genetic alternatives.
Telomeres (TL) are DNA nucleoprotein complexes that form the ends of chromosomes and erode progressively with each cell division, which means that the telomeric length declines with age, stress and disorders such as depression. In contrast, physical exercise and effective treatment can prevent TL shortening and rebuild TL s through telomerase activity. Antidepressants have been found to protect against blood leucocyte TL shortening. In this project we have found that Li-treated bipolar patients had 35% longer leucocyte telomeres compared with controls and in line with findings in unipolar depressive episodes TL was negatively associated with an increasing number of depressive episodes, see selected publications.
Epigenetic changes are reversible changes in gene expression but not in the DNA sequence, fundamental to the physiological processes that control the genetic activity. These changes may be caused by the influence of environmental factors or disease state, but also contributes to the likelihood that the disease arises and precedes.
In a prospective study we follow telomere length, telomerase activity and epigenetic changes associated with Li-response. Positive findings from this project, might be of great importance in the clinical everyday life, save a great deal of suffering, many lives and reduce the high costs for society.
SLSO, M59, Huddinge sjukhus