• Pan Zhang Tianjin Yinghua International School, Tianjin, China



Depression, Emotion, Monoamine Neurotransmitter, Antidepressant Drug, Side Effects


Depression is the most common and widespread psychiatric disorder severely affecting people’s lives at all ages. Factors from social, psychological, and biological aspects can contribute to depression, and many hypotheses are associated with biological factors involved in the aetiology of depression such as genes and neurotransmitters. As three monoamine neurotransmitters, dopamine, serotonin, and norepinephrine, are involved in the regulation of mood and motivation in emotion and reward system, the dysfunction of neurotransmitters of depressive patients can lead to their abnormal symptoms. This paper will discuss how the behaviour of these neurotransmitters has helped develop antidepressant drugs for treating depression. Although helpful, antidepressant drugs have other negative health outcomes on users such as side effects. Research on antidepressants has led to the development of new drugs such as nasal spray and skin patch which has shown to alleviate symptoms of depressive patients. Current treatments with a potential reduction of side effects are suggested on new applications for improving public health condition. Furthermore, other non-medical factors such as social engagement and physical activity are also involved in treating depression.


Aan het Rot, M., Mathew, S.J. and Charney, D.S. (2009). Neurobiological Mechanisms in Major Depressive Disorder. Canadian Medical Association Journal, 180(3), pp.305–313. Retrieved from

Admon, R. and Pizzagalli, D.A. (2015). Dysfunctional Reward Processing in Depression. Current Opinion in Psychology, 4, pp.114–118.

Alan, S., Bakir, E., Surucu, S.G., & Yildirim, E. (2018). Identify Menstruation Related Problems and Suicide. LIFE: International Journal of Health and Life-Sciences, 3(3). Retrieved from

Andrade, C. and Rao, S.K. (2010). How Antidepressant Drugs act: a Primer on Neuroplasticity as the Eventual Mediator of Antidepressant Efficacy. Indian Journal of Psychiatry, 52(4), p.378.

Asnis, G. and Henderson, M. (2014). EMSAM (deprenyl patch): How a Promising Antidepressant was underutilized [Corrigendum]. Neuropsychiatric Disease and Treatment, p.2069.

Baghai, T., Moller, H.-J. and Rupprecht, R. (2006). Recent Progress in Pharmacological and Non-Pharmacological Treatment Options of Major Depression. Current Pharmaceutical Design, 12(4), pp.503–515.

Banerjee, S. P., Kung, L. S., Riggi, S. J., & Chanda, S. K. (1977). Development of β-adrenergic receptor subsensitivity by antidepressants. Nature, 268(5619), 455.

Barnes, N. M., & Sharp, T. (1999). A review of central 5-HT receptors and their function. Neuropharmacology, 38(8), 1083-1152.

Beauchaine, T.P., Klein, D.N., Knapton, E. and Zisner, A. (2019). Anhedonia in Depression: Mechanisms, Assessment, and Therapeutics. Neurobiology of Depression, pp.31–41.

Belmaker, R.H. and Agam, G. (2008). Major Depressive Disorder. New England Journal of Medicine, 358(1), pp.55–68.

Blier, P. (2016). Neurobiology of Depression and Mechanism of Action of Depression Treatments. The Journal of Clinical Psychiatry, 77(03), pp.e319–e319.

Bönisch, H., Sitte, H. H., & Bönisch. (2016). Neurotransmitter Transporters. Springer Science+ Business Media New York.

Briere, J., Kwon, O., Semple, R.J. and Godbout, N. (2019). Recent Suicidal Ideation and Behavior in the General Population. The Journal of Nervous and Mental Disease, 207(5), pp.320–325.

Briguglio, M., Dell’Osso, B., Panzica, G., Malgaroli, A., Banfi, G., Zanaboni Dina, C., Galentino, R. and Porta, M. (2018). Dietary Neurotransmitters: a Narrative Review on Current Knowledge. Nutrients, 10(5), p.591.

Briley, M. and Chantal, M. (2011). The importance of norepinephrine in depression. Neuropsychiatric Disease and Treatment, p.9.

Cacioppo, J.T., Hughes, M.E., Waite, L.J., Hawkley, L.C. and Thisted, R.A. (2006). Loneliness as a Specific Risk Factor for Depressive symptoms: Cross-sectional and Longitudinal analyses. Psychology and Aging, 21(1), pp.140–151.

Caligiuri, M. P., & Ellwanger, J. (2000). Motor and cognitive aspects of motor retardation in depression. Journal of Affective Disorders, 57(1-3), 83–93. doi:10.1016/s0165-0327(99)00068-3

Carlson, N.R. and Birkett, M.A. (2017). Physiology of Behavior. Harlow, Essex: Pearson.

Chakrabarti, S. and Mohanakumar, K.P. (2016). Aging and Neurodegeneration: a Tangle of Models and Mechanisms. Aging and Disease, 7(2), p.111.

Chow, W., Doane, M.J., Sheehan, J., Alphs, L. and Le, H. (2019). Economic Burden among Patients with Major Depressive Disorder: An Analysis of Healthcare Resource Use, Work Productivity, and Direct and Indirect Costs by Depression Severity. AJMC. Available at:

Cipriani, A., Zhou, X., Del Giovane, C., Hetrick, S. E., Qin, B., Whittington, C., … Xie, P. (2016, August 27). Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis. Retrieved from

Comijs, H.C., van Exel, E., van der Mast, R.C., Paauw, A., Oude Voshaar, R. and Stek, M.L. (2013). Childhood Abuse in late-life Depression. Journal of Affective Disorders, 147(1–3), pp.241–246.

Davies, F.R. and Morris, B.J. (2006). Molecular Biology of the Neuron. Oxford ; New York: Oxford University Press.

Dean, J. and Keshavan, M. (2017). The Neurobiology of depression: an Integrated View. Asian Journal of Psychiatry, 27, pp.101–111.

Der-Avakian, A. and Markou, A. (2012). The Neurobiology of Anhedonia and Other reward-related Deficits. Trends in Neurosciences, 35(1), pp.68–77.

Elias, L. J, & Saucier, D. M. (2005). Neuropsychology: Clinical and Experimental Foundations. Boston: Pearson

Elliott, W. and Chan, J. (2019). Esketamine Nasal Spray (Spravato) CIII. Retrieved from (2017). Major Depressive Disorder Treatment | EMSAM®. Retrieved from [Accessed 20 Jul. 2019]

Fakhoury, M. (2015). Revisiting the Serotonin Hypothesis: Implications for Major Depressive Disorders. Molecular Neurobiology, 53(5), 2778–2786.

Firth, J., Marx, W., Dash, S., Carney, R., Teasdale, S.B., Solmi, M., Stubbs, B., Schuch, F.B., Carvalho, A.F., Jacka, F. and Sarris, J. (2019). The Effects of Dietary Improvement on Symptoms of Depression and Anxiety. Psychosomatic Medicine, 81(3), pp.265–280.

Fischer, A.G. and Ullsperger, M. (2017). An Update on the Role of Serotonin and its Interplay with Dopamine for Reward. Frontiers in Human Neuroscience, 11.

Fon, E. A., & Edwards, R. H. (2001). Molecular mechanisms of neurotransmitter release. Muscle & Nerve: Official Journal of the American Association of Electrodiagnostic Medicine, 24(5), 581-601.

Foong, A.-L., Grindrod, K.A., Patel, T. and Kellar, J. (2018). Demystifying serotonin syndrome (or serotonin toxicity). Canadian family physician Medecin de famille canadien, 64(10), pp.720–727. Retrieved from

Frank, C. (2008). Recognition and treatment of serotonin syndrome. Canadian family physician Medecin de famille canadien, 54(7), pp.988–92. Retrieved from

Freeman, A., Tyrovolas, S., Koyanagi, A., Chatterji, S., Leonardi, M., Ayuso-Mateos, J.L., Tobiasz-Adamczyk, B., Koskinen, S., Rummel-Kluge, C. and Haro, J.M. (2016). The role of socio-economic status in depression: results from the COURAGE (aging survey in Europe). BMC Public Health, 16(1).

García-Cazorla, À., & Artuch, R. (2015). Neurotransmitter Disorders. Rosenberg’s Molecular and Genetic Basis of Neurological and Psychiatric Disease, 703–712.

Gerke, J., Koenig, A.M., Conrad, D., Doyen-Waldecker, C., Pauly, M., Gündel, H., Wilker, S. and Kolassa, I.-T. (2018). Childhood maltreatment as risk factor for lifetime depression: The role of different types of experiences and sensitive periods. Mental Health & Prevention, 10, pp.56–65.

Goldstein-Piekarski, A. N., & Williams, L. M. (2019). A Neural Circuit-Based Model for Depression Anchored in a Synthesis of Insights From Functional Neuroimaging. Neurobiology of Depression, 241–256.

Hamon, M. and Blier, P. (2013). Monoamine neurocircuitry in depression and strategies for new treatments. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 45, pp.54–63.

Harmer, C. J., Duman, R. S., & Cowen, P. J. (2017). How do antidepressants work? New perspectives for refining future treatment approaches. The Lancet Psychiatry, 4(5), 409-418.

Hasler, G. (2010). Pathophysiology of depression: do we have any solid evidence of interest to clinicians? World Psychiatry: Official Journal of the World Psychiatric Association (WPA),

Howard, D.M., Adams, M.J., Clarke, T.-K., Hafferty, J.D., Gibson, J., Shirali, M., Coleman, J.R.I., Hagenaars, S.P., Ward, J., Wigmore, E.M., Alloza, C., Shen, X., Barbu, M.C., Xu, E.Y., Whalley, H.C., Marioni, R.E., Porteous, D.J., Davies, G., Deary, I.J., Hemani, G., Berger, K., Teismann, H., Rawal, R., Arolt, V., Baune, B.T., Dannlowski, U., Domschke, K., Tian, C., Hinds, D.A., Trzaskowski, M., Byrne, E.M., Ripke, S., Smith, D.J., Sullivan, P.F., Wray, N.R., Breen, G., Lewis, C.M. and McIntosh, A.M. (2019). Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions. Nature Neuroscience, 22(3), pp.343–352.

Isbister, G.K., Bowe, S.J., Dawson, A. and Whyte, I.M. (2004). Relative Toxicity of Selective Serotonin Reuptake Inhibitors (SSRIs) in Overdose. Journal of Toxicology: Clinical Toxicology, 42(3), pp.277–285.

Jaso, B., Niciu, M., Iadarola, N., Lally, N., Richards, E., Park, M., Ballard, E., Nugent, A., Machado-Vieira, R. and Zarate, C. (2016). Therapeutic Modulation of Glutamate Receptors in Major Depressive Disorder. Current Neuropharmacology, 15(1), pp.57–70.

Jennings, L. (2018). Antidepressants. Clinical Psychopharmacology for Neurologists, pp.45–71.

Karg, K., Burmeister, M., Shedden, K. and Sen, S. (2011). The Serotonin Transporter Promoter Variant (5-HTTLPR), Stress, and Depression Meta-analysis Revisited. Archives of General Psychiatry, 68(5), p.444. ttps://

Kim, J., Farchione, T., Potter, A., Chen, Q. and Temple, R. (2019). Esketamine for Treatment-Resistant Depression - First FDA-Approved Antidepressant in a New Class. New England Journal of Medicine, 381(1), pp.1–4.

Krishnan, K. (2009). Monoamine Oxidase Inhibitors. The American Psychiatric Publishing Textbook of Psychopharmacology.

Lam, R.W., Kennedy, S.H., McIntyre, R.S. and Khullar, A. (2014). Cognitive Dysfunction in Major Depressive Disorder: Effects on Psychosocial Functioning and Implications for Treatment. The Canadian Journal of Psychiatry, 59(12), pp.649–654.

Lin, T.-W. and Kuo, Y.-M. (2013). Exercise Benefits Brain Function: the Monoamine Connection. Brain Sciences, 3(4), pp.39–53.

Lodish, H.F. and National Library of Medicine (2000). Molecular Cell Biology. 4th ed. New York: W.H. Freeman; Basingstoke.

López-Muñoz, F., Álamo, C., Juckel, G. and Assion, H.-J. (2007). Half a Century of Antidepressant Drugs. Journal of Clinical Psychopharmacology, 27(6), pp.555–559.

Mathew, B., E Mathew, G., Suresh, J., Ucar, G., Sasidharan, R., Anbazhagan, S., ... & Jayaprakash, V. (2016). Monoamine oxidase inhibitors: Perspective design for the treatment of depression and neurological disorders. Current Enzyme Inhibition, 12(2), 115-122.

MELTZER, H.Y. (1990). Role of Serotonin in Depression. Annals of the New York Academy of Sciences, 600(1 The Neurophar), pp.486–499.

Naranjo, C.A., Tremblay, L.K. and Busto, U.E. (2001). The role of the brain reward system in depression. Progress in neuro-psychopharmacology & biological psychiatry, 25(4), pp.781–823. Available at:

National Institute of Mental Health (2019). Depression. Retrieved from

Nautiyal, K.M., Tritschler, L., Ahmari, S.E., David, D.J., Gardier, A.M. and Hen, R. (2016). A Lack of Serotonin 1B Autoreceptors Results in Decreased Anxiety and Depression-Related Behaviors. Neuropsychopharmacology, 41(12), pp.2941–2950.

Neve, K. (Ed.). (2009). The dopamine receptors. Springer Science & Business Media.

Noerhidajati, E.,Makarim, F. R.,& Albab, A. U. (2018). Stress, Anxiety, and Depression Relationship among Undergraduate Medical Students and Their Final Exam Mark. LIFE: International Journal of Health and Life-Sciences, 4(3), 26-37

Nordqvist, C. (2018). Antidepressants: Types, side effects, uses, and effectiveness. Medical News Today. Available at:

Paykel, E.S. (2008). Basic concepts of depression. Dialogues in clinical neuroscience, 10(3), pp.279–89. Retrieved from

Pizzagalli, D. A., Holmes, A. J., Dillon, D. G., Goetz, E. L., Birk, J. L., Bogdan, R., … Fava, M. (2009). Reduced Caudate and Nucleus Accumbens Response to Rewards in Unmedicated Individuals with Major Depressive Disorder. American Journal of Psychiatry, 166(6), 702–710.

Popova, V., Daly, E.J., Trivedi, M., Cooper, K., Lane, R., Lim, P., Mazzucco, C., Hough, D., Thase, M.E., Shelton, R.C., Molero, P., Vieta, E., Bajbouj, M., Manji, H., Drevets, W.C. and Singh, J.B. (2019). Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined with a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: a Randomized Double-Blind Active-Controlled Study. American Journal of Psychiatry, 176(6), pp.428–438.

Ruhé, H.G., Mason, N.S. and Schene, A.H. (2007). Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies. Molecular Psychiatry, 12(4), pp.331–359.

Salamone, J.D. and Correa, M. (2012). The Mysterious Motivational Functions of Mesolimbic Dopamine. Neuron, 76(3), pp.470–485.

Santini, Z.I., Koyanagi, A., Tyrovolas, S., Mason, C. and Haro, J.M. (2015). The Association between Social Relationships and depression: a Systematic Review. Journal of Affective Disorders, 175, pp.53–65.

Sarris, J., O’Neil, A., Coulson, C.E., Schweitzer, I. and Berk, M. (2014). Lifestyle Medicine for Depression. BMC Psychiatry, 14(1).

Schotte, C.K.W., Van Den Bossche, B., De Doncker, D., Claes, S. and Cosyns, P. (2006). A biopsychosocial model as a guide for psychoeducation and treatment of depression. Depression and Anxiety, 23(5), pp.312–324.

Shadrina, M., Bondarenko, E.A. and Slominsky, P.A. (2018). Genetics Factors in Major Depression Disease. Frontiers in Psychiatry, 9.

Shankman, S.A., Gorka, S.M., Katz, A.C., Klein, D.N., Markowitz, J.C., Arnow, B.A., Manber, R., Rothbaum, B.O., Thase, M.E., Schatzberg, A.F., Keller, M.B., Trivedi, M.H. and Kocsis, J.H. (2017). Side Effects to Antidepressant Treatment in Patients with Depression and Comorbid Panic Disorder. The Journal of Clinical Psychiatry, 78(04), pp.433–440.

Smith, M. (2019, November 5). Depression Symptoms and Warning Signs. Retrieved from

Spravato® (esketamine). (2019). Starting SpravatoTM. Retrieved from

Steven D., H. (2011). Cognitive and Behavior Therapy in the Treatment and Prevention of Depression. Depression and Anxiety, 28(4), pp.263–266.

Tank, A.W. and Lee Wong, D. (2015). Peripheral and central effects of circulating catecholamines. Comprehensive Physiology, 5(1), pp.1–15. Retrieved from

Timmermans, P.B.M.W.M. and Thoolen, M.J.M.C. (1987). Autoreceptors in the Central Nervous System. Medicinal Research Reviews, 7(3), pp.307–332.

U.S. Food & Drug Administration (2019). Janssen Presentations for the February 12, 2019 Joint Meeting of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee | FDA. Retrieved from

Wacker, J., Dillon, D.G. and Pizzagalli, D.A. (2009). The role of the nucleus accumbens and rostral anterior cingulate cortex in anhedonia: Integration of resting EEG, fMRI, and volumetric techniques. NeuroImage, 46(1), pp.327–337.

Weilburg, J.B. (2004). An overview of SSRI and SNRI therapies for depression. Managed Care (Langhorne, Pa.), 13(6 Suppl Depression), pp.25–33. Retrieved from (2006). File:SynapseIllustration2.png - Wikimedia Commons. Retrieved from (2015). File:Dopaminergic pathways.svg - Wikimedia Commons. Retrieved from

World Health Organisation (2018). Depression. Retrieved from

Wurtman, R. J., Hefti, F., & Melamed, E. (1980). Precursor control of neurotransmitter synthesis. Pharmacological Reviews, 32(4), 315-335.

Zhou, X., Cipriani, A., Furukawa, T.A., Cuijpers, P., Zhang, Y., Hetrick, S.E., Pu, J., Yuan, S., Del Giovane, C. and Xie, P. (2018). Comparative Efficacy and Tolerability of new-generation Antidepressants for Major Depressive Disorder in Children and adolescents: Protocol of an Individual Patient Data meta-analysis. BMJ Open, 8(1), p.e018357.




How to Cite

Zhang, P. (2019). HOW CAN WE USE NEUROTRANSMITTERS IN EMOTION AND REWARD SYSTEM TO STUDY DEPRESSION?. LIFE: International Journal of Health and Life-Sciences, 5(3), 41–62.