Formation of a Normative Comparison Base by Physiological Factors, Personality Dimensions and Neural Correlates

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Authors

Mak, Lauren

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thesis

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eng

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MRI , Early Life Stress , Resting-State Functional Connectivity , Sleep , Personality , Preeclampsia , Resting-State Networks

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Introduction: There is variance in a healthy population, but it is poorly characterized and understood. Variations can come from common factors like demographics, experience of early life stress (ELS), physiological factors and personality dimensions. Characterizing the heterogeneity in a non-clinical sample is important to (1) understand what “normal” is; (2) better understand the differences between healthy and pathology and; (3) identify biomarkers of vulnerability and resilience. Methods: 253 healthy controls from three CAN-BIND cohorts were assessed. Demographic data, sleep quality, personality dimensions and resting-state functional connectivity (rs-FC) were collected and analyzed. Results: Those who experienced ELS had significantly different sleep duration, quality and efficiency compared to those who did not experience ELS. Those who experienced emotional neglect were more likely to score higher on the neurotic dimension. Lastly, females are more likely to be neurotic and agreeable compared to males. Our meta-analysis found that rs-FC of the default mode network (DMN) follows an inverse U-shape where it is strongest in adulthood and weakest in children and elderly. Cognitive function is positively correlated with DMN rs-FC. Females exhibit stronger intra-network connectivity compared to males. In the CAN-BIND cohorts, we found that there are sex and age differences with seeds in all six resting-state networks of interest. All five personality dimensions exhibited sex differences in rs-FC with seeds in the DMN, fronto-parietal, salience, meso-paralimbic networks. The presence of ELS impacted rs-FC in all personality dimensions and measures of sleep quality with seeds in all six of the resting-state networks. Lastly, children born from gestations complicated from preeclampsia exhibit altered rs-FC with the bilateral amygdalae and medial prefrontal cortex – offering evidence that in utero ELS also impact neural correlates. Conclusion: The impact of our results is as follows: (1) there is natural variance in a “normal” population; (2) to parse out true clinical findings, researchers must control for our results and cannot assume that healthy controls are homogeneous and; (3) identification of vulnerability and resilient biomarkers.

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