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Dysregulation of threat neurociruitry during fear extinction: the role of anhedonia.

Katherine S YoungSusan Y BookheimerRobin NusslockRichard E ZinbargKatherine S F DammeIris Ka-Yi ChatNicholas J KelleyMeghan VinogradMarcelina PerezKelly ChenAileen Echiverri CohenMichelle G Craske
Published in: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (2021)
Dimensional models of anxiety and depression highlight common and distinct symptom clusters that are thought to reflect disruptions in underlying functional processes. The current study investigated how functioning of threat neurocircuitry relates to symptom dimensions of anxiety and depression. Participants were aged 18-19 years (n = 229, 158 female) and were selected to ensure a range of scores on symptom measures. Symptom dimensions of "General Distress" (common to anxiety disorders and depression), "Fears" (more specific to anxiety disorders), and "Anhedonia-apprehension" (more specific to depression) were evaluated. Participants underwent functional magnetic resonance imaging during a Pavlovian fear conditioning paradigm. Multilevel modeling analyses estimated relationships between symptom dimensions and activation in threat neural circuitry. Exploratory whole brain analyses were also conducted. Threat-related neural activity was not associated with General Distress or Fears. Anhedonia-apprehension was associated with activation of bilateral amygdala, anterior insula and dACC during late extinction. We found no evidence to support an association between symptom dimensions of General Distress or Fears with threat circuitry activation in a large sample of young adults. We did, however, find that the symptom dimension of Anhedonia-apprehension was significantly associated with threat-related neural activation during fear extinction. This effect requires replication in future work but may reflect anhedonic impairments in learning when contingencies are altered, possibly linked to the rewarding relief of an unexpectedly absent threat.
Keyphrases
  • magnetic resonance imaging
  • young adults
  • patient reported
  • depressive symptoms
  • computed tomography
  • functional connectivity
  • prefrontal cortex
  • resting state
  • physical activity
  • drug induced