Is there any association between Toxoplasma gondii infection and bipolar disorder? A systematic review and meta-analysis
Introduction
Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite. Human infection occurs either after the ingestion of oocysts shed by infected cats or the consumption of undercooked meat derived from infected animals, particularly pork (Montoya and Liesenfeld, 2004). T. gondii infection is usually asymptomatic in healthy adults, and might reach the human central nervous system (CNS) where cysts persists lifelong (Opsteegh et al., 2011). However, immunocompromised patients might develop severe clinical complications, such as toxoplasmic encephalitis, chorioretinitis, and pneumonitis (Abedalthagafi et al., 2009). Moreover, infection during gestation could lead to congenital syndromes, seizures and intellectual impairment (Kaye, 2011). Infection with T. gondii has also shown to lead to psychotic symptoms (Hamidinejat et al., 2010) and changes in personality (Novotna et al., 2005, Khademvatan et al., 2013b). These symptoms are widely observed in several psychiatric conditions, including bipolar disorder.
Bipolar disorder (BD) is a severe mood disorder that affects approximately 2.4% of the world's population (Merikangas et al., 2011). BD is characterized by depressive and manic cycles, with depressive episodes tending to predominate over the course of the illness. The neurobiology of BD is highly complex and not fully understood (Shih et al., 2004, Escamilla and Zavala, 2008). Immunological abnormalities have been regarded as possible contributors to the pathophysiology of BD (Barbosa et al., 2014, Hamdani et al., 2012; Söderlund et al., 2011; Jakobsson et al.2013, Leboyer et al., 2012; Drexhage et al., 2011; Rege and Hodgkinson, 2013). One recent systematic review has shown that several studies suggested that infectious agents might be associated with the pathogenesis of BD, such as T. gondii, Herpes simplex virus (HSV)−1, HSV-2, human herpes virus 6 (HHV-6) cytomegalovirus, Epstein-Barr Virus (EBV), and Varicella zoster virus (Barichello et al., 2016). The specific nature of the association between T. gondii and BD is yet to be elucidated.
Given the aforementioned points, the main purpose of the present study was to evaluate whether T. gondii status is associated to BD and possibly predisposes this psychiatric condition, through a systematic review in addition to a confined meta-analysis of the previously published studies in the literature.
Section snippets
Methods
The preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines were used for conducting the systematic review (Moher et al., 2009). We performed a systematic search to find original studies that investigated the association between T. gondii and BD in MEDLINE, LILACS, PsycINFO and Embase databases using the keywords Bipolar Disorder AND toxoplasmosis OR Toxoplasma gondii.
Our inclusion criteria were as follows: (i) original articles; (ii) published in English,
Results
We extracted an initial cohort of 118 citations in MEDLINE, LILACS, PsycINFO and Embase databases. Fifty were duplicates and after an abstract and title screening, 43 articles were excluded for clearly not fully meeting our inclusion criteria. From the 25 remaining articles, 12 were excluded for not meeting our inclusion criteria. Finally, a total of 13 studies were included in our systematic review. Eight out of these 13 studies met our inclusion/exclusion criteria and were further included in
Discussion
In contrast to its well-documented relationship with schizophrenia (Prandovszky et al., 2011, Torrey and Yolken, 2003), T. gondii's relationship to BD is still relatively understudied with a relative paucity of documented findings. As we could observe in our systematic review, data are still controversial. While some studies demonstrated an association between T. gondii infection and BD, others failed to show the same findings. measured specific intrathecal antibody synthesis against T. gondii
Acknowledgements
The authors are grateful for the assistance provided by The National Medical Library of Cuba during the search for manuscripts.
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