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Diversity of the Body’s Neurobiological Stress Response: Racial/Ethnic and Sex Differences

There is an extensive body of literature in the field of neuroscience surrounding the stress response and its connections to poor psychological and physiological health outcomes. It is known that the Hypothalamic-Pituitary-Adrenal (HPA) axis, which is the central stress response, can lead to mood disorders or other possible diseases when it is chronically over-activated due to long term stress. Certain demographics of people, such as racial/ethnic minorities and females, are more susceptible to the negative physiological effects of stress and are disproportionately affected by these disorders. To explain this disparity, recent literature has elucidated the presence of racial/ethnic and sex differences in the neurobiology behind the stress response.

Racial/Ethnic Differences

In a recent review article, existing literature was summarized to show the changes in neurobiology caused by racial discrimination experienced by racial/ethnic minority groups. Racial discrimination has been found to increase allostatic load, which is the body’s to constantly adapt to changes in demands over time, contributing to wear and tear, and leading to higher risk of diseases. This relationship is mediated by chronically elevated levels of the stress hormone cortisol and dysregulated HPA axis in the stress response. 

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When an individual perceives acts of racial discrimination, this social stress leads to activation of the HPA axis, the autonomic nervous system and other neurotransmitter pathways, such as dopamine, noradrenaline, and serotonin. As a result, allosteric overload of the body can occur from the over activation of the HPA axis producing excess cortisol and over activation of the autonomic nervous system causing heart rate variability.  In addition to causing poor physical health outcomes through the allosteric overload, those three types of neural pathways activated by social stress can also affect functional brain networks. Brain regions such as the prefrontal cortex, anterior cingulate cortex, and salience networks receive the hormonal and neurotransmitter inputs causing hypervigilance and salience network dysfunction that is associated with poor mental health outcomes.

Diving deeper into the functional brain networks affected, neuroimaging has also shown effects of racial discrimination on the anterior cingulate cortex (ACC). The ACC is responsible for integrating social cues and experiences. It is closely involved with emotional reactivity and connected the limbic system. fMRI brain scans have shown that this region is activated by experiences of social exclusion and altered by perceived social stress. These are characteristic of the experiences of racial discrimination. Altered activity of this region as a result of racial discrimination is relevant because a region of the ACC has a high density of glucocorticoid receptors, meaning that increased activation and structural changes of this region during perceived discrimination is indicative of an altered stress pathway.

In these ways, racial discrimination can have neurobiological effects on the stress pathway of the brain. Racial/ethnic minority groups who are more likely to experience situations of discrimination throughout their lives are more susceptible to these chronic stress effects and are more at risk of developing psychiatric mood disorders, as a result.

Sex Differences

There are disparities of biological sex in the prevalence of various psychiatric disorders, which can be explained by the role of stress in the onset and severity of these disorders. For instance, post-traumatic stress disorder and depression occur more frequently in women than men. A recent study revealed underlying sex differences in the neurological response to stress, causing these disparities. 

A comparison of stress response by the HPA axis showed that female rats have a greater release of corticotropin releasing factor (CRF) from the hypothalamus, adrenocorticotropic hormone (ACTH) from the pituitary gland and glucocorticoids from the adrenal gland cortex. This can be explained by sex differences in these regions of the brain due to the ovarian hormones of females. For instance, in the adrenals, the female hormone estrogen can enhance ACTH sensitivity and increase glucocorticoid release for this sex. Estrogen can directly regulate vasopressin and CRF gene expression using the promoter region of these genes. The overall implication of this neuroendocrine difference in sexes is that females tend to release more glucocorticoids in response to stress compared to males, which can be more harmful for their health.

Female rats were also found to have reduced negative feedback effect of glucocorticoids due to sex differences in the GABAergic inhibition and glucocorticoid receptor (GR) expression and translocation. In a normal stress response, glucocorticoids provide feedback to limit the activation of the HPA axis by inhibiting hypothalamic release of CRF and pituitary release of ACTH. In this case, the decreased feedback effect is indicated by the fact that it takes longer for glucocorticoid levels to return to baseline for female rats since the hormones in the HPA axis are still being released. One explanation for this sex difference is that estrogen in females reduces GABAergic inhibition in the hypothalamus, thus impairing the feedback. Additionally, estrogen can also downregulate the expression of GR. The normal process of negative feedback requires GRs to be translocated, or moved from the cytosol to the nucleus, in order to repress gene transcription of CRF, CRF receptors, and ACTH precursors. However, this translocation is reduced in female rats as chronic stress exposure upregulates co-chaperone proteins that inhibit the movement of GRs into the nucleus, thus reducing the glucocorticoid negative feedback. As a result, females are more likely to have a dysregulated HPA-axis stress response, making them more susceptible to damaging psychiatric disorders.

Although this study was conducted on rats, its findings can still help draw conclusion about human neuroscience as well. For instance, the resulting increased glucocorticoid levels in female rats can explain the hormonal differences in women with depressions compared to men with depression. It also can help to explain previous literature on why women with psychiatric disorders tend to have greater HPA axis dysregulation than men. In general, these findings provide insights into the neurobiological mechanisms behind the sex disparities of stress-related psychiatric disorders.

References: 

Bangasser, D. A. & Valentino, R. J. (2014). Sex differences in stress-related psychiatric disorders: Neurobiological perspectives. Frontiers in Neuroendocrinology, 35, 303-319. 

Berger, M. & Sarnyai, Z. (2015). “More than skin deep:” Stress neurobiology and mental health consequences of racial discrimination. Stress, 18(1), 1-10.

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Diagram of sex differences in the stress response of the HPA axis

Bangasser, D. A. & Valentino, R. J. (2014). Sex differences in stress-related psychiatric disorders: Neurobiological perspectives. Frontiers in Neuroendocrinology, 35, 303-319.

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Diagram of the relationship between racial discrimination, stress pathway, and other brain networks, leading to poor mental health outcomes

Berger, M. & Sarnyai, Z. (2015). “More than skin deep:” Stress neurobiology and mental health consequences of racial discrimination. Stress, 18(1), 1-10.

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Images of the brain showing grey matter density and brain activity from different mental illnesses.

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As the interest in neuroscience grows within the public, researchers are exploring new ways to display their findings, like this awesome pop art piece of MRI brain scans. (Chase Sherwell/QBI)

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“The cosmos is within us. We are made of star-stuff. We are a way for the universe to know itself.” ― Carl Sagan

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Anatomical MRI gif of the brain, concurrently showing progressive slices through transverse, saggital, and coronal planes.

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Internal Vibrations..

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Just looking around....