Associations Between Statin Use and Negative Affective Bias During COVID-19: An Observational, Longitudinal UK Study Investigating Depression Vulnerability

Abstract

Background: There is growing interest in the antidepressant potential of statins. We tested whether statin use is associated with cognitive markers previously found to indicate psychological vulnerability to depression within the context of the COVID-19 pandemic.

Methods: Between April 2020 and February 2021, we conducted an observational online study of 2043 adults in the United Kingdom. Participants completed cognitive tasks assessing processes related to depression vulnerability, including affective bias and reward processing. We also measured working memory, medication use, and current psychiatric symptoms. Using mixed analysis of covariance and regression models, we compared participants on statins alone (n = 81), antihypertensive medication alone (n = 126), both medications (n = 111), and on neither medication (n = 1725).

Results: Statin use was associated with reduced recognition of angry and fearful faces (F₁ = 9.19, p = .002; F₁ = 6.9, p = .009) and with increased misclassification of these expressions as positive. Increased recognition of angry faces at baseline predicted increased levels of depression and anxiety 10 months later (β = 3.61, p = .027; β = 2.37, p = .002). Statin use was also associated with reduced learning about stimuli associated with loss (F_1,1418 = 9.90, p = .002). These indicators of reduced negative bias were not seen in participants taking antihypertensive medication alone, suggesting that they were related to statin use in particular rather than nonspecific demographic factors. In addition, we found no evidence of an association between statin use and impairment in working memory.

Conclusions: Statin use was associated with cognitive markers indicative of reduced psychological vulnerability to depression, supporting their potential use as a prophylactic treatment for depression.

Keywords: Affective bias; Cognitive neuroscience; Depression; Emotional processing; Experimental medicine; Statins.

Figure 1

Emotional processing task performance (facial expression recognition task) by medication group. (A) Mean unbiased hit rate for each emotion displayed during facial expression recognition task. (B) Mean group accuracy for identification of angry faces at each intensity level of anger. (C) Mean group accuracy for identification of fearful faces at each intensity level of fear. ∗∗∗p < .001. Error bars show ±1 standard error.

Figure 2

Reward learning task performance (probabilistic instrumental learning task) by medication group. (A) Mean percentage of trials during which participants choose the advantageous stimuli in a reward learning task (probabilistic instrumental learning task). (B) Learning curve showing proportion of participants in each group choosing the symbol associated with a high probability of loss or gain, trial by trial. High probability stimuli are advantageous in gain trials and not advantageous in loss trials. ∗∗p < .01. Error bars show ±1 standard error.

Figure 3

Baseline predictors of depression and anxiety at follow-up. Analysis was conducted on continuous measures of anger recognition. For these plots, participants were split into those above (high) and below (low) the median anger recognition performance. (A) Mean depressive symptoms at 10-month follow-up, split by those with high and low anger recognition at baseline. (B) Mean change in depressive symptoms between baseline and 10-month follow-up, split by those with high and low anger recognition at baseline. (C) Mean anxiety symptoms at 10-month follow-up, split by those with high and low anger recognition at baseline. (D) Mean change in anxiety symptoms between baseline and 10-month follow-up, split by those with high and low anger recognition at baseline. ∗p < .05, ∗∗p < .01. Error bars show ±1 standard error. CESD, Center for Epidemiologic Studies Depression Scale; GAD7, 7-item General Anxiety Disorder scale.