We live in an era in which our quality of life is better than ever before. Science and medicine in particular have not only increased our average lifespan but have also improved it.
By Umar Bin Adnan
Certain diseases like smallpox have been eradicated completely, the public is generally more aware of health than ever before and medical treatments have not only become efficient but also accessible to most people. However, mental health disorders are more prevalent than ever before yet still misunderstood by many if not most people. Perhaps the most commonly known mental health disorder is depression that, according to the WHO, affects 280 million people worldwide. There are two ways of looking at depression; the biological and the psychological. In this article, I will address the former. What is depression and what causes it? I will be addressing these questions in biological terms.
What Exactly is Depression and Why You Should Care?
Depression or Major Depressive Disorder (MDD) according to Mayo Clinic ‘is a mood disorder that causes a persistent feeling of sadness and loss of interest’. As stated, depression affects approximately 280 million people worldwide yet there is a perception among many people that depression is a first world disease or is only prevalent in the developed world. While most countries that come in the 10 most depressed nations list (World Population Review) are developed nations, it cannot be ignored that depression is also prevalent in the developing world.
There are still some people with the perception that depression is only a first world problem. One in three individuals in Uganda suffer from depression according to a study published in October 2022 that analyzed a total of 127 studies and 123,859 individuals. This study obviously has its limitations, the sample for example consisted of people that were at a higher risk of developing depression such as refugees. A systemic review and meta-analysis that analyzed 26 studies and 7,652 participants showed that 42.77% Pakistani university students have depressive symptoms. Perhaps another reason why the developed nations seem to have a higher percentage of depression is because there is more public knowledge regarding it and people are more likely to report it. As someone who comes from a country where mental health is still a stigma, I find it important to address just how devastating the situation truly is before addressing the science behind it.
The Biological Basis of Depression
There are various factors that neuroscientists and biologists have found out to be linked with depression. While there are still a lot of unaddressed questions regarding the biological cause of depression, efforts are being made to understand the disorder more and more.
The monoamine hypothesis is perhaps the most widely known biological cause of depression. Monoamines are neurotransmitters that are involved in relaying information from one neuron to another and certain monoamines are associated with mood. One of these is Serotonin. The monoamine hypothesis states that depression occurs due to an imbalance or deficit in serotonin levels in the nervous system. This is supported by the fact that most antidepressants function by increasing serotonin levels. Most antidepressants like Selective Serotonin Reuptake Inhibitors (SSRIs) we know of act based off of this hypothesis. However, 30% MDD patients are refractory to most currently used antidepressants and artificially lowering serotonin in normal people doesn’t cause depression. This combined with the side effects of SSRIs, have caused scientists to research other possible causes of MDD.
We might be doomed by our genes too. A study published in nature in 2021 showed that 178 genes that are associated with depression that include the NEGR1 and DRD2 genes. Prenatal stress and maternal separation are said to modify the DNA methylation of the Corticotropin Releasing Factor (CRF) gene and causes dysregulation of CRF which has been associated with depression. Therefore, both genetic and epigenetic factors contribute to the development of this disorder.
Stress is another factor related to depression. Research has shown that changes in neuroplasticity and neurogenesis (genesis of new neuronal cells) are linked with MDD. Neuroplasticity is defined as the ‘capacity of neurons and neural networks in the brain to change their connections and behavior in response to new information’ and is essential for learning, memory and recovery from brain damage. Decrease in neurotrophic factors such as BDNF and its associated proteins has also been linked to depression in what is known as the neurotrophic theory of depression. Studies have shown that chronic stress decreases both neuroplasticity and neurogenesis while also contributing to the development of MDD.
Scientists have also linked changes in gray matter volume with depression. Gray matter contains a large number of various neurons and is said to regulate emotions. Thus, MDD patients often have reduction in gray matter volume in their brain causing them extreme emotional distress and as a result suffer from MDD.
Our immune system perhaps also has something to do with MDD. Cytokines are proteins produced by immune cells and can either stimulate or inhibit the immune system. Studies have shown increased peripheral cytokine production to be associated with the development of mood disorders. Proinflammatory cytokines such as IL-1 and TNFα inhibit neuronal plasticity and thus lead to the development of depression like behaviors.
Lastly, I would like to add that there are other hypotheses and theories that have been gaining ground as to the biological basis of depression. One of these is the association between the gut microbiome and MDD. Studies have shown that by providing certain probiotics, MDD pathogenesis can be inhibited. However, more research has to be done on this topic.
In conclusion it is important to know that depression is not a life sentence and there are treatments available. Cutting edge research on the biological basis of depression is being carried out day and night and by understanding the pathogenesis and pathology of the disorder, we will be able to devise more effective treatments in the future. Moreover, psychedelic research has taken the world of mental health by storm and the potential of psychedelic derived drugs seems pretty promising. I will discuss the current and future treatments of depression sometime in the future.
References
- https://www.who.int/news-room/fact-sheets/detail/depression
- https://worldpopulationreview.com/country-rankings/depression-rates-by-country
- https://www.mayoclinic.org/diseases-conditions/depression/symptoms-causes/syc-20356007
- Kaggwa MM, Najjuka SM, Bongomin F, Mamun MA, Griffiths MD. Prevalence of depression in Uganda: A systematic review and meta-analysis. PLoS One. 2022 Oct 20;17(10):e0276552. doi: 10.1371/journal.pone.0276552. PMID: 36264962; PMCID: PMC9584512.
- Khan MN, Akhtar P, Ijaz S, Waqas A. Prevalence of Depressive Symptoms Among University Students in Pakistan: A Systematic Review and Meta-Analysis. Front Public Health. 2021 Jan 8;8:603357. doi: 10.3389/fpubh.2020.603357. PMID: 33490022; PMCID: PMC7820542.
- Boku S, Nakagawa S, Toda H, Hishimoto A. Neural basis of major depressive disorder: Beyond monoamine hypothesis. Psychiatry Clin Neurosci. 2018 Jan;72(1):3-12. doi: 10.1111/pcn.12604. Epub 2017 Oct 19. PMID: 28926161.
- Moncrieff, J., Cooper, R.E., Stockmann, T. et al. The serotonin theory of depression: a systematic umbrella review of the evidence. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01661-0
- Pittenger, C., Duman, R. Stress, Depression, and Neuroplasticity: A Convergence of Mechanisms. Neuropsychopharmacol 33, 88–109 (2008). https://doi.org/10.1038/sj.npp.1301574
- Ménard C, Hodes GE, Russo SJ. Pathogenesis of depression: Insights from human and rodent studies. Neuroscience. 2016 May 3;321:138-162. doi: 10.1016/j.neuroscience.2015.05.053. Epub 2015 May 30. PMID: 26037806; PMCID: PMC4664582.
- Ancelin ML, Carrière I, Artero S, Maller J, Meslin C, Ritchie K, Ryan J, Chaudieu I. Lifetime major depression and grey-matter volume. J Psychiatry Neurosci. 2019 Jan 1;44(1):45-53. doi: 10.1503/jpn.180026. PMID: 30565905; PMCID: PMC6306287.
- Levey, D.F., Stein, M.B., Wendt, F.R. et al. Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions. Nat Neurosci 24, 954–963 (2021). https://doi.org/10.1038/s41593-021-00860-2