Background. Native Americans disproportionately experience adverse childhood experiences (ACEs) as well as health disparities,\r\nincluding high rates of posttraumatic stress, depression, and substance abuse.Many ACEs have been linked to methylation changes\r\nin genes that regulate the stress response, suggesting that these molecular changes may underlie the risk for psychiatric disorders\r\nrelated to ACEs. Methods.We reviewed published studies to provide evidence that ACE-related methylation changes contribute to\r\nhealth disparities in Native Americans. This frameworkmay be adapted to understand how ACEs may result in health disparities in\r\nother racial/ethnic groups. Findings. Here we provide evidence that links ACEs to methylation differences in genes that regulate the\r\nstress response. Psychiatric disorders are also associated withmethylation differences in endocrine, immune, and neurotransmitter\r\ngenes that serve to regulate the stress response and are linked to psychiatric symptoms and medical morbidity.We provide evidence\r\nlinking ACEs to these epigenetic modifications, suggesting that ACEs contribute to the vulnerability for developing psychiatric\r\ndisorders in Native Americans. Conclusion. Additional studies are needed to better understand how ACEs contribute to health and\r\nwell-being. These studies may inform future interventions to address these serious risks and promote the health and well-being of\r\nNative Americans.
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