The role of oxidative stress-induced damage to nucleic acids in mental disorders

Mental disorders are associated with signs of accelerated aging across diagnostic groups, both at the population, organ, cellular, and molecular level. Oxidative stress-induced damage to nucleic acids (DNA and RNA) (NA-OXS) is a well-established molecular aging mechanism that is implicated in aging per se as well as in a wide range of age-related disorders. Here, we review the work by us and others on the role of NA-OXS in mental disorders. NA-OXS is increased across diagnostic groups, with the highest levels found in disorders that are also linked to the highest mortality, such as dementias, schizophrenia, and bipolar disorder. NA-OXS appears to be mostly a trait phenomenon that may be sensitive to symptom changes in some disorders. NA-OXS on RNA predict mortality in the general population, patients with type-2 diabetes, and people with mental disorders. Finally, NA-OXS may be reduced by antidepressants. We suggest an overarching theory on how mental disorders and associated intermediate factors, such as poor health behaviors, medical care, chronic neurohormonal stress, and medication, may converge on affecting levels of NA-OXS, which in turn is driving accelerated aging and the risk of age-related somatic illness; a mechanism which could potentially be targeted by existing or future interventions.