Long term epigenetic and physiological effects of early life adversity

Study Objective

The overriding objective of EPIPATH is to understand the impact of  Early Life Adversity (ELA) on epigenetic methylation and the consequences for the stress response system and the long term risk of developing cardiovascular, mental health and immune disorders (CAMI), four of the most important public health burdens.
This is a monocentric academic observational study of the effects of ELA on adult pathology. A group of young adults having experienced severe ELA adopted by families living in Luxembourg will be recruited, together with a suitable control group

The scientific aims of EpiPath are to:
1. Identify measurable biochemical and physiological markers in early adulthood that are associated with severe ELA.
2. Identify genes, genomic regions, epigenetic patterns and pathways that are susceptible to epigenetic modulation by severe ELA.
3. Relate these epigenetic patterns and altered pathways to the results of the
functional/physiological evaluation of the CAMI and the stress response system.
4. Both ELA and psychosocial stress are risk factors for CAMI pathologies. EpiPath will provide clues whether ELA associated impaired stress response is a common risk factor for these diseases entities.
5. Identify characteristics of ELA (e.g. duration of institutionalisation, level of deprivation, time) that are particularly detrimental.
6. To examine the fundamental nature and identify characteristics of epigenetic methylation induced by severe ELA, especially with respect to the geography of the genomic regions implicated (e.g. genes, promoters, CpG islands, or CpG island shores).
7. To examine the significance of epigenetic modifications in circulating immune cells with respect to potentially impaired specific immune functions of these cells.
8. To re-examine the use of PBMCs as surrogate readouts for methylation levels relevant for other organ systems in particular those involved in the stress response and CAMI.

Participation conditions

Inclusion criteria for adoptees:

EpiPath will recruit ELA subjects that have been institutionalised and adopted in early life irrespective of their gender, age at adoption, ethnic or geographical origin and current or past nationality. To have an optimal response to the SLST all participants will be between 18 and 30 years old. Since the recruitment will continue into 2016 donors born between 1983 and 1998 will be eligible. Current psychotic mental health problems that would put participants at risk from suffering adverse consequences of taking part in the study (e.g. psychotic disorders) are formal exclusion criteria in addition to health conditions that are not compatible with the examinations such as Raynaud’s syndrome or cold agglutinin disease. Obviously, participation is entirely voluntary and written informed consent of all participants will be obtained.

Exclusion criteria for adoptees:

Exclusion criteria for control subjects will be any preexisting chronic health problem or any form of early life adversity, such as divorce of parents, or the death of a close relative (e.g. parent or sibling) etc. Control donors will be characterised the same way as the adoptees, and those with questionnaire scores above a predefined level will be excluded.

Centre de Recherche Public de la Santé- CIEC