Toxoplasma gondii, Suicidal Behavior, and Intermediate Phenotypes for Suicidal Behavior

Abstract

Within the general literature on infections and suicidal behavior, studies on Toxoplasma gondii (T. gondii) occupy a central position. This is related to the parasite's neurotropism, high prevalence of chronic infection, as well as specific and non-specific behavioral alterations in rodents that lead to increased risk taking, which are recapitulated in humans by T. gondii's associations with suicidal behavior, as well as trait impulsivity and aggression, mental illness and traffic accidents. This paper is a detailed review of the associations between T. gondii serology and suicidal behavior, a field of study that started 15 years ago with our publication of associations between T. gondii IgG serology and suicidal behavior in persons with mood disorders. This “legacy” article presents, chronologically, our primary studies in individuals with mood disorders and schizophrenia in Germany, recent attempters in Sweden, and in a large cohort of mothers in Denmark. Then, it reviews findings from all three meta-analyses published to date, confirming our reported associations and overall consistent in effect size [ranging between 39 and 57% elevation of odds of suicide attempt in T. gondii immunoglobulin (IgG) positives]. Finally, the article introduces certain links between T. gondii and biomarkers previously associated with suicidal behavior (kynurenines, phenylalanine/tyrosine), intermediate phenotypes of suicidal behavior (impulsivity, aggression) and state-dependent suicide risk factors (hopelessness/dysphoria, sleep impairment). In sum, an abundance of evidence supports a positive link between suicide attempts (but not suicidal ideation) and T. gondii IgG (but not IgM) seropositivity and serointensity. Trait impulsivity and aggression, endophenotypes of suicidal behavior have also been positively associated with T. gondii seropositivity in both the psychiatrically healthy as well as in patients with Intermittent Explosive Disorder. Yet, causality has not been demonstrated. Thus, randomized interventional studies are necessary to advance causal inferences and, if causality is confirmed, to provide hope that an etiological treatment for a distinct subgroup of individuals at an increased risk for suicide could emerge.

Epigenetic Manipulation of Psychiatric Behavioral Disorders Induced by Toxoplasma gondii

“…A recent casecontrol study also consistent with the above observations found a higher seroprevalence among schizophrenia patients especially in suicide attempters, against the control groups, and patients with no history of suicide attempts (Akgul et al, 2021) by emotional irritation (Gohardehi et al, 2018;Sutterland et al, 2019). In addition, numerous studies demonstrated T. gondii as a replicated risk factor in human psychiatric disorders such as unknown temporal lobe epileptic seizure (Ngoungou et al, 2015;Uzorka and Arend, 2017;Sadeghi et al, 2019), Alzheimer's disease (Bayani et al, 2019), cognitive impairment in several cognitive domains including short-term verbal memory and processing speed (Gale et al, 2015;de Haan et al, 2021), depression (Kamal et al, 2020), autism (Flegr and Horacek, 2019;Nayeri et al, 2020;Al et al, 2021), suicide and suicidal behavior (Kamal et al, 2020;Soleymani et al, 2020;Postolache et al, 2021), and other neurological disorders (Desmettre, 2020;Nayeri et al, 2021). Moreover, for human hosts, latent infection may also be associated with systemic changes in human personality (Lafferty, 2006).…”

Comprehensive Overview of Toxoplasma gondii-Induced and Associated Diseases

“…Elderly women (aged 60 or above) are more prone to suicidal attempts when seropositive for T. gondii [108]. A detailed review involving three wide metaanalyses in different European countries on the associations between T. gondii serology and suicidal behavior reported a 39 to 57% elevation of odds of suicide attempts in T. gondii IgG-positive patients [109]. One case report showed that a depressed 32-year-old male did not respond to antidepressant therapy until he was treated for acute toxoplasmosis, suggesting a probable association between toxoplasmosis and depression [110].…”

Behavioral and Neuropathological Changes After Toxoplasma gondii Ocular Conjunctival Infection in BALB/c Mice

“…Toxoplasma gondii is an intracellular parasite that can infect most warm-blooded animals, where it may invade the central nervous system and provoke neuroinflammation and behavioral changes (for recent reviews, see Mendez and Koshy, 2017 ; Martinez et al., 2018 ; Chen et al., 2019 ; de Haan et al., 2021 ; Nasuhidehnavi and Yap, 2021 ; Nayeri et al., 2021 ; Postolache et al., 2021 ). It is estimated that approximately 30% of the world’s population is infected with this protozoan, but there is much greater prevalence in African and South American countries ( Agordzo et al., 2019 ; Karshima and Karshima, 2020 ; Rahmanian et al., 2020 ; de Lima Bessa et al., 2021 ).…”