The role of stress in the biological embedding of experience.

Exposure to early adversity is one of the most important and pervasive risk factors for the development of nearly all major mental disorders across the lifespan. In the search for the mediating mechanisms and processes that underlie long-term stability of these effects, changes to stress-associated hormonal and cellular signalling have emerged as prime candidates. This review summarises evidence showing that experience of early adversity in the form of childhood abuse or neglect and exposure to severe institutional deprivation influences multiple interconnected bio-behavioural, physiological and cellular processes. This paper focusses on dysregulations of hormonal stress regulation, altered DNA methylation pattern, changes to transcriptomic profiles in the context of stress-immune interplay, and mitochondrial biology. Consistent findings that have emerged include a relative cortisol hypoactivity and hyporeactivity in response to challenge, increased activity of pro-inflammatory genes, and altered mitochondrial function. The majority of investigations have focussed on single outcomes, but there is a clear rationale of conceiving the implicated physiological processes as interconnected parts of a wider stress-associated regulatory network, which in turn is connected to behaviour and mental disorders. This calls for integrated and longitudinal investigations to come to a more comprehensive understanding of the role of stress in the biological embedding of experience. The review concludes with considerations of how stress research can contribute to translational efforts through characterising subtypes of mental disorders which arise as a function of early adversity, and have distinct features of behavioral and biological stress processing.