UCLA

Adolescence is characterized by marked development in neurobiological, neuroendocrine, and psychosocial domains that are posited to contribute to the increased onset and prevalence of depression and other psychiatric disorders. Emerging research also suggests an association between inflammation and affective symptoms in adolescents; however, the neural correlates that link immune functioning and affective symptoms in adolescents have been relatively understudied. The current dissertation utilized a multi-method approach (daily diary, fMRI, venipuncture samples) to investigate the role of inflammation in modulating neural function of stress/affective circuitry in a sample of adolescents (14-15 years). Results revealed that negative affect and poor sleep (short sleep duration and high sleep variability) moderated the associations between peripheral inflammatory markers and neural activation in stress-related circuitry. Specifically, among adolescents who reported high negative affect and short sleep duration, greater levels of the pro-inflammatory tumor necrosis factor (TNF)-alpha were associated with heightened activation in frontolimbic regions (e.g., amygdala, medial prefrontal cortex [MPFC]) on an fMRI stressor task, which was associated with greater stress-related anxiety and negative appraisals. Among adolescents who exhibited high sleep variability, greater levels of interferon (IFN) gamma were associated with lower activation in lateral PFC regions during stress, which was associated with poorer cognitive performance on the stress task. These immune-brain associations were attenuated among those who reported low negative affect, long sleep duration, and low sleep variability, suggesting that negative affect and poor sleep habits may sensitize the brain to peripheral immune signaling. When homeostasis is imbalanced (e.g., insufficient sleep), higher levels of TNF-alpha and IFN gamma may reflect a homeostatic drive to induce sickness-type behaviors/states (e.g., negative affect, increased anxiety, poorer cognition) to restore homeostasis (e.g., promote sleep) via modulation of respective neurocircuitry in adolescents.