====== Depression ======
====== History ====== The Ancient Greeks hypothesized that depression was caused by an imbalance of bodily fluid, or humor. The presence of different humors led to different dominant personalities. As such, an excess of bile resulted in melancholia - characterised by Hippocrates as a distinct disease, consisting of “fears and despondancies, if they last for a long time.” ^[14] Physicians in the muslim and persian world developed ideas about depression in the Islamic golden age. The 11th century Persian physician Avicenna theorized that depression was a mood disorder in which sufferers become suspicious and develop phobias. Ishaq in Imran (d.908) associated depression with the inflammation of the brain and meninges. ^[10] Various theories of melancholia flourished in medieval Europe, alongside the theories of Hypocrates, Avicenna and Galen. Acedia, or lethargy, was thought to be linked to be isolation. ^[14] During the age of enlightenment (18th and 19th century) depression was thought be inheritable and untreatable weakness in temperament. Thus, depressed individuals were locked up in mental institutions and were subject to homelessness and poverty. ^[14]
====== Types and Symptoms ====== **Major depressive disorder**: also known as unipolar disorder; severe form of depression. A person with major depressive disorder has had at least one episode of severe depression that lasted almost everyday for at least two weeks. ^[3] During the episode, the individual has felt at least five of the following symptoms ^[1]: * decreased interest in activities * feelings of low self-esteem or guilt * significant increase or decrease in weight or appetite * excessive or insufficient sleep * fatigue or loss of energy * impaired concentration or decision–making * speeded or slowed psychomotor activity * thoughts of suicide However, a person that experiences these symptoms within two months of bereavement does not have major depressive disorder. **Persistent depressive disorder:** previously known as Dysthymic disorder ^[11]; mild, chronic form of depression. A person with persistent depressive disorder has experienced milder symptoms of depression, including ^[11]: * increase or decrease in appetite * feelings of low self-esteem or guilt * impaired concentration or decision–making * feeling of hopelessness * insomnia or hypersomnia The individual with persistent depressive disorder experiences these symptoms for most days for at least two years, with the symptoms being absent for no more than two months at once during that period. **Postpartum depression:** may start during pregnancy or up to a year after the birth of the child. A mother or father with postpartum depression may not enjoy the baby and have frequent thoughts that they’re a bad parent. They may also have scary thoughts around harming themselves or their baby ^[5]. **Bipolar I & II:** also known as manic depression; when depression is accompanied with mania. - A person with bipolar I disorder has experienced at least one manic or mixed episodes. In the manic episode, one experiences at least three of the following symptoms for at least a week: delusional self-esteem, low need for sleep, increased talkativeness, poor judgment, and distractibility with many thoughts. In the mixed episode, one experiences symptoms of both major depressive disorder and manic episodes for at least a week.^[2] - A person with bipolar II disorder has experienced at least one major depressive episode and one hypomanic episode. The hypomanic episode lasts for at least four days and has same but less severe symptoms of manic episode.^[4] **Cyclothymic disorder**: mild, chronic form of Bipolar disorder. A person with cyclothymic disorder experiences both hypomanic episodes and milder symptoms of major depressive disorder for most days for at least two years, with the symptoms being absent for no more than two months at once during that period ^[6].
====== Risk Factors ====== Almost all community epidemiological studies find that gender, age, and marital status are associated with depression ^[12]. Depression usually presents during the teens, 20s and 30s in both men and women. Women are two times more likely to be diagnosed with depression, but it is still not yet clear whether this is in part due to women being more likely to seek treatment. Individuals who are separated or divorced have significantly higher rates of major depression than the currently married and prevalence of major depression generally goes down with age. Factors that seem to increase the risk of developing or triggering depression include ^[8]: * Personality Traits e.g. pessimism, low self-esteem, self criticism * Traumatic events (PTSD, death of a loved one, sexual abuse etc.) * Drug abuse * History of mental health disorders * Family history and genetic factors * Other chronic illness e.g. cancer, heart disease, chronic pain * Certain prescription drugs
====== Pathophysiology ====== The limbic brain regions associated with mood and depression include the hippocampus and the prefrontal cortex. Studies suggest that stress and depression are associated with atrophy and loss of neurons and glia, which contribute to the decreased size and function of these brain areas. There are two main hypotheses for the underlying mechanism of depression.

====== Treatment ====== There are several known, effective treatments for depression that vary from medicinal to psychological in nature. Despite these known methods, fewer than half of those affected in the world receive them. Barriers to effective care include a lack of resources, misdiagnosis, a lack of trained health care providers, and social stigma associated with mental disorders. ^[12] **Antidepressant:** Two of the major classes of drugs used to treat this disorder are Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin–norepinephrine reuptake inhibitors (SNRIs). The mechanisms of these drugs are described below. **SSRIs:** As the name suggests, these drugs prevent the reuptake of serotonin. They do this by inhibiting a monoamine transporter protein, SERT [Figure 3], that transports serotonin from the synaptic cleft to the presynaptic neuron. The SSRIs block the reuptake of serotonin, leading to increased concentrations of the neurotransmitter in the synaptic cleft [Figure 3] and, ultimately, to greater postsynaptic neuronal activity. SSRIs are actually a “successor” to SNRIs, as they are “selective” to serotonin, and usually do not affect other hormones in the nervous system. They are by far the most common drugs prescribed. Some examples of SSRIs include: Fluoxetine (Prozac), sertraline (Zoloft), and citalopram (Celexa). Side effects include: Sexual Dysfunction, Sleep Disorders, and headaches if treatment is suddenly stopped ^[13].
====== Conclusion ====== Overall, depression is a heterogenous, burdensome disorder that exhibits a highly variable course, an inconsistent response to treatment and an incomplete understanding of the underlying neurobiology. Its onset is gradual and it can manifest itself not only in psychological symptoms but physical symptoms as well. Future initiatives are focusing on novel treatments that can start to take effect quicker than the 4-5 weeks required for antidepressants. Research is beginning to look at the use of theta-burst stimulation which involves delivering magnetic pulses to the brain. It is a fast acting, simple, non invasive form of treatment. These magnetic pulses stimulate electric current in the brain and the hope is that repeated treatment can capitalize on the brain's neuroplasticity by changing the way in which the brain's neurons fire. However, this is a very new field and much more research needs to be done surrounding the efficacy and safety of this treatment.
====== References ====== [1] American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (DSM-5®). American Psychiatric Pub. [2] Anderson, IM, Haddad, PM, Scott, J (2012). Bipolar disorder. BMJ (Clinical research ed.) 345: e8508. doi:10.1136/bmj.e8508. PMID 23271744. [3] Belmaker, R.H. and G. Agam (2008): Major depressive disorder. N. Eng. J. Med 358: 55-68. [4] Benazzi, F. (2007). Bipolar II disorder. CNS drugs, 21(9), 727-740. [5] Canadian Mental Health Association. (2016). Postpartum Depression. Retrieved 24 January, 2016, from https://www.cmha.ca/mental_health/postpartum-depression/ [6] Drevets, W. C., & Todd, R. D. (2005). Depression, Mania, and Related Disorders. [7] Duman, R & Voleti, B. (2012). Signaling pathways underlying the pathophysiology and treatment of depression: novel mechanisms for rapid-acting agents. Trends in Neurosciences, 35(1), 47-56. [8] Fast Facts About Mental Illness. (2015). Retrieved January 26, 2016, from http://www.cmha.ca/media/fast-facts-about-mental-illness/#. [9] Hofmann SG, Asnaani A, Vonk IJJ, Sawyer AT, Fang A. The Efficacy of Cognitive Behavioral Therapy: A Review of Meta-analyses. Cognitive therapy and research. 2012;36(5):427-440. doi:10.1007/s10608-012-9476-1. [10] Jacquart D. "The Influence of Arabic Medicine in the Medieval West" in Morrison & Rashed 1996, pp. 980 [11] John M. Grohol, Psy.D. (2013). DSM-5 Changes: Depression & Depressive Disorders. Psych Central. [12] Kessler, R. C., & Bromet, E. J. (2013). The epidemiology of depression across cultures. Annual Review of Public Health, 34, 119–138. http://doi.org/10.1146/annurev-publhealth-031912-114409 [13] Marken PA, Munro JS. Selecting a Selective Serotonin Reuptake Inhibitor: Clinically Important Distinguishing Features. Primary Care Companion to The Journal of Clinical Psychiatry. 2000;2(6):205-210 [14] Radden, J (March 2003). "Is this dame melancholy? Equating today's depression and past melancholia". Philosophy, Psychiatry, & Psychology 10 (1): 37–52. doi:10.1353/ppp.2003.0081. [15] World Health Organization. (2008). The Global Burden of Disease 2004 update. Retrieved 24 January, 2016, from http://www.who.int/healthinfo/global_burden_disease/GBD_ report_2004update_full.pdf [16] World Health Organization. (2015). Depression Fact Sheet. Retrieved 24 January, 2016, from http://www.who.int/mediacentre/factsheets/fs369/en/