Stress is ubiquitous.
Oftentimes, we experience stressful situations involving intrapersonal, interpersonal, and societal issues. Stress can affect anyone in various form, be it as traumatic events (e.g., abuse; violence), negative life events (e.g., layoff; severed relationships), and even minor hassles (e.g., road traffic; poor Wi-Fi reception). Although not all stress is ‘bad’ (distress), it can be ‘good’ (eustress) when it promotes motivation, performance, and even survival.
When we encounter stressful situations, the noxious feeling that we experience is a complex interaction between the mind and body. Although acute or short-lived stress can be beneficial and adaptive (e.g., when the sympathetic nervous system kicks in to promote immediate action to manage or escape from threat), excessive and chronic stress can damage both the mind and body. This is also known as allostatic load, which is the cumulative wear-and-tear on the body from exposure to such chronic stress.
Prolific research over the years has shown the association of stress with myriad physical illnesses, such as cardiovascular diseases, stroke, obesity, and compromised immune system. However, how the stress-inflammation pathway affects mental health is largely neglected and undermined. This may be partly due to the public’s underestimation of the deleterious effects of poor mental health on well-being and mortality.
I strongly believe that the public should understand how stress can affect our mental health in addition to physical health. Mental disorders are as deliberating as physical illnesses, and that stress is a common pathway to developing and perpetuating such disorders. Hence, in this article, I hope to provide a biopsychosocial approach to understand how stress affects mental health, with a focus on depression that is primarily based on the review by Slavich and Irwin (2014), who proposed the Social Signal Transduction of Depression theory.
DEFINITION OF STRESS
Before we proceed into the physiological and psychological sequelae of stress, let us understand what stress is, and how it is operationally defined to be systematically measured and studied.
Traditionally, stress has been defined as stimulus/response-based. The stimulus-based definition conceptualizes stress as an aversive stimulus (unsurprisingly), which causes a disturbing, noxious psychological experience. Naturally, the response-based approach describes stress as a physiological reaction (i.e., activation of the nervous system) to the aversive stimuli. This physiological reaction was first conceptualized by Selye (1946) and further developed into a three-phased theoretical model– the General Adaptation Syndrome. First, the body is triggered by the aversive stimuli and reacts by releasing hormones to prepare the individual to manage the stressor/situation (analogous to the fight-or-flight response). If exposure to the stressor prolongs, the body enters the resistance phase where it starts to adapt to the situation. Lastly, if the stress continues for an extended period and exceeds the body’s ability to resist, it enters the exhaustion phase whereby the chronic stress damages the physiological system leading to physical and mental illnesses (Selye, 1946).
However, these definitions may be incomplete. Not all individuals perceive the same event as stressors nor experience the same physiological reaction. For example, imagine a student was asked to give a 10-minute presentation about stress and inflammation within the next 5-minutes, as compared to an experienced health researcher to do the same. Although the same objective event, the intensity of stress is different for everyone. Further, physiological changes can also ensue when experiencing events that are not threatening, such as receiving an unexpected reward or surprise.
A more recent conceptualization of stress by Lazarus and Folkman (1984) addressed the aforementioned limitations by including cognitive responses, appraisals, and resources. For example, different types of stressors may carry more significance for one individual than another due to different goals, beliefs, values, and psychosocial resources. Thus, stress is defined as something that can be real or imagined (e.g., a real threat or anticipating what may happen) that exceeds the individual’s ability to cope, thus triggering the physiological response. In other words, a stressful situation is the discrepancy between the individual’s perceived demands and perceived resources.
WHY IS IT IMPORTANT, AND HOW IS IT LINKED TO MENTAL HEALTH?
One of the most common mental disorders is depression, affecting approximately 300million individuals worldwide (World Health Organization, 2017). The symptomologies of depression include depressed mood, anhedonia, feelings of worthlessness, and sleeplessness, which are strongly correlated with suicidal ideation, attempts, and even death. Given the deleterious effects, it is unsurprising that depression is ranked as the third leading cause of disability worldwide (Mathers, Fat, & Boerma, 2008).
Much research has identified stress as a strong predictor for developing depression. One of the most robust types of stress that triggers the onset of depression is major life events, which evokes significant distress, disturbance, and disruption to one’s life (Monroe, Rohde, Seeley, & Lewinsohn, 1999). These events include, but not limited to, severed relationships, financial loss, and receiving a diagnosis of major illnesses (e.g., cancer). In fact, there is evidence showing a causal link between major stressful events and the onset of depression (controlling for genetic influence; Kendler, Karkowsi, & Prescott, 1999). Interestingly, these severe events that involve interpersonal loss and social rejection are among the strongest risk factors for developing depression (Slavich & Irwin, 2014). For instance, research by Kendler et al (2013) found that individuals who initiated estrangement (also experiencing interpersonal loss) were 10.2% more likely to develop depression. Remarkably, individuals who were estranged or broken up with (i.e., interpersonal loss and social rejection) had a 21.6% increased risk of developing depression. These results suggest that the risk of developing depression doubled for individuals who experience both interpersonal loss and social rejection. Using a retrospective-interview approach, Slavich, Thornton, Torres, Monroe, & Gotlib (2009) have also found comparable results among individuals with depression. Specifically, individuals who experienced stressful events involving social rejection were three times faster in developing depression than who experienced other forms of stressful events. Together, these findings show that psychosocial stressors, particularly those that involve interpersonal loss and rejection, are strong precipitators of the onset of depression.
Although we now know major stressful events are risk factors for depression, an immediate question that comes to mind is that how these stressors trigger the onset of depression. Substantial amount of correlational evidence shows that individuals with greater stressful events, such as lower socioeconomic status and negative daily interactions, were positively associated with higher levels of inflammatory activity (Fuligni et al., 2009; Pollitt et al., 2007). As supported by experimental studies, laboratory-induced psychosocial stressors (e.g., inducing stress via conflict or social rejection) can also evoke strong inflammatory responses (Denson, Spanovic, & Miller, 2009). These studies indicate that not only real physical threats (e.g., escaping from an armed robbery) can up-regulate our internal physiological processes, but modern-day stressors involving social, imagined, and anticipated threats can also evoke such physiological reaction.
The next question that comes to mind is whether inflammation causes depression. As discussed earlier, prolonged stressors can do more harm than good to both the mind and body. Because human beings have a high capacity for cognitive and symbolic thought (e.g., worrying, planning, anticipating, imagining), these modern-day, chronic stressors can persistently up-regulate the physiological responses and in turn impair our health. Amongst the initial evidence to suggest such relationship came from the observation of high co-morbidity between inflammation-related disorders and depression (Slavich & Irwin, 2014). Several studies have shown that individuals with asthma, rheumatoid arthritis, inflammatory bowel disease, and chronic pain have increased likelihood of developing depression and anxiety disorders than the general population (Bair, Robinson, Katon, & Kroenke, 2003; Byrne et al., 2017; Dickens, McGowan, Clark-Carter, & Creed, 2002; Goodwin, Fergusson, & Horwood, 2004). Similarly, individuals diagnosed with major depressive disorders also show elevated levels of multiple markers of inflammatory activity, such as IL-1, IL-6, TNF-alpha, cortisol, and CRP (Burke, Davis, Otte, & Mohr, 2005; Dowlati et al., 2010; Howren, Lamkin, & Suls, 2009)
Although convincing, these findings are still mostly correlational and do not provide strong causal evidence to whether inflammation causes depression. Providentially, there is substantial evidence from immunotherapy and vaccination research showing that exposure to immunological challenges, which up-regulates inflammatory activity, can evoke depressive symptoms. For example, approximately 50% of individuals with cancer and hepatitis C reported severe level of depression following IFN-alpha treatment (which up-regulates the inflammatory activity to boost the immune system and facilitate recovery), particularly increased levels of depressed mood, sleep problems, and irritability (Bonaccorso et al., 2002). Additionally, these patients also showed abnormal neural activity in the brain regions that have been implicated in depression following the IFN-alpha treatment (Capuron et al., 2012). These findings shed light into the potential causal pathway between inflammation and depression.
Lastly, and most astonishingly, anti-inflammatory medications can reduce depressive symptoms. A double-blind, placebo-controlled study by Muller et al. (2006) showed that patients diagnosed with major depression who received anti-inflammatory and antidepressant medications exhibited approximately 55% reduction in depression severity after 6-weeks, whereas those who only received the antidepressant and placebo showed 33% reduction.
Together, these studies provide a biopsychosocial approach to understand how stress can affect our mental health, particularly in evoking depressive symptoms. First, major stressful events, particularly those involving social rejection and interpersonal loss, are well-documented as precipitators of the onset of depression. These psychosocial stressors, just like real, physical threats, can activate the physiological responses. Given that humans have high capacity in cognition and symbolic thinking (e.g., planning, imagining, ruminating, anticipating, worrying), these psychosocial stressors can cause cognitive dysfunction and chronically activate the stress response. The stress response, in turn, up-regulates the inflammatory activity that evoke depressive symptoms, including depressed mood, anhedonia, and sleep problems. This stress-inflammation-depression pathway is also known as the Social Signal Transduction Theory, which is proposed by Slavich and Irwin (2014). This article is largely based upon their review, and I do recommend everyone to read it for more information (click here for article). All things considered, I do hope that I have provided a better appreciation and realisation on how stress can affect our mental health, particularly how depression develops in a biopsychosocial manner. However, it should be noted that this is not a complete picture, given that depression and every other mental illness have multifaceted aetiology.
HOW TO MANAGE STRESS?
Given the deleterious effects of stress, it appears we should eliminate stress entirely from our lives. This is untrue. The only people without stress in their lives are dead people. We need stress to motivate ourselves to achieve our goals. We need stress to help us increase our performances. We need stress to promote survival. We need stress to spice up our lives. My point here is that stress is ubiquitous, and it is nearly impossible to avoid or fully eradicate it from our lives. As discussed, prolonged, unresolved stressors can significantly impair our health; thus, we do not necessarily need to eliminate the stressor, but we should learn to identify and how to cope with it. Everyone has his/her ways of coping with stressors (both adaptive and maladaptive, e.g., directly resolving the issue or drinking alcohol), and we should learn the most effective and adaptive ways of coping that are applicable and relevant for ourselves. Here are some tips on how to cope with stress suggested by the American Psychological Association and National Institute of Mental Health.
*Note to editor: Below are the hyperlinks that I have used to encourage quicker access for the articles I strongly recommend.
https://www.nimh.nih.gov/health/publications/stress/index.shtml (National Institute of Mental Health – how to deal with stress)
http://www.apa.org/helpcenter/manage-stress.aspx (APA on how to deal with stress)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006295/ (Slavich & Irwin 2014’s social transduction theory)
Bair, M. J., Robinson, R. L., Katon, W., & Kroenke, K. (2003). Depression and pain comorbidity: A literature review. Archives of Internal Medicine, 163(20), 2433-2445.
Bonaccorso, S., Marino, V., Biondi, M., Grimaldi, F., Ippoliti, F., & Maes, M. (2002). Depression induced by treatment with interferon-alpha in patients affected by hepatitis C virus. Journal of Affective Disorders, 72(3), 237-241.
Burke, H. M., Davis, M. C., Otte, C., & Mohr, D. C. (2005). Depression and cortisol responses to psychological stress: A meta-analysis. Psychoneuroendocrinology, 30(9), 846-856.
Capuron, L., Pagnoni, G., Drake, D. F., Woolwine, B. J., Spivey, J. R., Crowe, R. J., … & Miller, A. H. (2012). Dopaminergic mechanisms of reduced basal ganglia responses to hedonic reward during interferon alfa administration. Archives of General Psychiatry, 69(10), 1044-1053.
Denson, T. F., Spanovic, M., & Miller, N. (2009). Cognitive appraisals and emotions predict cortisol and immune responses: A meta-analysis of acute laboratory social stressors and emotion inductions. Psychological Bulletin, 135(6), 823-853
Dickens, C., McGowan, L., Clark-Carter, D., & Creed, F. (2002). Depression in rheumatoid arthritis: A systematic review of the literature with meta-analysis. Psychosomatic Medicine, 64(1), 52-60.
Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E. K., & Lanctôt, K. L. (2010). A meta- analysis of cytokines in major depression. Biological psychiatry, 67(5), 446-457.
Fuligni, A. J., Telzer, E. H., Bower, J., Cole, S. W., Kiang, L., & Irwin, M. R. (2009). A preliminary study of daily interpersonal stress and C-reactive protein levels among adolescents from Latin American and European backgrounds. Psychosomatic Medicine, 71(3), 329-333.
Goodwin, R. D., Fergusson, D. M., & Horwood, L. J. (2004). Asthma and depressive and anxiety disorders among young persons in the community. Psychological Medicine, 34(8), 1465-1474.
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Kendler, K. S., Hettema, J. M., Butera, F., Gardner, C. O., & Prescott, C. A. (2003). Life event dimensions of loss, humiliation, entrapment, and danger in the prediction of onsets of major depression and generalized anxiety. Archives of General Psychiatry, 60(8), 789-796.
Kendler, K. S., Karkowski, L. M., & Prescott, C. A. (1999). Causal relationship between stressful life events and the onset of major depression. American Journal of Psychiatry, 156(6), 837-841.
Lazarus, R. S., & Folkman, S. (1984). Stress, appraisal and coping. New York: Springer.
Mathers, C., Fat, D. M., & Boerma, J. T. (2008). The global burden of disease: 2004 update. World Health Organization. Retrieved from http://www.who.int/healthinfo/global_burden_disease/2004_report_update/en/
Monroe, S. M., Rohde, P., Seeley, J. R., & Lewinsohn, P. M. (1999). Life events and depression in adolescence: Relationship loss as a prospective risk factor for first onset of major depressive disorder. Journal of Abnormal Psychology, 108(4), 606-614.
Müller, N., Schwarz, M. J., Dehning, S., Douhe, A., Cerovecki, A., Goldstein-Müller, B., … & Möller, H. J. (2006). The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: Results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Molecular Psychiatry, 11(7), 680-684.
Pollitt, R. A., Kaufman, J. S., Rose, K. M., Diez-Roux, A. V., Zeng, D., & Heiss, G. (2007). Early-life and adult socioeconomic status and inflammatory risk markers in adulthood. European Journal of Epidemiology, 22(1), 55-66.
Selye, H. (1946). The general adaptation syndrome and the diseases of adaptation. The Journal of Clinical Endocrinology, 6(2), 117-230.
Slavich, G. M., & Irwin, M. R. (2014). From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. Psychological Bulletin, 140(3), 774-815
Slavich, G. M., Thornton, T., Torres, L. D., Monroe, S. M., & Gotlib, I. H. (2009). Targeted rejection predicts hastened onset of major depression. Journal of Social and Clinical Psychology, 28(2), 223-243.
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