Skin Conductance Responses and Neural Activations During Fear Conditioning and Extinction Recall Across Anxiety Disorders

Abstract

IMPORTANCEThe fear conditioning and extinction neurocircuitry has been extensively studied in healthy and clinical populations, with a particular focus on posttraumatic stress disorder. Despite significant overlap of symptoms between posttraumatic stress disorder and anxiety disorders, the latter has received less attention. Given that dysregulated fear levels characterize anxiety disorders, examining the neural correlates of fear and extinction learning may shed light on the pathogenesis of underlying anxiety disorders.OBJECTIVES To investigate the psychophysiological and neural correlates of fear conditioning and extinction recall in anxiety disorders and to document how these features differ as a function of multiple diagnoses or anxiety severity. DESIGN, SETTING, AND PARTICIPANTSThis investigation was a cross-sectional, case-control, functional magnetic resonance imaging study at an academic medical center. Participants were healthy controls and individuals with at least 1 of the following anxiety disorders: generalized anxiety disorder, social anxiety disorder, specific phobia, and panic disorder. The study dates were between March 2013 and May 2015.EXPOSURES Two-day fear conditioning and extinction paradigm. CONCLUSIONS AND RELEVANCE Despite no skin conductance response group differences during extinction recall, brain activation patterns between anxious and healthy individuals differed. These findings encourage future studies to examine the conditions longitudinally and in the context of treatment trials to improve and guide therapeutics via advanced neurobiological understanding of each disorder.

Absence of conditioned responding in humans: A bad measure or individual differences?

“…Selected shock levels ranged from 0.6-4.0 mA. Following the procedure described by Milad and colleagues (Hwang et al, 2015;Linnman et al, 2012;Marin et al, 2016Marin et al, , 2017Milad et al, 2009Milad et al, , 2007, the fear conditioning phase consisted of 32 trials. For each trial, a depicted context (e.g., an office) first appeared for 3 s, during which the imbedded conditioned stimulus (CS; a lamp) was not lit.…”

Serotonin depletion impairs both Pavlovian and instrumental reversal learning in healthy humans

“…Behavioural inflexibility is a hallmark of obsessivecompulsive disorder (OCD) and substance use disorders, for instance, where learned behaviours persist inappropriately despite adverse consequences (APA 2013). Aberrations in threat and safety learning are characteristic of post-traumatic stress disorder (PTSD; Homan et al, 2019;Milad et al, 2009) and other anxiety disorders (Kim et al, 2011;Marin et al, 2017), and are also a feature of OCD (Milad et al, 2013;Apergis-Schoute et al, 2017) and schizophrenia (Holt et al, 2012). Drugs thought to boost serotonin transmission -selective serotonin reuptake inhibitors (SSRIs) -are first line treatments for OCD (Fineberg et al 2013) and PTSD (Baldwin et al 2014).…”

Effect of tryptophan depletion on conditioned threat memory expression: role of intolerance of uncertainty

“…Once a threat is no longer present, it is crucial to adapt emotional responses flexibly to reflect the safe environment, for normal functioning in daily life to continue. Dysfunction of threat and safety learning lies at the core of post-traumatic stress disorder (PTSD; Milad et al, 2009) and other anxiety disorders (Kim et al, 2011;Marin et al, 2017), and is also a feature of obsessivecompulsive disorder (OCD; Apergis-Schoute et al, 2017;McLaughlin et al, 2015;Milad et al, 2013) and schizophrenia (Holt et al, 2012). PTSD is unique amongst these in that exposure to a traumatic event is a defining feature, and it is characterised by subsequent pathological physiological reactions to cues reminiscent of the event (APA, 2013).…”