Late chronotype is associated with enhanced amygdala reactivity and reduced fronto-limbic functional connectivity to fearful versus happy facial expressions

Increasing evidence suggests late chronotype individuals are at increased risk of developing depression. However, the underlying neural mechanisms that confer risk are not fully understood. Here, fifty healthy, right-handed individuals without a current or previous diagnosis of depression, family history of depression or sleep disorder underwent functional magnetic resonance imaging (FMRI). Participants completed an implicit emotion processing task (gender discrimination) including happy and fearful facial expressions. Linear effects of chronotype on BOLD response in bilateral amygdala were tested for significance using nonparametric permutation tests. Functional connectivity between amygdala and prefrontal cortex was also investigated using psychophysiological interaction (PPI) analysis. A significant negative correlation between BOLD response and chronotype was observed in bilateral amygdala where later chronotype was associated with an enhanced amygdala response to fearful vs. happy faces. This response remained significant after sleep quality, age, gender, mood, and time of scan were included as covariates in the regression model. Later chronotype was also significantly associated with reduced functional connectivity between amygdala and dorsal anterior cingulate cortex (dACC). The current results appear consistent with theories of impaired emotion regulation of the limbic system (particularly the amygdala) associated with depression and may, in part, explain the increased vulnerability for depression in late chronotype individuals.