Association between toxoplasmosis and bipolar disorder: A systematic review and meta-analysis

Background: The relationship between toxoplasma gondii (T. gondii) infection and bipolar disorder (BD) is poorly understood. This review explores this relationship by estimating the strength of the association between the two conditions using data from published studies. Methods: Following PRISMA guidelines, we performed a review and meta-analysis of published articles obtained from a systematic search of PubMed, PsycINFO, EMBASE and the Cochrane library up to January 10th, 2021. We included observational studies that compared seroprevalence of IgG class antibodies against T. gondii in patients with a diagnosis of BD with healthy controls. We excluded studies that included <10 participants in each study arm and patients with a serious concomitant medical illness. Discrepancies between the two independent researchers were resolved by consulting a third experienced researcher. Summary data were extracted from published reports. Analysis was conducted using both fixed-effects and random-effects models. The study is registered with PROSPERO number CRD42021237809. Findings: The search yielded 23 independent studies with a total of 12690 participants (4021 with BD and 8669 controls). Persons with BD had a greater odd of seropositivity with toxoplasmosis than controls, both in the fixed-effects model (OR = 1.34 [95%CI: 1.19 to 1.51]) and the random-effects model (OR = 1.69 [95%CI: 1.21 to 2.36]). No publication bias was detected but reported results showed a high heterogeneity (I2 = 84% [95%CI:77%–89%]). Interpretation: The findings support the relationship between toxoplasmosis infection and BD and suggests a need for studies designed to explore possible causal relationship. Such studies may also improve our understanding of the pathophysiology of BD and open other avenues for its treatment. Funding: P.O.R. Sardegna F.S.E. 2014-2020