Abstract
Neuropsychiatric disorders (NPDs) have multiple etiological factors, mainly genetic background, environmental conditions and immunological factors. The host immune responses play a pivotal role in various physiological and pathophysiological process. In NPDs, inflammatory immune responses have shown to be involved in diseases severity and treatment outcome. Inflammatory cytokines and chemokines are involved in various neurobiological pathways, such as GABAergic signaling and neurotransmitter synthesis. Infectious agents are among the major amplifier of inflammatory reactions, hence, have an indirect role in the pathogenesis of NPDs. As such, some infections directly affect the central nervous system (CNS) and alter the genes that involved in neurobiological pathways and NPDs. Interestingly, the most of infectious agents that involved in NPDs (e.g., Toxoplasma gondii, cytomegalovirus and herpes simplex virus) is latent (asymptomatic) and co-or-multiple infection of them are common. Nonetheless, the role of co-or-multiple infection in the pathogenesis of NPDs has not deeply investigated. Evidences indicate that co-or-multiple infection synergically augment the level of inflammatory reactions and have more severe outcomes than single infection. Hence, it is plausible that co-or-multiple infections can increase the risk and/or pathogenesis of NPDs. Further understanding about the role of co-or-multiple infections can offer new insights about the etiology, treatment and prevention of NPDs. Likewise, therapy based on anti-infective and anti-inflammatory agents could be a promising therapeutic option as an adjuvant for treatment of NPDs.
Highlights
Neuropsychiatric disorders (NPDs) are among the most important morbidity and mortality worldwide [1,2]
▸Toxoplasma gondii is a protozoan parasite that infects most species of warmblooded animals, including humans, and causes the disease toxoplasmosis. ▸Domestic cats are only definitive host and warm-blooded animals and human are intermediated hosts. ▸Infection usually occurs by eating undercooked contaminated meat, drinking contaminated water and foods, exposure from infected cat feces, mother-to-child transmission during pregnancy, receiving an infected organ transplant or infected blood via transfusion. ▸According to estimation, more than one of the third of the human population have a history of T. gondii infection [74]. ▸CMV is a common virus for people of all ages with a seroprevalence ranging from 45 to 100% [75]. ▸CMV infected individuals may pass the virus in body fluids, such as urine, saliva, tears, blood, semen, and breast milk
herpes simplex virus (HSV)-2 can be transmitted from skin in the genital or anal area that looks normal and is often transmitted in the absence of symptoms. ▸Rubella, known as German measles, is a contagious viral infection that occurs most often in children and young adults. ▸ Rubella infection in pregnant women may cause fetal death or congenital defects known as congenital rubella syndrome (CRS). ▸There is no specific treatment for rubella but the disease is preventable by vaccination. ▸The rubella virus is transmitted by airborne droplets when infected people sneeze or cough
Summary
Neuropsychiatric disorders (NPDs) are among the most important morbidity and mortality worldwide [1,2]. HSV-2 infection increases the risk of acquiring a new HIV infection by approximately three-fold People with both HIV and HSV-2 infection are more likely to spread HIV to others (https://www.who.int/new s-room/fact-sheets/detail/herpes-simplex-virus). ▸The virus becomes latent after infection in some cases, the virus may reactivate This does not always cause symptoms, but people with weakened immune systems are more likely to develop symptoms if EBV reactivates (https://www.cdc.gov/epstein-barr/abo ut-ebv.html). The most of infectious agents that involved in NPDs, such as Toxoplasma gondii (T. gondii), cytomegalovirus (CMV), herpes simplex virus (HSV) and Epstein Barr virus (EBV) is asymptomatic (latent) and co-or-multiple infection of them are common [13, 14, 15, 16, 17]. Several indirect links proposed that co-or-multiple infections may be more involved in the etiopathogenesis of NPDs than single infection: 1) Some infections are associated with NPDs; 2) infections are associated with inflammation; 3) inflammation is associated with NPDs; 4) co-ormultiple infections enhanced a higher level of inflammatory biomarkers than single infections; 5) co-or-multiple infections have more severe outcome than single infection; 6) co-or-multiple infections may have more influence in the etiopathogenesis of NPDs than single infection
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