Neural Predictors of Functional Genomic Responses to Negative Social Evaluation in Adolescent Females

BackgroundSocial stress--particularly when experienced during adolescence, can have a lasting impact on health and well-being. Among other key biological pathways, inflammatory and innate immune signaling appear to play important roles in linking stress to physical and mental health problems. Individual differences in sensitivity to social threats may leave certain people more vulnerable to stress and its harmful sequelae than others, and a growing body of research has found that stress sensitivity is reflected in neural activity throughout the threat network. However, few studies have investigated whether heightened neural sensitivity to social threats is related to acute changes in immune and neuroendocrine pathways relevant to health, particularly among those for whom the effects of stress may be especially impactful. MethodIn the current research, 52 adolescent females (MAge = 14.90, SD = 1.35) participated in a functional magnetic resonance imaging study to examine brain activity and functional connectivity during a social evaluation task. Nearly half of the sample (n = 22) were identified as having a maternal history of depression. Blood samples were collected prior to the task, as well as 35 and 65 min. after the task began, and were used for transcriptional profiling. ResultsThe primary analyses tested whether threat network activity and connectivity predicted the magnitude of change in gene expression from baseline to the follow-up time points. Results revealed robust shifts in expression of genes in innate immune pathways in response to the task (e.g., hypoxia inducible factor-1, interferon signaling). Although activity across the entire threat network was related to individual differences in gene expression, anterior cingulate cortex-insula and insula-ventromedial prefrontal cortex connectivity were most consistently related to up- and down-regulation of immune pathways, respectively. These patterns were further moderated by differences in maternal depression history. ConclusionResults demonstrate that individual differences in threat network activity may have important implications for biological responses to social threat among adolescent females. In turn, these findings both provide insights into neural signatures of social stress vulnerability and the biological pathways that may contribute to poorer health outcome among those most vulnerable to stress.