HPA-Axis Multilocus Genetic Profile Score Moderates the Association Between Maternal Prenatal Stress and Offspring Depressive Symptoms in Young Adulthood Public

Abstract

Studies have demonstrated that maternal stress during pregnancy can cause alterations to the fetal HPA-axis, a phenomenon known as fetal programming, that may have lasting impacts on offspring outcomes. Evidence suggests that maternal prenatal stress particularly confers risk for offspring depression, but few studies have examined depressive outcomes in adulthood. Moreover, animal studies indicate that the influence of prenatal stress exposure on depression may vary with respect to offspring’s genetic risk. The present study builds upon the extant literature by examining the interaction of maternal prenatal stress and offspring HPA-axis polygenic risk to predict offspring depressive symptoms in early adulthood. 383 mother-child dyads participated in a prospective, longitudinal study spanning from pregnancy until offspring were 20 years of age. Polygenic risk was defined by a multilocus genetic profile score (MGPS) reflecting the additive risk of four HPA-axis candidate risk genes: CRHR1, FKBP5, NR3C1, and BDNF. Results indicated that the HPA-axis MGPS did not directly confer risk for offspring depressive symptoms at age 20, but the interaction of maternal prenatal stress with MGPS did. No individual risk genes were found to drive this effect. Further, our results supported the differential susceptibility model such that offspring at high genetic risk exhibited greater sensitivity to the presence or absence of maternal prenatal stress than offspring at low genetic risk. Finally, we demonstrated that this interaction was specific to maternal prenatal stress, as maternal stress during early childhood did not interact with genetic risk in the prediction of offspring depressive outcomes. Together, these findings provide the first evidence that genetic variants associated with the HPA-axis may act in a polygenic, additive fashion to moderate the association between fetal programming and offspring depression in early adulthood. 

Table of Contents

Introduction ........................................................................................... 1

Moderating Factors ......................................................................... 3

Multilocus Genetic Profile Scores ................................................... 6

The Present Study ........................................................................... 7

Methods ................................................................................................. 8

Participants ..................................................................................... 8

Measures ......................................................................................... 9

Results .................................................................................................. 11

Discussion ............................................................................................ 14

References ............................................................................................ 22

Figures and Tables ................................................................................ 33

Table 1 .......................................................................................... 33

Table 2 .......................................................................................... 33

Table 3 .......................................................................................... 34

Table 4 .......................................................................................... 35

Figure 1 ........................................................................................ 36 

About this Master's Thesis

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School	Laney Graduate School
Department	Psychology
Subfield / Discipline	Clinical Psychology
Degree	M.A.
Submission	Master's Thesis
Language	English
Research Field	Biology, Genetics Psychology, Psychobiology Psychology, Clinical
Mot-clé	GxE interaction HPA-axis Polygenic risk Prenatal stress Depression
Committee Chair / Thesis Advisor	Patricia A. Brennan, Emory University
Committee Members	Kim Wallen, Emory University Edward Craighead, Emory University

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