ARE SOME MALTREATED INDIVIDUALS 'IMMUNE' TO LATER LIFE DEPRESSION? AN INVESTIGATION OF 41 INFLAMMATORY MARKERS IN OVER 600 U.K. ADULTS

Background Childhood maltreatment is widely reported across the world and the incidence of child cruelty and neglect offences is reportedly on the rise. Childhood maltreatment is strongly associated with a range of negative health outcomes in adulthood and represents the strongest environmental risk factor for Major Depressive Disorder (MDD). Immuno-inflammatory activation is one biological mechanism activated in response to maltreatment, and a possible mediator of this increased risk for MDD. Immune modulators, such as the inflammatory cytokines are reported to be increased in patients with MDD and play a role in brain development, neurogenesis and synaptic remodelling. We hypothesize that: (i) maltreatment subtypes will have effects on specific inflammatory markers in adulthood; and (ii) maltreatment will have differential effects on inflammatory markers in adulthood depending on whether or not an individual develops MDD. Methods 616 U.K. participants (276 MDD cases and 340 controls) were recruited as part the South East London Community Health Study (SELCoH) and the Antiglucocorticoid augmentation (metyrapone) of antiDepressants in Depression (ADD) Study. MDD status was defined using either DSM-IV, or the Clinical Interview Schedule-Revised (which generates ICD-10 diagnoses). Childhood maltreatment was determined using the Childhood Trauma Questionnaire and ordinal measures of maltreatment subtype severity were generated. The expression of 41 inflammatory markers were quantified using multiplex electrochemiluminescence methods applied to participant serum samples. General linear models were used to investigate the main effects of maltreatment severity on immune marker expression, and MDD case-control by maltreatment interactions whilst covarying for a broad range of potential confounders. Within each test we performed, we corrected for the number of inflammatory markers assessed using the False Discovery Rate (q Results 34 out of 41 inflammatory markers were expressed in over 70% of our sample, and these were carried forward into downstream analyses. Main effect analyses showed that a higher severity of emotional neglect in childhood was associated with higher Vascular Endothelial Growth Factor D (VEGF-D) levels in adulthood (q Discussion VEGF-D is a cytokine responsible for vascularisation and angiogenesis. The effect we observed was irrespective of MDD case-control status, suggesting that if higher levels of VEGF-D levels do have a long-lasting impact on health, this may relate to disorders other than MDD, or it requires interaction with other factors to lead to MDD. Our MDD case-control by maltreatment interaction analyses revealed heightened levels of IL-12p70 in control subjects relative to depressed cases in association with emotional and physical neglect severity. IL-12p70 has been shown to have neuroprotective properties and we hypothesise that this marker may be involved in a mechanism which confers resilience to MDD in response to childhood neglect, or that it represents a biological proxy for a protective environmental factor (e.g. social support). Further work is now needed to understand if IL12p70 represents a novel drug target to treat MDD in those who have experienced childhood neglect.