Advertisement

Toxoplasma gondii as a Risk Factor for Early-Onset Schizophrenia: Analysis of Filter Paper Blood Samples Obtained at Birth

      Background

      Infections during fetal life or neonatal period, including infections with Toxoplasma gondii, may be associated with a risk for schizophrenia and other mental disorders. The objectives of this study were to study the association between serological markers for maternal and neonatal infection and the risk for schizophrenia, related psychoses, and affective disorders in a national cohort of newborns.

      Methods

      This study was a cohort-based, case-control study combining data from national population registers and patient registers and a national neonatal screening biobank in Denmark. Patients included persons born in Denmark in 1981 or later followed up through 1999 with respect to inpatient or outpatient treatment for schizophrenia or related disorders (ICD-10 F2) or affective disorders (ICD-10 F3).

      Results

      Toxoplasma gondii immunoglobulin G (IgG) levels corresponding to the upper quartile among control subjects were significantly associated with schizophrenia risk (odds ratio [OR] = 1.79, p = .045) after adjustment for urbanicity of place of birth, year of birth, gender, and psychiatric diagnoses among first-degree relatives. There was no significant association between any marker of infection and other schizophrenia-like disorders or affective disorders.

      Conclusions

      Our study supports an association between Toxoplasma gondii and early-onset schizophrenia. Further studies are needed to establish if the association is causal and if it generalizes to cases with onset after age 18.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Barr C.E.
        • Mednick S.A.
        • Munk Jorgensen P.
        Exposure to influenza epidemics during gestation and adult schizophrenia.
        Arch Gen Psychiatry. 1990; 47: 869-874
        • Boronow J.
        • Dickerson F.
        • Stallings C.
        HSV-1 and toxoplasma serology predict cognitive deficits in schizophrenia.
        Schizophr Res. 2002; 53: 85
        • Boulanger L.M.
        • Shatz C.J.
        Immune signalling in neural development, synaptic plasticity and disease.
        Nat Rev Neurosci. 2004; 5: 521-531
        • Brown A.S.
        • Begg M.D.
        • Gravenstein S.
        • Schaefer C.A.
        • Wyatt R.J.
        • Bresnahan M.
        • et al.
        Serologic evidence of prenatal influenza in the etiology of schizophrenia.
        Arch Gen Psychiatry. 2004; 61: 774-780
        • Brown A.S.
        • Cohen P.
        • Greenwald S.
        • Susser E.
        Nonaffective psychosis after prenatal exposure to rubella.
        Am J Psychiatry. 2000; 157: 438-443
        • Brown A.S.
        • Schaefer C.A.
        • Quesenberry Jr, C.P.
        • Liu L.
        • Babulas V.P.
        • Susser E.S.
        Maternal exposure to toxoplasmosis and risk of schizophrenia in adult offspring.
        Am J Psychiatry. 2005; 162: 767-773
        • Brown A.S.
        • Schaefer C.A.
        • Wyatt R.J.
        • Goetz R.
        • Begg M.D.
        • Gorman J.M.
        • et al.
        Maternal exposure to respiratory infections and adult schizophrenia spectrum disorders: A prospective birth cohort study.
        Schizophr Bull. 2000; 26: 287-295
        • Buka S.L.
        • Tsuang M.T.
        • Torrey E.F.
        • Klebanoff M.A.
        • Bernstein D.
        • Yolken R.H.
        Maternal infections and subsequent psychosis among offspring.
        Arch Gen Psychiatry. 2001; 58: 1032-1037
        • Caroff S.N.
        • Mann S.C.
        • Gliatto M.F.
        • Sullivan K.A.
        • Campbell E.C.
        Psychiatric manifestations of acute viral encephalitis.
        Psychiatr Ann. 2001; 31: 193-204
        • Chen Z.H.
        The relationship between toxoplasma infection and schizophrenia 136 cases.
        Neo-Med. 1999; 4: 179-180
        • Desmonts G.
        • Couvreur J.
        Toxoplasmosis in pregnancy and its transmission to the fetus.
        Bull N Y Acad Med. 1974; 50: 146-159
        • Gu H.
        • Yolken R.H.
        • Phillips M.
        Evidence of toxoplasma gondii infection in recent-onset schizophrenia.
        Schizophr Res. 2001; 49: 53
      1. Huilang W, Gaohua W, Qiuying L (submitted): Prevalence of toxoplasma infection in first-episode schizophrenia and comparison between toxoplasma-positive and toxoplasma-negative schizophrenia.

        • Kessing L.V.
        Validity of diagnoses and other register data in patients with affective disorder.
        Eur Psychiatry. 1998; 13: 392-398
        • Laursen T.M.
        • Labouriau R.
        • Licht R.W.
        • Bertelsen A.
        • Munk-Olsen T.
        • Mortensen P.B.
        Family history of psychiatric illness as risk factor for schizoaffective disorder.
        Arch Gen Psychiatry. 2005; 62: 841-848
        • Lebech M.
        • Andersen O.
        • Christensen N.C.
        • Hertel J.
        • Nielsen H.E.
        • Peitersen B.
        • et al.
        Feasibility of neonatal screening for toxoplasma infection in the absence of prenatal treatment.
        Lancet. 1999; 353: 1834-1837
        • Leweke F.M.
        • Gerth C.W.
        • Koethe D.
        • Klosterkotter J.
        • Ruslanova I.
        • Krivogorsky B.
        • et al.
        Antibodies to infectious agents in individuals with recent onset schizophrenia.
        Eur Arch Psychiatry Clin Neurosci. 2004; 254: 4-8
        • Lian D.Y.
        An investigation of Toxoplasma gondii antibodies in patients with mental diseases.
        Chin J Parasit Dis Contr. 1996; 9: 299-300
        • Lu Z.M.
        Serological investigation of toxoplasma gondii infection in schizophrenia patients.
        Chin J Parasit Dis Contr. 2002; 15: 299-300
        • Ly U.C.
        Investigation of Toxplasma infection in patients with mental disorders.
        J Clin Psychol Med Settings. 1995; 5: 86-87
        • Malig C.
        The civil registration system in Denmark.
        Technical Papers IIVRS. 1996; 66: 1-6
        • McGrath J.
        • Saha S.
        • Welham J.
        • El Saadi O.
        • MacCauley C.
        • Chant D.
        A systematic review of the incidence of schizophrenia: The distribution of rates and the influence of sex, urbanicity, migrant status and methodology.
        BMC Med. 2004; 2: 13
        • Mednick S.A.
        • Huttunen M.O.
        • Machon R.A.
        Prenatal influenza infections and adult schizophrenia.
        Schizophr Bull. 1994; 20: 263-267
        • Mortensen P.B.
        • Pedersen C.B.
        • Westergaard T.
        • Wohlfahrt J.
        • Ewald H.
        • Mors O.
        • et al.
        Effects of family history and place and season of birth on the risk of schizophrenia.
        N Engl J Med. 1999; 340: 603-608
        • Munk-Jørgensen P.
        Faldende førstegangsindlæggelsesrater for skizofreni i Danmark 1970-1991 [Decreasing first admission rates in schizophrenia in Denmark 1970–1991].
        Dissertation, Department of Psychiatric Demography, Aarhus, Denmark. 1995
        • Munk-Jørgensen P.
        • Mortensen P.B.
        The Danish Psychiatric Central Register.
        Dan Med Bull. 1997; 44: 82-84
        • Niebuhr D.W.
        • Yolken R.H.
        • Millikan A.M.
        The military new-onset psychosis project: A resource for the study of gene-environment interactions among persons with severe mental illness.
        Schizophr Bull. 2005; 31: 233
        • Nørgaard-Pedersen B.
        • Simonsen H.
        Biological specimen banks in neonatal screening.
        Acta Paediatr Suppl. 1999; 88: 106-109
        • Qiuying L.
        • Xiaonian L.L.L.
        The control study of schizophrenia and affective disorders and toxoplasma infections.
        J Acta Academiae Medicinae Hubei. 1999; 20: 223-225
        • Suvisaari J.
        • Haukka J.
        • Tanskanen A.
        • Hovi T.
        • Lonnqvist J.
        Association between prenatal exposure to poliovirus infection and adult schizophrenia.
        Am J Psychiatry. 1999; 156: 1100-1102
        • Torrey E.F.
        Functional psychoses and viral encephalitis.
        Integr Psychiatry. 1986; 4: 224-236
        • Torrey E.F.
        • Rawlings R.
        • Waldman I.N.
        Schizophrenic births and viral diseases in two states.
        Schizophr Res. 1988; 1: 73-77
        • Torrey E.F.
        • Yolken R.H.
        Could schizophrenia be a viral zoonosis transmitted from house cats?.
        Schizophr Bull. 1995; 21: 167-171
        • Torrey E.F.
        • Yolken R.H.
        Toxoplasma gondii and schizophrenia.
        Emerg Infect Dis. 2003; 9: 1375-1380
        • Wang S.J.
        Detection of antibody against Toxoplasma gondii in schizophrenia patients by methods ELISA and IHA.
        Chin J Parasit Dis Contr. 1995; 12: 68
        • Yolken R.H.
        • Bachmann S.
        • Ruslanova I.
        • Lillehoj E.
        • Ford G.
        • Torrey E.F.
        • et al.
        Antibodies to Toxoplasma gondii in individuals with first-episode schizophrenia.
        Clin Infect Dis. 2001; 32: 842-844
        • Yu W.Q.
        Study of the correlation of toxoplasma gondii infection and schizophrenia.
        Chin J Parasit Dis Contr. 1999; 12: 69-70
      2. Zhu S, Lun S-R, Chin X-G (submitted): More epidemiological evidence support that psychosis is linked to toxoplasma gondii infection.