Reduced neural differentiation of rewards and punishment during passive avoidance learning in adolescents with generalized anxiety disorder

Abstract

Background: It has been proposed that individuals with generalized anxiety disorder (GAD) show dysfunctional computations related to approach-avoidance decisionmaking. However, few studies have examined the neural basis of this impairment, particularly in adolescents with GAD. The goal of the current study was to address this gap in the literature. Method: The study involved 51 adolescents with GAD and 51 typically developing (TD) comparison individuals matched on age (16.10 and 15.75 respective means), gender (30 F/21 M and 24 F/27 M), and IQ (103.20 and 103.18 respective means).Participants underwent functional magnetic resonance imaging during a passive avoidance task. Results:We found a significant Group-by-Reinforcement interaction within rewardrelated brain regions including the caudate, putamen, mid cingulate/paracentral lobule, and superior and middle frontal gyrus. TD adolescents showed a greater differential response to reward versus punishment feedback within these regions relative to adolescents with GAD. In particular, this reflected reduced responses to rewards in the adolescents with GAD. There were no group differences in neural responses when making approach/avoidance responses. Conclusion:The results of this study suggest reduced differential responsiveness to reinforcement as a component of the pathophysiology seen in adolescents with GAD. This dysfunction likely underpins decision-making impairments that may exacerbate the participants' worry. K E Y W O R D S anxiety, decision-making, fMRI, GAD, neuroimaging 1 | INTRODUCTION Generalized anxiety disorder (GAD) is an anxiety disorder from which affected individuals indicate pervasive, sustained, uncontrollable worry as their major symptomatic complaint (Bell & Bell, 2001;Duval et al., 2015). GAD is the most common anxiety disorder in primary care, with a lifetime prevalence rate of up to 6%

Neural response to rewards moderates the within‐person association between daily positive events and positive affect during a period of stress exposure

“…The current results may also be relevant to understand the development of psychopathology following life stress exposure as they suggest that individuals with a smaller RewP may be limited in their ability to display PA in response to positive events—thus making them more susceptible to the effects of stress. Abnormal neural response to rewards have been observed in depression (Kendler et al, 1999; Proudfit, 2015; Tennant, 2002), generalized anxiety disorder (Bashford‐Largo et al, 2021; Kessel et al, 2015), psychosis and schizophrenia (Van Winkel et al, 2008; Waltz et al, 2009; Whitton et al, 2015), substance abuse (Baker, Stockwell, et al, 2016; Baker, Wood, & Holroyd, 2016; Joyner et al, 2019), problem gambling (Hewig et al, 2010; Oberg et al, 2011), as well as in individuals at risk for these disorders (Bart et al, 2021; Bress et al, 2013; Burani et al, 2021; Cope et al, 2019; Foti et al, 2011; Gruber et al, 2018). Each of these disorders is also frequently precipitated by stress exposure (Burani et al, 2021; Kendler et al, 1999; Koob, 2008; McCreary & Sadava, 2000; Monroe & Harkness, 2005; Myin‐Germeys et al, 2001; Pizzagalli, 2014; Pizzagalli et al, 2007; Van Winkel et al, 2008).…”

Neuropsychology of Generalized Anxiety Disorder in Clinical Setting: A Systematic Evaluation

“…Fear of uncertainty: People with GAD frequently have a high intolerance for uncertainty, which hinders their ability to make decisions in ambiguous situations [41][42][43][44].…”

Striatal reactivity during emotion and reward relates to approach–avoidance conflict behaviour and is altered in adults with anxiety or depression

“…One fMRI study of AAC in adolescents with generalized anxiety disorder found reduced responsivity to rewards and punishment in the striatum (i.e., caudate and putamen) compared to typically developing adolescents, but no neural differences during decision-making. 31 Given the high comorbidity of anxiety and depression, [32][33][34][35] studies of AAC decision-making could be useful for delineating transdiagnostic and disorder-specific disruptions.…”