Prenatal Maternal Depressive Symptoms Impact Neonatal Brain via Insulin-IGF-IGFBF pathways
Poster No:
2129
Submission Type:
Abstract Submission
Authors:
Xiang Zhou1, Yap Seng Chong2, Peter Gluckman2, Michael Meaney2,3,4, Anqi Qiu1,5,6
Institutions:
1Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, 2Institute for Human Development and Potential, Singapore, Singapore, 3Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Canada, Canada, 4Sackler Program for Epigenetics & Psychobiology at McGill University, Canada, Canada, 5Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore, 6Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, United States
First Author:
Xiang Zhou
Department of Health Technology and Informatics, The Hong Kong Polytechnic University
Hung Hom, Hong Kong
Department of Health Technology and Informatics, The Hong Kong Polytechnic University
Hung Hom, Hong Kong
Co-Author(s):
Michael Meaney
Institute for Human Development and Potential|Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University|Sackler Program for Epigenetics & Psychobiology at McGill University
Singapore, Singapore|Canada, Canada|Canada, Canada
Institute for Human Development and Potential|Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University|Sackler Program for Epigenetics & Psychobiology at McGill University
Singapore, Singapore|Canada, Canada|Canada, Canada
Anqi Qiu
Department of Health Technology and Informatics, The Hong Kong Polytechnic University|Department of Biomedical Engineering, National University of Singapore|Department of Biomedical Engineering, The Johns Hopkins University
Hung Hom, Hong Kong|Singapore, Singapore|Baltimore, United States
Department of Health Technology and Informatics, The Hong Kong Polytechnic University|Department of Biomedical Engineering, National University of Singapore|Department of Biomedical Engineering, The Johns Hopkins University
Hung Hom, Hong Kong|Singapore, Singapore|Baltimore, United States
Introduction:
Maternal depression during pregnancy is associated with adverse neural, behavioral, and psychological outcomes in offspring (Van den Bergh et al., 2020). Previous studies suggest that insulin, insulin-like growth factors (IGFs), and IGF-binding proteins (IGFBPs) may play pivotal roles in linking maternal depression and fetal brain development (Fernandez-Pereira et al., 2023; Rethelyi et al., 2023). Moreover, gestational diabetes mellitus(GDM), associated with cognitive impairment in offspring(Marra et al., 2024), is also linked to IGF1 levels(Zhu et al., 2016). However, physiological mechanisms underlying these effects remain poorly understood.
Here, we utilized a longitudinal birth cohort to investigate the role of insulin-IGF-IGFBP pathways in moderating the relationship between prenatal maternal depressive symptoms, child brain morphology at birth and developmental outcomes at two years.
Here, we utilized a longitudinal birth cohort to investigate the role of insulin-IGF-IGFBP pathways in moderating the relationship between prenatal maternal depressive symptoms, child brain morphology at birth and developmental outcomes at two years.
Methods:
This study included 1,013 mother-child dyads with gestational ages above 34 weeks. Of these, 988 mothers provided placental blood samples at 26–28 gestational weeks; 183 neonates underwent brain imaging; and 412 children completed Bayley Scales of Infant Development Third Edition(BSID-III) at two years.
Maternal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS) at 26 weeks and 3 months postpartum. Levels of insulin, IGFs, and IGFBPs were measured from maternal blood samples collected at 26-28 gestational weeks. Neonatal cortical thickness was derived from processed T2-weighted MRI data. Infant developmental outcomes at 24 months were assessed using the BSID-III, covering 5 domains: cognitive, language, motor, social-emotional, and adaptive behavior.
Demographic differences between the full sample and those with neonatal imaging were analyzed using Student's t-tests and chi-square tests for continous and categorical variables, respectively.
Linear regression models examined interactions between plasma markers and prenatal depressive symptoms on neonatal cortical thickness, adjusting for sex, gestational age, maternal education, GDM, and ethnicity. The same models assessed interactions with child neurodevelopmental outcomes, with postnatal depressive symptoms as an additional covariate.
Maternal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS) at 26 weeks and 3 months postpartum. Levels of insulin, IGFs, and IGFBPs were measured from maternal blood samples collected at 26-28 gestational weeks. Neonatal cortical thickness was derived from processed T2-weighted MRI data. Infant developmental outcomes at 24 months were assessed using the BSID-III, covering 5 domains: cognitive, language, motor, social-emotional, and adaptive behavior.
Demographic differences between the full sample and those with neonatal imaging were analyzed using Student's t-tests and chi-square tests for continous and categorical variables, respectively.
Linear regression models examined interactions between plasma markers and prenatal depressive symptoms on neonatal cortical thickness, adjusting for sex, gestational age, maternal education, GDM, and ethnicity. The same models assessed interactions with child neurodevelopmental outcomes, with postnatal depressive symptoms as an additional covariate.
Results:
Demographic characteristics of the study population, including the full sample (n=1,013) and the neonatal imaging subset (n=183), are summarized in Fig. 1.
The interplay between maternal depressive symptoms and specific plasma levels of IGFBP1, IGFBP4, and IGFBP7 during pregnancy reveals a compelling influence on neonatal brain development. Notably, lower levels of IGFBP1 amplified the negative link between maternal depressive symptoms and cortical thickness in the left temporal cortex (t = -4.22, p < 0.001; Fig. 2A). Similarly, for IGFBP4, reduced levels exacerbated the negative association observed in the left superior frontal cortex (t = -3.89, p < 0.001; Fig. 2B). Interestingly, the pattern shifted for IGFBP7, where lower levels moderated a positive relationship between maternal depressive symptoms and cortical thickness in the left temporal cortex (t = 2.63, p = 0.01; Fig. 2C). These findings underscore the nuanced role of IGFBPs in shaping the neonatal brain in the context of prenatal maternal mental health.
Greater maternal depressive symptoms were linked to poorer cognitive and motor functions at two years of age in children whose mothers had higher plasma levels of IGFBP1 and IGFBP4 (Fig. 2D-E). These findings suggest that elevated IGFBP1 and IGFBP4 levels may amplify the adverse effects of prenatal maternal depressive symptoms on offspring neurodevelopment.
The interplay between maternal depressive symptoms and specific plasma levels of IGFBP1, IGFBP4, and IGFBP7 during pregnancy reveals a compelling influence on neonatal brain development. Notably, lower levels of IGFBP1 amplified the negative link between maternal depressive symptoms and cortical thickness in the left temporal cortex (t = -4.22, p < 0.001; Fig. 2A). Similarly, for IGFBP4, reduced levels exacerbated the negative association observed in the left superior frontal cortex (t = -3.89, p < 0.001; Fig. 2B). Interestingly, the pattern shifted for IGFBP7, where lower levels moderated a positive relationship between maternal depressive symptoms and cortical thickness in the left temporal cortex (t = 2.63, p = 0.01; Fig. 2C). These findings underscore the nuanced role of IGFBPs in shaping the neonatal brain in the context of prenatal maternal mental health.
Greater maternal depressive symptoms were linked to poorer cognitive and motor functions at two years of age in children whose mothers had higher plasma levels of IGFBP1 and IGFBP4 (Fig. 2D-E). These findings suggest that elevated IGFBP1 and IGFBP4 levels may amplify the adverse effects of prenatal maternal depressive symptoms on offspring neurodevelopment.
·Figure 1 Demographics
·Figure 2. Interactions between plasma markers and prenatal maternal depression on neonatal cortical thickness and developmental functions.
Conclusions:
This study highlights the critical role of the insulin-IGF-IGFBP pathway in shaping the effects of prenatal maternal depressive symptoms on offspring neurodevelopment. The findings underscore the need for targeted interventions addressing maternal psychological and metabolic health during pregnancy to improve children's neurodevelopmental outcomes.
Higher Cognitive Functions:
Higher Cognitive Functions Other
Modeling and Analysis Methods:
Multivariate Approaches 2
Physiology, Metabolism and Neurotransmission:
Physiology, Metabolism and Neurotransmission Other 1
Keywords:
Other - Prenatal Maternal Depression
1|2Indicates the priority used for review
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Rethelyi, J. M., Vincze, K., Schall, D., Glennon, J., & Berkel, S. (2023). The role of insulin/IGF1 signalling in neurodevelopmental and neuropsychiatric disorders - Evidence from human neuronal cell models. Neurosci Biobehav Rev, 153, 105330. https://doi.org/10.1016/j.neubiorev.2023.105330
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Zhu, Y., Mendola, P., Albert, P. S., Bao, W., Hinkle, S. N., Tsai, M. Y., & Zhang, C. (2016). Insulin-Like Growth Factor Axis and Gestational Diabetes Mellitus: A Longitudinal Study in a Multiracial Cohort. Diabetes, 65(11), 3495-3504. https://doi.org/10.2337/db16-0514