TY - JOUR
T1 - Maternal complement C1q and increased odds for psychosis in adult offspring
AU - Severance, Emily G.
AU - Gressitt, Kristin L.
AU - Buka, Stephen L.
AU - Cannon, Tyrone D.
AU - Yolken, Robert H.
N1 - Funding Information:
This work was supported by an NIMH P50 Silvio O. Conte Center at Johns Hopkins (grant# MH-94268) and by the Stanley Medical Research Institute. These funding sources had no involvement in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
Publisher Copyright:
© 2014 Elsevier B.V.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - 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 (R2=0.26, p≤0.004), herpes simplex virus type 2 (R2=0.21, p≤0.02), and adenovirus (R2=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.
AB - 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 (R2=0.26, p≤0.004), herpes simplex virus type 2 (R2=0.21, p≤0.02), and adenovirus (R2=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.
KW - Inflammation
KW - Innate immune activation
KW - Maternal exposure
KW - Maternal-fetal interface
KW - Synapses
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U2 - 10.1016/j.schres.2014.07.053
DO - 10.1016/j.schres.2014.07.053
M3 - Article
C2 - 25195065
AN - SCOPUS:84907981195
SN - 0920-9964
VL - 159
SP - 14
EP - 19
JO - Schizophrenia Research
JF - Schizophrenia Research
IS - 1
ER -