Neuroprogression and depression: a literature review




Depressive disorder; Neuropsychiatry; Biological psychiatry; Neurodegenerative diseases.


This review aims to show evidence of possible neuroprotective agents, and to identify new avenues for possible intervention, in search of neuroprotection in patients affected by depression. It is a narrative review that used PubMed, Lilacs, Scielo, Cochrane and Latindex as a database, in the period between 2015 to 2020, resulting in 1009 articles and 19 different articles using selection criteria. Neuropsychiatric disorders, including depression, often exhibit a neuroprogressive course from the prodrome to chronicity. There are a variety of agents exhibiting the ability to attenuate biological mechanisms associated with neuroprogression. Signs of evidence of clinical neuroprotection are evident when evaluating studies by different authors. The adjuvant use of multiple drug agents may present a viable path for the clinical realization of neuroprotection. Definitive prospective studies on neuroprotection with multimodal assessment are needed.

Author Biographies

Vinicius Oliveira de Andrade, Centro de Atenção Integrada à Saúde Mental

Médico Residente de Psiquiatria.

Matheus Gonçalves Chaves Mello, Universidade para Desenvolvimento da Região do Pantanal (anhanguera-UNIDERP)

Acadêmico do quinto ano de Medicina.

José Carlos Souza, Universidade Estadual de Mato Grosso do Sul

Médico psiquiatra, PhD em saúde mental.


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Baxter, P. S., & Hardingham, G. E. (2016). Adaptive regulation of the brain’s antioxidant defences by neurons and astrocytes. Free Radical Biology and Medicine, 100, 147-152. DOI: 10.1016/j.freeradbiomed.2016.06.027

Bell, K. F. S., Al-Mubarak, B., Martel, M.-A., McKay, S., Wheelan, N., Hasel, P.,Márkus, N.M, Baxter, P., Deighton, R, F., Serio, A.,Bilican, B., Chowdhry, S., Meakin, P.J., Ashford, M. L. J., Wyllie, D. J. A., Scannevin, R. H., Chandran, S., Hayes, J. D., & Hardingham, G. E. (2015). Neuronal development is promoted by weakened intrinsic antioxidant defences due to epigenetic repression of Nrf2. Nature Communications, 6, 1-15. DOI:10.1038/ncomms8066

Ignácio Z. M., Réus, G. Z., Abelaira, H. M., Moura, A. B., Souza, T. G., Matos, D., Goldin, M. P, Mathias, K., Garbossa, L., Petronilho, F., Quevedo, J. (2017). Acute and chronic treatment with quetiapine induces antidepressant-like behavior and exerts antioxidant effects in the rat brain. Metabolic Brain Disease, 32(4), 1195-1208. DOI: 10.1007/s11011-017-0028-y

Krivoy A., Hochman, E., Sendt, K.-V., Hollander, S., Vilner, Y., Selakovic, Weizman, A., M.Taler, M. (2018). Association between serum levels of glutamate and neurotrophic factors and response to clozapine treatment. Schizophrenia Research, 192, 226-231. DOI: 10.1016/j.schres.2017.05.040

Leonard B. E., & Wegener G. (2019). Inflammantion, insulin resistance and neuroprogression in depression. Acta Neuropsychiatrica, 32(1) 1-19. Acesso em 8 setembro, em 10.1017/neu.2019.17. DOI: 10.1017/neu.2019.17

Meine, I. R., Cheiram, M. C., Jaeger, F. P. (2019). Depressão e suicídio: o adolescente frente a fatores de risco socioculturais. Research, Society and Development; 8(12), 1-15. Acesso em 8 setembro. DOI: 10.33448/rsd-v8i12.1882

Mendoza, C., Perez-Urrutia, N., Alvarez-Ricartes, N., Barreto, G. E., Pérez-Ordás, R., Iarkov, A., & Echeverria, V. (2018). Cotinine plus krill oil decreased depressive behavior, and increased astrocytes survival in the hippocampus of mice subjected to restraint stress. Frontiers in Neuroscience, 12, 1-11. DOI: 10.3389/fnins.2018.00952

Morris, G., Puri, B. K., Walker, A. J., Maes, M., Carvalho, A. F., Bortolasci, C. C.,Walder, K., Berk, M. (2019). Shared pathways for neuroprogression and somatoprogression in neuropsychiatric disorders. Neuroscience and Biobehavioral Reviews, 107, 862-882. DOI: 10.1016/j.neubiorev.2019.09.025

Ogyu, K., Kubo, K., Noda, Y., Iwata, Y., Tsugawa, S., Omura, Y., Wada, M., Tarumi, R., Graff-Guerrero, A., Mimura, M. & Nakajima, S. (2018). Kynurenine pathway in depression: A systematic review and meta-analysis. Neuroscience & Biobehavioral Reviews, 90, 16-25. DOI: 10.1016/j.neubiorev.2018.03.023

Oliveira, E. N., Carvalho, A. G., Moreira, R. M. M., Melo, B. T., Lima, G. F., & Ximenes Neto, F. R. G. (2020). Interfaces entre o uso abusivo de substâncias psicoativas, presença de comorbidades e risco de suicídio. Research, Society and Development, 9(7), 1-18. DOI: 10.33448/rsd-v9i7.4172

Poletti, S., Aggio, V., Hoogenboezem, T. A., Ambrée, O., Wit, H., Wijkhuijs, Locatelli, C., Colombo, C., Arolt, V., Drexhage, H. A., & Benedetti, F.. (2017). Brain-derived Neurotrophic Factor (BDNF) and gray matter volume in bipolar disorder. European Psychiatry, 40, 33-37. DOI: 10.1016/j.eurpsy.2016.06.008

Robertson, O. D., Coronado, N. G., Sethi, R., Berk, M. & Dodd, S. (2019). Putative neuroprotective pharmacotherapies to target the staged progression of mental illness. Early Intervention In Psychiatry, 13(5), 1032-1049. DOI: 10.1111/eip.12775

Ruiz, N. A. L., Ángel, D. S., Olguín, H. J. & Silva, M. L. (2018). Neuroprogression: the hidden mechanism of depression. Neuropsychiatric Disease and Treatment, 14, 2837-2845. DOI: 10.2147/NDT.S177973

Savitz, J., Drevets, W. C., Wurfel, B. E, Ford, B. N., Bellgowan, P. S. F, Victor, T. A., Bodurka, J., Teague, T. K., & Dantzer, R. (2015). Reduction of kynurenic acid Victor to quinolinic acid ratio in both the depressed and remitted phases of major depressive disorder. Brain, Behavior, and Immunity, 46, 55-59. DOI: 10.1016/j.bbi.2015.02.007

Schmidt, M., Brandwein, C., Luoni, A., Sandrini, P., Calzoni, T., Deuschle, M., Cirulli, F. Riva M. A., & Gass, P. (2016). Morc1 knockout evokes a depression-like phenotype in mice. Behavioural Brain Research, 296, 7-14. DOI: 10.1016/j.bbr.2015.08.005

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How to Cite

Andrade, V. O. de, Mello, M. G. C., & Souza, J. C. . (2020). Neuroprogression and depression: a literature review. Research, Society and Development, 9(9), e191996740.



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