The literature has been provided the evidence for existence of association of
T. gondii infection with mood disorders such as schizophrenia [
32], bipolar disorder [
33,
34] and suicide [
35]. In a review paper published by Pao-Chu Hsu, it was concluded that
T. gondii is associated with mental health disorders such as schizophrenia, suicide attempt, depression, and other neuropsychiatric diseases [
36]. Moreover, in an ecological study investigated association of
T. gondii with Suicide rates in women, it revealed that there is a positive association between rates of infection with
T. gondii and suicide in 20 European countries and suicide is more common in women of postmenopausal age [
31] .
The studies explained the mechanism of association of
T. gondii infection with behavioral changes well. After proliferation of this protozoan parasite in different organs during the acute phase, the parasite preferentially forms cysts in the brain and establishes a chronic infection that is a balance among parasite’s evasion of the immune response and host immunity. Different cells of brain, such as neurons and astrocytes, can be infected. In laboratory surveys using non-brain cells have showed deep effects of the infection on gene expression of host cells, containing molecules that increase the immune response and those involved in signal transduction pathways, suggesting that similar effects could happen in infected cells of brain.
T. gondii infection also appears to affect signaling pathways in the brain. Consequently, chronic infection reactivation with the parasite (rupture of cyst and proliferation of tachyzoites) in the brain may play a role in the onset of the disease [
37]. In fact,
T. gondii act on suicide behavioral through two pathways: disturbance in dopamine synthesis and activation of indoleamine-2,3-dioxygenase (IDO) that reduce amount of serotonin in brain [
36]. The studies show that individuals who suicide had a significantly higher IgG antibody to
T. gondii compared with those without a suicide [
17]. Moreover, a study showed the association of
T. gondii antibodies and suicidal behavior in patients with schizophrenia, which is consistent with reports on associations between
T. gondii and suicidal behavior in patients with mood disorders [
17], overall psychiatric patients [
20,
31].
T. gondii infection plays a role in the higher later occurrence of suicide in lifespan [
31]. Experimental studies have shown that the relationship between
T. gondii infection and suicide is reinforced by the relative tropism of
T. gondii cysts in greater density in the amygdala nucleus or the frontal cortex, which are normally involved in regulating behavior [
38]. The following explanations can illuminate the probable mechanisms of a relationship between
T. gondii and suicidal behavior. First,
T. gondii induces the production of pro-inflammatory cytokines (IFN- γ, IL-6, and IL-12) by activating lymphocytes and macrophages [
39]. Interferon-gamma, by triggering lymphocytes and macrophages, blocks the development of
T. gondii [
40]. In response to the
T. gondii, cytokines are produced, leading to an increase in the activity of enzymes kynurenine monooxygenase (KMO) and indoleamine 2, 3-dioxygenase (IDO). In the metabolism of the amino acid tryptophan, KMO and IDO are restricted. Tryptophan evacuation via the kynurenine pathway (3-hydroxyl kynurenine, 3-OH-kynurenine, and quinolinic acid, QUIN) limits the growth and spread of infection [
39]. Moreover, it can decrease neurotransmitter serotonin synthesis in the brain and may raise the susceptibility to triggering suicide risk factors such as depression, impulsivity, and aggression [
41]. Changes in glutamate and dopamine neurotransmission have shown a key role in suicide and suicidal behavior [
42,
43]. Finally, changes in neurotransmitters can play a role in behavioral development that increases the risk of suicide [
35,
44].
In this study, we had several limitations. One major limitation of the present study is that we just included English language studies and overlooked non-English ones. Therefore, we cannot assess the effect of non-English studies on our results. Second, we included only studies had full text, and therefore, we excluded the studies without full text. However, it seems that more investigations on the association of T. gondii infection with suicide, especially on mechanisms of pathogenesis of T. gondii infection in suicidal behavior in required. Furthermore, updating the review articles about T. gondii infection and suicidal behavior without time and language limitations is suggested.
Despite the mentioned limitation, this study provides important clues to inform policy-makers about the serious role of T. gondii infection in a suicide. Therefore, considering the consequences and complications of T. gondii infection such as suicide, control, prevention, and its treatment, this parasitic infection must be highly considered.