Starting the pill during adolescence: The influence of age of onset and duration of use on fear-related grey matter brain volumes

Abstract

Oral contraceptives (OC) have been shown to modulate the brain regions involved in fear conditioning and extinction. OC use is often initiated during adolescence, a sensitive period for brain development. During this period, certain brain regions involved in fear circuitry are still undergoing important reorganization, such as the amygdala-prefrontal cortex (PFC) pathway. It remains unknown whether OC use during adolescence may induce long-lasting changes in the fear circuitry. To explore this question, we collected MRI data in 98 healthy women aged 23 to 35 (61 current users, 37 past users) and extracted region of interest-based grey matter volumes (GMV) for the amygdala, hippocampus, insula, dorsal anterior cingulate cortex (dACC), and ventromedial PFC. Controlling for total intracranial volume, age, and education, linear regressions revealed an interaction effect between the age of OC onset and duration of use for the left amygdala (p=.010), where a positive association with duration of use was obtained only when OC intake was initiated at an early age (β=0.323, p=.023). Although an interaction effect was found for the dACC (p=.043), we observed a non-significant negative association between duration of use and GMV at an early age of onset. Moreover, age of onset alone predicted right posterior hippocampus volume (β=0.378, p=.010). Our results suggest that OC use during adolescence may induce lasting effects on structural correlates of fear learning and its regulation. These findings support the further investigation into the timing of OC use to better comprehend whether OC disrupt normal brain development processes.