Elsevier

Microbial Pathogenesis

Volume 149, December 2020, 104587
Microbial Pathogenesis

Effects of Toxoplasma gondii infection and schizophrenia comorbidity on serum lipid profile: A population retrospective study from Eastern China

https://doi.org/10.1016/j.micpath.2020.104587Get rights and content

Highlights

  • 1.

    Chronic T. gondii infection comorbidity with psychiatric disorders is common in populations.

  • 2.

    Schizophrenic patinets infected by T. gondii have less favorable lipid profile.

  • 3.

    Coinfection patients have increased serum IL-6 level.

Abstract

Introduction

Toxoplasma gondii (T. gondii), a parasitic protozoa that is associated with various psychiatric disorders. Both T. gondii infection and disturbed host's lipid profile are common in schizophrenia patients. However, the underlying pathophysiological mechanisms remain speculative. Also, the characteristics of serum lipid levels in schizophrenia patients comorbid with T. gondii infection are not clear. Therefore, it is necessary to explore the influence of chronic T. gondii infection on the characteristic physiological indexes of schizophrenia patients so as to provide some insights into finding target therapeutic drugs.

Methods

In this study, the effect of chronic T. gondii infection on serum lipid profile was retrospectively analysed in 1719 schizophrenic patients and 1552 healthy subjects from Eastern China.

Results

The overall prevalence of Immunoglobulin G (IgG) antibodies against T. gondii (17.98%) in schizophrenia patients was significantly higher than healthy controls (7.35%, χ2 = 81.831, P = 0.000). Compared to T. gondii IgG-seronegative schizophrenia patients, IgG-seropositive group had higher high-density lipoprotein (HDL) (P = 0.000) and triglycerides (TG) (P = 0.000) levels, while total cholesterol (TC) (P = 0.000) levels showed an opposite tendency in IgG-seropositive cases. We also found significant correlation between T. gondii seropositivity and increased TG (P = 0.000) and TC levels (P = 0.000) in schizophrenia patients. Binary regression analysis also showed that decreased TC level was more common among schizophrenia patients with T. gondii seropositivity compared to seronegative subjects (OR = 0.617, 95%CI = 0.509–0.749, P = 0.000).

Conclusion

Patients with chronic T. gondii infection and comorbid schizophrenia had higher HDL and TG levels, while cholesterol levels showed an opposite trend. To the best of our knowledge, this is the first report focus on the host's lipid profile of chronic T. gondii infection and comorbid schizophrenia patients.

Introduction

Schizophrenia is a heterogeneous behavioral and cognitive syndrome, which is caused by genetic and/or environmental damages to brain development. The main characteristics of schizophrenia include positive symptoms (delusions and hallucinations), negative symptoms (impaired motivation, reduced self-talk and social withdrawal) and cognitive impairment [1]. Clinical characteristics of schizophrenia are of limited predictive values, as the diagnosis currently rely on the clinical symptoms presented by patients subjectively [2]. As a result, excavating biological predictors of schizophrenia will have huge values [3,4]. Moreover, if one certain pathogen is highly associated with the occurrence of schizophrenia, it is of great significance to thoroughly understand the biological impact of this pathogen on patients with schizophrenia.

Toxoplasma gondii (T. gondii) exposure is confirmed to be consistently associated with increased rate of schizophrenia incidence [5]. T. gondii, a neurotropic protozoan that was characterised at the turn of the 20th century and later proved to be associated with a series of congenital sensory and neurological conditions [6]. The publishing of a scientific American editorial in 1896, which proposed that “Is insanity due to a microbe?” was the starting point of discussions on the infectious etiology of schizophrenia. Mounting evidence showed a strong association between T. gondii and schizophrenia [7,8]. Increased exposure to T. gondii has been found in a range of mental disorders, including: psychotic symptoms, bipolar disorder [9], self-directed violence [10] and suicide attempts, generalized anxiety disorder [11], mixed anxiety and depression [12], obsessive-compulsive disorder [13], autism [14] and depression during pregnancy [15]. Emerging research suggested that T. gondii exposure was not only a risk factor for schizophrenia, but also for a series of other diseases.

Dyslipidemia is a critical risk factor for cardiovascular diseases [16]. Emerging evidence showed that T. gondii was associated with increased incidence of dyslipidemia [17,18]. Preclinical research confirmed a complex correlation between T. gondii infection and host's lipid metabolism. As T. gondii is unable to synthesize cholesterol by itself, so that it can only utilize endocytosed low-density lipoprotein (LDL) from the hosts to form cholesterol, which is an important composition of the parasitophorous vacuole [19,20]. As a result, T. gondii infection may generally reduce serum total cholesterol (TC) levels in animal models [21] or human beings [22], due to its increased uptake. Patients with schizophrenia also had been reported to have dyslipidemia [23,24]. T. gondii infection and disorder of serum lipid profile are common pheonomena of schizophrenia. However, the profile of serum lipid in patients with T. gondii infection and comorbid schizophrenia is almost unknown. In this paper, the biochemical indexes of serum lipids in schizophrenia patients comorbid with T. gondii infection in Eastern China were analysed retrospectively. The aim of our study was to provide some valuable indicators for the diagnosis of dyslipidemia in this special population: T. gondii infection and comorbid schizophrenia patients.

Section snippets

Study population and data collection

A retrospective study was conducted on schizophrenic patients who were screened for anti-T. gondii IgG antibody in Suzhou Guangji Hospital (Suzhou Institute of Mental Health, Jiangsu Province, China) and Wuxi Mental Health Center from 2002 to 2007. During this period, 1719 patients were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV. Structured Clinical Interview for DSM-IV (SCID-IV) was used for extensive psychiatric assessment [25]. In addition, we also

The association between chronic Toxoplasma gondii infection and psychiatric disorders

A total of 1552 healthy participants and 1719 schizophrenia patients were involved in our study as shown in Fig. 1. Based on selection criteria described in “Materials and Methods” part, 114 subjects were defined as anti-T. gondii IgG positive cases (7.35%) in healthy group, while the number of schizophrenia group was 309 (17.98%). The rate of anti-T. gondii antibody positivity in schizophrenic was significantly higher than that in healthy controls (Trend χ2 = 81.831; P = 0.000) (Fig. 2A).

In

Discussions

Previous epidemiological studies have shown that patients with mental illness may have a high incidence of T. gondii infection, which is associated with physiological and mental disorders of the hosts [13,[35], [36], [37], [38]]. However, little is known about the interaction between T. gondii infection and mental illness. In this study, we retrospectively studied schizophrenia patients screened for T. gondii infection in Eastern China. Our results showed that the positive rate of T. gondii-IgG

Conclusion

In conclusion, our study confirmed that chronic T. gondii infection was associated with schizophrenia. We also suggested that psychiatric patients were at higher risk of infection with T. gondii. We further confirmed the existence of a profoundly association between T. gondii infection and the serum lipid modulation in schizophrenia patients. This study indicated that coinfection of other pathogens should be considered in the clinical intervention to lipid levels of schizophrenic patients.

Author statement

Yonghua Zhou: Conceptualization, Supervision, Funding acquisition; Fei Xu: Conceptualization, Methodology, Writing - Original draft preparation, Methodology, Funding acquisition, Resources, Data curation;Xinyu Ma: Data curation, Writing- Original draft preparation, Methodology, Resources; Yuwei Zhu: Data curation, Writing- Original draft preparation, Methodology, Investigation; Arjen Sutterland: Writing- Reviewing and Editing,Validation,Data curation, Methodology; Ruitang Cheng: Writing-

Funding

This work was supported by grants from Natural Science Foundation of Jiangsu Province (Grant no. BK20190597), Wuxi Science and Technology Development Fund 2018 (Grant no.WX18IIAN010), Chinese Postdoctoral Science Fund (Grant no. 2019M661729), Health Project of Science and Education (Grant no. ZDXKA2016016), Medical Science and Technology Project of Health Commission of Jiangsu Province (Grant no. YB2017048). This study was also funded by the Social Development Foundation of Jiangsu Provence (

Availability of data and materials

All the data supporting the study findings are within the manuscript. Additional detailed information will be shared upon request addressed to the corresponding author.

Ethics approval and consent to participate

The study was reviewed and approved by permission from the Ethical Committee of Jiangsu Institute of Parasitic Diseases (the Institutional Review Board, IRB 00004221, JIPD-2001-005).

Consent for publication

Not applicable.

Declaration of competing interest

The authors declare that they have no competing interests.

Acknowledgements

We thank Quanyong Guo, Rongsheng Zhang, Hongyuan Li from Suzhou Guangji Hospital and Zhiqiang Wang from Wuxi Mental Health Center for their help in the process of specimen diagnosis and collection. We also thank the general support of experimental public platform, Wuxi School of medicine, Jiangnan University and Jiangsu Institute of Parasitic Diseases and Public Health Research Center.

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      These studies were: 4 from US (Frye et al., 2019; Parks et al., 2018; Tanaka et al., 2017; Yolken et al., 2017), 7 from Europe (France: 3 (Hamdani et al., 2015; Hamdani et al., 2018); Germany: 3 (Gerber et al., 2012; Hinze-Selch et al., 2010; Oliveira et al., 2016; Stich et al., 2015); The Netherlands: 1 (Snijders et al., 2019)), 4 from Asia (China: 3 (Chen et al., 2019; Xiao et al., 2010; Xu et al., 2020)); India: 1 (Sundaresh et al., 2018)), 5 from Middles East or Arabic countries (Iran: 4 (Abdollahian et al., 2017; Dalimiasl et al., 2016; Khademvatan et al., 2013; Kheirandish et al., 2016); Saudi Arabia: 1 (Afifi et al., 2018)), 2 from Africa (Egypt: 1 (Hussein et al., 2020); Ethiopia: 1 (Tedla et al., 2011)), 1 from Mexico (Alvarado-Esquivel et al., 2019). Clinical diagnosis was carried out according to the DSM criteria in 15 studies (DSM-IV in 14 studies (Afifi et al., 2018; Chen et al., 2019; Frye et al., 2019; Gerber et al., 2012; Hamdani et al., 2015; Hamdani et al., 2018; Khademvatan et al., 2013; Oliveira et al., 2016; Snijders et al., 2019; Stich et al., 2015; Sundaresch et al., 2018; Tanaka et al., 2017; Xu et al., 2020; Yolken et al., 2017), DSM-5 in 1 study (Hussein et al., 2020). In the remaining studies, the ICD-10 criteria were used in 3 studies (Alvarado-Esquivel et al., 2019; Hinze-Selch et al., 2010; Tedla et al., 2011), and 5 studies applied clinical criteria without detailing the procedure for the diagnosis (Abdollahian et al., 2017; Dalimiasl et al., 2016; Kheirandish et al., 2016; Parks et al., 2018; Xiao et al., 2010).

    1

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