Abstract Body

Major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) are two serious mental illnesses that are associated with excessive physical morbidity and with an earlier average age at death, even after accounting for lifestyle factors and suicide. The medical conditions with higher prevalence in these disorders are generally those that are more commonly seen in older individuals, such as cardiovascular disease and others. This raises the possibility that these disorders are not only “mental illnesses,” but that they may be accompanied by core somatic pathology. Indeed, these illnesses may be characterized by an accelerated biological aging process at the cellular level. Consistent with this, previous studies in these illnesses often found accelerated telomere shortening, one form of accelerated cell aging. A newer measure of biological aging, that provides superior correspondence with disease and mortality rates, is “epigenetic aging.” As individuals age, certain highly predictable locations (CpG sites) in the DNA become sequentially methylated, altering gene transcription and protein translation. The rate at which these site-specific epigenetic changes occur, is often characterized by “epigenetic clocks,” which are among the best current measures of biological aging. In our studies in PTSD and in MDD we found significantly accelerated epigenetic aging using two separate epigenetic clocks: accelerated “Horvath clock” aging in PTSD and accelerated “GrimAge clock” aging in MDD. These findings complement those with telomere length in supporting accelerated biological/ cellular aging in these two conditions. It remains unknown whether these cellular changes contribute to the increased somatic morbidity and mortality, or whether they are merely correlational. Nonetheless, these findings may add to our understanding of MDD and PTSD pathophysiology and may suggest novel treatments for the psychiatric symptoms as well as their somatic comorbidities.