title: Fear load: The psychophysiological over-expression of fear as an intermediate phenotype associated with trauma reactions.
abstract: Psychophysiological measures of fear expression provide observable intermediate phenotypes of fear-related symptoms. Research Domain Criteria (RDoC) advocate using neurobiological intermediate phenotypes that provide dimensional correlates of psychopathology. Negative Valence Systems in the RDoC matrix include the construct of acute threat, which can be measured on a physiological level using potentiation of the acoustic startle reflex assessed via electromyography recordings of the orbicularis oculi muscle. Impairments in extinction of fear-potentiated startle due to high levels of fear (termed fear load) during the early phases of extinction have been observed in posttraumatic stress disorder (PTSD). The goals of the current work were to examine dimensional associations between fear-related symptoms of PTSD and fear load variables to test their validity as an intermediate phenotype. We examined extinction of fear-potentiated startle in a cohort (n=269) of individuals with a broad range of civilian trauma exposure (range 0-13 traumatic events per person, mean=3.5). Based on previously reported findings, we hypothesized that fear load would be significantly associated with intrusion and fear memories of an index traumatic event. The results indicated that early extinction was correlated with intrusive thoughts (p=0.0007) and intense physiological reactions to trauma reminders (p=0.036). Degree of adult or childhood trauma exposure, and depression severity were not associated with fear load. After controlling for age, sex, race, income, level of prior trauma, and level of fear conditioning, fear load during extinction was still significantly predictive of intrusive thoughts (p=0.004). The significance of these findings is that they support dimensional associations with symptom severity rather than diagnostic category and, as such, fear load may emerge as a transdiagnostic intermediate phenotype expressed across fear-related disorders (e.g., specific phobia, social phobia).
authors.affiliation: Atlanta Veterans Affairs Medical Center, Mental Health Service Line, Decatur, GA, United States; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States.
authors.forename: Seth Davin
authors.initials: SD
authors.lastname: Norrholm
authors.affiliation: Department of Psychology, Kennesaw State University, Kennesaw, GA, United States.
authors.forename: Ebony M
authors.initials: EM
authors.lastname: Glover
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Stevens
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States.
authors.forename: Negar
authors.initials: N
authors.lastname: Fani
authors.affiliation: Department of Psychiatry, NYU School of Medicine, New York, NY, United States.
authors.forename: Isaac R
authors.initials: IR
authors.lastname: Galatzer-Levy
authors.affiliation: Atlanta Veterans Affairs Medical Center, Mental Health Service Line, Decatur, GA, United States; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States.
authors.forename: Bekh
authors.initials: B
authors.lastname: Bradley
authors.affiliation: Howard Hughes Medical Institute, Bethesda, MD, United States; Yerkes National Primate Research Center, Atlanta, GA, United States.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Ressler
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States. Electronic address: tjovano@emory.edu.
authors.forename: Tanja
authors.initials: T
authors.lastname: Jovanovic
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003214:Conditioning, Classical / Q000502:physiology; D004576:Electromyography; D005108:Extinction, Psychological / Q000502:physiology; D005239:Fear / Q000502:physiology*; D005260:Female; D006801:Humans; D008016:Life Change Events; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000503:physiopathology; D010641:Phenotype; D013216:Reflex, Startle / Q000502:physiology*; D013313:Stress Disorders, Post-Traumatic / Q000175:diagnosis* / Q000503:physiopathology; D055815:Young Adult
keywords: Extinction; Fear conditioning; PTSD; RDoC; Startle; Trauma