In humans, stress can be defined as an actual or anticipated disruption of homeostasis in an individual (Ulrich-Lai & Herman, 2009). The brain plays a central role in the experience of stressful events and the regulation of stress: it adapts to stress both functionally and structurally, and dictates how individuals cope with stress (McEwen & Gianaros, 2011).
Specifically, psychological stress leads to the activation of the hypothalamus-pituitary-adrenal (HPA) axis, increasing the release of cortisol and coordinating several physiological processes, including cardiovascular activation, emotional processing, and memory consolidation (Sapolsky et al., 2000).
In other words, the more stressed an individual feels, the more cortisol their brain secretes (Gaab et al., 2005). This apparent intertwinement of stress and cortisol secretion opens a window on the relationship between mental and physical processes, and the potential dysfunction of these processes that may result in impaired brain activity.
To better understand this relationship, it is important to distinguish between two specific stress responses. The first is the acute stress response, where individuals produce short-term coping responses based on the appraisal of the perceived threat (Folkman et al., 1986). For example, individuals may temporarily show an increased hormonal activity that maximises the potential for muscular exertion (Cannon, 1929).
These coping responses are achieved through higher levels of cortisol in the brain: cortisol helps the brain release more neurotransmitter, enabling neuronal connections to adapt (Groc et al., 2008), and also increases the number of neurotransmitter receptors (Popoli et al., 2012), effectively making the brain more efficient. This process, which momentarily redirects the body’s energy to the brain and suppresses other functions such as immunity, inflammatory response, reproduction, and digestion, has been essential to mammals’ survival (Boonstra, 2005).
However, if stress is constant, the long-term effects can be damaging to an individual’s health (Schneiderman et al., 2005). While acute stress is often caused by topical factors, such as being stuck in traffic jam or having to go to the hospital, chronic stress can arise with very little external provocation, and be aggravated by chronic circumstances such as poor living conditions (Jones et al., 2001). The brain is not designed to handle the persistent elevation of cortisol caused by chronic stress, which can be extremely harmful (Tsigos, & Chrousos, 2002; Jankord & Herman, 2008).
This is because some neurotransmitters such as glutamate are helpful in small quantities, but neurotoxic in larger ones (Choi, 1988). Glial cells, which provide support and protection to neurons (Jessen & Mirsky, 1980), usually recycle these neurotransmitters, but the higher levels of neurotransmitters can become unmanageable over the long term (Rodríguez & Ortega, 2017).
This excess of neurotransmitters can in turn increase the risk of ulcers, strokes, and mental illnesses (Sapolsky, 2004). In addition, the increase in neurotransmitter receptor numbers can lead to damaging changes to the neurons’ structure, such as dentrite shrinkage (McEwen et al., 2016).
Acute stress responses show how psychological stresses impact biological functions, and chronic stress responses highlight some of the dysfunctions stress can cause in brain activity. Notwithstanding this evidence, our knowledge of cortisol and its impact on the brain is still quite limited. For example, the acute stress response can also be dysfunctional: besides the traditional fight-flight-freeze reaction to stress (Maack et al., 2015), researchers have identified an additional faint response, which is specific to Homo Sapiens facing a threat perceived as inescapable, and most visible in individuals suffering from blood-injection-injury type-specific phobia (Bracha, 2004).
Another recent meta-analysis found that much of the variability in the HPA axis activation can be attributed to an individual’s personal features or to the specificities of the stressor (Miller et al., 2007). Alongside showing that subjective distress plays an important role in HPA activity, the study highlights cases that may be prime for further research to better understand the complex relationship between psychological stress and physiological dysfunctions in the brain, such as lower HPA axis activation in individuals with post-traumatic stress disorder.
This limited knowledge we have of cortisol is best illustrated by the current absence of medication to directly influence its levels: cortisol is a future target for therapeutic processes, and modulatory neurotransmission in pathophysiology a priority area of research in psychiatry (Stephan et al., 2016). While research is underway, psychological processes may remain an important focus of prevention and intervention (Gaab et al., 2005).
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