Associations between statin use and negative affective bias during COVID-19: an observational, longitudinal UK study investigating depression vulnerability

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 (F1,1418 = 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

Direct serotonin release in humans shapes aversive learning and inhibition

The role of serotonin in human behaviour is informed by approaches which allow in vivo modification of synaptic serotonin. However, characterising the effects of increased serotonin signalling in human models of behaviour is challenging given the limitations of available experimental probes, notably selective serotonin reuptake inhibitors. Here we use a now-accessible approach to directly increase synaptic serotonin in humans (a selective serotonin releasing agent) and examine its influence on domains of behaviour historically considered core functions of serotonin. Computational techniques, including reinforcement learning and drift diffusion modelling, explain participant behaviour at baseline and after week-long intervention. Reinforcement learning models reveal that increasing synaptic serotonin reduces sensitivity for outcomes in aversive contexts. Furthermore, increasing synaptic serotonin enhances behavioural inhibition, and shifts bias towards impulse control during exposure to aversive emotional probes. These effects are seen in the context of overall improvements in memory for neutral verbal information. Our findings highlight the direct effects of increasing synaptic serotonin on human behaviour, underlining its role in guiding decision-making within aversive and more neutral contexts, and offering implications for longstanding theories of central serotonin function

Qualtrics template files

The Master Template file includes the following questionnaires: • BDI (Beck Depression Inventory - 21Q)* • EPQ (Eysenck Personality Questionnaire 90Q)* • Locus of Control (29Q)* • STAI-T (State-Trait Anxiety Inventory - Trait 20Q)* • STAI-S (State-Trait Anxiety Inventory - State 20Q)* • PANAS (Positive and Negative Affect Scale 20Q)* • SHAPS (Snaith-Hamilton Pleasure Scale 14Q)* • VAS (Visual Analogue Scales -combined 6Q) • VAS (Visual Analogue Scales -individual 16Q) • EHI (Edinburgh Handedness Inventory) • BIS (Barratt Impulsiveness Scale 30Q) • AGQ (Buss Perry Aggression Questionnaire 29Q) • ASEC (Anti-depressant Side Effect Checklist 18Q) • PHQ-9 (Patient Health Questionnaire 9Q) • GAD-7 (Generalised Anxiety Disorder 7Q) • BFNE (Brief Fear of Negative Evaluation 8Q) • FPES (Fear of Positive Evaluation 10Q) • BFIN (Big Five Inventory 8Q) • RESES (Rosenberg Self Esteem 10Q) • DAS24 (Derriford Appearance - short 24Q) • STAXI-S (State-Trait Anger Expression Inventory - State) • STAXI-T (State-Trait Anger Expression Inventory - Trait) • STAXI-AEC (State-Trait Anger Expression Inventory - Anger Expression and Control) • AMI (Apathy Motivation Index 18Q) • Epworth Sleepiness Scale (8Q) • HADS (Hospital Anxiety and Depression Scale 14Q) • PDQ (Perceived Deficits Questionnaire 20Q) • QUIP (Questionnaire for Impulsive-compulsive disorders in Parkinson's 15Q) • UDPRS Part I nM-EDL (Unified Parkinson's disease rating scale) Part 1 - Non Motor Aspects Experiences of Daily Living (7Q) • UDPRS Part II M-EDL (Unified Parkinson's disease rating scale) Part 2 - Non Motor Aspects Experiences of Daily Living (13Q) • PDQ (Perceived Deficits Questionnaire 20Q) • RBDSQ (REM Sleep Behaviour Disorder Screening 16Q) • BADS (behavioural activation for depression scale 25Q) • EROS (environmental reward observation scale 10Q) • MSPSS (multidimension scale of perceived social support 12Q) * = with scoring To use, download the file, then on qualtrics choose to Create a Project from Existing, select From a File and then navigate to select the Master Template file. This will be added to your library, and you can then rename it and remove or add questionnaires to suit your study. If you would like to to help add to the Master Template, feel free to do the above, and then add additional blocks of questions, and re-upload here (keeping the same file name as the download). The UDPRS III Motor Examination template is seperate, as an examiner rated scale - all the others are completed by participants

In Public Domain

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