Prenatal Adversity and Inflammation at Birth Predict White Matter Integrity at Age 7 Years
Poster No:
1230
Submission Type:
Abstract Submission
Authors:
Justin Yuan1, Jessica Buthmann1, Zhen Ming Ngoh2, Aisleen Manahan2, Ai Peng Tan2, Michael Meaney2,3,4, Ian Gotlib1
Institutions:
1Stanford University, Stanford, CA, 2Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research in Singapore, Singapore City, Singapore, 3Liggins Institute, University of Auckland, Grafton, Auckland, New Zealand, 4Douglas Hospital Research Centre, McGill University, Montreal, Quebec, Canada
First Author:
Co-Author(s):
Zhen Ming Ngoh
Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research in Singapore
Singapore City, Singapore
Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research in Singapore
Singapore City, Singapore
Aisleen Manahan
Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research in Singapore
Singapore City, Singapore
Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research in Singapore
Singapore City, Singapore
Ai Peng Tan
Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research in Singapore
Singapore City, Singapore
Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research in Singapore
Singapore City, Singapore
Michael Meaney
Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research in Singapore|Liggins Institute, University of Auckland|Douglas Hospital Research Centre, McGill University
Singapore City, Singapore|Grafton, Auckland, New Zealand|Montreal, Quebec, Canada
Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research in Singapore|Liggins Institute, University of Auckland|Douglas Hospital Research Centre, McGill University
Singapore City, Singapore|Grafton, Auckland, New Zealand|Montreal, Quebec, Canada
Introduction:
Elevated levels of inflammation are associated with difficulties in psychological functioning. Specifically, neuroimaging studies have shown that even in nonclinical populations, such as typically developing adolescents, higher concentrations of inflammatory markers are associated with problems in emotion regulation and reward processing1, suggesting an important role of immune function in neurodevelopment. This may occur through the impact of acute inflammation on developmental processes such as cell migration, synaptogenesis, and pruning2, associations that appear to be potentiated by the experience of adversity early in life3. Evidence of these relations in humans has typically come from studies of samples of adolescents or older individuals4-7. Here we examined whether these associations are present in early childhood. Specifically, we examined whether prenatal adversity significantly moderates the association between inflammatory status at birth and white matter maturation in the cingulum tract at age seven years.
Methods:
We analyzed data from 201 mother-child dyads participating in the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study. Participants provided data relevant to three constructs: prenatal adversity, inflammatory cytokine concentration at birth, and limbic white matter maturation at age 7. Prenatal adversity was assessed by creating a composite score derived from multiple adversity factors, including maternal physical and mental health, socioeconomic status, family function, and the child's birthweight and preterm status. Inflammatory levels were assessed by measuring the concentration of the proinflammatory cytokine interleukin 6 (IL-6) from a sample of cord blood obtained at birth. Concentration values were measured using a Quanterix SIMOA HD-1 3-plex immunoassay and log-transformed. White matter maturation was assessed using data from an MRI scan conducted when the child was age 7 years (M[SD]; range=7.0[0.1]; 6.9-7.3 years). We assessed fractional anisotropy (FA) of the cingulum tract (cingulate gyrus portion), yielding an index of maturation of a brain structure underlying limbic system function. FA values were obtained from a 3T multi-shell diffusion weighted sequence, processed using FSL's probabilistic tractography pipeline (BEDPOSTX and PROBTRACKX). To analyze the data, we conducted stepwise regression, first testing for the main effects of prenatal adversity and IL-6, separately, predicting cingulum FA. To test whether adversity moderated this association, we modeled the interaction of prenatal aversity and IL-6 predicting cingulum FA at age 7 years. The interaction was probed using simple slopes analysis and the Johnson-Neyman technique. Child sex, race, and exact age at scan were included as covariates in the model.
Results:
There was a significant positive main effect of prenatal adversity (β=0.16, p=0.031), but not of cord blood IL-6 (β=0.06, p=0.379), predicting year 7 cingulum FA. There was also a significant interaction between prenatal aversity and cord blood IL-6 predicting cingulum FA (β=0.16, p=0.028). Specifically, in children exposed to higher levels of prenatal adversity, elevated IL-6 was associated with higher cingulum FA (Figure 1).
Conclusions:
We found in this study that exposure to prenatal adversity significantly moderated the association between inflammatory status at birth and maturation of the cingulum. These findings are consistent with past neuroimmune research, suggesting that the immune system influences neurodevelopment at a younger age than has previously been documented. Further, our results are consistent with theoretical frameworks suggesting that adversity exposure is associated with accelerated development8 across various indices of biological aging9. Overall, these findings underscore the long-term effects of experiencing prenatal adversity and highlight how the immune system may shape early neurodevelopment.
Emotion, Motivation and Social Neuroscience:
Emotion and Motivation Other
Lifespan Development:
Early life, Adolescence, Aging 1
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis
Physiology, Metabolism and Neurotransmission :
Physiology, Metabolism and Neurotransmission Other 2
Keywords:
Development
Emotions
Limbic Systems
MRI
PEDIATRIC
STRUCTURAL MRI
White Matter
Other - Inflammation;Adversity;Stress
1|2Indicates the priority used for review
Provide references using author date format
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