title: Maternal complement C1q and increased odds for psychosis in adult offspring.
abstract: The presence of maternal antibodies to food and infectious antigens may confer an increased risk of developing schizophrenia and psychosis in adult offspring. Complement factor C1q is an immune molecule with multiple functions including clearance of antigen-antibody complexes from circulation and mediation of synaptic pruning during fetal brain development. To determine if maternal C1q was associated with offspring schizophrenia and psychosis, we evaluated 55 matched case-control maternal serum pairs from the National Collaborative Perinatal Project. Sample pairs were composed of mothers whose offspring developed psychoses as adults and those whose offspring were free from psychiatric disease. Matching criteria for offspring included birth date, delivery hospital, race, and gender, with further matching based on mother's age. IgG markers of C1q, bovine milk casein, egg ovalbumin, and wheat gluten were measured with enzyme-linked immunosorbent assays. C1q levels were compared to food antigen IgG and to previously generated data for C-reactive protein, adenovirus, herpes simplex viruses, influenza viruses, measles virus, and Toxoplasma gondii. C1q was significantly elevated in case mothers with odds ratios of 2.66-6.31 (conditional logistic regressions, p ≤ 0.008-0.05). In case mothers only, C1q was significantly correlated with antibodies to both food and infectious antigens: gluten (R(2)=0.26, p ≤ 0.004), herpes simplex virus type 2 (R(2)=0.21, p ≤ 0.02), and adenovirus (R(2)=0.25, p ≤ 0.006). In conclusion, exposure to maternal C1q activity during pregnancy may be a risk factor for the development of schizophrenia and psychosis in offspring. Prenatal measurement of maternal C1q may be an important and convergent screening tool to identify potentially deleterious immune activation from multiple sources.
authors.affiliation: Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 1105, Baltimore, MD 21287-4933 USA. Electronic address: eseverance@jhmi.edu.
authors.forename: Emily G
authors.initials: EG
authors.lastname: Severance
authors.affiliation: Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 1105, Baltimore, MD 21287-4933 USA.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Gressitt
authors.affiliation: Department of Epidemiology, School of Public Health, Brown University, Providence, RI, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Buka
authors.affiliation: Department of Psychology, Yale University, 2 Hillhouse Avenue, New Haven, CT, USA.
authors.forename: Tyrone D
authors.initials: TD
authors.lastname: Cannon
authors.affiliation: Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 1105, Baltimore, MD 21287-4933 USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Yolken
mesh_terms: D032721:Adult Children; D016022:Case-Control Studies; D015922:Complement C1q / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005512:Food Hypersensitivity / Q000453:epidemiology; D006801:Humans; D008137:Longitudinal Studies; D009035:Mothers; D016017:Odds Ratio; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000453:epidemiology; D015597:Pregnancy Complications, Parasitic / Q000453:epidemiology; D011297:Prenatal Exposure Delayed Effects; D011446:Prospective Studies; D011618:Psychotic Disorders / Q000453:epidemiology / Q000276:immunology*; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology / Q000276:immunology*; D055815:Young Adult
chemical_list: D015922:Complement C1q
keywords: Inflammation; Innate immune activation; Maternal exposure; Maternal–fetal interface; Synapses