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The influence of temperament traits on bipolar disorder (BD) has been investigated. Both temperament traits and BD are partially genetically determined and seem to be influenced by variations in the CACNA1C gene. These variations presented a significant interactive effect with biological sex, although studies that evaluate this relationship are scarce. Here, we assessed the mediation effect of temperament traits on the relationship between two polymorphisms in the CACNA1C gene (rs1006737 and rs4765913) and BD according to sex. This is a cross-sectional study consisting of 878 Caucasian individuals (508 women and 370 men), aged 18–35, enrolled in a population-based study in the city of Pelotas, Southern Brazil. BD diagnosis was evaluated using the clinical interview MINI 5.0, and temperament traits were assessed via the application of the Affective and Emotional Composite Temperament Scale (AFECTS). Mediation models were tested using the modeling tool PROCESS (version 3.3) for SPSS. Bootstrapping-enhanced mediation analyses in women indicated that traits anger (39%) and caution (27%) mediated the association between the rs4765913 SNP and BD, while traits volition (29%), anger (35%), and caution (29%) mediated the association between the AA haplotype (rs1006737–rs4765913) and the BD. No effect was encountered for cisgender men. Our model revealed that paths from CACNA1C SNPs to BD are mediated by specific temperament traits in women, reinforcing the definition of temperament traits as endophenotypes. [ABSTRACT FROM AUTHOR]

• IL-1β levels were increased in young adults with a history of childhood trauma (CT). • Temperaments anger and sensitivity increased in response to CT severity. • Anger, volition and sensitivity moderated the impact of CT on IL-1β levels. • The moderating effect of anger was stronger in men. Early life stressors, such as childhood trauma, have been associated to alterations in immune response that can last until adulthood. In this context, interleukin 1β (IL-1β) emerges as a pro-inflammatory cytokine with a pivotal role. Also, considering the temperament differences in stress susceptibility, and even immune dysfunction, studies investigating the complex interaction between these factors are scarce. Thus, the aim of the present study was to evaluate the moderating role of temperament traits in the relationship between childhood trauma and serum IL-1β levels. This cross-sectional study consisted of 325 individuals, men and women, aged 18-35, enrolled from a population-based study in the city of Pelotas, Southern Brazil. Our main results indicate that higher serum levels of IL-1β were associated with trauma severity (p < 0.01), and the variance of anger could explain 29% of IL-1β increase in individuals who suffered severe trauma (p < 0.05). The effect of anger was considerably stronger in men than in women (46% and 25%, respectively). Moreover, the variance of sensitivity also explained 15% of IL-1β increase (p < 0.05) as well as the variance of volition explained 11% of IL-1β decrease (p < 0.05) in individuals who suffered severe trauma in the general population. Our results indicate that emotional individual differences can moderate the impact of childhood trauma on low-grade inflammation in young adults. [ABSTRACT FROM AUTHOR]