title: Conditioned fear and extinction learning performance and its association with psychiatric symptoms in active duty Marines.
abstract: BACKGROUND
  Posttraumatic Stress Disorder (PTSD) is a major public health concern, especially given the recent wars in Iraq and Afghanistan. Nevertheless, despite a sharp increase in the incidence of psychiatric disorders in returning veterans, empirically based prevention strategies are still lacking. To develop effective prevention and treatment strategies, it is necessary to understand the underlying biological mechanisms contributing to PTSD and other trauma related symptoms.
  
  
  METHODS
  The "Marine Resiliency Study II" (MRS-II; October 2011-October 2013) Neurocognition project is an investigation of neurocognitive performance in Marines about to be deployed to Afghanistan. As part of this investigation, 1195 Marines and Navy corpsmen underwent a fear conditioning and extinction paradigm and psychiatric symptom assessment prior to deployment. The current study assesses (1) the effectiveness of the fear potentiated startle paradigm in producing fear learning and extinction and (2) the association of performance in the paradigm with baseline psychiatric symptom classes (healthy: n=923, PTSD symptoms: n=42, anxiety symptoms: n=37, and depression symptoms: n=12).
  
  
  RESULTS
  Results suggest that the task was effective in producing differential fear learning and fear extinction in this cohort. Further, distinct patterns emerged differentiating the PTSD and anxiety symptom classes from both healthy and depression classes. During fear acquisition, the PTSD symptom group was the only group to show deficient discrimination between the conditioned stimulus (CS+) and safety cue (CS-), exhibiting larger startle responses during the safety cue compared to the healthy group. During extinction learning, the PTSD symptom group showed significantly less reduction in their CS+ responding over time compared to the healthy group, as well as reduced extinction of self-reported anxiety to the CS+ by the end of the extinction session. Conversely, the anxiety symptom group showed normal safety signal discrimination and extinction of conditioned fear, but exhibited increased baseline startle reactivity and potentiated startle to CS+, as well as higher self-reported anxiety to both cues. The depression symptom group showed similar physiological and self-report measures as the healthy group.
  
  
  CONCLUSIONS
  These data are consistent with the idea that safety signal discrimination is a relatively specific marker of PTSD symptoms compared to general anxiety and depression symptoms. Further research is needed to determine if deficits in fear inhibition vs. exaggerated fear responding are separate biological "domains" across anxiety disorders that may predict differential biological mechanisms and possibly treatment needs. Future longitudinal analyses will examine whether poor learning of safety signals provides a marker of vulnerability to develop PTSD or is specific to symptom state.
authors.affiliation: Department of Psychiatry, University of California San Diego, United States.
authors.forename: D T
authors.initials: DT
authors.lastname: Acheson
authors.affiliation: Department of Psychiatry, University of California San Diego, United States; Mental Illness Research, Education and Clinical Center, VA San Diego Healthcare System, United States.
authors.forename: M A
authors.initials: MA
authors.lastname: Geyer
authors.affiliation: Department of Psychiatry, University of California San Diego, United States; Center for Excellence in Stress and Mental Health, VA San Diego Healthcare System, United States.
authors.forename: D G
authors.initials: DG
authors.lastname: Baker
authors.affiliation: Department of Psychiatry, University of California San Diego, United States; Center for Excellence in Stress and Mental Health, VA San Diego Healthcare System, United States.
authors.forename: C M
authors.initials: CM
authors.lastname: Nievergelt
authors.affiliation: Center for Excellence in Stress and Mental Health, VA San Diego Healthcare System, United States.
authors.forename: K
authors.initials: K
authors.lastname: Yurgil
authors.affiliation: Department of Psychiatry, University of California San Diego, United States; Center for Excellence in Stress and Mental Health, VA San Diego Healthcare System, United States. Electronic address: vrisbrough@ucsd.edu.
authors.forename: V B
authors.initials: VB
authors.lastname: Risbrough
mesh_terms: D000328:Adult; D001007:Anxiety / Q000523:psychology; D003214:Conditioning, Classical / Q000502:physiology*; D003863:Depression / Q000523:psychology; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology / Q000523:psychology*; D006801:Humans; D007858:Learning / Q000502:physiology; D008016:Life Change Events; D008297:Male; D008889:Military Personnel / Q000523:psychology*; D013216:Reflex, Startle / Q000502:physiology; D055500:Resilience, Psychological; D013313:Stress Disorders, Post-Traumatic / Q000523:psychology*; D055815:Young Adult
keywords: Anxiety; Extinction; Fear; Fear inhibition; Military; PTSD; Safety signal; Startle