Background to the network

The social environments in which we live provide daily challenges that influence our behaviour and sense of well-being. It is far from clear exactly how our experiences affect us at a physical level, but recent research in biology has discovered molecules that are found in all of our cells, which respond to experiences, such as social interactions, by switching genes on or off in particular cell types. These molecules, or "epigenetic" mechanisms, bind to DNA and control gene activity, which in turn change biological activities of our cells, tissues and organs, including the brain, and thus affect what we think, feel and do. We are beginning to understand that epigenetic mechanisms are modified by environmental factors that can affect our health, and recent evidence indicates that social stress is one such factor.

Biological links between social and health inequalities

Social stress is the physiological change produced by a challenge to wellbeing that originates in the social environment.

Growing evidence suggests that the unequal distribution of chronic social stressors within contemporary society is responsible for the close correspondence between social and health inequalities. These stressors include the structural, material and physical circumstances of deprivation; such as poor nutrition and housing, as well as the emotional, cognitive and social challenges of daily life on or below the breadline.

bread

Epigenetic responses elicited by the stressors mentioned above have impacts that may be felt across the lifecourse, gradually eroding physiological and psychological resilience, and engendering susceptibility to chronic ill-health. Although the adverse health impacts of material and psychosocial stress are more prevalent in more deprived socioeconomic groups within highly unequal societies (including the UK), psychosocial stress has been identified as a significant determinant of chronic ill-health across the socioeconomic spectrum. Societies with lower overall levels of inequality also tend to exhibit lower burdens of chronic ill-health than more unequal societies.

The tendencies of excessive social threats, such as competitive behaviours and aggression, to erode community cohesion, weaken social networks and inhibit mutual support, may impose additional constraints on the social behaviours that define fundamental aspects of human well-being. An emerging literature identifies social networks as important health protective factors, and suggests that weakening or shrinking of social networks may be both causes and consequences of chronic social stress, creating a vicious cycle of feedback which could further accentuate the poor health outcomes of low SES groups. Thus, induction of epigenetic changes by stressful social environments could modify social interactions, leading to further adversity in the social environment which could then create additional epigenetic changes. Such potential feedback loops may be conceptualized as characteristic features of a dynamic ‘biosocial’ system, the properties of which are sensitive to changes in epigenetic, behavioural and social factors, along with aspects of the material environment.

biosocialloop

If adverse social circumstances generate epigenetic changes that are disadvantageous to health and well-being, then improvements to them might be able to remove or reduce the disadvantageous epigenetic modifications, and even replace them with beneficial modifications.

Accordingly, better understanding of how the impacts of social stressors become physiologically embedded, through modification of epigenetic processes, could provide an evidence-base and a biomarker toolkit for prioritising, implementing and measuring the effectiveness of health and other policy interventions to counteract the adversity engendered by social inequality.

Epigenetic and biomarker studies of inequalities in human cohorts

Human population research, such as the Whitehall II cohort studies, shows that increased stress hormone levels and inflammation are significantly associated with low SES. Moreover, recent studies of other populations indicate that stressful life experiences, including poverty and social deprivation, leave an epigenetic legacy that is significantly associated with chronic ill-health. The population for one of these studies, the Glasgow pSoBid cohort, is remarkable for the particularly steep gradients of highly correlated social and health inequalities, and the existence of a difference in life expectancy of 28.7 years between males from the most- and least-deprived areas.

However, statistical inferences identifying components of risk often fall short of defining causal relationships, whereas whole-organism-based laboratory or field experiments, in which variables can be manipulated, can reveal causal relationships. There is a pressing need to develop tractable experimental paradigms, using animal models with relevant social behaviours and biology, in which epigenomic analysis can be done conveniently.

Epigenetic embedding of stress responses

At a biological level, the adverse effects of persistent, stressful stimuli are mediated by factors such as the stress hormone cortisol, which exerts many of its effects through regulation of genes involved in metabolism, immune responses and behaviour. Molecular analysis of the biological impacts of stress indicates that altered gene activities are accompanied by epigenetic changes that affect health well-being across the life-course.

Zebrafish: a tractable model for investigating the epigenetic embedding of social stress

Combining behavioural and molecular studies of social interactions in various animals becomes very challenging when interactions between members of large social groups are of interest. In humans, these data are difficult to obtain across the life course. By contrast, experimental studies of large group social behaviour in a model organism such as the shoaling zebrafish is possible with new techniques for behavioural tracking to analyse how fish interact with one another in shoals. 

fish

Zebrafish have a useful repertoire of measurable social and affective behaviours relevant to stress in humans. These features, together with its genetic, epigenetic, transcriptomic and pharmacological tractability makes the zebrafish an attractive subject for systems-based analysis of social and other stress responses. Its short generation time (2-3 months) and long lifespan (>3 yrs) also makes the zebrafish suitable for lifecourse and transgenerational studies.

Social and ethical implications of the epigenetic embedding of stress responses

The link between social stress, epigenetic changes and increased health risks raise important questions about understandings of disease aetiology, responsibility for health, and the possibility of different forms of medical and social intervention. Can relevant epigenetic changes be diagnosed early? To what extent are individuals culpable for detrimental epigenetic changes? Are community-based preventative programme possible? An important part of the network’s activities will be to analyse and debate these issues with a range of stakeholders.