Neuroplasticity and depression: Rewiring the brain's networks through pharmacological therapy (Review)

Abstract

In modern society, depression is one of the most common mental illness; however, its pathophysiology is not yet fully understood. A great body of evidence suggests that depression causes changes in neuroplasticity in specific regions of the brain which are correlated to symptom severity, negative emotional rumination as well as fear learning. Depression is correlated with atrophy of neurons in the cortical and limbic brain regions that control mood and emotion. Antidepressant therapy can exhibit effects on neuroplasticity and reverse the neuroanatomical changes found in depressed patients. The investigation of fast-acting agents that reverse behavioral and neuronal deficiencies of chronic depression, especially the glutamate receptor antagonist NMDA ketamine, and the cellular mechanisms underlying the rapid antidepressant actions of ketamine and related agents are of real interest in current research. Actual medication such as serotonin (5-HT) selective reuptake inhibitor (SSRI) antidepressants, require weeks to months of administration before a clear therapeutic response. The current review aimed to underline the negative effects of depression on neuroplasticity and present the current findings on the effects of antidepressant medication.

The tryptophan catabolite or kynurenine pathway in major depressive and bipolar disorder: a systematic review and meta-analysis

“…The lowered levels of TRP may suggest that MDD/BD patients show lowered neuroprotection. First, TRP and serotonin are antioxidants (Xu, Liu et al 2018), and serotonin has neuroprotective properties by preserving neuroplasticity and preventing neuronal injuries (Croonenberghs, Verkerk et al 2005, Radulescu, Dragoi et al 2021). In fact, the antioxidant role of TRP is indirect (Perez-Gonzalez, Muñoz-Rugeles et al 2014, Pérez-González, Alvarez-Idaboy et al 2015) via metabolites such as melatonin, serotonin, 3-HK and XA (Reiter, Tan et al 1999).…”

The tryptophan catabolite or kynurenine pathway in major depressive and bipolar disorder: A systematic review and meta-analysis

“…The lowered levels of TRP may suggest that MDD/BD patients show lowered neuroprotection. First, TRP and serotonin are antioxidants ( Xu et al, 2018 ), and serotonin has neuroprotective properties by preserving neuroplasticity and preventing neuronal injuries ( Croonenberghs et al, 2005 ; Rădulescu et al, 2021 ). In fact, the antioxidant role of TRP is indirect ( Pérez-González et al, 2015 ; Perez-Gonzalez et al, 2014 ) via metabolites such as melatonin, serotonin, 3-HK and XA ( Reiter et al, 1999 ).…”

The tryptophan catabolite or kynurenine pathway in a major depressive episode with melancholia, psychotic features and suicidal behaviors; a systematic review and meta-analysis

“…Second, lowered levels of TRP (in itself an antioxidant) may lead to decreased antioxidant metabolites, namely serotonin, melatonin, 3HK and XA (Reiter, Tan et al 1999, Xu, Liu et al 2018). Moreover, serotonin enhances proper neuroplasticity and maintains healthy neurons (Croonenberghs, Verkerk et al 2005, Rădulescu, Drăgoi et al 2021). Third, KA has a neuroprotective role by antagonizing the action of QA inhibiting excitatory receptors namely NMDA, α-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid (AMPA) and kainate glutamate ionotropic receptors, in addition, to impede alpha 7 nicotinic acetylcholine receptor (α7nAChr) and thereby decrease glutamate release (Morris, Carvalho et al 2016, Almulla and Maes 2022).…”