Fear Conditioning in Adolescents With Anxiety Disorders: Results From a Novel Experimental Paradigm

Mood and Anxiety Disorders Program, National Institute of Mental Health /National Institutes of Health, 15K North Drive, MSC 2670, Bethesda, MD 20892-2670, USA.
Journal of the American Academy of Child & Adolescent Psychiatry (Impact Factor: 7.26). 02/2008; 47(1):94-102. DOI: 10.1097/chi.0b01e31815a5f01
Source: PubMed


Considerable research examines fear conditioning in adult anxiety disorders but few studies examine youths. Adult data suggest that anxiety disorders involve elevated fear but intact differential conditioning. We used a novel paradigm to assess fear conditioning in pediatric anxiety patients.
Sixteen individuals with anxiety disorders and 38 healthy comparisons viewed two photographs of actresses displaying neutral expressions. One picture served as the conditioned stimulus (CS), paired with a fearful expression and a shrieking scream (CS+), whereas the other picture served as a CS unpaired with the aversive outcome (CS-). Conditioning was indexed by self-reported fear. Subjects participated in two visits involving conditioning and extinction trials.
Both groups developed greater fear of the CS+ relative to CS-. Higher fear levels collapsed across each CS characterized anxious relative to healthy subjects, but no significant interaction between group and stimulus type emerged. Fear levels at visit 1 predicted avoidance of visit 2. Fear levels to both CS types showed stability even after extinction.
Consistent with adult data, pediatric anxiety involves higher fear levels following conditioning but not greater differential conditioning. Extending these methods to neuroimaging studies may elucidate neural correlates of fear conditioning. Implications for exposure therapies are discussed.

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    • "Posttraumatic stress disorder (PTSD) is characterized by failure to maintain extinction learning (Milad et al, 2009) and inhibit the fear memory, even in the presence of safety cues (Jovanovich and Norrholm, 2011; Jovanovich and Ressler, 2010). Anxiety disorders are associated with exaggerated fear responses during conditioning and extinction learning (Craske et al, 2008; Lau et al, 2008). In contrast, externalizing psychopathology is associated with blunted fear conditioning and poor discrimination between threat and safety cues (Fairchild et al, 2008). "
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    ABSTRACT: Alterations in learning processes and the neural circuitry that supports fear conditioning and extinction represent mechanisms through which trauma exposure might influence risk for psychopathology. Few studies examine how trauma or neural structure relates to fear conditioning in children. Children (n=94) aged 6-18 years, 40.4% (n=38) with exposure to maltreatment (physical abuse, sexual abuse, or domestic violence), completed a fear conditioning paradigm utilizing blue and yellow bells as conditioned stimuli (CS+/CS-) and an aversive alarm noise as the unconditioned stimulus. Skin conductance responses (SCR) and self-reported fear were acquired. Magnetic resonance imaging data were acquired from 60 children. Children without maltreatment exposure exhibited strong differential conditioning to the CS+ versus CS-, based on SCR and self-reported fear. In contrast, maltreated children exhibited blunted SCR to the CS+ and failed to exhibit differential SCR to the CS+ versus CS- during early conditioning. Amygdala and hippocampal volume were reduced among children with maltreatment exposure and were negatively associated with SCR to the CS+ during early conditioning in the total sample, although these associations were negative only among non-maltreated children and were positive among maltreated children. The association of maltreatment with externalizing psychopathology was mediated by this perturbed pattern of fear conditioning. Child maltreatment is associated with failure to discriminate between threat and safety cues during fear conditioning in children. Poor threat-safety discrimination might reflect either enhanced fear generalization or a deficit in associative learning, which may in turn represent a central mechanism underlying the development of maltreatment-related externalizing psychopathology in children.Neuropsychopharmacology accepted article preview online, 18 December 2015. doi:10.1038/npp.2015.365.
    No preview · Article · Dec 2015 · Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology
    • "Research in infant rats has provided insight into the ontogeny of threat learning by identifying the gradual development of the neural circuitry supporting aversive conditioning (Landers & Sullivan 2012; Pattwell et al. 2013). The study of the ontogeny of threat conditioning in humans has been less developed, although the past decade has seen great progress, indicating the human brain circuit is likely homologous to that seen in rodents (Glenn et al. 2012; Jovanovic et al. 2013; Lau et al. 2008; Shechner et al. 2015; Sterzer 2010; Tottenham et al. 2015). Additionally, an essential aspect of learning associations is the detection and memorization of temporal intervals between events (Balsam et al. 2010; Pavlov 1927). "
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    ABSTRACT: Pavlovian fear or threat conditioning, where a neutral stimulus takes on aversive properties through pairing with an aversive stimulus, has been an important tool for exploring the neurobiology of learning. In the past decades, this neurobehavioral approach has been expanded to include the developing infant. Indeed, protracted postnatal brain development permits the exploration of how incorporating the amygdala, prefrontal cortex and hippocampus into this learning system impacts the acquisition and expression of aversive conditioning. Here we review the developmental trajectory of these key brain areas involved in aversive conditioning and relate it to pups' transition to independence through weaning. Overall, the data suggests that adult-like features of threat learning emerge as the relevant brain areas become incorporated into this learning. Specifically, the developmental emergence of the amygdala permits cue learning and the emergence of the hippocampus permits context learning. We also describe unique features of learning in early life that block threat learning and enhance interaction with the mother or exploration of the environment. Finally, we describe the development of a sense of time within this learning and its involvement in creating associations. Together these data suggest that the development of threat learning is a useful tool for dissecting adult-like functioning of brain circuits, as well as providing unique insights into ecologically relevant developmental changes.
    No preview · Article · Nov 2015 · Genes Brain and Behavior
    • "Both Neumann et al. (2008) and Haddad et al.'s (2011) studies examined fear conditioning and extinction in healthy adolescents. In an earlier study conducted by Lau et al. (2008) using the Screaming Lady procedure described above, fear conditioning and extinction were compared in anxious versus healthy adolescents. Following conditioning, both anxious and healthy adolescents rated the CSþ as more fear provoking than the CSÀ and the size of this difference was comparable across the two groups. "
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    ABSTRACT: This study investigated differences between adolescents and adults on fear conditioning, extinction, and reinstatement (i.e., the recovery of conditioned fear following re-exposure to the unconditioned stimulus [US] post-extinction). Participants underwent differential conditioning (i.e., the Screaming Lady) where one neutral face (CS+) was followed by the same face expressing fear and a loud scream (US) while another neutral face (CS-) remained neutral. Extinction involved non-reinforced presentations of both CSs, after which participants were reinstated (2xUSs) or not. On two self-report measures, both ages showed conditioning, good extinction learning and retention, and reinstatement-induced relapse. However, only adolescents showed conditioning, extinction, and reinstatement on the eye tracking measure; relapse on this measure could not be assessed in adults given they did not show initial conditioning. Lastly, higher levels of depression predicted stronger conditioning and weaker extinction in adolescents only. These findings are discussed in terms of their implications for adolescent anxiety disorders. © Dev Psychobiol. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Jun 2015 · Developmental Psychobiology
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