A German Multicenter Study on Toxoplasma Gondii in First-episode Schizophrenia

Environmental risk factors for the development of schizophrenia include infections during the perinatal period or later in life with Toxoplasma gondii (TG) being one of the candidate agents. A recent review (Torrey and Yolken, 2003) on TG in schizophrenia and other serious mental disorder reported higher antibodies to TG in patients compared to controls in 18 of 19 studies, one having been conducted by the investigators group. In a second, independent study on first-episode schizophrenia (n=56) and control subjects (n=32), sera were sampled and standard instruments used to assess diagnoses and psychopathology, respectively to screening controls.

For the total sample, contacts with animals during pregnancy and age emerged as a non-significant predictors of TG IgG titers. Means of patients' and controls' TG IgG titers did not differ significantly but variances did; a subgroup of patients' titers reached much higher levels than those of controls. Patients in the high TG IgG subgroup were older (p=0.001), also they were older when psychiatric symptoms appeared, more individuals had regular animal contacts during pregnancy, or rural upbringing including regular animal contact, more consumption of raw meat, and a higher absolute treatment response (all trend levels). Regarding the short term course of patients, the investigators detected decreasing IgG titers in several individuals A power analysis demonstrated that results fell short of significance due to lack of statistical power. Based on the power analysis, the investigators propose an opel label, multicenter study at three regionally different sites within Germany (Halle, Hamm, Heidelberg). The investigators intent to study 173 first-episode patients with schizophrenia, schizoaffective, and schizophreniform disorder and 173 matched controls.

The investigators hypothesize that - according to the heterogeneity of the illness - a subgroup of patients will exhibit higher TG IgG titers compared to the remaining patients and to controls; that this subgroup will have had regular contact with animals during pregnancy and early life as well as developmental delays; and that clinical improvement, response to treatment, and subjective well-being will run parallel with TG IgG decrease.

Patients shall be assessed on admission to hospital, at discharge and at 6- and 12-month-follow-up with respect to TG antibody titers, symptomatology, neuropsychology, predictors of outcome, quality of life, and neurological soft signs. In controls two assessments shall be performed, 12 months apart. All foreseen assessments will be performed using standard measurement instruments with sound reliability and validity such as the SCID and the PANSS. Exposure to cats, other warm-blooded life-stock, and raw meat will be assessed using a special questionnaire.

Study Overview

• Status: Unknown
• Conditions: Schizophrenia; Schizoaffective Disorder; Schizophreniform Disorder
• Intervention / Treatment: Other: TAU = treatment as usual

• Study Type: Observational
• Enrollment (Anticipated): 360

Contacts and Locations

Study Locations

• Germany
  • Frankfurt/Main, Germany, 60528
    • Recruiting
    • Dpt. of Psychiatry, University of Frankfurt
    • Contact: Johannes Pantel, Professor; Phone Number: 7094 +49-69-6301; Email: johannes.pantel@kgu.de
    • Contact: Daniela Hainz, MA; Phone Number: 7094 +49-69-6301; Email: daniela.hainz@kgu.de
    • Principal Investigator: Johannes Pantel, Professor
    • Sub-Investigator: Daniela Hainz, MA
  • Halle (Saale), Germany, 06112
    • Recruiting
    • Dept. of Psychiatry, University of Halle (Saale)
    • Contact: Silke Bachmann, Deputy Director; Phone Number: 3624 +49-345-557; Email: silke.bachmann@medizin.uni-halle.de
    • Sub-Investigator: Michaela Beck, MA
    • Sub-Investigator: Friederike Haupt, PhD
  • Heidelberg, Germany, 69115
    • Recruiting
    • Dept. of Psychiatry, University of Heidelberg
    • Contact: Johannes Schroeder, Professor; Phone Number: 4403 +49-6221-56; Email: johannes.schroeder@med.uni-heidelberg.de
    • Contact: Kira Krapf, MA; Phone Number: 4403 +49-6221-56; Email: kira.krapf@med.uni-heidelberg.de
    • Principal Investigator: Johannes Schroeder, Professor
    • Principal Investigator: Kira Krapf, MA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

patients who are admitted to inpatient treatment due to a first episode of psychotic symptoms, diagnoses of schizophrenia, schizophreniform and schizoaffective disorder age- and gender-matched control subjects

Description

Inclusion Criteria:

• Key inclusion criteria will be a first episode of schizophrenia, schizoaffective or schizophreniform disorder.

Exclusion Criteria:

• Exclusion criteria will be major organic and substance induced disorders, refusal or withdrawal of IC.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1: FE; FE = first episode schizophrenia	Other: TAU = treatment as usual; medication and psychosocial interventions to be chosen by treating psychiatrist
2: CO; CO = age and gender-matched control subjects

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
falling levels of Toxoplasma IgG titers parallel clinical improvement over time, 2 follow-ups at 6 and 12 months are planned	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
clinical improvement; outcome: functioning and psychopathology	3 years

Collaborators and Investigators

• Sponsor: Martin-Luther-Universität Halle-Wittenberg
• Collaborators: Heidelberg University
• Investigators: Principal Investigator: Silke Bachmann, MD, assistant prof. psychiatry, Dept. of Psychiatry, Psychotherapy and Psychosomatics, University of Halle (Saale), Germany

Publications and helpful links

General Publications

• Torrey EF, Yolken RH. Toxoplasma gondii and schizophrenia. Emerg Infect Dis. 2003 Nov;9(11):1375-80. doi: 10.3201/eid0911.030143.
• Yolken RH, Bachmann S, Ruslanova I, Lillehoj E, Ford G, Torrey EF, Schroeder J. Antibodies to Toxoplasma gondii in individuals with first-episode schizophrenia. Clin Infect Dis. 2001 Mar 1;32(5):842-4. doi: 10.1086/319221. Epub 2001 Feb 28. Erratum In: Clin Infect Dis 2001 Apr 15;32(8):1247. Rouslanova I [corrected to Ruslanova I].
• Bachmann S, Schroder J, Bottmer C, Torrey EF, Yolken RH. Psychopathology in first-episode schizophrenia and antibodies to Toxoplasma gondii. Psychopathology. 2005 Mar-Apr;38(2):87-90. doi: 10.1159/000085349. Epub 2005 Apr 22.

Helpful Links

• The SMRI funds this study, sample analyses wil be made at the Stanley Laboratory of Developmental Neurovirology at the Johns Hopkins University, Baltimore, MD, USA

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Anticipated): December 1, 2010
• Study Completion (Anticipated): May 1, 2011

Study Registration Dates

• First Submitted: May 27, 2008
• First Submitted That Met QC Criteria: May 28, 2008
• First Posted (Estimate): May 29, 2008

Study Record Updates

• Last Update Posted (Estimate): January 25, 2010
• Last Update Submitted That Met QC Criteria: January 22, 2010
• Last Verified: May 1, 2008

More Information

Terms related to this study

• Keywords: schizophrenia; infection; Toxoplasma gondii; first-episode; levels of IgG antibodies to TG
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Disease; Psychotic Disorders
• Other Study ID Numbers: 07R-1815, SMRI