Article 6b: Psychoneuroimmunology of Early-Life Stress: The Hidden Wounds of Childhood Trauma (Danese & Lewis, 2017)

Question 1

Mechanism of psychoneuroimmunology

Answer 1

The brain and the immune system are not fully developed at birth. They mature in response to the postnatal environment. This is why their development can be affected by childhood psychological stressors, which can affect its long-term functioning.

Question 2

Design of the study

Answer 2

This review-study described how early life stress (ELS) can influence the developing immune system and thereby the risk for psychopathology.

Question 3

Findings in human observational studies

Answer 3

• Childhood maltreatment was associated with elevated levels of inflammation biomarkers 20 years later.
• Maltreated children showed elevated CRP levens (inflammation levels) at age 12, especially those who developed depression.
• Adults with a history of childhood maltreatment showed heightened inflammatory responses to acute psychosocial stressors and to chronic stressors.

Mechanism: childhood maltreatment may prime immune and inflammatory systems, leading to a heightened reactivity to stress throughout life (due to epigenetic changes, altered immune development, stress-induce changes in neuro-inflammatory pathways).

Question 4

Inflammation and depression

Answer 4

people with depressive symptoms showed higher levels of inflammation. Chronic and treatment-resistant depression is more associated with inflammation, suggesting inflammation as a possible trait marker (causal factor) for vulnerability.

Question 5

Inflammation and bipolar disorder

Answer 5

Bipolar patients exhibit small to moderate elevations in CRP and cytokines (inflammation) during phases with symptoms (symptomatic) and phases without symptoms (euthymic) –> indicating inflammation as a latent vulnerability factor.

Question 6

Inflammation and schizophrenia

Answer 6

Elevated inflammation markers (cytokines, CRP) were observed in schizophrenia across different stages and persist despite treatment. High baseline inflammation may predict poor treatment outcomes.

Question 7

Inflammation and PTSD

Answer 7

Patients with PTSD have elevated inflammatory markers (also without depression). Inflammation might predispose individuals to PTSD after trauma.

Question 8

Latent vulnerability

Answer 8

The way in which neurocognitive and biological systems adapt to early adverse environment. This may be functional in the long-term, but increase risk for psychopathology in the long-term.

Question 9

Link between inflammation and psychopathology

Answer 9

1. Neurotoxic effects
2. Deficits in memory attention and learning
3. Diminished reward processing
4. Enhanced responses to social threats
5. Disruption of early life-processes like synaptogenesis, synaptic pruning, myelination.
6. Childhood inflammation
7. Glial priming of brain immune cells (–> hypersensitivity to future inflammation).
8. HPA axis cross-sensitisation (heightened stress sensitivity)

Question 10

There are 5 mechanisms by which childhood trauma is linked to immune activation AND to psychopathology

Answer 10

1. Analogy (comparison)
2. Synergy
3. Specificity
4. Reversibility
5. Mediation

Question 11

(1) Analogy (=comparison)

Answer 11

Childhood trauma and early-life immune activation have very similar long-term effects:
- Impaired neurogenesis and cognition
- Blunted sensitivity to reward
- Heightened reactivity to threats
Both factors increase the risk for psychiatric disorders and contribute to worse illness progression and treatment response.

Question 12

(2) Synergy (=interaction/cooperation)

Answer 12

Genetic factors may moderate the effect of increased inflammatory response to later stress after childhood maltreatment, suggesting a shared pathway for trauma and inflammation in influencing brain function and behaviour.

Question 13

(3) Specificity

Answer 13

Elevated inflammation is specifically observed in psychiatric patients with a history of childhood trauma, but not in those without such a history.

Question 14

(4) Reversibility

Answer 14

Experimental studies (with animals) showed that anti-inflammatory interventions can mitigate trauma-related effects on brain and behaviour.

Question 15

(5) mediation

Answer 15

Inflammation might explain why individuals with a history of childhood trauma are at a higher risk for psychopathology, however, existing findings do not definitely confirm this role, because anti-inflammatory medications may work through different mechanisms (like reducing neurotoxicity).

Question 16

Clinical challenges

Answer 16

Patients with a history of childhood maltreatment are twice as likely to respond poorly to combined psychotherapy and pharmacotherapy, and have an unfavourable illness course.

Question 17

Bipolar disorder

Answer 17

People with a trauma history have more severe manic, depressive and psychotic symptoms, greater risk for earlier onset, more frequent episodes and comorbid conditions and a higher risk for suicide attempts.

Question 18

Depression

Answer 18

Depression linked to childhood trauma shows elevated inflammation biomarkers compared to non-traumatised counterparts (potential for anti-inflammatory therapies).