Maternal cortisol during pregnancy and offspring schizophrenia: Influence of fetal sex and timing of exposure

Maternal stress during pregnancy has been repeatedly linked to increased risk for schizophrenia; however, no study has examined maternal cortisol during pregnancy and risk for the disorder. Study aims were to determine whether prenatal cortisol was associated with risk for schizophrenia and risk for...

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Published inSchizophrenia research Vol. 213; pp. 15 - 22
Main Authors Ellman, Lauren M., Murphy, Shannon K., Maxwell, Seth D., Calvo, Evan M., Cooper, Thomas, Schaefer, Catherine A., Bresnahan, Michaeline A., Susser, Ezra S., Brown, Alan S.
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier B.V 01.11.2019
Subjects
Adult
Birth weight
Birth Weight - physiology
Cohort Studies
Cortisol
Female
Fetal Development - physiology
Fetal growth
Humans
Hydrocortisone - blood
Male
Obstetric complications
Phenotype
Pregnancy - blood
Prenatal Exposure Delayed Effects - etiology
Schizophrenia
Schizophrenia - etiology
Sex Factors
Stress
Time Factors
Young Adult
Fetal growth
Schizophrenia
Cortisol
Birth weight
Obstetric complications
Stress
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Summary:Maternal stress during pregnancy has been repeatedly linked to increased risk for schizophrenia; however, no study has examined maternal cortisol during pregnancy and risk for the disorder. Study aims were to determine whether prenatal cortisol was associated with risk for schizophrenia and risk for an intermediate phenotype—decreased fetal growth—previously linked to prenatal cortisol and schizophrenia. Timing of exposure and fetal sex also were examined given previous findings. Participants were 64 cases diagnosed with schizophrenia spectrum disorders (SSD) and 117 controls from a prospective birth cohort study. Maternal cortisol was determined from stored sera from each trimester and psychiatric diagnoses were assessed from offspring using semi-structured interviews and medical records review. Maternal cortisol during pregnancy was not associated with risk for offspring schizophrenia. There was a significant interaction between 3rd trimester cortisol and case status on fetal growth. Specifically, cases exposed to higher 3rd trimester maternal cortisol had significantly decreased fetal growth compared to controls. In addition, these findings were restricted to male offspring. Our results indicate that higher prenatal cortisol is associated with an intermediate phenotype linked to schizophrenia, fetal growth, but only among male offspring who developed schizophrenia. Findings were consistent with evidence that schizophrenia genes may disrupt placental functioning specifically for male fetuses, as well as findings that males are more vulnerable to maternal cortisol during pregnancy. Finally, results suggest that examining fetal sex and intermediate phenotypes may be important in understanding the mechanisms involved in prenatal contributors to schizophrenia.
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Dr. Ellman came up with the idea for the manuscript and the present study, she was involved with the processes of cortisol analyses (i.e., interactions with the lab for serological analyses), she wrote the majority of the manuscript, she contributed to the statistical analyses (and supervised the statistical analyses of the data analyst in her lab), and she coordinated communication between all of the co-authors. Shannon Murphy contributed to writing the introduction and editing the manuscript. Seth Maxwell conducted most of the statistical analyses (under the supervision of Dr. Ellman), cleaned the data, provided descriptive statistics, and edited the manuscript. Evan Calvo created all of the tables for the manuscript, conducted some literature reviews, edited the manuscript, and checked the descriptive statistics for accuracy. Thomas Cooper conducted all of the serological analyses of cortisol in his lab and consulted on issues pertaining to cortisol analyses. Dr. Schaefer was integrally involved in data collection for the original PDS study, including locating potential cases and obtaining diagnoses through chart review and semi-structured interviews. Dr. Bresnahan was very involved in the original PDS study; including maintaining/creating the PDS databases and being involved with accurately documenting consensus call decisions. Dr. Susser was the PI of the original PDS study and was involved in every aspect of the study design and execution. Dr. Brown also was involved in the original PDS study, including participating on consensus calls, and was Dr. Ellman's postdoctoral mentor when she conceived of the present study; therefore, he advised her on every aspect of this study and funded the cortisol analyses. All authors contributed edits to the final manuscript.
Contributors
ISSN:0920-9964
1573-2509
DOI:10.1016/j.schres.2019.07.002