Abstract
Background
While translational theories link neurodevelopmental changes in threat learning to
pathological anxiety, findings from studies in patients inconsistently support these
theories. This inconsistency may reflect difficulties in studying large patient samples
with wide age ranges using consistent methods. A dearth of imaging data in patients
further limits translational advances. We address these gaps through a psychophysiology
and structural brain imaging study in a large sample of patients across the lifespan.
Methods
A total of 351 participants (8–50 years of age; 209 female subjects; 195 healthy participants
and 156 medication-free, treatment-seeking patients with anxiety) completed a differential
threat conditioning and extinction paradigm that has been validated in pediatric and
adult populations. Skin conductance response indexed psychophysiological response
to conditioned (CS+, CS−) and unconditioned threat stimuli. Structural magnetic resonance
imaging data were available for 250 participants. Analyses tested anxiety and age
associations with psychophysiological response in addition to associations between
psychophysiology and brain structure.
Results
Regardless of age, patients and healthy comparison subjects demonstrated comparable
differential threat conditioning and extinction. The magnitude of skin conductance
response to both conditioned stimulus types differentiated patients from comparison
subjects and covaried with dorsal prefrontal cortical thickness; structure–response
associations were moderated by anxiety and age in several regions. Unconditioned responding
was unrelated to anxiety and brain structure.
Conclusions
Rather than impaired threat learning, pathological anxiety involves heightened skin
conductance response to potential but not immediately present threats; this anxiety-related
potentiation of anticipatory responding also relates to variation in brain structure.
These findings inform theoretical considerations by highlighting anticipatory response
to potential threat in anxiety.
Keywords
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Article info
Publication history
Published online: November 15, 2019
Accepted:
November 7,
2019
Received in revised form:
October 16,
2019
Received:
August 23,
2019
Identification
Copyright
Published by Elsevier Inc on behalf of Society of Biological Psychiatry.
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