Dataset Information

Hypothyroxinemia During Gestation and Offspring Schizophrenia in a National Birth Cohort.

ABSTRACT: Evidence from animal and human studies indicates that thyroid hormone deficiency during early gestation alters brain development. As schizophrenia is associated with prenatal brain insults and premorbid cognitive deficits, we tested the a priori hypothesis that serologically defined maternal thyroid deficiency during early gestation to mid-gestation is associated with schizophrenia in offspring.The investigation is based on the Finnish Prenatal Study of Schizophrenia, a nested case-control study that included archived maternal sera from virtually all pregnancies since 1983 (N = >1 million). We identified all offspring in the cohort with a diagnosis of schizophrenia based on the national inpatient and outpatient register and matched them on sex, date of birth, and residence in Finland at time of onset of the case to comparison subjects (1:1) from the cohort. Maternal sera of 1010 case-control pairs were assessed for free thyroxine, and sera of 948 case-control pairs were assessed for thyroid-stimulating hormone.Maternal hypothyroxinemia (free thyroxine ?10th percentile, normal thyroid-stimulating hormone) was associated with an increased odds of schizophrenia (odds ratio = 1.75, 95% confidence interval = 1.22-2.50, p = .002). When adjusted for maternal psychiatric history, province of birth, and maternal smoking during pregnancy, the association remained significant (odds ratio = 1.70, 95% confidence interval = 1.13-2.55, p = .010).In a large, national birth cohort, prospectively documented hypothyroxinemia during early gestation to mid-gestation was associated with increased odds of schizophrenia in offspring. This information can inform translational studies of maternal hypothyroxinemia examining molecular and cellular deviations relevant to schizophrenia.

SUBMITTER: Gyllenberg D

PROVIDER: S-EPMC4684794 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hypothyroxinemia During Gestation and Offspring Schizophrenia in a National Birth Cohort.

Gyllenberg David D Sourander Andre A Surcel Heljä-Marja HM Hinkka-Yli-Salomäki Susanna S McKeague Ian W IW Brown Alan S AS

Biological psychiatry 20150619 12

<h4>Background</h4>Evidence from animal and human studies indicates that thyroid hormone deficiency during early gestation alters brain development. As schizophrenia is associated with prenatal brain insults and premorbid cognitive deficits, we tested the a priori hypothesis that serologically defined maternal thyroid deficiency during early gestation to mid-gestation is associated with schizophrenia in offspring.<h4>Methods</h4>The investigation is based on the Finnish Prenatal Study of Schizop ...[more]

PMID: 26194598

Similar Datasets

Project description:All subjects were recruited at Centennial Women?s Hospital and the Perinatal Research Center in Nashville, TN beginning in 2003. Pregnant women were enrolled during their first clinical visit after obtaining informed consent as described previously. Demographic and clinical data specific to the fetus was collected from clinical records. Gestational age of the neonate was determined by maternal reporting of the last menstrual period and corroboration by ultrasound dating. Accurate knowledge of gestational age (GA) is essential for proper monitoring and care of neonates. However, accurate GA measures are often not available. DNA methylation has previously been shown to associate with GA, and has been used to accurately predict chronological age in adults. In the current study, we examine whether DNA methylation in cord blood can be used to predict gestational age at birth. Results: We found that GA can be accurately predicted from DNA methylation of neonatal cord blood and blood spot samples (DNAm GA), using 148 CpG sites selected through elastic net regression in six training datasets (N=207). We evaluated predictive accuracy in six testing datasets (N=1,202), and found that the accuracy of DNAm GA meets or exceeds accuracy of gestational age estimates based on established methods. We also found an increased DNAm GA, relative to clinical GA, was associated with increased birthweight percentile (p=.00057), adjusting for GA, sex, and ancestry, suggesting that DNAm GA could represent developmental age more accurately than clinical estimates of GA. Conclusions: Further development of this predictor could provide a method of accurate neonatal estimation of GA for use in resource-limited populations, or in cases where GA cannot be estimated clinically. When clinical estimates are available, the predictor can be used to test hypotheses related to developmental age and other early life circumstances, and may provide increased accuracy beyond clinical estimates.

Dataset Information

Hypothyroxinemia During Gestation and Offspring Schizophrenia in a National Birth Cohort.

Publications

Hypothyroxinemia During Gestation and Offspring Schizophrenia in a National Birth Cohort.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure