Monoamine Neurotransmitters Control Basic Emotions and Affect Major Depressive Disorders

Abstract

Major depressive disorder (MDD) is a common and complex mental disorder, that adversely impacts an individual’s quality of life, but its diagnosis and treatment are not accurately executed and a symptom-based approach is utilized in most cases, due to the lack of precise knowledge regarding the pathophysiology. So far, the first-line treatments are still based on monoamine neurotransmitters. Even though there is a lot of progress in this field, the mechanisms seem to get more and more confusing, and the treatment is also getting more and more controversial. In this study, we try to review the broad advances of monoamine neurotransmitters in the field of MDD, and update its effects in many advanced neuroscience studies. We still propose the monoamine hypothesis but paid special attention to their effects on the new pathways for MDD, such as inflammation, oxidative stress, neurotrophins, and neurogenesis, especially in the glial cells, which have recently been found to play an important role in many neurodegenerative disorders, including MDD. In addition, we will extend the monoamine hypothesis to basic emotions; as suggested in our previous reports, the three monoamine neurotransmitters play different roles in emotions: dopamine—joy, norepinephrine—fear (anger), serotonins—disgust (sadness). Above all, this paper tries to give a full picture of the relationship between the MDD and the monoamine neurotransmitters such as DA, NE, and 5-HT, as well as their contributions to the Three Primary Color Model of Basic Emotions (joy, fear, and disgust). This is done by explaining the contribution of the monoamine from many sides for MDD, such the digestive tract, astrocytes, microglial, and others, and very briefly addressing the potential of monoamine neurotransmitters as a therapeutic approach for MDD patients and also the reasons for its limited clinical efficacy, side effects, and delayed onset of action. We hope this review might offer new pharmacological management of MDD.

Effects of (S)-ketamine on depression-like behaviors in a chronic variable stress model: a role of brain lipidome

“…More than 350 million people suffer from MDD, with a prevalence rate of about 5.7% worldwide (Ferrari et al, 2013 ). For many years, studies mainly focused on monoaminergic antidepressants in the treatment of MDD due to the relatively well-accepted monoamine hypothesis of depression (Bristow et al, 2021 ; Jiang et al, 2022 ). However, monoaminergic antidepressants show limitations in the clinic, such as a delayed onset of response, inevitable side effects, and partial efficacy (Machado-Vieira et al, 2017 ).…”

Editorial: Natural products and brain energy metabolism: Astrocytes in neurodegenerative diseases Volume II

“…We are the first to hypothesize that there might be three primary emotions: joy, disgust and fear ( Figure 1 ) ( Gu, et al, 2018 ), which can be combined to form many other emotions like the three primary colors ( Liang, et al, 2021 ). We also integrated the three primary emotion with emotional dimensions, and hypothesized that the joy represents the left pole of valence, while the disgust represents the right pole of valence, and the fear (together with anger) represents the vertical pole of dimension (arousal) ( Figure 1 ) ( Gu et al, 2019b ; Jiang et al, 2022 ; Dong et al, 2022 ).…”

Glymphatic Dysfunction Induced Oxidative Stress and Neuro-Inflammation in Major Depression Disorders

“…Monoamine deficiency was previously suggested as the major cause of MDD, and most antidepressants are used to increase the amount of monoamine neurotransmitters [ 73 ]. However, this might be an outdated explanation for the cause of MDD and needs to be revised to reflect the more complex changes in the brain associated with the illness.…”