Poster No:
1293
Submission Type:
Abstract Submission
Authors:
Shi Yu Chan1, Eamon Fitzgerald2, Zhen Ming Ngoh3, Janice Lee1, Jasmine Chuah1, Marielle Fortier4, Juan Helen Zhou5, Patricia Silveira2, Michael Meaney3, Ai Peng Tan6
Institutions:
1Singapore Institute for Clinical Sciences, Singapore, Singapore, 2McGill University, Montreal, Quebec, 3Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research in Singapore, Singapore City, Singapore, 4KK Women's and Children's Hospital, Singapore, Singapore, 5National University of Singapore, Singapore, Singapore, 6National University Hospital, Singapore, Others
First Author:
Shi Yu Chan
Singapore Institute for Clinical Sciences
Singapore, Singapore
Co-Author(s):
Zhen Ming Ngoh
Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research in Singapore
Singapore City, Singapore
Janice Lee
Singapore Institute for Clinical Sciences
Singapore, Singapore
Jasmine Chuah
Singapore Institute for Clinical Sciences
Singapore, Singapore
Michael Meaney
Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research in Singapore
Singapore City, Singapore
Ai Peng Tan
National University Hospital
Singapore, Others
Introduction:
The biological embedding of early life experiences on neurodevelopment is postulated to be mediated through the immune system (Berens, Jensen et al. 2017). As the brain's resident immune cell, microglia play a role in environmental surveillance and respond to both adverse and enriched environments (Cathomas, Holt et al. 2022). Microglia have also been shown to regulate neurodevelopment, including synaptic plasticity (Cathomas, Holt et al. 2022). White matter development, indexed by changes in fractional anisotropy (FA), affect a variety of psychopathological outcomes (Stephens, Langworthy et al. 2020), and is shaped by early life environment and genetic factors (Lebel and Deoni 2018). Thus, individual variation in microglia function may interact with early life experiences to influence white matter development. In this study, we examined the associations between microglia function, early life environment and white matter FA slopes. We also explored the sex-dependency of these associations.
Methods:
Diffusion imaging data and T1-weighted images were collected from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) cohort (Soh, Tint et al. 2014) over three time-points (age 4.5, 6.0, 7.5 years) from early to mid-childhood. 351 participants had diffusion imaging data collected at more than one time-point and were included in the current study. Diffusion datasets were processed in FMRIB's Software Library (FSL v6.0.4) (Smith, Jenkinson et al. 2004) to calculate parametric maps of FA. T1-weighted images were processed with the FreeSurfer v6.0 recon-all pipeline (Fischl 2012) to obtain bilateral cerebral white matter masks. We applied the bilateral white matter mask to the FA maps to extract mean white matter FA. Individual variation in microglia function was indexed by an expression-based microglia polygenic score (ePGS). Two cumulative prenatal environment scores (adverse and advantageous) were derived from demographic and maternal health measures during pregnancy (Silveira, Pokhvisneva et al. 2017). Linear mixed effects models were used to estimate white matter FA slopes over childhood for each participant. Spearman's correlation and linear regression models were used to examine the associations between microglia ePGS, white matter FA slopes, sex and prenatal environment.
Results:
We observed a significant association between individual estimates of white matter FA slopes and microglia ePGS scores (Spearman's rho = 0.144, p = 0.008). This association was modulated by sex (Microglia ePGS:sex interaction: p = 0.026), where a significant positive correlation was only observed for females (Spearman's rho = 0.243, p = 0.0013). Similarly, a significant interaction between microglia ePGS and an advantageous prenatal environment on white matter FA slopes was observed for females (estimate = -0.221, Std Error = 0.084, t-value = -2.63, p = 0.01), but not for males (p = 0.745). In addition, we did not observe a significant interaction between microglia ePGS and an adverse prenatal environment on white matter FA slopes for both males and females (all p > 0.3).
Conclusions:
We show that a significant association between an advantageous prenatal environment and white matter development was only observed in females with high microglia ePGS. Our findings suggest that variations in microglia function may explain the heterogeneity in individual susceptibility to early life environment on white matter development.
Genetics:
Genetic Association Studies
Lifespan Development:
Normal Brain Development: Fetus to Adolescence 1
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
White Matter Anatomy, Fiber Pathways and Connectivity 2
Keywords:
Development
Glia
Modeling
MRI
PEDIATRIC
Sexual Dimorphism
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
1|2Indicates the priority used for review
Provide references using author date format
Berens, A. E. (2017). "Biological embedding of childhood adversity: from physiological mechanisms to clinical implications." BMC Medicine 15(1): 135.
Cathomas, F. (2022). "Beyond the neuron: Role of non-neuronal cells in stress disorders." Neuron 110(7): 1116-1138.
Fischl, B. (2012). "FreeSurfer." Neuroimage 62(2): 774-781.
Lebel, C. (2018). "The development of brain white matter microstructure." Neuroimage 182: 207-218.
Silveira, P. P. (2017). "Cumulative prenatal exposure to adversity reveals associations with a broad range of neurodevelopmental outcomes that are moderated by a novel, biologically informed polygenetic score based on the serotonin transporter solute carrier family C6, member 4 (SLC6A4) gene expression." Development and Psychopathology 29(5): 1601-1617.
Smith, S. M. (2004). "Advances in functional and structural MR image analysis and implementation as FSL." Neuroimage 23 Suppl 1: S208-219.
Soh, S. E. (2014). "Cohort profile: Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort study." International Journal of Epidemiology 43(5): 1401-1409.
Stephens, R. L. (2020). "White Matter Development from Birth to 6 Years of Age: A Longitudinal Study." Cerebral Cortex 30(12): 6152-6168.