Toxoplasma gondii (T. gondii) is an intracellular parasitic protozoon which can infect almost all warm-blooded animals, including humans, and results in zoonotic toxoplasmosis. T. gondii infection is primarily acquired through consumption of foods contaminated with oocysts, and undercooked or raw meats containing tissue cysts, or coming into contact with cat's feces (Guo et al., 2015). T. gondii infection is typically asymptomatic or mild in immunocompetent individuals (Elsheikha et al., 2021), but results in severe and even fatal diseases such as encephalitis, retinochoroiditis, or multiple organ damages in immunocompromised patients (Daher et al., 2021). T. gondii primary infection during pregnancy may cause serious damages to the fetus (Abamecha and Awel, 2016).

T. gondii infection is also reported to be associated with traffic accident (Gohardehi et al., 2018), immune function (Layton et al., 2023) and high population mortality rates (Huang et al., 2022). Furthermore, numerous studies have revealed T. gondii infection is corelated with different types of mental illness (Barichello et al., 2016; Chen et al., 2019; Nessim et al., 2023), including schizophrenia (Ansari-Lari et al., 2017; Burgdorf et al., 2019; Chen et al., 2019; Fond et al., 2018; Kezai et al., 2020; Savitz, 2020; Sutterland et al., 2015), depression(Alvarado-Esquivel et al., 2017a; Demirel Ö et al., 2023; Gale et al., 2021; Kamal et al., 2022; Markkula et al., 2020; Nasirpour et al., 2020; Nayeri Chegeni et al., 2019b; Suvisaari et al., 2017; Yalın Sapmaz et al., 2019), epilepsy(Alizadeh Khatir et al., 2021; Babaie et al., 2017; Sadeghi et al., 2019), substance abuse and addiction (Sutterland et al., 2015), Parkinson's (Alvarado-Esquivel et al., 2017b; Bayani et al., 2019; Zhou et al., 2019), Alzheimer's/dementia(AD) (Bayani et al., 2019; Bouscaren et al., 2018; Mahami-Oskouei et al., 2016; Nayeri Chegeni et al., 2019a; Nayeri et al., 2021), anxiety (Markkula et al., 2020) and nervous system cognitive function (Gale et al., 2020; Kruszon-Moran et al., 2023; Mendy et al., 2015; Torniainen-Holm et al., 2019; Wyman et al., 2017).

Mental illnesses are accountable for the majority of ‘years lived with disability’ (YLDs). Depression and anxiety are the most prevalent, affecting an estimated 280 million and 301 million people, respectively. Importantly, mental disorders have significant economic implication, with depression and anxiety alone resulting in the loss of 12 billion productive workdays per year, costing almost US$1 trillion (Cuijpers et al., 2023).

Though the link between T. gondii infection and neuropsychiatric disorders has been established in these reports,it remains uncertain if T. gondii directly contributes to these conditions, or if other associated factors are involved. Most of these researches rely on cross-sectional and case-control studies, with a limited number of prospective cohort studies, which makes it challenging to establish causality. Additionally, the small sample size and the influence of confounding bias limit the interpretation of study findings. Therefore, further prospective cohort study and case-control study focusing on specific diseases are required to elucidate the correlation between T. gondii infection and neuropsychiatric disorders.

The UK Biobank (UKB) project is a prospective cohort study that tracks the health conditions of around 500,000 volunteers (Bycroft et al., 2018). It collects comprehensive data, including genetic information, lifestyle factors, biomarkers, and a wide range of health outcomes. The extensive and detailed dataset available in this database provides an exceptional opportunity to study the connection between T. gondii infection and neuropsychiatric disorders on a large scale among a diverse population.

To further identify the association of T. gondii infection with neuropsychiatric disorders, we conducted both a cohort study based on UKB database and a case control study.