Associations between childhood maltreatment and oxidative nucleoside damage in affective disorders

Background: Childhood maltreatment is an established risk factor for incident unipolar disorder 24 (UD) and bipolar disorder (BD). It is separately observed that affective disorders (AD) are also 25 associated with higher nucleoside damage by oxidation. Childhood maltreatment may induce higher 26 levels of nucleoside damage by oxidation, and thus contribute to the development of AD; however, 27 this relation is only sparsely investigated. 28 Methods: In total, 860 participants (468 patients with AD, 151 unaffected first-degree relatives (UR), 29 and 241 healthy control persons (HC)) completed the Childhood Trauma Questionnaire (CTQ). The 30 association between CTQ scores and markers of systemic DNA and RNA damage by oxidation as 31 measured by urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-32 dihydroguanosine (8-oxoGuo) levels, respectively, were investigated. 33 Results: In multiple regression models adjusted for sex- and age, 8-oxodG and 8-oxoGuo levels were 34 found to be higher in individuals who had experienced more childhood maltreatment. These 35 associations persisted in models additionally adjusted for BMI, alcohol, and current smoking status. 36 Emotional abuse, sexual abuse and emotional neglect were principally responsible for the foregoing 37 associations. 38 Conclusion: Our findings of an association between childhood maltreatment and oxidative stress 39 markers suggest that childhood maltreatment overall, notably emotional abuse and emotional neglect, is associated with enhanced systemic damage to DNA and RNA in adulthood. Further, 41 individuals with AD reported a higher prevalence of childhood maltreatment, which may induce 42 higher levels of nucleoside damage by oxidation in adulthood, possibly leading to increased risk of 43 developing AD. Longitudinal studies are needed to clarify this relationship further.