The effects of atorvastatin on emotional processing, reward learning, verbal memory, and inflammation in healthy volunteers: an experimental medicine study

Background: Growing evidence from clinical trials and epidemiological studies suggests that statins can have clinically significant antidepressant effects, potentially related to anti-inflammatory action on several neurobiological structures. However, the underlying neuropsychological mechanisms of these effects remain unexplored. Aims: In this experimental medicine trial, we investigated the seven-day effects of the lipophilic statin, atorvastatin on a battery of neuropsychological tests and inflammation in healthy volunteers. Methods: Fifty healthy volunteers were randomised to either seven days of atorvastatin 20mg or placebo in a double-blind design. Participants were assessed with psychological questionnaires and a battery of well-validated behavioural tasks assessing emotional processing, which is sensitive to putative antidepressant effects, reward learning, and verbal memory, as well as the inflammatory marker, C-reactive protein. Results: Compared to placebo, seven-day atorvastatin increased the recognition (p= 0.006), discriminability (p= 0.03), and misclassifications (p= 0.04) of fearful facial expression, independently from subjective states of mood and anxiety, and C-reactive protein levels. Otherwise, atorvastatin did not significantly affect any other psychological and behavioural measure, nor peripheral C-reactive protein. Conclusions: Our results reveal for the first time the early influence of atorvastatin on emotional cognition by increasing the processing of anxiety-related stimuli (i.e., increased recognition, discriminability, and misclassifications of fearful facial expression) in healthy volunteers, in the absence of more general effects on negative affective bias. Further studies exploring the effects of statins in depressed patients, especially with raised inflammatory markers, may clarify this finding and inform future clinical trials.