Impaired discriminative fear conditioning during later training trials differentiates generalized anxiety disorder, but not panic disorder, from healthy control participants

Abstract

Background Fear conditioning is implicated as a central psychopathological mechanism of anxiety disorders. People with anxiety disorders typically demonstrate reduced affective discrimination between conditioned danger and safety cues. Here, affective discrimination refers to the ability to selectively display fear to dangerous but not safe situations. Though both generalized anxiety disorder (GAD) and panic disorder (PD) are linked to impaired affective discrimination, the clinical phenomenology of these disorders suggests that people with GAD versus PD might be less able to overcome such deficits. It is unclear how this potential difference would manifest during lab-based conditioning. Methods We used a classical fear conditioning paradigm over two discrimination training sessions to examine whether those with GAD, but not PD, would display persistent discrimination deficits. Sixty-seven participants (21 GAD, 19 PD, 27 Healthy Controls) completed a task in which conditioned fear was measured psychophysiologically (fear-potentiated startle), behaviorally, and via self-report. Results Although similar levels of impaired discrimination were found for both GAD and PD groups during initial training, such impairments tended to persist across a subsequent training session only for patients with GAD when compared with Controls. Conclusion Our results provide a foundation for additional research of discrimination deficits in specific anxiety disorders, with an ultimate goal of improved customization of psychological treatments.

Watching with Argus eyes: Characterization of emotional and physiological responding in adults exposed to childhood maltreatment and/or recent adversity

“…In fact, affect modulation in SCRs was absent in individuals exposed to early‐life adversity and those exposed to recent adversity (i.e., comparable responding across picture valence). These findings resemble reports of reduced SCR discrimination between signals of danger and safety in children and adolescents exposed to childhood maltreatment (McLaughlin et al, 2016) and results from patients suffering from anxiety disorders (Cooper et al, 2018) which showed reduced EMG discrimination between conditioned danger and safety cues. In patients, such reduced discrimination has been suggested to derive from deficient inhibitory mechanisms resulting in stronger responding to the safe CS− (Cooper et al, 2018; Grasser & Jovanovic, 2021; Jovanovic et al, 2010, 2009)—particularly during fear acquisition training (Duits et al, 2015).…”

“…These findings resemble reports of reduced SCR discrimination between signals of danger and safety in children and adolescents exposed to childhood maltreatment (McLaughlin et al, 2016) and results from patients suffering from anxiety disorders (Cooper et al, 2018) which showed reduced EMG discrimination between conditioned danger and safety cues. In patients, such reduced discrimination has been suggested to derive from deficient inhibitory mechanisms resulting in stronger responding to the safe CS− (Cooper et al, 2018; Grasser & Jovanovic, 2021; Jovanovic et al, 2010, 2009)—particularly during fear acquisition training (Duits et al, 2015). However, reduced discrimination in non‐patient samples with exposure to adverse experiences have been reported to result from blunted responding to signals of danger, which also leads to reduced discrimination when responding to the safe CS− is comparable (e.g., McLaughlin et al, 2016; Scharfenort et al, 2016).…”

Intolerance of uncertainty and threat generalization: A replication and extension

“…Along these lines, future work may wish to include a longer acquisition training period to determine whether enhanced threat discrimination during extinction training might reflect delayed learning of threat cue pairings (i.e., with enough trials of acquisition, threat cue pairings would eventually be learned) or inability to extinguish threat (i.e., once an association between the CS+ and the US has been learned, it might be resistant to extinction). For instance, recent work has found that some anxiety phenotypes (e.g., generalized anxiety disorder) show poor threat discrimination across two sessions of threat acquisition training, whereas other phenotypes (e.g., panic disorder) show this only for the first session of acquisition training, suggesting the potential to overcome these deficits (Cooper, Grillon, & Lissek, ).…”

Optimizing exposure therapy with an inhibitory retrieval approach and the OptEx Nexus

“…Although not a topic of the current paper, individuals at risk for or suffering from anxiety show various signs of deficits in inhibitory regulation (Jovanovic et al, 2012) and processes of extinction learning (Cooper et al, 2018;Duits et al, 2015;Lissek et al, 2010), including dysregulation in neural regions implicated in long-term extinction learning (vmPFC) (Lissek et al, 2014). These deficits are posited to contribute to the spread and persistence of fear and anxiety and thereby the onset of anxiety disorders .…”