Proposed Pathway Linking Respiratory Infections with Depression

Abstract

Depression is one of the most important causes of disability and loss of useful life of people around the world. Acute respiratory infection caused a large number of severe illnesses and deaths of the world and most of these due to viral infections, which is estimated more than 80% of respiratory infections. Detection of viruses by immune pathogen recognition receptors activates the intracellular signaling cascade and eventually cause produces interferons. Inflammatory process begins with secretion of interferons and the expression of interferon-stimulated genes. One of the most important of these genes is indoleamine-pyrrole 2,3-dioxygenase (IDO), which plays a major role in tryptophan catabolism. IDO is an intracellular monomeric enzyme that is also responsible for breaking down and consuming tryptophan in the Kynurenine pathway. Increased inflammation has been linked to decrease tryptophan concentrations and increase kynurenine levels. We tried to explain the role of inflammation by viral respiratory infections in causing depression.

Microglia Involves in the Immune Inflammatory Response of Poststroke Depression: A Review of Evidence

“…Animal experiments and autopsy results suggested that microglia could be involved in the onset and progression of depression ( Table 1 ). Activation of microglia has a vital role in the pathogenesis of major psychiatric disorders associated with hippocampal atrophy and disconnection of cognitive structures [ 96 , 97 ].…”

“…Animal experiments and autopsy results suggested that microglia could be involved in the onset and progression of depression (Table 1). Activation of microglia has a vital role in the pathogenesis of major psychiatric disorders associated with hippocampal atrophy and disconnection of cognitive structures [96,97]. Progesterone attenuates stress-induced microglia activation by regulating polarized microglia and the inflammatory environment in the hippocampus after ischemic injury.…”

Stress circuitry: mechanisms behind nervous and immune system communication that influence behavior

“…Indeed, inflammatory cytokine levels are increased in the brains of individuals suffering from depression ( 27 ) and animal models of stress ( 28 , 29 ). Inflammatory molecules can affect neuronal activity by reducing serotonin levels and altering neurotransmitter function ( 30 , 31 ). Together, these findings demonstrate that stress-related mood disorders are associated with increased inflammatory processes, which contribute to their pathology.…”

“…In response to inflammation, interferons and interleukins are released and levels of indoleamine 2,3 deoxygenase (IDO) are increased. IDO is responsible for catabolizing tryptophan into kynurenine, which further catabolizes into metabolites like quinolinic acid in microglia and kynurenic acid in astrocytes ( 30 , 31 , 115 ). Because tryptophan is a key precursor for serotonin, this reduces the amount of tryptophan available for serotonin synthesis, thus reducing levels of serotonin in the brain ( 31 ).…”

“…IDO is responsible for catabolizing tryptophan into kynurenine, which further catabolizes into metabolites like quinolinic acid in microglia and kynurenic acid in astrocytes ( 30 , 31 , 115 ). Because tryptophan is a key precursor for serotonin, this reduces the amount of tryptophan available for serotonin synthesis, thus reducing levels of serotonin in the brain ( 31 ). Quinolinic acid can have excitotoxic effects via activation of N-methyl-D-aspartate (NMDA) receptors whereas kynurenic acid can antagonize NDMA receptors and α7 nicotinic acetyl choline receptors ( 30 ).…”