Abstract
Background:
Longitudinal studies reveal that raised inflammatory markers and trauma in childhood associate with psychopathology in adulthood.
Aims:
We aim to examine whether inflammation in childhood mediates effects of genetic risk and trauma on psychopathology in early adulthood.
Methods:
Measures of trauma exposure, inflammation and psychopathology were collected from the Avon Longitudinal Study of Parents and Children (ALSPAC). Exposure to trauma was measured from 5-11 years, C-reactive protein (CRP) and interleukin (IL)-6 levels were measured at 9 years, and depression, anxiety disorder, negative symptoms and psychotic experiences were assessed at 24 years. Polygenic risk scores (PRSs) were created for schizophrenia, depression, anxiety and psychotic experiences. Mediation analyses were conducted using imputed data (N=7859 to 8700) to investigate whether inflammation mediates the association between genetic risk and childhood trauma with psychopathology.
Results:
Most psychiatric PRSs were associated with multiple psychopathological outcomes in adulthood with the exception of PRS for psychotic experiences. Childhood trauma was associated with all psychopathology. However, there was no strong evidence that inflammatory markers in childhood mediated associations between PRSs, trauma and psychopathology. Sensitivity analyses using outcomes from age 18 and PRSs based on SNPs meeting more stringent evidence of association gave consistent results with our primary analyses.
Conclusions:
We found little evidence that IL-6 or CRP mediates the pathway between genetic liability for psychiatric phenotypes or trauma and subsequent psychopathology. Investigating other inflammatory as well as non-inflammatory pathways longitudinally is required to identify modifiable targets and inform novel treatment strategies for individuals at genetic- or trauma-related risk of psychiatric illness.
Longitudinal studies reveal that raised inflammatory markers and trauma in childhood associate with psychopathology in adulthood.
Aims:
We aim to examine whether inflammation in childhood mediates effects of genetic risk and trauma on psychopathology in early adulthood.
Methods:
Measures of trauma exposure, inflammation and psychopathology were collected from the Avon Longitudinal Study of Parents and Children (ALSPAC). Exposure to trauma was measured from 5-11 years, C-reactive protein (CRP) and interleukin (IL)-6 levels were measured at 9 years, and depression, anxiety disorder, negative symptoms and psychotic experiences were assessed at 24 years. Polygenic risk scores (PRSs) were created for schizophrenia, depression, anxiety and psychotic experiences. Mediation analyses were conducted using imputed data (N=7859 to 8700) to investigate whether inflammation mediates the association between genetic risk and childhood trauma with psychopathology.
Results:
Most psychiatric PRSs were associated with multiple psychopathological outcomes in adulthood with the exception of PRS for psychotic experiences. Childhood trauma was associated with all psychopathology. However, there was no strong evidence that inflammatory markers in childhood mediated associations between PRSs, trauma and psychopathology. Sensitivity analyses using outcomes from age 18 and PRSs based on SNPs meeting more stringent evidence of association gave consistent results with our primary analyses.
Conclusions:
We found little evidence that IL-6 or CRP mediates the pathway between genetic liability for psychiatric phenotypes or trauma and subsequent psychopathology. Investigating other inflammatory as well as non-inflammatory pathways longitudinally is required to identify modifiable targets and inform novel treatment strategies for individuals at genetic- or trauma-related risk of psychiatric illness.
| Original language | English |
|---|---|
| Journal | BJPsych Open |
| Publication status | Accepted/In press - 8 May 2025 |
Research Groups and Themes
- ALSPAC
- High Performance Computing