title: Reduced maternal levels of common viruses during pregnancy predict offspring psychosis: potential role of enhanced maternal immune activity?
abstract: Viral infections during the prenatal or early childhood periods are one of the environmental factors which might play an etiological role in psychoses. Several studies report higher antibody levels against viruses during pregnancy in blood of mothers of offspring with psychotic disorders, but the presence of such viruses has never been demonstrated. The goal of this study was to investigate the potential association between viral infections during pregnancy and progeny with psychotic disorders and, for this purpose, we performed a nested case-control study involving pregnant mothers of offspring with schizophrenia or bipolar disorder with psychotic features (cases, N=43) and pregnant women with healthy offspring (controls, N=95). Since several potential viral candidates have been suggested in prior work, a broad-spectrum virus detection system was necessary. A metagenomic analysis performed with the virus discovery method VIDISCA-454 revealed only common blood-associated viruses in all cohorts. However, a significantly lower viral prevalence was detected in the group of cases and in the sub-population of pregnant mothers of offspring with schizophrenia (p<0.05). Consistent with the existing inverse correlation between the level of these viruses and the immunocompetence of an individual, we hypothesized the presence of a higher immune activity during pregnancy in mothers whose offspring later develop a psychotic disorder as compared to controls. Combining our results with previously available literature data on antibody levels during the gestation period suggests that a more prominent maternal immune activity can be considered a risk factor for developing psychosis.
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands. Electronic address: marta.canuti@gmail.com.
authors.forename: Marta
authors.initials: M
authors.lastname: Canuti
authors.affiliation: Department of Epidemiology, Brown University, Providence, RI, USA. Electronic address: stephen_buka@brown.edu.
authors.forename: Stephen
authors.initials: S
authors.lastname: Buka
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Seyed Mohammad
authors.initials: SM
authors.lastname: Jazaeri Farsani
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Bas B
authors.initials: BB
authors.lastname: Oude Munnink
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Maarten F
authors.initials: MF
authors.lastname: Jebbink
authors.affiliation: Antes, Institute for Mental Health Care, Rotterdam, The Netherlands; Erasmus University Medical Center, Department of Neuroscience, Rotterdam, The Netherlands; Department of Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Nico J M
authors.initials: NJ
authors.lastname: van Beveren
authors.affiliation: Department of Psychiatry, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Lieuwe
authors.initials: L
authors.lastname: de Haan
authors.affiliation: Connors Center for Women's Health and Gender Biology, Brigham and Women's Hospital, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Goldstein
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Seidman
authors.affiliation: Center for Behavioral Genomics, Department of Psychiatry, Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA; Harvard Institute of Psychiatric Epidemiology and Genetics, Boston, USA.
authors.forename: Ming T
authors.initials: MT
authors.lastname: Tsuang
authors.affiliation: Department of Psychiatry, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Jitschak G
authors.initials: JG
authors.lastname: Storosum
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Lia
authors.initials: L
authors.lastname: van der Hoek
mesh_terms: D000293:Adolescent; D000328:Adult; D001714:Bipolar Disorder / Q000453:epidemiology*; D016022:Case-Control Studies; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D008297:Male; D054892:Metagenome; D008875:Middle Aged; D016017:Odds Ratio; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000453:epidemiology* / Q000276:immunology; D011297:Prenatal Exposure Delayed Effects; D012559:Schizophrenia / Q000453:epidemiology*; D014777:Virus Diseases / Q000453:epidemiology* / Q000276:immunology; D055815:Young Adult
chemical_list: D004279:DNA, Viral
keywords: Anelloviruses; Bipolar disorder; Psychosis; Schizophrenia; VIDISCA; Viral hypothesis for schizophrenia; Virus discovery