The multifaceted nature of depression

 

 

According to the World Health Organisation (WHO, 2020), depression is a highly prevalent disorder with more than 300 million people affected globally. Unlike mood alterations that everyone can experience from time to time, depression may develop into the debilitating, potentially fatal illness. Causes of depression are complex, not entirely identified, and influenced by multiple sources including highly heterogeneous genetic and biological factors as well as psychosocial and environmental influences. Several models have been proposed to explicate origins of depression, based on biological, psychological, and environmental influences. 

Biological theories

One of the well-established biological theories which sheds light on the aetiology of depression is the cytokine theory.  Cytokines, which act primarily as cell signalling substances regulating inflammation in the immune system, may incite and aggravate depression. This statement was robustly supported by evidence of depression-like conditions that were induced by proinflammatory cytokines. Among other famous theories elucidating the causes of depression are the corticosteroid receptor (CRH) hypothesis of dysregulated hypothalamus–pituitary–adrenal (HPA) axis, resulting from stress and raised levels of stress hormones, and the monoaminergic theory of depression.

Genetic influences

A large body of evidence from family and twin studies points to genetic contributions into causes of depression. A meta-analysis of Sullivan, Neale and Kendler (2000) reports the estimated heritability of depression at about 37% and reveals that the risk of depression in children of individuals suffering from depression is elevated threefold.

Numerous candidate genes have been explored to establish possible genetic links to depression; however, no solid genetic associations are defined, implying that depression is a complex heterogeneous illness. It seems highly plausible that the synchronised action of various genes and their interaction with each other and with environment governs the onset and development of depression.

Environmental causes

Converging evidence suggests that environmental exposures such as exposure to air contamination may contribute to the onset of depression. Air contaminants can affect the activity of serotonergic and dopaminergic neurons and inflammatory cytokines, alter the morphology of the hippocampal neurons and cause oxidative stress in the striatum and prefrontal cortex.

Psychosocial causes

A female preponderance in depression has been recently confirmed by Wang et al. (2016), highlighting that socioeconomic status and the severity of depression are negatively related. Among psychosocial factors, stressful severe life events, especially in early life, undoubtedly contribute to the onset of depression as confirmed in many studies. A fourfold increased risk of depression was associated with women who had been sexually or physically abused in childhood compared to those without such an experience.

Attachment theory of Bowlby (1977) may be a valuable basis to explore causes of depression – it claims that disrupted affectional bonds between children and caregivers are the key contributors to the development of psychopathology, including depression and anxiety.

Gene-environment interaction

However, despite the higher risk of depression in individuals with stressful childhood experiences, responses of people to the same type of adversity are different and this may be indicative of the co-influence of genetic factors. Caspi (2003) was among pioneers to establish an interaction between genes and environment, GxE interaction. He identified an important relationship between the serotonin gene (5-HTTLPR), stress, and depression. Individuals with the short allele of the 5-HTTLPR gene are remarkably susceptible to the adverse effects of childhood stress such as neglect or abuse.

Other possible pathways

Beck (2008) proposed the pathway to depression starts with genetic susceptibility. He posited that hyperreactivity of amygdala caused by the 5-HTTLPR polymorphism triggers negative bias and cognitive reactivity. Subsequently, this leads to the formation of dysfunctional beliefs and negative interpretations of experiences, which affect the HPA- axis and ultimately cause depression.

One more possible cause of depression can be explained by the developmental pathway from early conduct problems to adult depression.

Treatment

Antidepressant medications have been known to alleviate symptoms of depression, especially in severe cases. Psychotherapeutic interventions have also been shown effective, either alone or combined with pharmacology. The major challenge, however, is 30% of treatment-resistant individuals.

Conclusion

Depression is a common illness that restricts psychosocial functioning and markedly decreases quality of life. It is a complex disorder resulting from the interaction of genes and environment. Uncertain origins and an unpredictable trajectory of depression often pose challenges for health care professionals. Further research into the female preponderance may shed more light on genesis of depression. Better insight into the aetiology of depression may be especially beneficial for the development of treatment for the treatment-resistant population. 

 

Bibliography
Al-Harbi K. S. (2012). Treatment-resistant depression: therapeutic trends, challenges, and future directions. Patient preference and adherence, 6, 369–388. https://doi.org/10.2147/PPA.S29716
American Psychological Association (APA). (2020). OVERCOMING DEPRESSION: HOW PSYCHOLOGISTS HELP WITH DEPRESSIVE DISORDERS. Retrieved from https://www.apa.org/helpcenter/depression
Anisman, H., Merali, Z., Poulter, M., & Hayley, S. (2005). Cytokines as a Precipitant of Depressive Illness: Animal and Human Studies. Current Pharmaceutical Design, 11(8), 963-972. doi: 10.2174/1381612053381701
Beck, A. (2008). The Evolution of the Cognitive Model of Depression and Its Neurobiological Correlates. American Journal Of Psychiatry, 165(8), 969-977. doi: 10.1176/appi.ajp.2008.08050721
Bowlby, J. (1977). The Making and Breaking of Affectional Bonds. British Journal Of Psychiatry, 130(3), 201-210. doi: 10.1192/bjp.130.3.201
Caspi, A. (2003). Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene. Science, 301(5631), 386-389. doi: 10.1126/science.1083968
Child sexual abuse and subsequent psychopathology: results from the National Comorbidity Survey. (2001). American Journal Of Public Health, 91(5), 753-760. doi: 10.2105/ajph.91.5.753
Currier, M. B., & Nemeroff, C. (2010). Inflammation and mood disorders: Proinflammatory cytokines and the pathogenesis of depression. Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry, 9(3), 212-220.
Holsboer, F. (2000). The Corticosteroid Receptor Hypothesis of Depression. Neuropsychopharmacology, 23(5), 477-501. doi: 10.1016/s0893-133x(00)00159-7
James, S., Abate, D., Abate, K., Abay, S., Abbafati, C., & Abbasi, N. et al. (2018). Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. The Lancet, 392(10159), 1789-1858. doi: 10.1016/s0140-6736(18)32279-7
Malhi, G., & Mann, J. (2018). Depression. The Lancet, 392(10161), 2299-2312. doi: 10.1016/s0140-6736(18)31948-2
McCauley, J. (1997). Clinical Characteristics of Women With a History of Childhood Abuse. JAMA, 277(17), 1362. doi: 10.1001/jama.1997.03540410040028
Mullen, P., Martin, J., Anderson, J., Romans, S., & Herbison, G. (1996). The long-term impact of the physical, emotional, and sexual abuse of children: A community study. Child Abuse & Neglect, 20(1), 7-21. doi: 10.1016/0145-2134(95)00112-3
Paterniti, S., Sterner, I., Caldwell, C., & Bisserbe, J. C. (2017). Childhood neglect predicts the course of major depression in a tertiary care sample: a follow-up study. BMC psychiatry, 17(1), 113. https://doi.org/10.1186/s12888-017-1270-x
Saveanu, R., & Nemeroff, C. (2012). Etiology of Depression: Genetic and Environmental Factors. Psychiatric Clinics Of North America, 35(1), 51-71. doi: 10.1016/j.psc.2011.12.001
Shadrina, M., Bondarenko, E. A., & Slominsky, P. A. (2018). Genetics Factors in Major Depression Disease. Frontiers in psychiatry, 9, 334. https://doi.org/10.3389/fpsyt.2018.00334
Stringaris, A., Lewis, G., & Maughan, B. (2014). Developmental pathways from childhood conduct problems to early adult depression: findings from the ALSPAC cohort. British Journal Of Psychiatry, 205(1), 17-23. doi: 10.1192/bjp.bp.113.134221
Sullivan, P., Neale, M., & Kendler, K. (2000). Genetic Epidemiology of Major Depression: Review and Meta-Analysis. American Journal Of Psychiatry, 157(10), 1552-1562. doi: 10.1176/appi.ajp.157.10.1552
van den Bosch, M., & Meyer-Lindenberg, A. (2019). Environmental Exposures and Depression: Biological Mechanisms and Epidemiological Evidence. Annual Review Of Public Health, 40(1), 239-259. doi: 10.1146/annurev-publhealth-040218-044106
Wang, K., Lu, H., Cheung, E. F., Neumann, D. L., Shum, D. H., & Chan, R. C. (2016). “Female Preponderance” of Depression in Non-clinical Populations: A Meta-Analytic Study. Frontiers in psychology, 7, 1398. https://doi.org/10.3389/fpsyg.2016.01398
Weissman, M. (1977). Sex Differences and the Epidemiology of Depression. Archives Of General Psychiatry, 34(1), 98. doi: 10.1001/archpsyc.1977.01770130100011
World Health Organisation (WHO). (2017). “Depression: let’s talk” says WHO, as depression tops list of causes of ill health. Retrieved from https://www.who.int/news-room/detail/30-03-2017–depression-let-s-talk-says-who-as-depression-tops-list-of-causes-of-ill-health
World Health Organisation (WHO). (2020). Depression. Retrieved from https://www.who.int/news-room/fact-sheets/detail/depression

Leave a Reply

Please log in using one of these methods to post your comment:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s