Dataset Information

FKBP5 Moderates the Association between Antenatal Maternal Depressive Symptoms and Neonatal Brain Morphology.

ABSTRACT: Antenatal maternal depressive symptoms influence fetal brain development and increase the risk for depression in offspring. Such vulnerability is often moderated by the offspring's genetic variants. This study aimed to examine whether FKBP5, a key regulator of the hypothalamic-pituitary-adrenal (HPA) axis, moderates the association between antenatal maternal depressive symptoms and in utero brain development, using an Asian cohort with 161 mother-offspring dyads. Antenatal maternal depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS) during the second trimester of pregnancy. Neonatal structural brain images were acquired using magnetic resonance imaging (MRI) shortly after birth. Maternal and neonatal FKBP5 gene was genotyped using Illumina OmniExpress arrays. A gene set-based mixed effect model for gene-environment interaction (MixGE) was used to examine interactive effects between neonatal genetic variants of FKBP5 and antenatal maternal depressive symptoms on neonatal amygdala and hippocampal volumes, and cortical thickness. Our study revealed that genetic variants in neonatal FKBP5 moderate the association between antenatal maternal depressive symptoms and right hippocampal volume but only show a trend for such moderation on amygdala volumes and cortical thickness. Our findings are the first to reveal that the association between maternal depressive symptoms and in utero neurodevelopment of specific brain regions is modified through complex genetic variation in neonatal FKBP5. Our results suggest that an increased risk for depression may be transmitted from mother to child during fetal life and that the effect is dependent upon neonatal FKBP5 genotype.

SUBMITTER: Wang C

PROVIDER: S-EPMC5770768 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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FKBP5 Moderates the Association between Antenatal Maternal Depressive Symptoms and Neonatal Brain Morphology.

Wang Changqing C Shen Mojun M Guillaume Bryan B Chong Yap-Seng YS Chen Helen H Fortier Marielle V MV Meaney Michael J MJ Qiu Anqi A

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20171003 3

Antenatal maternal depressive symptoms influence fetal brain development and increase the risk for depression in offspring. Such vulnerability is often moderated by the offspring's genetic variants. This study aimed to examine whether FKBP5, a key regulator of the hypothalamic-pituitary-adrenal (HPA) axis, moderates the association between antenatal maternal depressive symptoms and in utero brain development, using an Asian cohort with 161 mother-offspring dyads. Antenatal maternal depressive sy ...[more]

PMID: 28975925

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Project description:Maternal prenatal depression is associated with increased likelihood of neurodevelopmental and psychiatric conditions in offspring. The relationship between maternal depression and offspring outcome may be mediated by in-utero changes in brain development. Recent advances in magnetic resonance imaging (MRI) have enabled in vivo investigations of neonatal brains, minimising the effect of postnatal influences. The aim of this study was to examine associations between maternal prenatal depressive symptoms, infant white matter, and toddler behaviour. 413 mother-infant dyads enrolled in the developing Human Connectome Project. Mothers completed the Edinburgh Postnatal Depression Scale (median = 5, range = 0-28, n = 52 scores ≥ 11). Infants (n = 223 male) (median gestational age at birth = 40 weeks, range 32.14-42.29) underwent MRI (median postmenstrual age at scan = 41.29 weeks, range 36.57-44.71). Fixel-based fibre metrics (mean fibre density, fibre cross-section, and fibre density modulated by cross-section) were calculated from diffusion imaging data in the left and right uncinate fasciculi and cingulum bundle. For n = 311, internalising and externalising behaviour, and social-emotional abilities were reported at a median corrected age of 18 months (range 17-24). Statistical analysis used multiple linear regression and mediation analysis with bootstrapping. Maternal depressive symptoms were positively associated with infant fibre density in the left (B = 0.0005, p = 0.003, q = 0.027) and right (B = 0.0006, p = 0.003, q = 0.027) uncinate fasciculus, with left uncinate fasciculus fibre density, in turn, positively associated with social-emotional abilities in toddlerhood (B = 105.70, p = 0.0007, q = 0.004). In a mediation analysis, higher maternal depressive symptoms predicted toddler social-emotional difficulties (B = 0.342, t(307) = 3.003, p = 0.003), but this relationship was not mediated by fibre density in the left uncinate fasciculus (Sobel test p = 0.143, bootstrapped indirect effect = 0.035, SE = 0.02, 95% CI: [-0.01, 0.08]). There was no evidence of an association between maternal depressive and cingulum fibre properties. These findings suggest that maternal perinatal depressive symptoms are associated with neonatal uncinate fasciculi microstructure, but not fibre bundle size, and toddler behaviour.

Project description:BackgroundAntenatal depression and antenatal anxiety adversely affect several obstetric and foetal outcomes, and increase the rate of postnatal mental illness. Thus, to tackle these challenges the need for social support during pregnancy is vital. However, an extensive literature search failed to show a published study on the relationship between domains of social support and antenatal depressive, as well as antenatal anxiety symptoms in Australia. This study examined the association between domains of social support and antenatal depressive and anxiety symptoms among Australian women.MethodsThe current study used data obtained from the 1973-78 cohort of the Australian Longitudinal Study on Women's Health (ALSWH), focusing upon women who reported being pregnant (n = 493). Depression and anxiety were assessed using the 10 item Center for Epidemiological Studies Depression (CES-D-10) scale, and the 9-item Goldberg Anxiety and Depression scale (GADS) respectively. The 19 item-Medical Outcomes Study Social Support index (MOSS) was used to assess social support. A logistic regression model was used to examine the associations between domains of social support and antenatal depressive and anxiety symptoms after adjusting for potential confounders.ResultThe current study found 24.7 and 20.9% of pregnant women screened positive for depressive and anxiety symptoms respectively. After adjusting for potential confounders, our study found that the odds of antenatal depressive symptoms was about four and threefold higher among pregnant women who reported low emotional/informational support (AOR = 4.75; 95% CI: 1.45, 15.66; p = 0.010) and low social support (overall support) (AOR = 3.26; 95%CI: 1.05, 10.10, p = 0.040) respectively compared with their counterpart. In addition, the odds of antenatal anxiety symptoms was seven times higher among pregnant women who reported low affectionate support/positive social interaction (AOR = 7.43; 95%CI: 1.75, 31.55; p = 0.006).ConclusionA considerable proportion of pregnant Australian women had depressive symptoms and/or anxiety symptoms, which poses serious health concerns. Low emotional/informational support and low affectionate support/positive social interaction have a significant association with antenatal depressive and anxiety symptoms respectively. As such, targeted screening of expectant women for social support is essential.

Dataset Information

FKBP5 Moderates the Association between Antenatal Maternal Depressive Symptoms and Neonatal Brain Morphology.

Publications

FKBP5 Moderates the Association between Antenatal Maternal Depressive Symptoms and Neonatal Brain Morphology.

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