An Inflammatory Pathway Links Atherosclerotic Cardiovascular Disease Risk to Neural Activity Evoked by the Cognitive Regulation of Emotion

Background: Cognitive reappraisal is a form of emotion regulation that alters emotional responding by changing the meaning of emotional stimuli. Reappraisal engages regions of the prefrontal cortex that support multiple functions, including visceral control functions implicated in regulating the immune system. Immune activity plays a role in the preclinical pathophysiology of atherosclerotic cardiovascular disease (CVD), an inflammatory condition that is highly comorbid with affective disorders characterized by problems with emotion regulation. Here, we tested whether prefrontal engagement by reappraisal would be associated with atherosclerotic CVD risk and whether this association would be mediated by inflammatory activity.

Methods: Community volunteers (n = 157; 30-54 years of age; 80 women) without DSM-IV Axis-1 psychiatric diagnoses or cardiovascular or immune disorders performed a functional neuroimaging task involving the reappraisal of negative emotional stimuli. Carotid artery intima-media thickness and inter-adventitial diameter were measured by ultrasonography and used as markers of preclinical atherosclerosis. Also measured were circulating levels of interleukin-6 (IL-6), an inflammatory cytokine linked to CVD risk and prefrontal neural activity.

Results: Greater reappraisal-related engagement of the dorsal anterior cingulate cortex was associated with greater preclinical atherosclerosis and IL-6. Moreover, IL-6 mediated the association of dorsal anterior cingulate cortex engagement with preclinical atherosclerosis. These results were independent of age, sex, race, smoking status, and other known CVD risk factors.

Conclusions: The cognitive regulation of emotion might relate to CVD risk through a pathway involving the functional interplay between the anterior cingulate region of the prefrontal cortex and inflammatory activity.