Early life stress and the role of environmental and molecular moderators in the ontology of pathological and resilient behavioral phenotypes

Early life stress (ELS) in the form of trauma or caregiver abuse and neglect is often associated with psychopathology. However, not everyone exposed to ELS develops a pathology; others display resilience, or the ability to adapt and persevere despite ongoing adversity. Several molecular moderator variables between ELS and behavioral phenotypes have been proposed, including single nucleotide polymorphisms (SNPs) and epigenetic markers. Specifically, several SNPs and aberrant methylation or expression of genes associated with neurotransmitter systems and brain-derived neurotrophic factor have been associated with anxiety, depression or schizophrenia. The present review seeks to explore the relationship between SNPs, epigenomics and disease, and offer data to suggest several SNPs may also predict specific treatment efficacy and psychological resilience. Due to these different mental health outcomes as a function of ELS, it is critical that environmental moderators be equally considered in determining the ontology of resilient or pathological phenotypes; this includes the infant-caregiver relationship, and the degree of control, magnitude, and type of the stressor experienced. Finally, we will offer evidence to suggest that several intervention strategies, including drug treatment, environmental enrichment, or exercise can ameliorate many of the psychological, biological, and molecular consequences of ELS exposure, and help shift one toward a resilient phenotype.