Palavras-chave
Neuroplasticidade
Neuroinflamação
Como Citar
Copyright © | Todos os direitos reservados.
A revista detém os direitos autorais exclusivos de publicação deste artigo nos termos da lei 9610/98.
Reprodução parcial
É livre o uso de partes do texto, figuras e questionário do artigo, sendo obrigatória a citação dos autores e revista.
Reprodução total
É expressamente proibida, devendo ser autorizada pela revista.
Resumo
Objetivo: Analisar os principais mecanismos envolvidos na neuroplasticidade associados à fisiopatologia do Transtorno Depressivo Maior (TDM) e suas implicações terapêuticas. Revisão bibliográfica: A neuroplasticidade exerce papel central na fisiopatologia do TDM, envolvendo alterações estruturais, funcionais e sinápticas, além da participação de mecanismos relacionados à neuroinflamação, ao estresse crônico e à sinalização neurotrófica. A redução da atividade das vias BDNF-TrkB e mTORC1, a perda de espinhas dendríticas, a diminuição da conectividade neuronal e alterações na atividade de redes cerebrais contribuem para a manutenção das manifestações clínicas do transtorno. Em contrapartida, diferentes intervenções terapêuticas, incluindo antidepressivos convencionais, cetamina e estratégias não farmacológicas, podem favorecer a reorganização dos circuitos neurais, a sinaptogênese e a recuperação da plasticidade cerebral. Considerações finais: A compreensão da neuroplasticidade no Transtorno Depressivo Maior evidencia novos alvos terapêuticos, favorecendo estratégias capazes de restaurar a conectividade neural e promover maior eficácia no tratamento da depressão.
Referências
AMERICAN PSYCHIATRIC ASSOCIATION. DSM-5-TR: neurocognitive disorders supplement – updated excerpts for delirium codes, major and mild neurocognitive disorders. Washington, DC: American Psychiatric Association Publishing, 2022.
CASTRÉN E, MONTEGGIA LM. Brain-derived neurotrophic factor signaling in depression and antidepressant action. Biological Psychiatry, 2021; 90(2): 128–136.
DUMAN RS, et al. Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants. Nature Medicine, 2016; 22(3): 238–249.
FAISAL H, et al. Effect of ketamine on reward processing in depressive disorders: a systematic review of neuroimaging studies. CNS Spectrums, 2026; 31(1): e9.
FOGAÇA MV, DUMAN RS. Cortical GABAergic dysfunction in stress and depression: new insights for therapeutic interventions. Frontiers in Cellular Neuroscience, 2019; 13: 87.
HUANG YJ, et al. New treatment strategies of depression: based on mechanisms related to neuroplasticity. Neural Plasticity, 2017; 2017: 4605971.
LIAO C, et al. Structural neural plasticity evoked by rapid-acting antidepressant interventions. Nature Reviews Neuroscience, 2025; 26(2): 101–114.
LIU W, et al. The role of neural plasticity in depression: from hippocampus to prefrontal cortex. Neural Plasticity, 2017; 2017: 6871089.
LIU Y, et al. Emotional roles of mono-aminergic neurotransmitters in major depressive disorder and anxiety disorders. Frontiers in Psychology, 2018; 9: 2201.
LOVRENČIĆ MV, et al. Improvement in depressive symptoms is associated with reduced oxidative damage and inflammatory response in type 2 diabetic patients with subsyndromal depression: the results of a randomized controlled trial comparing psychoeducation, physical exercise, and enhanced treatment as usual. International Journal of Endocrinology, 2015; 2015: 210406.
MA K, et al. The molecular mechanism underlying GABAergic dysfunction in nucleus accumbens of depression-like behaviours in mice. Journal of Cellular and Molecular Medicine, 2019; 23: 7397–7409.
MAGARAGGIA I, et al. Improving cognitive function in major depressive disorder with psychedelics: a dimensional approach. Neurobiology of Learning and Memory, 2021; 183: 107467.
PAGE CE, et al. Beyond the serotonin deficit hypothesis: communicating a neuroplasticity framework of major depressive disorder. Molecular Psychiatry, 2024; 29(12): 3802–3813.
PAREKH PK, et al. Synaptic mechanisms regulating mood state transitions in depression. Annual Review of Neuroscience, 2022; 45: 581–601.
PISANU C, et al. Effect of ketamine and esketamine on RNA expression and its relevance for depression: a systematic review. Pharmacological Research, 2025; 219: 107894.
PRICE RB e DUMAN R. Neuroplasticity in cognitive and psychological mechanisms of depression: an integrative model. Molecular Psychiatry, 2020; 25: 530–543.
RĂDULESCU I, et al. Neuroplasticity and depression: rewiring the brain’s networks through pharmacological therapy (review). Experimental and Therapeutic Medicine, 2021; 22(4): 1131.
SACCARO L, et al. Proton magnetic resonance spectroscopy of N-acetyl aspartate in first depressive episode and chronic major depressive disorder: a systematic review and meta-analysis. Journal of Affective Disorders, 2024; 355: 265–282.
TAYYAB M, et al. Sonic hedgehog, Wnt, and brain-derived neurotrophic factor cell signaling pathway crosstalk: potential therapy for depression. Journal of Neuroscience Research, 2018; 96(1): 53–62.
UMEMORI J, et al. iPlasticity: induced juvenile-like plasticity in the adult brain as a mechanism of antidepressants: antidepressant-induced plasticity. Psychiatry and Clinical Neurosciences, 2018; 72(9): 633–653.
VAISHNAVI S, et al. Changes in neural activities and neuroplasticity related to nonpharmacological interventions for major depressive disorder: a systematic literature review. Biological Psychiatry Global Open Science, 2025; 5(6): 100572.
VOSE LR, STANTON PK. Synaptic plasticity, metaplasticity and depression. Current Neuropharmacology, 2017; 15(1): 71–86.
WILKINSON ST, et al. Leveraging neuroplasticity to enhance adaptive learning: the potential for synergistic somatic-behavioral treatment combinations to improve clinical outcomes in depression. Biological Psychiatry, 2019; 85(6): 454–465.
WU A, ZHANG J. Neuroinflammation, memory, and depression: new approaches to hippocampal neurogenesis. Journal of Neuroinflammation, 2023; 20: 283.
YUKSEL D, et al. Longitudinal brain volume changes in major depressive disorder. Journal of Neural Transmission, 2018; 125: 1433–1447.
ZARZA-REBOLLO JA, et al. The relationship between BDNF and physical activity on depression. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 2024; 134: 111033.