We found that trauma early in life is associated with increased inflammation as measured by CRP and IL-6 when twins are treated as individuals, but after separating within and between effects, significant effects were not observed within twin pairs, a comparison that effectively controls for familial factors. We only observed significant effects between twin pairs; in pairs where both members suffered early trauma inflammation was elevated the most. These results suggest that familial factors confound the relationship between early trauma and inflammation, or represent important antecedents to this association.
There are many ways through which familial factors may affect the relationship between early trauma and inflammation. First, there could be familial confounding factors. For example, individuals raised with an unfavorable socioeconomic status have shown a greater expression of pro-inflammatory genes, increased production of pro-inflammatory cytokines, and greater resistance to glucocorticoid signaling (31
). In turn, an unfavorable social environment may facilitate traumatic experiences. Glucocortioids are important for inhibiting inflammation, thereby controlling the hypothalamic-pituitary-adrenal axis response to stress (33
). These damaging effects of the social environment are irreversible even after upward social class mobility later in life, and remain after adjusting for life stress and poor health practices (i.e., smoking, alcohol consumption). In our study, socioeconomic status or education status did not attenuate the relationship between early trauma exposure and inflammation. This is most likely due to the use of adult socioeconomic status compared to income during childhood. Childhood income, although not available in our study, was accounted for in the within-pair analysis since twins were raised in the same family. Because the within-pair results were considerably attenuated compared with the between pair results, our results suggest that parental or other familial factors influencing trauma exposure, including income, may be important in the relationship between trauma and health. Furthermore, the influence of familial factors on trauma exposure is independent of behavioral, cardiovascular, and psychiatric disorders.
Familial factors may also be necessary antecedents to early stress, or more severe forms of early stress. Since twins are matched for parental and other familial factors, our within-pair comparisons excluded trauma exposures shared by both members of the pair. Pairs where both members were affected by early trauma may signal family environments at high risk for childhood abuse. For example, previous literature has shown that increased risk for childhood sexual abuse is observed when parental alcohol abuse was reported in one parent and even greater risk when both parents reported alcohol abuse (35
). A meta-analysis of 166 studies reported that environmental factors such as low socioeconomic status, paternal unemployment, and living with one or neither parent was associated with increasing risk for sexual abuse (36
). It seems plausible that shared familial factors play a role in the link between early trauma and adult inflammation.
Our study is in agreement with previous cross-sectional (6
) and longitudinal life-course reports (5
) that have observed a positive relationship between exposure to early trauma and adult inflammation in individuals exposed to various forms of abuse, neglect, and/or childhood maltreatment. Of these studies, only one was conducted in a U.S. population (6
). The remaining studies were all based on the same New Zealand population where the oldest person was 32 (5
). In contrast to a previous study (8
), after accounting for behavioral, cardiovascular, and psychiatric risk factors, the relationship between early trauma and inflammation was attenuated; after accounting for familial factors, it was eliminated. In this previous study, the relationship between early trauma and adult inflammation was assessed in younger individuals that were approximately 32 years of age. On the other hand, our participants were older (average age of 55), so it is possible that the years of exposure to damaging risk factors had a larger impact on adult inflammation. Overall, the present study extends this literature by assessing a U.S. population of twins in middle age, a time when cardiovascular risk rises considerably. The advantage of studying twins is the ability to control for familial factors when examining the association of early trauma and inflammation.
Of the different forms of abuse, emotional abuse was most strongly linked to higher, clinically significant, CRP levels. Emotional abuse, specifically, has been shown to be highly associated with chronic stress or long-term psychopathology outcomes, such as PTSD (37
). These long-term effects of emotional abuse may affect brain regions, such as the limbic system, which play a major role in emotions and memory (40
). This in turn, could lead to greater dysfunction in the stress pathways of young children, subsequently altering inflammatory processes later on in life (8
A significant relationship between trauma exposure and inflammation was observed in non-obese individuals but not in obese individuals. It is likely that obesity, which is associated with inflammation (41
), may confound the relationship between early trauma and inflammation. However, in the absence of obesity, the relationship between early trauma and higher inflammation still exists.
The heritibability of inflammatory biomarkers such as IL-6 and CRP has been previously shown (9
) and trauma exposure is also partially heritable (10
), therefore a shared genetic component is theoretically possible. However, we found no significant within-pair association between trauma exposure and inflammation in either dizygotic or monozygotic twin pairs. Therefore it is unlikely that a genetic link between early trauma and inflammation exists.
This study has limitations that should be acknowledged. It has a cross-sectional design, and thus we are unable to address the temporal relationship between exposure to early trauma and inflammation. In addition, the inclusion of only middle aged males limits the generalizability of the results to women or individuals in other age groups. Nevertheless, our study is unique in that the twin study design allows for taking into account genetic and/or shared familial factors. In contrast to previous literature, we were able to uncover substantial familial confounding on this relationship. Lastly, because participants were asked to recall events that occurred in the distant past, recall bias may have been an issue in our sample. However, previous literature suggests that harmful memories are typically underreported rather than overreported (42