Neurobiology of Stress and Resilience
Time to read: 9 minutes
The stress response is a physiological and psychological reaction that is activated when an individual is confronted by a challenging situation. [Seyle 1973]
When confronted by a stressful life event such as trauma, tragedy, or a perceived threat, there are structural and functional alterations to the brain [McEwen et al 2015]:
- Remodelling of the neural architecture is indicative of successful adaptation and neuronal plasticity through a physiological response known as allostasis.
- Allostatic overload can be caused by multiple and/or chronic stressors, which are known risk factors for psychiatric disorders such as depression and anxiety.
- However, most individuals display resilience to adversity, whereby the negative impact of stressful events is reduced.
- Stress resilience is designed to maintain allostasis and is an ordinarily common outcome that allows individuals to withstand, or even thrive, despite these stressful circumstances.
- In contrast, there is a significant minority that are psychologically vulnerable to the negative consequences of trauma and thus develop chronic debilitating psychological symptoms.
CONCEPT OF RESILIENCE
Much of the earlier research into stress resilience was aimed at defining protective psychological factors such as self-regulation, problem-solving ability, optimism, parenting, and social cohesion. [Maston 2004; Rutter 2007]
However, resilience is multidimensional and to further understand adaptation to adversity requires a clear and operational definition.
Resilience is a dynamic process whereby an individual can withstand challenging conditions while still maintaining relatively normal physical and physiological functioning. [Fletcher and Sarkar 2013]
However, this definition may be narrow. A more recent definition implies that there is a response, a bending, but that there is a return to a prestress state or perhaps to a new level of homeostasis (allostasis). [Bhatnagar, 2021]
Resilience can be conceptualised as an adaptation to adversity, whether that be defined as an outcome, a process, or a trait:
- A resilient outcome – The capacity to endure early-life trauma and recover, which therefore makes an individual more resilient as a result of experiencing those adverse circumstances. [Masten 2001]
- A resilient process – In contrast, resilience can also be defined as a dynamic process by which an individual successfully and positively adapts to extreme or chronic stress over time. [Luthar et al 2000]
- A resilient trait – Whilst others believe that it is a personal trait or characteristic that enables an individual to be resilient. [Connor and Davidson 2003]
Modern research into stress resilience focuses on the identification of intrinsic and extrinsic variables that determine resilience whether it be genetic, epigenetic, developmental or neurobiological domains as well as social system constructs such as family, cultural, economic, and political factors. [King 2016; Osorio et al 2017; Liu et al 2018]
MISUNDERSTANDING OF RESILIENCE
While resilience is difficult to define, we can attempt to define what is not resilience.
Resilience is not simply reductions in stress responses compared to those of a control group.
On the other hand, the individual may not return to the same baseline that preceded the stress exposure but may shift to a ‘new normal’ consistent with the concept of allostasis. This shift may occur across multiple domains and vary from individual to individual. [Bhatnagar, 2021]
Allostasis :
Allostasis means maintaining stability, or homeostasis, through change; it refers to the process of adaptation to acute stress. [McEwen, 2000]
Allostatic load:
The definition of allostatic load reflects the cumulative effect of experiences in daily life that involve ordinary events (subtle and long-standing life situations) as well as major challenges (life events), and also includes the physiological consequences of the resulting health-damaging behaviours, such as poor sleep and circadian disruption, lack of exercise, smoking, alcohol consumption and unhealthy diet. When environmental challenges exceed the individual ability to cope, then allostatic overload ensues as a transition to an extreme state where stress response systems are repeatedly activated and buffering factors are not adequate. [Guidi et al., 2021]
NEUROBIOLOGY OF RESILIENCE
The two main neurotransmitter systems involved in resilience are the Hypothalamic-Pituitary Axis (HPA) and Sympathetic Nervous System (SNS).
In addition, there is also an important relationship with the activity of dopaminergic and serotonergic neural circuits in stress regulation.
Sympathetic nervous system
Noradrenaline is a catecholamine neurotransmitter that is released from the locus coeruleus to enhance instinctive responses and improve cognitive alertness and vigilant concentration.
However, the systemic SNS stress response can vary from individual to individual. [Southwick et al. 1999; Feder et al. 2009]
- Neuropeptide Y is a neurotransmitter produced in the hypothalamus (among other regions), where it serves to lower BP and reduce anxiety, pain perception, and stress. [Heilig et al. 1995; Sah et al. 2009] Neuropeptide Y prevents noradrenaline overstimulation and reduces the risk of stress-induced anxiety.
- Galanin is another neuropeptide secreted during SNS activation, and it modulates locus coeruleus activity during stressful circumstances. Galanin is hypothesised to confer a neuroprotective effect that prevents the anxiogenic effects of noradrenaline.
In summary, a hyper-sensitive SNS response can increase the risk of chronic anxiety and PTSD, whereas individuals with reduced noradrenaline responsiveness display resilience.
In contrast, reduced levels of neuropeptide Y and galanin are linked to PTSD and MDD. Therefore there is a balance between noradrenaline, neuropeptide Y, and galanin neurotransmission that vary an individual’s stress resilience level.
Hypothalamic-pituitary axis
Corticotrophin-releasing hormone (CRH) is released by the hypothalamus when a stressor challenges an individual. CRH stimulates the release of adrenocorticotropic hormone from the pituitary, which in turn stimulates the release of two steroid hormones: cortisol and dehydroepiandrosterone (DHEA). [Charney 2004]
The human brain has two types of receptor for cortisol. One has a six to tenfold higher affinity for the molecule than the other, and so is activated earlier, by smaller amounts of cortisol.
The hippocampus (which is pivotal for memory) and the amygdala (the centre for emotions) contain lots of the high-affinity receptors, and are, therefore, activated by slight rises in the hormone. The frontal lobe, which is involved in executive planning and control, has only the low-affinity receptor, and is activated later, after the tide has risen. And, as Lupien and colleagues found, both memory formation and recall in adults can be influenced by cortisol.
The existence of two receptor types means that response to stress is not linear. “The relationship between circulating stress hormone and memory is an inverted U-shape function.
“Up to a certain level, stress hormones are good for your memory” — when the cortisol binds only to the high-affinity receptors, the ability to lay down and retrieve memory is enhanced. When the low-affinity receptors are activated, the relationship enters the right-hand side of the U-shape and the response shifts. [Kaufer D]
- Increased expression of CRH receptors (CRH-1 and CRH-2) is associated with PTSD, MDD, and anxiety, whereas individuals with reduced CRH expression levels display more significant levels of stress resilience.
- In general, cortisol is elevated following trauma; however, PTSD can be associated with both hypo- and hyperactivity of the HPA axis, whereby lower basal levels of cortisol blunt cortisol’s response and enhance HPA feedback, resulting in progressive sensitisation of the HPA axis.
- DHEA and its sulfate ester derivative, DHEA-S, are secreted by the adrenal cortex and are hypothesised to provide a neuroprotective role against stress by offsetting some of the detrimental effects of sustained cortisol levels.
In summary, an elaborate negative feedback system counteracts stress reactivity and promotes equilibrium and optimal functioning. Several studies suggest that the DHEA-cortisol ratio is a potential risk factor for developing psychopathology, including depression, anxiety, and chronic fatigue syndrome.
Dopaminergic and serotonergic systems
Stress also affects other neural functions, notably dopamine and serotonin.
An acute stress response is linked to the inhibition of dopamine release in the nucleus accumbens and activation of dopamine release in the medial prefrontal cortex.
There is also an increase in serotonin in the lateral hypothalamus, amygdala, prefrontal cortex, and nucleus accumbens, which results in the downstream regulation of anxiety-like behaviours.
- Stress-induced increases in dopamine affect decision making, personality, and cognition, and abnormally reduced dopamine levels in the prefrontal cortex is associated with the maintenance of the fear response as observed in cases of PTSD.
- Stimulation of the serotonin 2A receptor has anxiogenic effects, which assist in adaptive processes during the stress response. However, serotonin also has anxiolytic effects via stimulation of serotonin 1A receptors.
Neuroinflammation:
The is strong evidence of the link between stress and neuroinflammation.
Furthermore, the influence of stress on the gut microbiome and neuroinflammation is also relatively unexplored.
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GENETIC FACTORS IN STRESS RESILIENCE
Trait inheritance has a major influence on the risk or resilience to stress and psychiatric disorders. [Feder 2009; Wu et al. 2013]
- SNS genes – Stress exposure and polymorphisms linked to autonomic hyper-responsiveness have been found in the gene encoding neuropeptide Y [Kallio et al. 2001],
- HPA axis genes – Polymorphisms in the CRH1 gene have been shown to be predictive of later life PTSD and MDD. [Heim et al. 2009]
- BDNF gene – The BDNF Val66Met polymorphism has recently been shown to be associated with differences in stress resilience and vulnerability to depression and anxiety. [Colzato et al. 2011]
- Epigenetic factors – DNA methylation and histone methylation/acetylation are biochemical processes that effect gene expression levels. Previous studies have shown that psychiatric patients have notable epigenetic differences; however, their precise role in the stress response and development of mood disorders remains unknown. [Fraga et al. 2005]
DEVELOPMENTAL FACTORS IN STRESS RESILIENCE
The normal development of the HPA axis and overall stress response can be negatively affected by several different types of toxic stress during early life. [Rende 2012; Shonkoff and Garner 2012]
Thus, the experience of adversity during childhood increases the risk of stress-related disorders in later life. [Dannlowski et al. 2012]
- The degree of control and the possibility of changing the situation can affect whether an individual can learn stress resilience through experience.
- Physical and emotional abuse, chronic neglect, exposure to violence, and long-lasting ill health can cause an individual to believe that they cannot change their circumstances.
- Learned helplessness is characterised by the individual having decreased capacity and/or unwilling to avoid consequent stressful events and the realisation that it cannot be avoided.
- Therefore, if an individual can develop appropriate coping strategies, then this will facilitate adaptation and the successful recovery from stressful events in adult life.
SUMMARY
Stress resilience is an adaptation in the face of adversity and the ability to ‘bounce back’ from these circumstances.
Stress resilience is not an uncommon trait and most people display a degree of resilience however stressful life events can overload these mechanisms.
Understanding these risks and the factors that promote successful adaptation are considered essential for enhancing resilience and mitigating the deleterious effects of stress.