Understanding the Relation Between Early-Life Adversity and Depression Symptoms: The Moderating Role of Sex and an Interleukin-1β Gene Variant

Pro-inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-alpha), are thought to play a fundamental role in the pathogenesis of depression within a subset of individuals. However, the involvement of IL-1 beta has not been as consistently linked to depression, possibly owing to difficulties in detecting this cytokine in blood samples or that changes in circulating levels might only be apparent in a subgroup of patients who have experienced early-life adversity. From this perspective, the association between early-life adversity and depressive illness might depend on genetic variants regulating IL-1 beta activity. Considering the inflammatory-depression link, and that women are twice as likely to experience depression compared to men, the current study (N = 475 university students) examined the moderating role of three independent cytokine single nucleotide polymorphisms (SNPs; IL-1 beta rs16944, IL-6 rs1800795 SNP, TNF-alpha rs1800629) in the relationship between early-life adversity and depressive symptoms, and whether these relations differed between males and females. The relation between childhood adversity and depressive symptoms was moderated by the IL-1 beta SNP, and further varied according to sex. Specifically, among females, higher childhood maltreatment was accompanied by elevated depressive symptoms irrespective of the IL-1 beta SNP, but among males, this relationship was particularly pronounced for those carrying the GG genotype of the IL-1 beta SNP. These findings suggest that, in the context of early life adversity, genetic variations of IL-1 beta functioning are related to depressive symptomatology and this may vary among males and females. The present study also, more broadly, highlights the importance of considering the confluence of experiential factors (e.g., early life adversity) and personal characteristics (e.g., sex and genetics) in understanding depressive disorders, an approach increasingly recognized in developing personalized treatment approaches to this illness.