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Genet Med. 2016 Apr;18(4):350-5. doi: 10.1038/gim.2015.84. Epub 2015 Jun 18.

Fetal growth and gestational factors as predictors of schizophrenia in 22q11.2 deletion syndrome.

Van L1,2, Butcher NJ1,3, Costain G1,2, Ogura L1, Chow EW1,4, Bassett AS1,3,4,5,6,7,8.

Author information

1
Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
2
Undergraduate Medical Education, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
3
Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
4
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
5
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
6
Department of Psychiatry, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
7
Division of Cardiology, Department of Medicine, University Health Network, Toronto, Ontario, Canada.
8
The Dalglish Family Hearts and Minds Clinic for Adults with 22q11.2 Deletion Syndrome, University Health Network, Toronto, Ontario, Canada.

Abstract

PURPOSE:

Schizophrenia occurs in 20-25% of adults with 22q11.2 deletion syndrome (22q11.2DS). General population studies of schizophrenia report associations with perinatal complications, although effect sizes are generally low. We aimed to determine whether such factors are associated with expression of schizophrenia in individuals with 22q11.2DS.

METHODS:

We investigated the relationship of small for gestational age (SGA) birth weight (<3rd percentile for sex and gestational age) and prematurity (<37 weeks gestation) to expression of schizophrenia in a well-characterized cohort of 123 adults with 22q11.2DS. Outcome measures included adjusted odds ratios and positive and negative predictive values (PPV and NPV) for schizophrenia.

RESULTS:

SGA birth weight (OR = 3.52, 95% CI = 1.34-9.22) and prematurity (OR = 5.38, 95% CI = 1.63-17.75), but not maternal factors, were significant risk factors for schizophrenia in 22q11.2DS. Being born SGA or premature resulted in a PPV of 46% for schizophrenia; NPV in the absence of both features was 83%. Post hoc analyses suggested these perinatal complications were also associated with factors indicative of increased severity of schizophrenia.

CONCLUSION:

In 22q11.2DS, fetal growth and gestation may have a clinically significant impact on future risk for schizophrenia. These data advance our understanding of determinants of disease-specific expression in 22q11.2DS, with implications for other genomic disorders.Genet Med 18 4, 350-355.

PMID:
26087175
DOI:
10.1038/gim.2015.84
[Indexed for MEDLINE]

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