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      Is there any association between Toxoplasma gondii infection and depression? A systematic review and meta-analysis

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          Abstract

          Background

          Toxoplasma gondii ( T. gondii) is an obligate intracellular opportunistic parasite that is the causative agent of toxoplasmosis. This parasite accounts for mental disorders; however, the relationship between T. gondii infection and depressive disorder is unclear. Regarding this, the present systematic review and meta-analysis was conducted to investigate the scientific evidence regarding the potential association between major depression disorder (MDD) and Toxoplasma infection.

          Methods

          For the purpose of the study, the articles related to the subject of interest were systematically searched in seven electronic databases. Special attention was given to the studies examining T. gondii seropositivity level in depressed patients and controls.

          Results

          The search process resulted in the identification of a total of 30 publications meeting the inclusion criteria and published up to April 2018 for the systematic review. Furthermore, 29 studies met the inclusion criteria to be entered into meta-analysis. Our meta-analysis involved the review of cross-sectional studies including 1657 depressed patients and 19565 individuals as controls and case-control studies entailing 1311 depressed cases and 6015 controls without depression. 1582 depressed people participated in cross-sectional studies whose results were reported as odds ratio (OR). In addition, the total number of participants was 15068 in this type of studies. Statistical analysis indicated that the pooled OR of the risk of anti- T. gondii IgG antibody in depressed individuals in case-control and cross-sectional studies was 1.15 (95% confidence interval (CI): 0.95–1.39).

          Conclusions

          As the findings of the reviewed articles indicated, toxoplasmosis is not a risk factor for MDD. However, it is necessary to perform further research to clarify the detailed association between T. gondii and dysthymia or mild and moderate depression. Furthermore, it is recommended to better investigate the effect of antibody titers on the relationship between depression and T. gondii infection.

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          Most cited references54

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          Toxoplasmosis.

          JG Montoya, O. Liesenfeld (2004)
          Toxoplasma gondii is a protozoan parasite that infects up to a third of the world's population. Infection is mainly acquired by ingestion of food or water that is contaminated with oocysts shed by cats or by eating undercooked or raw meat containing tissue cysts. Primary infection is usually subclinical but in some patients cervical lymphadenopathy or ocular disease can be present. Infection acquired during pregnancy may cause severe damage to the fetus. In immunocompromised patients, reactivation of latent disease can cause life-threatening encephalitis. Diagnosis of toxoplasmosis can be established by direct detection of the parasite or by serological techniques. The most commonly used therapeutic regimen, and probably the most effective, is the combination of pyrimethamine with sulfadiazine and folinic acid. This Seminar provides an overview and update on management of patients with acute infection, pregnant women who acquire infection during gestation, fetuses or infants who are congenitally infected, those with ocular disease, and immunocompromised individuals. Controversy about the effectiveness of primary and secondary prevention in pregnant women is discussed. Important topics of current and future research are presented.
          Article 0 comments Cited 374 times – based on 0 reviews     Review now
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            Beyond the association. Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: systematic review and meta-analysis.

            A L Sutterland, G Fond, Rosanna Kuin … (2015)
            To perform a meta-analysis on studies reporting prevalence of Toxoplasma gondii (T. gondii) infection in any psychiatric disorder compared with healthy controls. Our secondary objective was to analyze factors possibly moderating heterogeneity.
            Article 0 comments Cited 151 times – based on 0 reviews     Review now
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              Gender differences in dopaminergic function in striatum and nucleus accumbens.

              Jill Becker (1999)
              In female rats the gonadal hormones estrogen and progesterone modulate dopamine (DA) activity in the striatum and nucleus accumbens. For example, there is estrous cycle-dependent variation in basal extracellular concentration of striatal DA, in amphetamine (AMPH)-stimulated DA release, and in striatal DA-mediated behaviors. Ovariectomy attenuates basal extracellular DA, AMPH-induced striatal DA release, and behaviors mediated by the striatal DA system. Estrogen rapidly and directly acts on the striatum and accumbens, via a G-protein-coupled external membrane receptor, to enhance DA release and DA-mediated behaviors. In male rats, estrogen does not affect striatal DA release, and removal of testicular hormones is without effect. These effects of estrogen also result in gender differences in sensitization to psychomotor stimulants. The effects of the gonadal hormones on the striatum and ascending DA systems projecting to the striatum and nucleus accumbens are hypothesized to occur as follows: estrogen induces a rapid change in neuronal excitability by acting on membrane receptors located in intrinsic striatal GABAergic neurons and on DA terminals. The effect of these two actions results in enhanced stimulated DA release through modulation of terminal excitability. These effects of gonadal hormones are postulated to have important implications for gender differences in susceptibility to addiction to the psychomotor stimulants. It is suggested that hormonal modulation of the striatum may have evolved to facilitate reproductive success in female rats by enhancing pacing behavior.
              Article 0 comments Cited 114 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Tooran Nayeri Chegeni: Role: Data curationRole: MethodologyRole: VisualizationRole: Writing – original draft
                Mehdi Sharif: Role: Validation
                Shahabeddin Sarvi: Role: Conceptualization
                Mahmood Moosazadeh: Role: Formal analysisRole: Software
                Mahbobeh Montazeri: Role: Visualization
                Sargis A. Aghayan: Role: Visualization
                Nader Jafari Balalami: Role: Validation
                Shirzad Gholami:
                ORCID: http://orcid.org/0000-0003-2429-7702
                Role: Investigation
                Zahra Hosseininejad: Role: Data curation
                Reza Saberi: Role: Data curation
                Davood Anvari: Role: Data curation
                Shaban Gohardehi: Role: Data curation
                Ahmad Daryani:
                ORCID: http://orcid.org/0000-0001-8571-5803
                Role: ConceptualizationRole: Project administrationRole: Writing – review & editing
                Xenia Gonda: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 13 June 2019
                Publication date Collection: 2019
                Volume: 14
                Issue: 6
                Electronic Location Identifier: e0218524
                Affiliations
                [1 ] Toxoplasmosis Research Center, Mazandaran University of Medical Sciences, Sari, Iran
                [2 ] Department of Parasitology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
                [3 ] Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran
                [4 ] Health Sciences Research Center, Addiction Institute, Mazandaran University of Medical Sciences, Sari, Iran
                [5 ] Laboratory of Zoology, Research Institute of Biology, Yerevan State University, Yerevan, Armenia
                [6 ] Department of Humanity and Social Science, Mazandaran University, Babolsar, Iran
                Semmelweis University, HUNGARY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-2429-7702
                http://orcid.org/0000-0001-8571-5803
                Article
                Publisher ID: PONE-D-18-35203
                DOI: 10.1371/journal.pone.0218524
                PMC ID: 6564815
                PubMed ID: 31194852
                SO-VID: 6feb434b-17a1-40a8-9082-801da52409bf
                Copyright © © 2019 Nayeri Chegeni et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 9 December 2018
                Date accepted : 4 June 2019
                Page count
                Figures: 6, Tables: 2, Pages: 17
                Funding
                The authors received no specific funding for this work.
                Categories
                Subject: Research Article
                Subject: Biology and Life Sciences
                Subject: Organisms
                Subject: Eukaryota
                Subject: Protozoans
                Subject: Parasitic Protozoans
                Subject: Toxoplasma
                Subject: Toxoplasma Gondii
                Subject: Medicine and Health Sciences
                Subject: Mental Health and Psychiatry
                Subject: Mood Disorders
                Subject: Depression
                Subject: Medicine and Health Sciences
                Subject: Parasitic Diseases
                Subject: Protozoan Infections
                Subject: Toxoplasmosis
                Subject: Research and Analysis Methods
                Subject: Immunologic Techniques
                Subject: Immunoassays
                Subject: Enzyme-Linked Immunoassays
                Subject: Research and Analysis Methods
                Subject: Mathematical and Statistical Techniques
                Subject: Statistical Methods
                Subject: Metaanalysis
                Subject: Physical Sciences
                Subject: Mathematics
                Subject: Statistics
                Subject: Statistical Methods
                Subject: Metaanalysis
                Subject: Research and Analysis Methods
                Subject: Research Assessment
                Subject: Systematic Reviews
                Subject: Research and Analysis Methods
                Subject: Research Design
                Subject: Cross-Sectional Studies
                Subject: Research and Analysis Methods
                Subject: Research Design
                Subject: Case-Control Studies
                Custom metadata
                Data Availability All relevant data are within the manuscript and its Supporting Information files.

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