Glutamatergic hypothesis and hypofunction of NMDA receptors in the pathophysiology of schizophrenia
DOI:
https://doi.org/10.33448/rsd-v11i12.34893Keywords:
Schizophrenia; Glutamate; NMDA; Pathophysiology.Abstract
Introduction: Schizophrenia is a severe, episodic and persistent disease with a characteristic time course in which acute episodes, characterized by positive psychotic symptoms such as delusions and hallucinations, are followed by a chronic phase in which disabling negative and cognitive symptoms and impairments social groups tend to be prominent. The amino acid glutamate is the main excitatory neurotransmitter of the central nervous system (CNS), present in approximately 30 to 40% of brain synapses and in 80% of areas involved in cognitive processes, mainly in the cerebral cortex and hippocampus. Objective: to demonstrate the glutamatergic hypothesis in the pathophysiology of schizophrenia. Methodology: This is an integrative literature review, and the search was performed through online access in the National Library of Medicine (PubMed MEDLINE), Scientific Electronic Library Online (Scielo), Google Scholar, Virtual Health Library (BVS) and EBSCO Information Services, September 2021. Results and discussion: The relationship of glutamatergic neurotransmission with the symptoms presented by schizophrenic individuals can be validated by evaluating the close interaction between NMDA glutamate receptors in the mesocortical pathway, responsible for normal cognitive functions and motivation, and the consequent release of dopamine. In situations of hypofunction of the glutamate pathway, there is little release of dopamine in the cortex, which results in negative and cognitive symptoms. Conclusion: a lot of evidence suggests the involvement of NMDA-type glutamatergic receptors in schizophrenia.
References
Allen, J. A., et al. (2011). Descoberta de ligantes D2 de dopamina polarizados por β-arrestina para sondar as vias de transdução de sinal essenciais para a eficácia antipsicótica. Proc. Natl. Acad. Sci., 108 (8), 18488–18493.
Beck, K., et al. (2016). Targeting glutamate to treat schizophrenia: lessons from recente clinical studies. Revist Psychopharmacology, 233 (1), 2425-2428.
Björkholm, C., Marcus, M. M., Konradsson-Geuken, Å., Jardemark, K., Svensson, T. H. (2017). O novo antipsicótico brexpiprazol, sozinho e em combinação com escitalopram, facilita a transmissão glutamatérgica pré-frontal por meio de um mecanismo dependente do receptor D1 da dopamina. Neuropsychopharmacol., 27 (8), 411–417.
Borba, L. O., et al. (2017). Adesão do portador de transtorno mental à terapêutica medicamentosa no tratamento em saúde mental. Revista da Escola de Enfermagem da Universidade de São Paulo, 52 (3), 1-10.
Celotto, A. C., Durigin, L., Calfi, G. S. & Rosa, M. L. N. M. (2019). Participação dos receptores metabotrópicos de glutamato e da via de sinalização por óxido nítrico no desenvolvimento da esquizofrenia. Manuscripta Médica, 2 (3), 1-15.
Coyle, J. T. & Balu, D. T. (2018). O papel da serina racemase na fisiopatologia das doenças cerebrais. Adv. Pharmacol., 82 (8), 35 – 56.
Dias, P., et al. (2020). Bem-estar, qualidade de vida e esperança em cuidadores familiares de pessoas com esquizofrenia. Revista Portuguesa de Enfermagem de Saúde Mental, 17 (23), 23-30.
Gao, X. M., Sakai, K., Roberts, R. C., Conley, R. R. & Dean, B. (2000). CA ionotrópicos receptores de glutamato e expressão de N -metil- D subunidades do receptor aspartato em sub-regiões do hipocampo humano: Efeitos da esquizofrenia. Sou. J. Psychiatry, 157 (5), 1141-1149.
Goff, D. C. (2000). Glutamate receptores em esquizofrenia e drogas antipsicóticas. Em receptores de neurotransmissores em ações de medicamentos antipsicóticos. Lidow, 4 (8), 126–141.
González-Maeso, J., et al. (2008). Identificação de um complexo receptor de serotonina / glutamato implicado na psicose. Nature, 452 (8), 93–97.
Herman, E. J., Bubser, M., Conn, P. J. & Jones, C. K. (2012). Metabotropic glutamate receptors for new treatment in esquizofrenia. Handb. Exp. Pharmacol., 8 (1), 297–365.
Howes, O., et al. (2015). Glutamate and dopamine in schizophrenia: na update for the 21 century. Journal Psychopharmacol, 29 (2), 97-115.
Jackson, J., et al. (2012). Uma dieta sem glúten em pessoas com esquizofrenia e anticorpos anti-transglutaminase tecidual ou anti-gliadina. Esquizofr. Res., 140 (7), 262-263.
Kaiser, L. G., Schuff, N., Cashdollar, N. & Weiner, M. W. (2005). Age-related glutamate and glutamine concentração changes in normal human brain: 1H MR espectroscopy study at 4 T. Neurobiol. Envelhecimento, 26 (8), 665-672.
Kumar, J., et al. (2018). Glutationa e glutamato na esquizofrenia. Revista Psiquiatria Molecular, 25 (1), 873-882.
Laruelle, M. (2014). Schizophrenia: From dopaminergic to glutamatérgic intervenções. Curr. Opiniões Pharmacol., 14 (8), 97–102.
Lim, J. et al. (2016). A relação entre subdomínios de sintomas negativos e cognição. Psychol. Med., 46 (4), 2169 – 2177.
Lin, C. H. & Lane, H. Y. (2019). Early Identification and Intervention of Schizophrenia: Insight from Hypotheses of Glutamate Disfunction and Oxidative Stress. Revist Frontiers in Psychiatry, 27 (10), 1-9.
Madeira, C., et al. (2018). Níveis de glutamato e glutamina no sangue no início recente e na esquizofrenia crônica. Revista Fronteiras em Psiquiatria, 9 (173), 1-8.
Martínez, C. J. & Roman, V. R. (2015). Propuesta de un modelo de respuesta de los delírios esquizofrénicos a los antipsicóticos. Revista Associação Espanhola de Neuropsiquiatria, 36 (129), 15-28.
Matosin, N., Fernandez-Enright, F., Frank, E., Deng, C., Wong, J., Huang, X.-F. & Newell, K. A. (2014). Receptor de glutamato metabotrópico mGluR2 / 3 e mGluR5 ligando-se ao córtex cingulado anterior em depressão psicótica e não psicótica, transtorno bipolar e esquizofrenia: implicações para novas terapêuticas baseadas em mGluR. J. Psychiatry Neurosci., 39 (8), 407–416.
Meador-Woodruff, J. H. (2000). Healy, expressão do receptor DJ Glutamato no cérebro esquizofrênico. Brain Res. Brain Res. Rev., 31(8), 288–294.
Menniti, F. S., Lindsley, C. W., Conn, P. J., Pandit, J. & Zagouras, P. (2013). Volkmann, RA Allosteric modulators for the treatment of esquizofrenia: Targeting glutamatérgic networks. Curr. Principal. Med. Chem., 13 (4), 26–54.
Stepnicki, P., Kondej, M. & Kaczor, A. A. (2018). Conceitos e tratamentos atuais da esquizofrenia. Molecules, 23 (8), 1-9.
Stone, J. M., Morrison, P. D. & Pilowsky, L. S. (2007). Glutamato e desregulação da dopamina na esquizofrenia – A síntese e revisão seletiva. J. Psychopharmacol. Oxf. Engl., 21 (8), 440–452.
Thiebes, S., et al. (2017). Glutamatergic deficit and negative schizophrenia type: new evidence of incompatible and ketamine-induced negative changes in healthy men. Journal Psychiatry Neuroscience, 42 (4), 273-283.
Tomaka, J., et al. (2017). Gluten-related transtornos e esquizofrenia-potencial linking engines, diagnostic andapeutic challenge. Curr. Probl. Psychiatry.,18 (7), 9–24.
Uno, Y., et al. (2019). Glutamate hypothesis in schizophrenia. Psychiatry and Clinical Neurosciences, 73 (1), 204-215.
Yui, K., Ikemoto, S., Ishiguro, T. & Goto, K. (2000). Estudos de psicose por anfetamina ou metanfetamina no Japão: Relação da psicose por metanfetamina com a esquizofrenia. Ann. NY Acad. Sci., 914 (3),1 – 12.
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Copyright (c) 2022 Ítalo Íris Boiba Rodrigues da Cunha; Thainara Pereira da Silva; Bárbara Queiroz de Figueiredo; Adenei da Silva Xavier; Carolina Vital de Brito Vieira; Gabriel Antunes Ribeiro Mendes; Itiel Elanã Soares Alencar; Camila Rodrigues Rosa; Lino Holanda Jorge Neto; Ronaldo Cesar Brito
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