Early Life Trauma Predicts Affective Phenomenology and the Effects are Partly Mediated by Staging Coupled with Lowered Lipid-Associated Antioxidant Defences

Abstract Background Early life trauma (ELT) may drive mood disorder phenomenology, neuro-oxidative and neuro-immune pathways and impairments in semantic memory. Nevertheless, there are no data regarding the impact of ELT on affective phenomenology and whether these pathways are mediated by staging or lowered lipid-associated antioxidant defences. Methods This study examined healthy controls (n=54) and patients with affective disorders including major depression, bipolar disorder and anxiety disorders (n=118). ELT was assessed using the Child Trauma Questionnaire. In addition, we measured affective phenomenology and assayed advanced oxidation protein products; malondialdehyde, paraoxonase 1 (CMPAase) activity, high-sensitivity C-reactive protein (hsCRP), and high-density lipoprotein (HDL) cholesterol. Results ELT was associated with increased risk for mood and comorbid anxiety disorders and a more severe phenomenology, including staging characteristics (number of mood episodes), severity of depression and anxiety, suicide attempts, suicidal ideation, type of treatments received, disabilities, body mass index, smoking behaviour and hsCRP, as well as lowered health-related quality of life, socio-economic status, antioxidant defences and semantic memory. The number of mood episodes and CMPAase/HDL-cholesterol levels could be reliably combined into a new vulnerability staging-biomarker index, which mediates in part the effects of ELT on affective phenomenology, while lowered antioxidant defences are associated with increased oxidative stress. Moreover, the effects of female sex on mood disorders and affective phenomenology are mediated by ELT. Discussion The cumulative effects of different types of ELT drive many aspects of affective phenomenology either directly or indirectly through effects of staging and/or lipid–associated antioxidant defences. The results show that children, especially girls, with ELT are at great risk to develop mood disorders and more severe phenotypes of affective disorders.