When Bad Things Happen To Good People: The Neurobiology of Resilience (Part 1)



sharma-obesity-child-abuseTo those, who have been to any of my “Dr. Sharma Shows“, my interest in the topic of resilience should come as no surprise.

If my work with obese clients has taught me anything, it is the simple fact that for those who use food as a coping strategy, the solution will not lie in diet or exercise plans. To them, the discussions for and against sugar-sweetend beverages and the pros or cons of resistance vs. endurance training are irrelevant to a point that makes these discussions almost funny – they seem to exist in a parallel universe.

Indeed, the solution to emotional overeating (including its most severe form namely “binge eating disorder”), can only come from recognizing the relationship between their emotions and their eating behaviours, with the goal to ultimately developing healthier, non-food coping strategies.

Not that these will necessarily lead to weight loss – as I always hasten to point out – eliminating the cause of weight gain does not translate into weight loss – it merely translates into stopping the gain and often, a far better quality of life.

But then again, stopping the gain should be the first step in any weight management program and skipping this step (or fast-forwarding through it), can only guarantee failure.

This is why I firmly believe that for all of us working in the field of obesity, understanding the complex neurobiology of resilience (the successful adaptation and swift recovery after experiencing life adversities), is as essential as understanding the physiology of energy balance.

Readers interested in a rather comprehensive overview of resilience (in the context of mental health) are referred to a paper by Bart Rutten and colleagues from Maastricht University, published in Acta Psychiatrica Scandinavica.

In their extensive and systematic review of the literature, they find that the term “resilience” is used for phenomena ranging from susceptibility to mental health disturbances to adaptation and recovery from adverse experiences.

They describe three possible trajectories that can follow a severe stressor/trauma:

“…ranging from a trajectory showing consistent decline in mental health following exposure to adversity without subsequent recovery of mental health for a prolonged period of time, to a decline in mental health following the exposure that recovers quickly to preexposure levels of mental health and continues to increase thereby surpassing preexposure levels of mental health. This latter response, known as post-traumatic growth, is a very interesting form of adaptation, in which the individual may have obtained a better understanding of his life, possibly from a new perspective, or may have learned to respond efficaciously to similar challenges in the future.”

As the authors point out,

“The neurocircuitries mediating the stress response and reward experience are thought to be crucially involved in the neurobiology of resilience. The efficiency in activating and terminating the response to stress is regulated by elaborate negative feedback systems in the brain and the rest of the body….The hypothalamus–pituitary–adrenal (HPA) axis, the sympathetic nervous system (SNS) and the dopaminergic and serotonergic neurotransmitter systems are major neural systems that govern the stress response..”

There is indeed increasing recognition that experiences profoundly effect brain plasticity:

“These experience-dependent mechanisms regulate the sensitivity and plasticity of the central nervous system and act at several biological levels (likely partly in parallel with each other): i) cellular changes such as neurogenesis, pruning and sprouting of synapses, myelination of axons and alterations to the number of dendritic spines, ii) subcellular changes, such as alterations to the cytoskeleton and the extracellular matrix and changes in the levels of intracellular signalling molecules and iii) molecular (epi) genetic changes such as DNA methylation and chromatin changes. Thus, one can envision that aberrant regulation at any of these levels may moderate risk for and resilience to the consequences of stress and that resilience thus depends on a range of environmental and genetic factors during life.”

Although adverse life experiences can occur and have effects throughout life, there are key times of developmental vulnerability – times, when adverse effects can have “permanent” effects on the individual.

The first period is in early childhood development – beginning right after birth.

In animal studies,

“…parental care during early life induces long-term changes in behaviour as well as in gene expression mediated by epigenetic changes in the hippocampus of rats. As compared with offspring of mother rats with low-nurturing behaviour, offspring of high-nurturing mother rats (displaying more licking and grooming behaviour) were less anxious, had attenuated corticosterone responses after stress exposure and expressed higher levels of the glucocorticoid receptor (GR) in the hippocampus in adulthood. Interestingly, the methylation level of the promoter region of Nr3c1, i.e. the gene encoding the GR, was elevated already the first week of life in the hippocampus of pups that received less and lower quality nurturing , an effect that persisted into adulthood…..other studies have shown that the mother–infant interaction has long-lasting effects on endocrine and behavioural responses later in life.”

“Another interesting line of research has explored the effects of maternal separation on biology and behaviour. Although most studies observed detrimental effects of maternal separation, studies where rat pups were separated from their mother for a very brief period, i.e. 15 min, indicated that these pups, compared with non-separated pups, were more stress resistant later in life. Interestingly, as compared with offspring not separated from their mother for these brief spells in very early life, animals with brief spells of maternal separation showed higher levels of glucocorticoids (GCs) directly after stress exposure in adulthood, with a fast return to basal levels. Thus, type, severity and/or duration of stressful experience early in life seem to influence differential stress reactivity later in life.”

The other vulnerable period appears to be in adolescence, particularly in response to the “social defeat paradigm”,

“In the social defeat paradigm, male test mice aged 6–10 weeks (corresponding to puberty and adolescence in humans) are placed into the territory of a larger and more aggressive resident mouse. The mice are left in this physically and socially stressful situation for approximately 10 min, which leads to subordinate behaviour of the test mouse. After these 10 min, the mice remain in sensory (but not physical contact) with each other for the rest of the day, and the procedure is repeated for 10 consecutive days. The experimental paradigm is known to induce anxiety-like behaviour, prolonged elevations in corticosterone levels and a range of other molecular and cellular changes. Mice that were subjected to chronic social defeat stress furthermore showed a prolonged reduction in orexin signalling in the hypothalamus. Orexin has been implicated in arousal and feeding behaviour, but more recently also in the mesolimbic reward pathway… Although all mice have the same genetic background, and are exposed to similar conditions of social defeat, this experimental paradigm has repeatedly been shown to elicit two distinct responses in the domain of social behaviour: one group of mice displaying social avoidance after the social defeat experience (these mice are called ‘susceptible’), whereas a second group of mice still showing social interaction rates that are comparable with the control group (and is therefore called ‘unsusceptible’ or ‘resilient’). Thus, only a distinct subpopulation (i.e. the ‘susceptible’ mice) displays social avoidance and behavioural signs of anhedonia, while all exposed animals (‘susceptible’ and ‘unsusceptible’ mice) show elevated corticosterone levels and increased anxiety-like behaviour.”

As discussed in the above quote, it is apparent that the molecular changes associated with the response to this stress paragigm are intimately related to the very neurons and areas of the brain known to be linked to eating behaviour. Thus, the impact of adverse life events, whether this is early separation from the mother or exposure to school yard bullying, on eating behaviour and weight trajectories should come as no surprise to anyone working in the field.

Based on their review of the literature, the authors identify three rather consistent predictors of resilience include secure attachment, positive emotional experiences and having a purpose in life.

I will discuss these factors individually in subsequent posts – stay tuned.

AMS
Edmonton, AB