Under Attack: Associations between childhood trauma and inflammation in adulthood
Trigger warning: This blog discusses topics of emotional, physical and sexual abuse and emotional and physical neglect. This content may be distressing for some readers. Resources for support are provided at the end of the blog.
Did you know, an estimated one in five adults across England and Wales have experienced at least one type (emotional, physical, and sexual) of childhood abuse (intentional harm toward a child by an adult or another child) before the age of 16?
That’s a staggering 8.5 million people in England and Wales alone.
Working as a Research Assistant in the Stress, Psychiatry and Immunology Lab (SPILab) at King’s College London, I had the opportunity to co-author a review (search and evaluation of the available literature in a topic area) on the associations between childhood trauma and inflammation in adulthood, for the journal Pharmacology, Biochemistry and Behavior. Updating a previous review by Baumeister and colleagues, the following studies postdated, and thus were not included in, the original review.
Briefly, inflammation is a protective immune response regulated by small molecules known as pro-inflammatory cytokines. When initiating inflammatory response, these cytokines promote ‘sickness behaviours’ that are often seen with physical and mental illness — for example, depressed mood, reduced social exploration and loss of appetite. These are also common in those with experience of childhood trauma.
As a topic of interest across several InSPIre the Mind blogs, the associations between inflammation and poor health outcomes are well known. Such associations have also been extended to experience of childhood trauma. In a previous blog, Eleonora Iob outlines the association between adverse childhood experiences and inflammation in her investigation of the gene-environment interplay in depression.
Discussing a wider range of inflammatory markers, the current blog shares greater detail on the effect of childhood trauma on inflammation, and the influence of variable factors on this association.
So, what did the studies in our review find?
Inflammation in adulthood may be associated with traumatic experiences in childhood though significance often varies across different types of inflammatory markers and traumatic experiences. Additional factors such as biological sex (male or female), body mass index (BMI) and presence of a psychiatric condition may also have an effect on the association.
Type of inflammatory marker
Let’s first consider the individual types of inflammatory markers investigated in this review: Tumour necrosis factor-alpha (TNFα), Interleukin 1 beta (IL-1β), C-reactive protein (CRP, an acute inflammatory protein primarily produced by the liver) and Interleukin 6 (IL-6).
Collectively, studies found that childhood trauma was more often associated with increased levels of CRP and IL-6 than TNFα and IL-1β. Of the six studies reporting on IL-1β, only two studies (Li et al., 2015; Bock et al., 2020) found significant elevation in those with experience of childhood trauma.
For TNFα, correlational analyses (a statistical technique that quantifies the strength of a linear relationship between two variables) found no association between childhood trauma and inflammatory levels in adulthood (Imai et al., 2018; Gouin et al., 2020). Only one regression analysis (a statistical technique that helps to find the effect of one variable on another) found trauma to significantly predict TNFα levels (Grosse et al., 2016). This, however, was dependent on the trauma type.
Comparatively, several studies found elevated levels of CRP to be associated with a history of childhood trauma (Fanning et al, 2015; Baldwin et al, 2018; Finy and Christian, 2018; Mitchell et al, 2018; Pinto Pereira et al, 2019; Powers et al, 2019). This, however, was dependent on the type of traumatic experience, the measurement of trauma history, and the participant’s characteristics (sex, BMI, and psychiatric condition). Similar findings were also reported for IL-6.
Overall, though predominantly a non-significant association, greatest consistency in findings were evident for TNFα and IL-1β; for CRP and IL-6 reports on significance varied more often between studies. This could, however, be related to a larger quantity of studies investigating CRP and IL-6.
Type of childhood trauma
So, what about specific types of trauma?
Studies in this review focused on 5 main forms of trauma: emotional, physical, and sexual abuse and emotional and physical neglect. Interestingly, abuse (intentionally harm by an adult or another child) more often than neglect (the persistent failure to meet a child’s basic needs) was significantly associated with elevated inflammatory marker levels in adulthood. More specifically, the experience of emotional trauma (abuse and neglect) was more often linked to higher inflammation than physical or sexual trauma. By contrast, the original review by Baumeister and colleagues found no association for emotional abuse.
Again, associations differed between inflammatory markers — for example, sexual abuse was more often associated with increased levels of IL-6 than TNFα and CRP, while physical abuse was often associated with elevated CRP. Conversely, in the original review sexual and physical abuse were significantly associated with TNFα.
The severity of traumatic experiences
Restricted to three studies (Takizawa et al., 2015; Powers et al., 2016; Boeck et al., 2016), investigations for the effects of trauma severity on the association in question suggested that levels of inflammation remain similar between those with low, moderate, and severe trauma. This was consistent across two different categorization systems for trauma severity (Powers et al., 2016; Boeck et al., 2016) and an additional form of childhood trauma (peer victimization, Takizawa et al., 2015).
Number of traumatic experiences
Based on the studies in this review, the additive effects of the number of traumatic experiences on inflammation in adulthood are inconclusive. Investigated in only 6 studies, findings were inconsistent and were predominantly restricted to association with CRP. While Baldwin et al (2018) found that participants with one type of trauma had significantly elevated CRP levels in adulthood, this was not the case for those with multiple traumas. Further to this, Kim et al (2019) found the total number of adverse childhood experiences to have no significant effect on CRP levels later in life.
Comparatively, Aas et al (2017) found that those with experience of 3 types of trauma had significantly higher CRP than ‘no trauma’ controls. This was further supported by Hostinar et al (2015); those with experience of 3 or 4 types of adversity had higher inflammatory marker levels than those with with experience of 1 or 2 types.
Effect of participant characteristics (biological sex and BMI)
So we’ve established that external variables may contribute to the association in question, but what about the individual’s characteristics?
A stratified analysis (a statistical technique using data sorted into distinct groups) found that CRP levels were significantly higher in female participants with a history of childhood trauma, but this was not translated to male participants (Baldwin et al., 2018). Though these sex differences were further reinforced by Kim et al (2019), 8 studies using female-only samples frequently reported non-significant associations. When adjusting for sex, further studies found no effect on the association.
Similar findings were reported for BMI. Thought 4 studies (Petrov et al., 2016; Mitchell et al., 2018; Aas et al., 2017; Powers et al., 2019) found that BMI had an effect on the link between childhood trauma and inflammation, most studies accounting for BMI found no effect on this association.
Similar to those reporting non-significant effects of sex and BMI, Baumeister and colleagues also found these factors did not moderate the association between childhood trauma and inflammation.
Association with clinical characteristics
And finally, as one of the main driving forces behind the investigation in question, what did our review reveal about the potential links with psychiatric health outcomes in adulthood?
Frequently, studies comparing association in patients with major depressive disorder (MDD) and healthy controls found significant association between childhood trauma and elevated levels of inflammatory markers to be restricted to patients with MDD only (Grosse et al., 2016; Pedrotti Moreira et al., 2018; Munjiza et al., 2018; Müller et al., 2019; Ng et al., 2020). Such reports have also been extended to other psychiatric disorders including schizophrenia and bipolar disorder (Quide et al., 2019). Findings may suggest inflammation as a biological mechanism through which childhood trauma can affect mental health outcomes in adulthood.
Conclusions To summarise, inflammation in adulthood may be associated with traumatic experiences in childhood, particularly experience of emotional trauma. Such associations are also dependent on the type of inflammatory marker with greater association for IL-6 and CRP than TNFα and IL-1β. Individual characteristics such as BMI and biological sex, however, may also have an effect on the association in question. Frequent restriction of significant association to patients with psychiatric conditions (when compared to healthy controls) may indicate a role of inflammation in the effect of childhood trauma on mental health in adulthood. Such findings warrant need for further investigation of the specific association between childhood trauma, inflammation and psychiatric conditions in adulthood. Resources Support for survivors of abuse:
Victim Support: Phone: 0808 168 911 | Website: www.victimsupport.org.uk
Support for children and young people facing abuse:
Childline: Phone: 0800 1111 | Website:childline.org.uk
YoungMinds: Parents helpline: 0808 802 5544 | Crisis Messenger for young people (text the letters YM) : 85258 | Website: youngminds.org.uk