Different presence of Chlamydia pneumoniae, herpes simplex virus type 1, human herpes virus 6, and Toxoplasma gondii in schizophrenia: meta-analysis and analytical study

In the present study we have performed both a meta-analysis and an analytical study exploring the presence of Chlamydia pneumoniae, herpes simplex virus type 1, human herpes virus 6, and Toxoplasma gondii antibodies in a sample of 143 schizophrenic patients and 143 control subjects. The meta-analysis was performed on papers published up to April 2014. The presence of serum immunoglobulin G and immunoglobulin A was performed by enzyme-linked immunosorbent assay test. The detection of microbial DNA in total peripheral blood was performed by nested polymerase chain reaction. The meta-analysis showed that: 1) C. pneumoniae DNA in blood and brain are more common in schizophrenic patients; 2) there is association with parasitism by T. gondii, despite the existence of publication bias; and 3) herpes viruses were not more common in schizophrenic patients. In our sample only anti-Toxoplasma immunoglobulin G was more prevalent and may be a risk factor related to schizophrenia, with potential value for prevention.

[1]  J. Lucas,et al.  Reduced striatal dopamine DA D2 receptor function in dominant-negative GSK-3 transgenic mice , 2014, European Neuropsychopharmacology.

[2]  S. Leucht,et al.  Haloperidol versus low-potency first-generation antipsychotic drugs for schizophrenia. , 2014, The Cochrane database of systematic reviews.

[3]  Xiaobai Li,et al.  Effects of prenatal chronic mild stress exposure on hippocampal cell proliferation, expression of GSK-3α, β and NR2B in adult offspring during fear extinction in rats , 2014, International Journal of Developmental Neuroscience.

[4]  Yong-Ku Kim,et al.  The role of pro-inflammatory cytokines in the neuroinflammation and neurogenesis of schizophrenia , 2014, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[5]  F. Dickerson,et al.  Exposure to herpes simplex virus, type 1 and reduced cognitive function. , 2013, Journal of psychiatric research.

[6]  D. Inta,et al.  Pharmacological blockade of GluN2B-containing NMDA receptors induces antidepressant-like effects lacking psychotomimetic action and neurotoxicity in the perinatal and adult rodent brain , 2013, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[7]  K. Hashimoto,et al.  Prenatal immune activation and subsequent peripubertal stress as a new model of schizophrenia , 2013, Expert review of neurotherapeutics.

[8]  R. Yolken,et al.  Antiherpes virus-specific treatment and cognition in schizophrenia: a test-of-concept randomized double-blind placebo-controlled trial. , 2013, Schizophrenia bulletin.

[9]  D. Inta,et al.  The differential effects of acute vs. chronic stress and their combination on hippocampal parvalbumin and inducible heat shock protein 70 expression , 2013, Neuroscience.

[10]  F. Bruschi,et al.  Toxoplasmosis and neuropsychiatric diseases: can serological studies establish a clear relationship? , 2013, Neurological Sciences.

[11]  J. Feldon,et al.  Stress in Puberty Unmasks Latent Neuropathological Consequences of Prenatal Immune Activation in Mice , 2013, Science.

[12]  G. McConkey,et al.  Toxoplasma gondii infection, from predation to schizophrenia: can animal behaviour help us understand human behaviour? , 2013, Journal of Experimental Biology.

[13]  F. Dickerson,et al.  Exposure to herpes simplex virus type 1 and cognitive impairments in individuals with schizophrenia. , 2012, Schizophrenia bulletin.

[14]  L. Klei,et al.  Persistent infection with neurotropic herpes viruses and cognitive impairment , 2012, Psychological Medicine.

[15]  R. Yolken,et al.  Maternal antibodies to infectious agents and risk for non-affective psychoses in the offspring—a matched case–control study , 2012, Schizophrenia Research.

[16]  B. Gutiérrez,et al.  Infectious agents associated with schizophrenia: A meta-analysis , 2012, Schizophrenia Research.

[17]  Dennis Velakoulis,et al.  Structural abnormalities in the cuneus associated with Herpes Simplex Virus (type 1) infection in people at ultra high risk of developing psychosis , 2012, Schizophrenia Research.

[18]  F. Dickerson,et al.  Additive effects of elevated C-reactive protein and exposure to Herpes Simplex Virus type 1 on cognitive impairment in individuals with schizophrenia , 2012, Schizophrenia Research.

[19]  D. Kelly,et al.  Adjunct minocycline to clozapine treated patients with persistent schizophrenia symptoms , 2011, Schizophrenia Research.

[20]  T. Werge,et al.  Association of GRIN1 and GRIN2A‐D With schizophrenia and genetic interaction with maternal herpes simplex virus‐2 infection affecting disease risk , 2011, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[21]  J. Marín,et al.  Estandarización y validación clínica de la prueba de reacción en cadena de la polimerasa (PCR) para diagnóstico de toxoplasmosis cerebral en pacientes infectados por el VIH , 2011 .

[22]  J. Dubey,et al.  The Neurotropic Parasite Toxoplasma Gondii Increases Dopamine Metabolism , 2011, PloS one.

[23]  T. Lerman-Sagie,et al.  Prenatal brain imaging in congenital toxoplasmosis , 2011, Prenatal diagnosis.

[24]  R. Yolken,et al.  Progressive gray matter loss and changes in cognitive functioning associated with exposure to herpes simplex virus 1 in schizophrenia: a longitudinal study. , 2011, The American journal of psychiatry.

[25]  P. Mortensen,et al.  Toxoplasma infection and later development of schizophrenia in mothers. , 2011, The American journal of psychiatry.

[26]  R. Wank,et al.  Increased prevalence of Chlamydophila DNA in post-mortem brain frontal cortex from patients with schizophrenia , 2011, Schizophrenia Research.

[27]  R. Yolken,et al.  Antibodies to infectious agents and the positive symptom dimension of subclinical psychosis: The TRAILS study , 2011, Schizophrenia Research.

[28]  M. Regulska,et al.  Prenatal lipopolysaccharide treatment enhances MK-801-induced psychotomimetic effects in rats , 2011, Pharmacology Biochemistry and Behavior.

[29]  Terry L. Jernigan,et al.  The Basics of Brain Development , 2010, Neuropsychology Review.

[30]  M. Pittler Systematic Reviews in Health Care: Meta‐analysis in Context , 2010 .

[31]  F. Dickerson,et al.  Neuroanatomic and cognitive abnormalities related to herpes simplex virus type 1 in schizophrenia , 2010, Schizophrenia Research.

[32]  B. Czéh,et al.  Stress Impairs GABAergic Network Function in the Hippocampus by Activating Nongenomic Glucocorticoid Receptors and Affecting the Integrity of the Parvalbumin-Expressing Neuronal Network , 2010, Neuropsychopharmacology.

[33]  Enrico Fainardi,et al.  Chlamydophila pneumoniae Infection and Its Role in Neurological Disorders , 2010, Interdisciplinary perspectives on infectious diseases.

[34]  F. Dickerson,et al.  Toxoplasma and schizophrenia , 2009, Parasite immunology.

[35]  Tyrone D. Cannon,et al.  Serological pattern consistent with infection with type I Toxoplasma gondii in mothers and risk of psychosis among adult offspring. , 2009, Microbes and infection.

[36]  D. Inta,et al.  Differential c-Fos induction by different NMDA receptor antagonists with antidepressant efficacy: potential clinical implications. , 2009, The international journal of neuropsychopharmacology.

[37]  J. Gutiérrez,et al.  Chlamydophila pneumoniae: desde su proteómica hasta la arteriosclerosis , 2008 .

[38]  A. Aker,et al.  The schizophrenia and Toxoplasma gondii connection: Infectious, immune or both? , 2008, Advances in therapy.

[39]  P. Boksa Maternal infection during pregnancy and schizophrenia. , 2008, Journal of psychiatry & neuroscience : JPN.

[40]  Douglas G. Altman,et al.  Systematic reviews in health care : meta-analysis in context , 2008 .

[41]  R. Yolken,et al.  Results From a Hypothesis Generating Case-Control Study: Herpes Family Viruses and Schizophrenia Among Military Personnel , 2007, Schizophrenia bulletin.

[42]  R. Yolken,et al.  Antibodies to Infectious Agents in Individuals at Ultra-High Risk for Psychosis , 2007, Biological Psychiatry.

[43]  Yasuhiro Suzuki,et al.  Effects of Toxoplasma gondii infection on the brain. , 2007, Schizophrenia bulletin.

[44]  R. Yolken,et al.  Early infections of Toxoplasma gondii and the later development of schizophrenia. , 2007, Schizophrenia bulletin.

[45]  O. Geçici,et al.  Anti-Toxoplasma gondii antibodies in patients with schizophrenia--preliminary findings in a Turkish sample. , 2007, Schizophrenia bulletin.

[46]  F. Dickerson,et al.  Toxoplasma gondii in individuals with schizophrenia: association with clinical and demographic factors and with mortality. , 2007, Schizophrenia bulletin.

[47]  R. Yolken,et al.  Antibodies to Toxoplasma gondii in patients with schizophrenia: a meta-analysis. , 2007, Schizophrenia bulletin.

[48]  J. Flegr Effects of toxoplasma on human behavior. , 2007, Schizophrenia bulletin.

[49]  D. Hinze‐Selch,et al.  A controlled prospective study of toxoplasma gondii infection in individuals with schizophrenia: beyond seroprevalence. , 2007, Schizophrenia bulletin.

[50]  R. Yolken,et al.  Editors' Introduction: Schizophrenia and Toxoplasmosis , 2007 .

[51]  R. Yolken,et al.  Toxoplasma gondii as a Risk Factor for Early-Onset Schizophrenia: Analysis of Filter Paper Blood Samples Obtained at Birth , 2007, Biological Psychiatry.

[52]  R. Wank,et al.  Associations between Chlamydophila infections, schizophrenia and risk of HLA-A10 , 2007, Molecular Psychiatry.

[53]  O. Liesenfeld,et al.  Seroepidemiology of Toxoplasma gondii infection in psychiatric inpatients in a northern Mexican city , 2006, BMC infectious diseases.

[54]  Hui-ling Wang,et al.  Prevalence of Toxoplasma infection in first‐episode schizophrenia and comparison between Toxoplasma‐seropositive and Toxoplasma‐seronegative schizophrenia , 2006, Acta psychiatrica Scandinavica.

[55]  Alan S. Brown,et al.  Prenatal infection as a risk factor for schizophrenia. , 2006, Schizophrenia bulletin.

[56]  Charles P Quesenberry,et al.  Maternal exposure to toxoplasmosis and risk of schizophrenia in adult offspring. , 2005, The American journal of psychiatry.

[57]  R. Yolken,et al.  Antibodies to infectious agents in individuals with recent onset schizophrenia , 2004, European Archives of Psychiatry and Clinical Neuroscience.

[58]  R. Yolken,et al.  Herpesviruses and Toxoplasma gondii in orbital frontal cortex of psychiatric patients , 2003, Schizophrenia Research.

[59]  R. Kahn,et al.  Schizophrenia after prenatal exposure to Toxoplasma gondii? , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[60]  J. Gutiérrez,et al.  ELISA test to detect Chlamydophila pneumoniae IgG , 2002, Journal of basic microbiology.

[61]  R. Yolken,et al.  Maternal infections and subsequent psychosis among offspring. , 2001, Archives of general psychiatry.

[62]  J. M. Rubio,et al.  Genotypic Characterization of Toxoplasma gondii Strains Associated with Human Toxoplasmosis in Spain: Direct Analysis from Clinical Samples , 2001, Journal of Clinical Microbiology.

[63]  R. Yolken,et al.  Antibodies to Toxoplasma gondii in individuals with first-episode schizophrenia. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[64]  P. Coyle,et al.  Description of a Nonlethal Herpes Simplex Virus Type 1 Glycoprotein D Deletion Mutant Affecting a Site Frequently Used for PCR , 2000, Clinical Diagnostic Laboratory Immunology.

[65]  R. Fukuda,et al.  No Changes in Paired Viral Antibody Titers during the Course of Acute Schizophrenia , 1999, Neuropsychobiology.

[66]  M. Isohanni,et al.  Schizophrenia as a long-term outcome of pregnancy, delivery, and perinatal complications: a 28-year follow-up of the 1966 north Finland general population birth cohort. , 1998, The American journal of psychiatry.

[67]  G. Smith,et al.  Bias in meta-analysis detected by a simple, graphical test , 1997, BMJ.

[68]  Y. Ohtsuki,et al.  Human herpesvirus 6 (HHV-6)-positive Burkitt's lymphoma: establishment of a novel cell line infected with HHV-6. , 1997, Blood.

[69]  C. Begg,et al.  Operating characteristics of a rank correlation test for publication bias. , 1994, Biometrics.

[70]  T. Kawayama,et al.  [Detection of Chlamydia pneumoniae by polymerase chain reaction]. , 1993, Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases.

[71]  M. Casanova,et al.  Search for evidence of herpes simplex virus, type 1, or varicella‐zoster virus infection in postmortem brain tissue from schizophrenic patients , 1992, Acta psychiatrica Scandinavica.

[72]  T. Crow,et al.  Search for viral nucleic acid sequences in the post mortem brains of patients with schizophrenia and individuals who have committed suicide. , 1987, Journal of neurology, neurosurgery, and psychiatry.

[73]  L. DeLisi,et al.  Herpes simplex virus, cytomegalovirus and Epstein–Barr virus antibody titres in sera from schizophrenic patients , 1986, Psychological Medicine.

[74]  N. Laird,et al.  Meta-analysis in clinical trials. , 1986, Controlled clinical trials.

[75]  T. Crow,et al.  Viruses in human brains: a search for cytomegalovirus and herpes virus 1 DNA in necropsy tissue from normal and neuropsychiatric cases , 1986, Psychological Medicine.

[76]  J. Stevens,et al.  A search for cytomegalovirus and herpes viral antigen in brains of schizophrenic patients. , 1984, Archives of general psychiatry.

[77]  Stefan Leucht,et al.  Fluphenazine versus low-potency first-generation antipsychotic drugs for schizophrenia. , 2014, The Cochrane database of systematic reviews.

[78]  A. Camacho,et al.  [Chlamydophila pneumoniae: from its proteomics to arteriosclerosis]. , 2008, Enfermedades infecciosas y microbiologia clinica.

[79]  D. Cowan,et al.  Selected infectious agents and risk of schizophrenia among U.S. military personnel. , 2008, The American journal of psychiatry.

[80]  W. Alexander American psychiatric association. , 2008, P & T : a peer-reviewed journal for formulary management.

[81]  R. Yolken,et al.  Schizophrenia and toxoplasmosis. , 2007, Schizophrenia bulletin.

[82]  R. Yolken,et al.  Brain morphological changes associated with exposure to HSV1 in first-episode schizophrenia , 2007, Molecular Psychiatry.

[83]  J. Zonis,et al.  Antibodies to Epstein-Barr virus, herpes simplex type 1, cytomegalovirus and measles virus in psychiatric patients , 2005, Archives of Virology.

[84]  R. Wank,et al.  High risk of schizophrenia and other mental disorders associated with chlamydial infections: hypothesis to combine drug treatment and adoptive immunotherapy. , 2005, Medical hypotheses.

[85]  S. Mesa-Castillo [An ultrastructural study of the temporal lobe and peripheral blood in schizophrenic patients]. , 2001, Revista de neurologia.

[86]  J. Kleinman,et al.  Search for viral nucleic acid sequences in brain tissues of patients with schizophrenia using nested polymerase chain reaction. , 1996, Archives of general psychiatry.

[87]  Y. Ginot,et al.  Herpes simplex virus and cytomegalovirus in the serum of schizophrenic patients versus other psychosis and normal controls. , 1992, The Israel journal of psychiatry and related sciences.