Abstract

The acquisition and extinction of conditioned fear underlies the pathophysiology of anxiety disorders, including PTSD. Women have higher lifetime prevalence and greater risk of PTSD than men. Such sex differences may be attributed to a combination of genetic and hormonal factors. The catechol-O-methyltransferase (COMT) gene encodes an enzyme that metabolizes catechol compounds, including dopamine. The COMT Val158Met polymorphism affects the enzymatic activity of dopamine and has been associated with altered fear memory performance. Besides, when estrogen secretion is elevated, women show a greater extinction of conditioned fear than men. Here, we investigated the relationship between the COMT genotype and sex in the acquisition and extinction of conditioned fear. In a 3-day cued fear conditioning experiment, acquisition and extinction performance of 75 healthy men (21.8 years) and 45 healthy women in follicular phase (21.2 years) were examined. Visual cues and electric shocks were used as the conditioned stimulus and unconditioned stimulus, respectively. Subjects with Met/Met homozygotes showed less fear acquisition (p

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