The Neurologist: Clinical & Therapeutics Journal
Open Access

Depressive disorder; Neuroprogression

Introduction

Clinically, it includes a poor response to treatment and an increase in depressive episodes, both of which make the brain more vulnerable and make it harder to perform functions that are linked to brain structural changes. This study aims to examine the metabolic processes that are responsible for the morphologic changes that have been observed in patients with MDD’s limbic system. It also aims to examine the neurologic bases of this complex pathology, which include changes in neurotransmission, changes in neuroplasticity, changes in neurotransmission due to environmental stress, genetic vulnerability, and other factors that have brought to light a mechanism of progressive neuronal damage.

One of the earliest psychiatric disorders for which evidence exists, depressive disorder (DD) is pathology of the mood characterized by feelings of deep pain, rage, frustration, and loneliness that prevent patients from leading normal lives. It manifests physiologically as a chemical imbalance in the brain, which is the most common symptom observed in more than half of outpatient psychological patients. According to epidemiological data, it is the fifth leading cause of disability worldwide and among women, accounting for 13% of all mental illnesses: ratio of affectation for men of 2:1. Dejection, anhedonia (loss of pleasure), general disinterest, diminished energy or fatigue, sleep and appetite disorders, somatic discomfort, memory and concentration problems, feelings of guilt and low self-esteem, poor vision of the future, comorbidity with other diseases, and frequently the possibility of suicide are the primary symptoms. Therefore, its attention is of the utmost importance [1-5].

Discussion

Like the rest of mental disorders, the origin of DD and its treatment were based on magic and empirical environmental therapy long before the emergence of psychiatric medical specialists. However, in the middle of the 20th century, the monoaminergic hypothesis, which suggested that 5-HT, an indolamine made from tryptophan, and the catecholamines (NA, adrenaline [A], and dopamine [DA]) made from tyrosine are concentrated within vesicles in the terminal region of the neurons, led to the genuine search for drugs that would specifically act on one or both monoamines.4 This hypothesis postulated that the pathophysiologic basis During the process of nerve transmission, they are released into the synaptic space from here. This evidence was based on the development of medications for the treatment of DD. The action of 5-HT comes to an end when it is recaptured and degraded by the monoamine oxidase (MAO) enzyme, which is found in the outer mitochondrial membrane of neurons and glial cells. During clinical trials, iproniazid, an antituberculous MAO inhibitor, was accidentally discovered to increase the availability and excitatory effects of neurotransmitters in the reward and pleasure centers of the NA and 5-HT systems in the hypothalamus and the limbic system’s surrounding regions. This discovery laid the foundation for the treatment approach. “Mood elevation” is a manifestation of this increase. This is how the first antidepressant, fluoxetine, a selective serotonin reuptake inhibitor, was developed in 1950. Imipramine, a better antidepressant tricyclic drug derived from chlorpromazine, was discovered shortly after. Several antidepressant medications, including fluvoxamine, paroxetine, sertraline, and citalopram, that function as inhibitors of the reuptake of 5-HT, NA, and selective of the MAO7 were developed as a result of this discovery. Subsequently, the reversible MAO inhibitor moclobemide and the 5-HT and DA reuptake inhibitor bupropion were discovered. Mirtazapine, a drug that works on both noradrenergic and serotoninergic receptors, and reboxetine, an NA reuptake inhibitor, were developed in the 1990s. Later, venlafaxine and duloxetine, a pair of drugs, were also developed. Due to their dual inhibition of 5-HT and NA reuptake, the last two are known as duals. For the treatment of DD, clinical psychiatry currently has more than 30 highly effective advanced medications, including agomelatine, a melatonin agonist.

Neuroprogression is a phasic and progressive process in which the brain establishes inefficient and incorrect alternative interconnection routes. Strictly speaking, neuroprogression is defined as neuronal changes that include mild degenerative processes, intracellular signaling dysfunctions, apoptosis, and decreased plasticity and neurogenesis. The brain is constantly reorganizing through neuroplasticity and attempting to achieve greater efficiency through neurodevelopment. In depression, the diminution of the size of the frontal lobes, prefrontal orbital cortex, circumvolution of the frontal corpus callosum, hippocampus, and amygdala appears to reflect a decrease in neurogenesis, mitochondrial dysfunction, and an imbalance in the HHS axis in depressed patients. This process begins with a mild onset, gets worse with each crisis episode, and eventually leads to loss of cognitive abilities like memory and decision-making. Disorganization affects the level of cerebral microcirculation and control of excitability, and it is reflected in loss of glia–neuronal interactions, the amount of synapsis, and regulation of neurotransmitters, particularly monoamines in the brain areas that regulate emotions. In DD patients, the neurons of these regions present failed reorganization or fewer efficacies in neuronal plasticity than atrophy or death. The induction of microglial activation is involved in the deviation of tryptophan metabolism to kynurenine, the stimulation of the HPA axis, and the resistance to glucocorticoid receptors. In response to a signal of inflammation, the neurons produce nitrogen and oxygen reactive species (RS) and secrete inflammatory cytokines that establish a continuous circuit of self-activation [6-10].

Conclusion

Microglia undergo reactive gliosis, a morphologic change known to make their cell bodies larger and dendrites thicker or completely disappear when the cell becomes amoeboid, thereby reducing the number of its branches. The serotonergic system, in particular, appears to have a more active participation in the neuroprogressive process because it typically acts as neurogenesis-stimulating factor by the expression of BDNF. This factor promotes inflammatory mechanism, activating the monocytes and NK cells. As a result, the synthesis and release of neurotrophic factors necessary for the survival, differentiation, cell growth, and regulation of glutamate are progressively reduced when reactive gliosis of the astrocytes By causing cytotoxicity, it indirectly controls the production of interferon gamma (IFN-). Serotonin also causes the hypothalamus to release corticotropin-releasing hormone, thereby activating the HHS axis to promote the release of cortisol into the bloodstream.43 Because of this, its synthesis and brain levels are delicately regulated.

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