Can glucose facilitate fear exposure? Randomized, placebo-controlled trials on the effects of glucose administration on fear extinction processes.

Previous studies showed that glucose has beneficial effects on memory function and can enhance contextual fear learning. To derive potential therapeutic interventions, further research is needed regarding the effects of glucose on fear extinction. In two experimental studies with healthy participants (Study 1: N = 68, 39 females; Study 2: N = 89, 67 females), we investigated the effects of glucose on fear extinction learning and its consolidation. Participants completed a differential fear conditioning paradigm consisting of acquisition, extinction, and return of fear tests: reinstatement, and extinction recall. US-expectancy ratings, skin conductance response (SCR), and fear potentiated startle (FPS) were collected. Participants were pseudorandomized and double-blinded to one of two groups: They received either a drink containing glucose or saccharine 20 min before (Study 1) or immediately after extinction (Study 2). The glucose group showed a significantly stronger decrease in differential FPS during extinction (Study 1) and extinction recall (Study 2). Additionally, the glucose group showed a significantly lower contextual anxiety at test of reinstatement (Study 2). Our findings provide first evidence that glucose supports the process of fear extinction, and in particular the consolidation of fear extinction memory, and thus has potential as a beneficial adjuvant to extinction-based treatments. Registered through the German Clinical Trials Registry (https://www.bfarm.de/EN/BfArM/Tasks/German-Clinical-Trials-Register/_node.html; Study 1: DRKS00010550; Study 2: DRKS00018933).

Fear learning and generalization during pandemic fear: How COVID-19-related anxiety affects classical fear conditioning with traumatic film clips.

The COVID-19 pandemic greatly disrupted our daily lives. Worldwide, people were confronted with health, financial, and existential fears or trauma-like experiences. Recent studies have identified an increase in stress, anxiety, and fear symptoms in connection with the pandemic. Furthermore, fear learning processes are central mechanisms in the development and maintenance of anxiety disorders. Patients commonly show impairments not only in fear learning but also in its generalization. Thus, pandemic-related anxiety may constitute a risk factor for both enhanced fear acquisition and generalization. In a pre-registered online study with a final sample of 220 healthy university students, we investigated whether participants with higher COVID-19-related anxiety (COVID-Anxiety) show impaired fear learning and generalization. For this purpose, we used a differential fear conditioning paradigm with a traumatic film clip as the unconditioned stimulus (US) and collected US-expectancy as the main measure of interest. Participants with high COVID-Anxiety show a tendency toward poorer discrimination between the reinforced conditioned stimulus (CS+) and the unreinforced conditioned stimulus (CS-) during acquisition and significantly poorer discrimination patterns during generalization. Furthermore, participants with high COVID-Anxiety show greater general fear throughout the whole experiment. Our results show that the subjective effects of the COVID-19 pandemic on psychological well-being are associated with impairments in both fear learning and fear generalization. As expected, high COVID-Anxiety leads to poorer performance in stimulus discrimination and greater levels of fear, which might contribute to a higher risk of anxiety disorders. GERMAN CLINICAL TRIAL REGISTER: DRKS00022761.

Effects of intranasal insulin as an enhancer of fear extinction: a randomized, double-blind, placebo-controlled experimental study.

Fear-extinction based psychotherapy (exposure) is the most effective method for treating anxiety disorders. Notwithstanding, since some patients show impairments in the unlearning of fear and insufficient fear remission, there is a growing interest in using cognitive enhancers as adjuvants to exposure. As insulin plays a critical role in stress processes and acts as a memory enhancer, this study aimed to assess the capacity of intranasal insulin to augment fear extinction. A double-blind, placebo-controlled differential fear-conditioning paradigm was conducted in 123 healthy participants (63 females). Pictures of faces with neutral expressions were used as conditioned stimuli and electric shocks as unconditioned stimuli. The paradigm consisted of four phases presented on three consecutive days: acquisition (day 1), extinction (day 2), reinstatement and re-extinction (day 3). A single intranasal dose of insulin (160 IU) or placebo was applied on day 2, 45 min before fear extinction. Skin conductance response (SCR), fear-potentiated startle (FPS) and expectancy ratings were assessed. During extinction, the insulin group (independent of sex) showed a significantly stronger decrease in differential FPS in comparison with the placebo group. Furthermore, a sex-specific effect was found for SCR, with women in the insulin group showing a greater decrease of differential SCR both at early extinction and at late re-extinction. Our results provide first evidence that intranasal insulin facilitates fear extinction processes and is therefore a promising adjuvant for extinction-based therapies in anxiety and related disorders. Sex-specific effects should be taken into consideration in future studies.