Serotonin and Depression for Depressive Disorder - MyAssignmenthelp

Question: Discuss about theSerotonin and Depression for Depressive Disorder. Answer: The essay aims to evaluate the role of dysregulation of serotonin, a neurotransmitter in the disordered physiological processes associated with major depressive disorder (MDD). Several lines of evidences will be discussed in order to establish the presence or absence of the mentioned correlation between the two variables. The American Psychiatric Association defines Depression as a common and serious mental disorder which has negative impacts on how the patient feels; think and acts ("define depression - Google Search", 2017). Globally more than 300 million people worldwide suffer from depression ("Depression", 2017). Depression can be long-lasting and recurrent and in severe cases may lead to suicide. Presently it can be reliably diagnosed and treated with medical and psychological interventions. Some of the symptoms include lack of interest and pleasure in daily activities, gain or loss of weight, insomnia or excessive sleeping, loss of energy, felling of worthlessness and guilt an d suicidal thoughts. Serotonin (5-Hydroxytryptamine, 5-HT) is an inhibitory neurotransmitter produced in the brain and intestines. It is mostly found in the Central Nervous System, the gastrointestinal Tract and the Blood platelets, having active influence on smooth muscle contraction, several metabolic processes and on the mood, happiness and wellbeing of a person. Many studies have provided evidences supporting several theories on the causal factors of depression. Serotonin theory of depression is one of the most widely studied among them and states that there is a net reduction serotonin transmission in depressive illness (Kerr, 2011). Several treatment approaches and biological bases in support of and against this theory will be discussed in the following sections of the essay. Tryptophan is the precursor amino acid of serotonin. In a study tryptophan intake was reduced by dietary manipulation in patients who have recovered from depression and is mediation free during the intervention. 5-hydroxyindoleacetic acid is a metabolite of serotonin; reduced concentration of the compound in the cerebrospinal fluid of brain and spinal cord has been associated with suicides and recovered patients with already low levels of serotonin were susceptible to dietary depletion of tryptophan and showed relapse of depressive symptoms (Leyton, Young Benkelfat, 1997). However, in normal patients dietary depletion of tryptophan showed no effect. Hence, impeding the metabolic pathway of serotonin cannot be solely accosted for the causal factor of depression in healthy patients. Selective serotonin reuptake inhibitors (SSRIs) are a group of widely used drugs used to treat depressive disorders. Treatment with SSRIs is proved to up regulate certain transcription factors and proteins such as cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) that play an important role in neural plasticity (Harmer, Goodwi Cowen, 2009). Neuronal plasticity is a fundamental neural process where the brain acquires information and makes adaptive changes in future settings. It influences the occurrence of mood disorders and anxiety in various ways. The reduction of depressive symptoms after SSRI treatment shave been attributed to a secondary influence of neural plasticity rather than a direct effect of increased serotonin levels. Serotonergic hallucinogens such as (+)-lysergic acid diethylamide, psilocybin, and mescaline; although derived from different chemical families have a common mode of action through 5-HT2Areceptor producing increased levels of serotonin (Halberstadt, 2015). One study evaluated the efficacy of such hallucinogens in cancer patients who suffered from mood disorders and anxiety. One of the drugs, psilocybin produced significant results. Patients treated with the hallucinogen reported significant reduction in clinician-rated as well as self-rated depression, anxiety and mood disorders. They experienced an improved quality of life, meaning of life, a better perception regarding death acceptance and increased optimism. The rate of symptom remission was 65% and 57% and over 80% of the participants reported increased wellbeing and life satisfaction (Griffiths et al., 2016). This provides substantial evidence that increased serotonin levels can have beneficial effects in patients with mood diso rders and anxiety. Another mode of study is to assess the biomarkers of major depressive disorders and gain insight regarding the probable causal factors from the same. Studies have revealed that 5-HT2A and 5-HT3A serotonin receptors are important components behind the incidence of major depression. One study measured the relative expression of mRNA of these receptors in peripheral blood mononuclear cells (PBMCs) of patients with major depressive disorder (MDD) to establish a relationship between the disorder and serotonin agonists. Relative 5-HTR2A mRNA expression was found to be significantly higher in the patients whereas levels of 5-HTR3A mRNA expression in the patients did not showed any significant difference when compared to healthy individuals (Amidfar et al., 2017). Hence study provides further evidence of direct relationship between serotonin activity and occurrence of MDD irrespective of treatment procedures. Another study measured a serotonin receptor subtype in certain immune cells of the immune system in major depressive disorder patients. The authors determined the presence of 5-HT1A receptors in lymphocytes of peripheral blood obtained from depressed patients and controls. It was observed that the ratio serotonin/5-hydroxyindoleacetic acid was increased in the patients but dopamine levels remained unchanged. Although receptor levels remained unchanged, coupling with different transduction mechanisms may be related to alteration in 5-HT turnover rate. Indoleamine-2,3-dioxygenase (IDO) is an enzyme that participated in the metabolism of tryptophan and reduces the serotonin levels. The role of this enzyme in diabetes related depression has been studied by Dias et al., (2015). They treated rats with several drugs and evaluated the cytokines, serotonin and norepinephrine levels of diabetic and normogycemic rats. The authors found that activation of Indoleamine-2,3-dioxygenase caused neuroinflammation of hippocampus with consequent decrease in 5-HT levels in diabetic rats can be the link between diabetes and depression in the study group. This study provides yet another evidence in support of low serotonin levels occurring concurrently with the incidence of depression. Some studies have looked into the genetic predisposition connection serotonin and depression. One such study investigated the combined effects of gene-linked polymorphic region (5-HTTLPR) of serotonin transporter and environmental stress on serotonin transporter (SERT) mRNA levels in peripheral blood cells. Participants that were exposed to both the risk factors produced significant resulting such that 32.8% (maternal prenatal stress) and 56.3% (child maltreatment) reduced levels of SERT mRNA were observed as compared to the control group (Wankerl et al., 2014). Reduced mRNA expression may be linked with serotonergic malfunctioning and pose incre4sed disease vulnerability. Thus environmental and genetic factors can play an important role in serotonin functioning and subsequently incidence of depressive disorders. It can be concluded the correlation between serotonin and major depressive disorder have been studied widely for many years now. There are ample evidences that establish a positive and signification relation between lowered levels of the neurotransmitter and occurrence of the disorder. Studies have explored the correlation by evaluating treatment methods that intervene with the cellular pathways of the action of serotonin, neural and biological causes, and genetic predisposition and so on. Our review of some of those studies elucidate that serotonin and depression does have a clear correlation among them, yet he nature and directness of the link is yet to be discovered. The apparent decrease of depression due to serotonin agonist treatments may be secondary effects of other physiological changes. Thus, further evidence regarding the relationship is required to establish any concrete conclusion. References Amidfar, M., Kim, Y. K., Colic, L., Arbabi, M., Mobaraki, G., Hassanzadeh, G., Walter, M. (2017). Increased levels of 5HT2A receptor mRNA expression in peripheral blood mononuclear cells of patients with major depression: correlations with severity and duration of illness.Nordic Journal of Psychiatry,71(4), 282-288. define depression - Google Search. (2017).Google.co.in. Retrieved 24 May 2017, from https://www.google.co.in/search?q=define+depressionoq=define+depressionaqs=chrome..69i57j0l5.3069j0j7sourceid=chromeie=UTF-8 Depression. (2017).World Health Organization. Retrieved 24 May 2017, from https://www.who.int/mediacentre/factsheets/fs369/en/ Dias, I. C. S., Carabelli, B., Ishii, D. K., Morais, H., Carvalho, M. C., de Souza, L. E. R., ... 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A cognitive neuropsychological model of antidepressant drug action.The British Journal of Psychiatry,195(2), 102-108. Kerr, C. W. (2011). The Serotonin Theory of Depression.Jefferson Journal of Psychiatry,12(1), 4. Leyton, M., Young, S. N., Benkelfat, C. (1997). Relapse of depression after rapid depletion of tryptophan.The Lancet,349(9068), 1840-1841. Wankerl, M., Miller, R., Kirschbaum, C., Hennig, J., Stalder, T., Alexander, N. (2014). Effects of genetic and early environmental risk factors for depression on serotonin transporter expression and methylation profiles.Translational psychiatry,4(6), e402.