Abstract
Hypotheses about the pathophysiology of depression have evolved over time. This chapter covers the most important findings in this regard. First, the classical monoamine hypothesis posited that depression is caused by an alteration in levels of one or more of the monoamines: serotonin, norepinephrine, and dopamine. More recently, research on the glutamatergic system has aroused great interest by examining the mechanism of action of ketamine, an N-methyl-D-aspartic acid (NMDA) receptor antagonist. Likewise, stressful life events can precipitate depressive episodes in vulnerable individuals. Abnormalities in the HPA axis have been associated with a hyperactive response to stress in depressed patients (the diathesis-stress model). Increased levels of inflammatory markers have been found in patients with depression and anti-inflammatory agents are being studied as antidepressants. Reduced production of BDNF and neuroplasticity can lead to depression. These pathophysiological mechanisms are reciprocally connected with each other. Major Depression is a heterogeneous entity and a variety of biological mechanisms may be involved.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Amidfar, M., Woelfer, M., Réus, G. Z., Quevedo, J., Walter, M., & Kim, Y. K. (2019). The role of NMDA receptor in neurobiology and treatment of major depressive disorder: Evidence from translational research. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 94(Aug 30), 109668. https://doi.org/10.1016/j.pnpbp.2019.109668
Bao, A. M., & Swaab, D. F. (2018). The human hypothalamus in mood disorders: The HPA axis in the center. IBRO Reports, 6(Dec 14), 45–53. https://doi.org/10.1016/j.ibror.2018.11.008
Bousman, C. A., Forbes, M., Jayaram, M., Eyre, H., Reynolds, C. F., Berk, M., Hopwood, M., & Ng, C. (2017). Antidepressant prescribing in the precision medicine era: A prescriber’s primer on pharmacogenetics tools. BMC Psychiatry, 17(1), 60. https://doi.org/10.1186/s12888-017-1230-5
Casey, B. J., Craddock, N., Cuthbert, B. N., Hyman, S. E., Lee, F. S., & Ressler, K. J. (2013). DSM-5 and RDoC: Progress in psychiatry research? Nature Reviews Neuroscience. Nov, 14(11), 810–814. https://doi.org/10.1038/nrn3621
Dantzer, R., O’Connor, J. C., Freund, G., Johnson, R. W., & Kelley, K. W. (2007). From information to sickness and depression: When the immune system subjugates the brain. Nature Reviews. Neuroscience, 9, 45–56.
Dean, J., & Keshavan, M. (2017). The neurobiology of depression: An integrated view. Asian Journal of Psychiatry. Jun, 27, 101–111. https://doi.org/10.1016/j.ajp.2017.01.025
Ding, Y., & Dai, J. (2019). Advance in stress for depressive disorder. Advances in Experimental Medicine and Biology, 1180, 147–178. https://doi.org/10.1007/978-981-32-9271-0_8
Duman, R. S. (2009). Neuronal damage and protection in the pathophysiology and treatment of psychiatric illness: Stress and depression. Dialogues in Clinical Neuroscience, 11(3), 239–255.
Duman, R. S., Shinohara, R., Fogaça, M. V., & Hare, B. (2019). Neurobiology of rapid-acting antidepressants: Convergent effects on GluA1-synaptic function. Molecular Psychiatry, 2019 Dec, 24(12), 1816–1832. https://doi.org/10.1038/s41380-019-0400-x
Ferrari, F., & Villa, R. F. (2017). The neurobiology of depression: An integrated overview from biological theories to clinical evidence. Molecular Neurobiology. Sep, 54(7), 4847–4865. https://doi.org/10.1007/s12035-016-0032-y
Gold, P. W. (2015). The organization of the stress system and its dysregulation in depressive illness. Molecular Psychiatry, Feb, 20(1), 32–47. https://doi.org/10.1038/mp.2014.163
Gould, E., Tanapat, P., Rydel, T., & Hastings, N. (2000). Regulation of hippocampal neurogenesis in adulthood. Biological Psychiatry, 48, 715–720.
Iadarola, N. D., Niciu, M. J., Richards, E. M., Vande Voort, J. L., Ballard, E. D., Lundin, N. B., Nugent, A. C., Machado-Vieira, R., & Zarate, C. A., Jr. (2015). Ketamine and other N-methyl-D-aspartate receptor antagonists in the treatment of depression: A perspective review. Therapeutic Advances in Chronic Disease. May, 6(3), 97–114. https://doi.org/10.1177/2040622315579059
Jesulola, E., Micalos, P., & Baguley, I. J. (2018). Understanding the pathophysiology of depression: From monoamines to the neurogenesis hypothesis model - are we there yet? Behavioural Brain Research, 341(Apr 2), 79–90. https://doi.org/10.1016/j.bbr.2017.12.025
Kanter, J. W., Busch, A. M., Weeks, C. E., & Landes, S. J. (2008). The nature of clinical depression: Symptoms, syndromes, and behavior analysis. Behavior Analyst, 31(1), 1–21.
Lamers, F., Vogelzangs, N., Merikangas, K. R., de Jonge, P., Beekman, A. T., & Penninx, B. W. (2013). Evidence for a differential role of HPA-axis function, inflammation and metabolic syndrome in melancholic versus atypical depression. Molecular Psychiatry. Jun, 18(6), 692–699. https://doi.org/10.1038/mp.2012.144
Leonard, B. E. (2001). Stress, norepinephrine and depression. Journal of Psychiatry & Neuroscience, 26(Suppl), S11.
Liang, S., Wu, X., Hu, X., Wang, T., & Jin, F. (2018). Recognizing depression from the microbiota-gut-brain axis. International Journal of Molecular Sciences, 19(6). https://doi.org/10.3390/ijms19061592
Liu, C. H., Zhang, G. Z., Li, B., Li, M., Woelfer, M., Walter, M., & Wang, L. (2019). Role of inflammation in depression relapse. Journal of Neuroinflammation. Apr 17, 16(1), 90. https://doi.org/10.1186/s12974-019-1475-7
Machado-Vieira, R., Salvadore, G., Diaz Granados, N., Ibrahim, L., Latov, D., Wheeler-Castillo, C., Baumann, J., Henter, I. D., & Zarate, C. A. (2010). New therapeutic targets for mood disorders. The Scientific World Journal, 10, 713–726. https://doi.org/10.1100/tsw.2010.65
Miller, H. L., Delgado, P. L., Salomon, R. M., Berman, R., Krystal, J. H., Heninger, G. R., et al. (1996). Clinical and biochemical effects of catecholamine depletion on antidepressant-induced remission of depression. Archives of General Psychiatry, 53, 117–128.
Monteleone, P., Serritella, C., Martiadis, V., & Maj, M. (2008). Decreased levels of serum brain-derived neurotrophic factor in both depressed and euthymic patients with unipolar depression and in euthymic patients with bipolar I and II disorders. Bipolar Disorders, 10(1), 95–100. https://doi.org/10.1111/j.1399-5618.2008.00459.x
Pitsillou, E., Bresnehan, S. M., Kagarakis, E. A., Wijoyo, S. J., Liang, J., Hung, A., & Karagiannis, T. C. (2020). The cellular and molecular basis of major depressive disorder: Towards a unified model for understanding clinical depression. Molecular Biology Reports. Jan, 47(1), 753–770. https://doi.org/10.1007/s11033-019-05129-3
Raison, C. L., Capuron, L., & Miller, A. (2006). Cytokines sing the blues: Inflammation and the pathogenesis of depression. Trends in Immunology, 27, 24–31.
Ruhé, H. G., Mason, N. S., & 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, 331–359.
Sanacora, G., Treccani, G., & Popoli, M. (2012). Towards a glutamate hypothesis of depression: An emerging frontier of neuropsychopharmacology for mood disorders. Neuropharmacology, 62, 63–77. https://doi.org/10.1016/j.neuropharm.2011.07.036
Steptoe, A., Hamer, M., & Chida, Y. (2007). The effects of acute psychological stress on circulating inflammatory factors in humans: A review and meta-analysis. Brain, Behavior, and Immunity, 21(7), 901–912.
Villas Boas, G. R., Boerngen de Lacerda, R., Paes, M. M., Gubert, P., Almeida, W. L. D. C., Rescia, V. C., De Carvalho, P. M. G., De Carvalho, A. A. V., & Oesterreich, S. A. (2019). Molecular aspects of depression: A review from neurobiology to treatment. European Journal of Pharmacology. May 15, 851, 99–121. https://doi.org/10.1016/j.ejphar.2019.02.024
Willner, P., Scheel-Krüger, J., & Belzung, C. (2013). The neurobiology of depression and antidepressant action. Neuroscience and Biobehavioral Reviews, 37(10 Pt 1), 2331–2371. Dec. https://doi.org/10.1016/j.neubiorev.2012.12.007
Woelfer, M., Kasties, V., Kahlfuss, S., & Walter, M. (2019). The role of depressive subtypes within the neuroinflammation hypothesis of major depressive disorder. Neuroscience, 403, 93–110. https://doi.org/10.1016/j.neuroscience.2018.03.034. Apr 1.
Wohleb, E. S., Franklin, T., Iwata, M., & Duman, R. S. (2016). Integrating neuroimmune systems in the neurobiology of depression. Nature Reviews Neuroscience. Aug, 17(8), 497–511. https://doi.org/10.1038/nrn.2016.69
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Silva, H. (2021). Neurobiology of Depression. In: Jiménez, J.P., Botto, A., Fonagy, P. (eds) Etiopathogenic Theories and Models in Depression. Depression and Personality. Springer, Cham. https://doi.org/10.1007/978-3-030-77329-8_8
Download citation
DOI: https://doi.org/10.1007/978-3-030-77329-8_8
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-77328-1
Online ISBN: 978-3-030-77329-8
eBook Packages: Behavioral Science and PsychologyBehavioral Science and Psychology (R0)