Prenatal Maternal Depression and Genes in Relation with Amygdala-Cortical Circuits from Birth to Childhood

Abstract

Background: Prenatal maternal depression and genetic risks for depression may have long-term impacts on amygdala-cortical development. This study explored influences of genetic and prenatal maternal depression risk factors on the amygdala-cortical structural covariance in a relatively large sample at birth (n=180), 4.5 (n=225) and 6 (n=256) years of age. Methods: Structural magnetic resonance imaging was performed to obtain the amygdala volume and cortical thickness at each time point and to assess structural covariance of amygdala-cortical circuits. Prenatal maternal depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS). Genetic risk was quantified using a polygenic risk score for major depressive disorder (PRSMDD). Regression analysis was used to examine effects of EPDS and PRSMDD on structural coupling between the amygdala volume and cortical thickness at each time point. Findings: Girls with high PRSMDD showed negative coupling between the amygdala volume and inferior temporal/fusiform thickness at both 4.5 (β=- 0.303, p= 0.028) and 6 years of age (β=-0.372, p=0.004) and negative coupling between the amygdala volume and middle frontal thickness only at 6 years of age (β=-0.315, p=0.019). On the other hand, girls with high prenatal maternal depressive symptoms showed positive coupling between the amygdala volume and insula thickness at birth (β=0.617, p=0.001) but negative coupling between amygdala volume and inferior frontal thickness at age of 4.5 years (β=-0.369, p=0.008). No findings were found in boys at any time point. Interpretation: The vulnerability of the development of the amygdala-cortical circuitry to environmental and genetic risk factors related to depression might be sex-dependent. Funding Statement: This research is supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Programme and administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC), SingaporeNMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014. Additional funding is provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore Ministry of Education (Academic research fund tier 1; NUHSRO/2017/052/T1-SRP-Partnership/01), and NUS Institute of Data Science, Singapore. Declaration of Interests: No author has conflict of interest. Ethics Approval Statement: The prospective Growing Up in Singapore Towards healthy Outcomes (GUSTO) longitudinal birth cohort study was approved by the National Healthcare Group Domain Specific Review Board (NHG DSRB) and the Sing Health Centralized Institutional Review Board (CIRB). Written informed consent was obtained from mothers.