There has been increased focus in recent years on the mechanisms which link early childhood trauma with poorer health outcomes later in life. In 2018, Rebecca Lacey from UCL’s ESRC International Centre for Lifecourse Studies led a major project looking into how such early adversities (ACEs) can be linked to increased risk of health conditions such as mental health concerns over the lifecourse. Now in a new paper, Eleanora Iob and colleagues, including Rebecca Lacey, have been looking at the extent to which early adversities and inflammatory markers in the blood are related to the risk of depression in early adulthood. Here they outline their findings and consider their implications.
In March 2021 Andrea Leadsom published her Early Years Healthy Development Review, which drew attention to the potentially damaging effects of ‘adverse childhood experiences’: traumatic events which can result from having parents with poor mental health, being abused or neglected or having parents involved in drug misuse amongst other things.
This wasn’t news to us at UCL’s Department of Epidemiology and Public Health, where we had been investigating ACEs for a number of years. Our previous research showed that ACEs increased the risk of all sorts of different mental health outcomes across the lifecourse.
Key outcomes from this research have included a scoring system which enables us to see how the risks build for children who experience more than one of these experiences. The studies have shown that for those who suffer more than two such issues, the risk of clinically significant psychological distress or of needing to see a mental health professional can be more than two times higher than for others.
They have also explored the types of ACE and their effects – for instance, they found harsh parenting and physical punishment were particularly strongly associated with poorer and more challenging behaviour.
The Leadsom Review explained: “Without the protection of adult support, toxic stress becomes built into the body by the processes that shape the architecture of the developing brain. This has long-term consequences for learning and a baby’s future physical and mental health.”
But what do we know about the biological mechanisms through which these effects take place? Research has suggested that ACEs are associated with an increased risk of depression in both children and adults. We also know adults who have been exposed to ACEs often have higher levels of inflammatory markers such as C-reactive protein (CRP): a necessary and natural reaction to short-term issues such as infection or injury, but which can cause issues if their presence becomes chronic.
But what is the connection between ACEs, depression, and inflammation? Do these increased levels of inflammation act as a mechanism through which ACEs may become biologically embedded and contribute to the development of depression? Our new research digs deeper into the issue.
We used data from almost 4000 participants in the Avon Longitudinal Study of Parents and Children, who gave blood samples as well as answering detailed questionnaires about their health and childhood experiences.
The available data on ACEs spanned children’s lives from the prenatal period through to adolescence, and were categorised as follows:
- Physical or emotional threat, such as physical abuse, emotional abuse or neglect, and low parent-child bonding
- Sexual abuse
- Household dysfunction, such as domestic violence, parental substance use problems, parental mental health problems, parental convictions, and parental separation.
Participants were asked whether they suffered from depression on four occasions between the ages of 18 and 23, using a recognised mood and feelings questionnaire.
Inflammatory markers, represented by CRP, were measured on three occasions at age nine, 15 and 18.
Greater likelihood of depression
We found most types of ACEs across all early-life periods were associated with a greater likelihood of depression, particularly in those who had faced threat-related adversities. Overall scores for accumulated ACEs as well as for individual ones across all phases of early life were related to moderate and severe levels of depressive symptoms in young adulthood.
Associations between ACEs during late childhood or adolescence and depressive symptoms were particularly strong, and the strongest links were for sexual abuse and physical or emotional threat in adolescence. Furthermore, multiple exposure to the same ACEs throughout childhood was more strongly linked with depression than exposure to a single adversity.
Those who had suffered bullying, victimisation and sexual abuse in late childhood or adolescence had higher levels of CRP, and exposure to sexual abuse in adolescence was related to elevated CRP levels in boys but not in girls.
Was there a link?
But was there a clear link between raised levels of inflammation and depression? We found that while associations between adverse events and depression were strong, they didn’t appear to work through inflammatory mechanisms.
Neither single measures of inflammation nor repeated measures over time during childhood and adolescence showed any link to depressive symptoms in young adulthood. So early-life CRP levels did not mediate the associations between ACEs and depressive symptoms.
The results add significantly to our knowledge on this topic: they expand the earlier work at UCL’s Department of Epidemiology and Public Health, which had already pointed to a need for early-life interventions to reduce inequalities in mental health.
This new research confirms again that ACEs experienced at any stage of childhood can increase an individual’s vulnerability to poor mental health in young adulthood. Andrea Leadsom’s review suggested families needed support during their children’s critical 1,001 early days to make sure babies grow up to be physically healthy and emotionally capable, and our wider research on links between mental health and ACEs supports that.
Our growing body of evidence clearly shows early interventions to prevent ACEs and ACE-related trauma could help reduce the risk of depression across the life course, as well as highlighting the importance of assessing exposure to ACEs in people affected by depression to provide targeted therapies.
But CRP levels are not consistently associated with ACEs and depression in children and young people, so interventions targeting inflammation in this population might not offer protection against depression.
Future studies should consider other inflammatory markers and different biological mechanisms, the researchers conclude.
Adverse childhood experiences and severity levels of inflammation and depression from childhood to young adulthood: A longitudinal cohort study is research by Eleonora Iob, Rebecca Lacey, Valentina Giunchiglia, and Andrew Steptoe and is published in Molecular Psychiatry, Nature.
Eleonora Iob and Andrew Steptoe are based at the Department of Behavioural Science and Health, University College London. Rebecca Lacey is based at the Department of Epidemiology and Public Health, University College London and Valentina Giunchiglia is based at the Department of Brain Sciences, Faculty of Medicine, Imperial College London.