Biology subjects

Lester, K. J.

Publications and source records attributed to Lester, K. J..

3 recordsLinked to original sources

bioRxiv2026

The heritability of reinforcement learning parameters and their association with anxiety

Impaired learning that both novel and previously dangerous stimuli are safe (safety and extinction learning, respectively) are long standing, robust, and heritable features of anxiety disorders, representing potential endophenotypes. The computational mechanisms underpinning them have demonstrated associations with anxiety severity in recent studies. We undertook a pre-registered replication in a tenfold larger independent sample of twins (n = 925). Extinction learning rates were associated with anxiety severity ({rho}replication = -0.14, BFr0 = 1189. 67) but safety learning rates were not. Conversely, although safety learning rates showed modest heritability (h2safety = 0.16), extinction learning rates were not heritable. Accordingly, we were unable to identify genetic overlap between anxiety and either learning rate. Although this suggests neither learning rate is an anxiety endophenotype, we confirmed a cognitive-behavioral mechanism underpinning a robust marker of anxiety severity. Furthermore, we demonstrated heritability of a computationally modelled learning parameter, a key step towards establishing its biological basis.

genetics↗

bioRxiv2025

Computational modelling reveals slower safety learning and threat extinction are associated with higher anxiety severity in remote fear conditioning

Anxiety disorders are are chronic, pervasive, and debilitating; characterised by a persistent or exaggerated response to distal or abstract threats. Impaired threat discrimination (distinguishing safe from threatening stimuli) and impaired threat extinction (learning a once threatening stimulus is now safe), are known risk factors in the development and persistence of anxiety disorders. These effects can be experimentally elicited through fear conditioning. First, repeated trials of paired aversive and neutral stimuli are delivered during a fear acquisition phase, followed by repeated trials with no aversive stimuli in a fear extinction phase. The effects are typically measured through comparison of end-phase data points, or simple descriptive or statistical models. Computational modelling, by contrast, can offer a hypothesis-driven, trial-by-trial mechanistic account of fear conditioning. This unmasks within subject task variance by estimating the rate of threat learning, safety learning, and threat extinction, examining individual differences in the cognitive mechanisms behind anxiety. A normative sample (n = 145) underwent a differential fear conditioning task on a bespoke smartphone app, in addition to completing an anxiety severity measure (GAD-7). Computational models fitted to task data estimated learning rates. Whilst the threat learning rate showed no association, the threat extinction and safety learning rates showed small negative associations with anxiety severity (r = -0.218, p = 0.008 & r = -0.214, p = 0.01 respectively). These findings are in keeping with prior studies using traditional analytical approaches, and indicate that anxious individuals are not quicker to develop fear of a stimulus, but take more time than their non-anxious counterparts to learn that a stimulus is safe. This study strengthens the evidence for impairments in fear extinction in those with anxiety, and the importance of learning rates as an index of anxiety severity, a previously hidden cognitive mechanism underlying anxiety persistence.

neuroscience↗

bioRxiv2020

Evidence for distinct genetic and environmental influences on fear acquisition and extinction

BackgroundAnxiety disorders are highly prevalent with an early age of onset. Understanding the aetiology of disorder emergence and recovery is important for establishing preventative measures and optimising treatment. Experimental approaches can serve as a useful model for disorder and recovery relevant processes. One such model is fear conditioning. We conducted a remote fear conditioning paradigm in monozygotic and dizygotic twins to determine the degree and extent of overlap between genetic and environmental influences on fear acquisition and extinction. Methods1937 twins aged 22-25 years, including 538 complete pairs from the Twins Early Development Study (TEDS) took part in a fear conditioning experiment delivered remotely via the Fear Learning and Anxiety Response (FLARe) smartphone app. In the fear acquisition phase participants were exposed to two neutral shape stimuli, one of which was repeatedly paired with a loud aversive noise, while the other was never paired with anything aversive. In the extinction phase the shapes were repeatedly presented again, this time without the aversive noise. Outcomes were participant ratings of how much they expected the aversive noise to occur when they saw either shape, throughout each phase. ResultsTwin analyses indicated a significant contribution of genetic effects to the initial acquisition and consolidation of fear, and the extinction of fear (15%, 30% and 15% respectively) with the remainder of variance due to the non-shared environment. Multivariate analyses revealed that the development of fear and fear extinction show moderate genetic overlap (genetic correlations .4-.5). ConclusionsFear acquisition and extinction are heritable, and share some, but not all of the same genetic influences.

genetics↗