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

Katherine S. Young, Susan Y. Bookheimer, Robin Nusslock, Richard E. Zinbarg, Katherine S.F. Damme, Iris Ka Yi Chat, Nicholas J. Kelley, Meghan Vinograd, Marcelina Perez, Kelly Chen, Aileen Echiverri Cohen, Michelle G. Craske*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1650-1657
Number of pages8
Issue number9
StatePublished - Aug 2021

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology


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