Article summary with Psychoneuroimmunology of early-life stress: the hidden wounds of childhood trauma? by Danese & Lewis - 2017

What are the objectives of this study?

The immune system and the brain are both not fully formed at birth. They carry on growing in reaction to their postnatal environment. Through experiences in the early periods of development, the brain and the immune system develop progressively. They expand their repository in adaptation to stimuli specific to one’s unique environment. The plasticity of brain development is best studied looking at basic brain functions, they are recognized to be predictors of one’s immune functions. In the current study, the relationship between early life stress and the development of the immune system with regards to the development of psychopathology is discussed.

What is the relationship between childhood trauma and inflammation?

Many studies have investigated the association between immune functioning and early life stress in rodents and non-human primates. They found that stress reactivity of the offspring depended on child care of the mother. Reduced maternal caregiving in rats leads to an increased stress reactivity. When looking at measures of immune functioning, unstimulated pro-inflammatory cytokines in the plasma, expression levels of pro-inflammatory genes in the brain and intestinal microflora were examined. They concluded the existence of links between early life stress and immunity.

In humans it was found that cumulative exposure to childhood trauma was related to significant elevation of inflammation twenty years later. Changes in the biomarkers for inflammation could not be explained by potential confounders such as birthweight or low IQ. Also, mediators like poor adult health or acute infections could not fully explain the effects. Thus, evidence was found for the influence of childhood maltreatment and other stressors in this period on elevated inflammation levels. Childhood maltreatment also predicts a bigger reactivity to psychosocial challenges. For example, adults with a history of maltreatment showed higher inflammation levels in the context of depression, caregiving stress and daily stressors in comparison to healthy control participants.  The conclusion was that the interaction between the immune system and the brain makes it possible for stressors caused by childhood maltreatment to affect the development of the immune system. This can affect the brain and its long-term functioning.  

What is the relationship between inflammation and psychopathology?

Inflammation is seen as a primary determinant in the functioning and development of the brain. Evidence was found for the effectiveness of anti-inflammatory medication in treatment of affective disorders such as depression. Also, Hart (1988) found that experimental administration of pro-inflammatory cytokines generated a response similar to depression. Also, depressed patients showed systemic activation of the immune system and a small increase in levels of inflammation biomarkers.  With regards to bipolar disorder, evidence was found for a small increase in pro-inflammatory cytokines. Inflammation might be a latent vulnerability factor both influencing the onset -and progression of bipolar disorder. In schizophrenia, the influence of inflammatory abnormalities has long been discussed. In 2015, Mondelli et al. found hat increased baseline levels of inflammation predict poor treatment outcomes in first-episode psychosis patients. In PTSD inflammation is a pre-existing vulnerability and correlates to subjective distress, maladaptive coping and disease severity.

Therefore, the researchers propose that early-life stress can provide an innovative framework to understand and treat psychopathology related to childhood trauma and early-life stress as a predictor of later inflammation. The key points derived from research on the relationship between inflammation and psychiatric disorders are:

1. Elevated inflammation levels are observed in several groups of patients. It was found that there are overlapping trans-diagnostic patterns of the relationship between childhood trauma and clinical outcomes of inflammation.
2. Several meta-analyses concluded that not all patients suffering from psychological disorders have elevated inflammation. Thus, it is important to identify what correlates there are to increased inflammation in psychiatric patients and aim interventions accordingly.
3. Inflammation is not related to just some cases of psychiatric disorders, it is a key marker displaying vulnerability.

What is the link between childhood trauma and psychopathology?

Studies discussed in the current review suggest that childhood trauma is related to the later activation of the immune system. This can affect the vulnerability for later psychopathology. Further support for the mediating role comes from the examination of analogy, synergy, specificity and reversibility.  One example of synergy is that both inflammation and childhood trauma are likely to be on the same pathways that influence the brain and its behaviour. Carpenter et al. (2010) found that participants with a history of childhood trauma have bigger inflammatory responses to experimental psychosocial stressors.

What did the researchers conclude?

The effect of childhood trauma should be remediated before the onset of clinical symptoms, including potentiation of adaptive immunity and anti-inflammatory interventions. Comparable methods may be used to alleviate the adverse reaction to treatment that is described in patients suffering from childhood trauma.

Summary:

• Through experiences in the early periods of development, the brain and the immune system develop progressively. They expand their repository in adaptation to stimuli specific to one’s unique environment. The plasticity of brain development is best studied looking at basic brain functions, they are recognized to be predictors of one’s immune functions.
• Studies discussed in the current review suggest that childhood trauma is related to the later activation of the immune system. This can affect the vulnerability for later psychopathology.
• The effect of childhood trauma should be remediated before the onset of clinical symptoms, including potentiation of adaptive immunity and anti-inflammatory interventions.

Study note:

• You should know that inflammatory markers are not always responsible for the onset -and course of psychopathology but are in most cases. You should be able to explain the role of inflammatory biomarkers on psychopathology and the relationship to childhood trauma.
• What mediators could be responsible for the high risk of psychopathology in children with a history of childhood trauma? This is explained in the last section of the article.