Anxiety in transition: Neuroendocrine mechanisms supporting the development of anxiety pathology in adolescence and young adulthood

[Display omitted] •A dual-mechanism model is proposed for affect dysregulation in adolescence.•Mechanisms include pubertal testosterone & prefrontal-amygdala circuit myelination.•The model addresses adolescent anxiety, chronic adult anxiety, & sex differences.•Meta-analysis of testosterone modulation of orbitofrontal cortex-amygdala coupling. Adolescence marks a key developmental window during which emotion dysregulation increases, along with risk for the onset of anxiety and other affect-related pathologies. Although emotion dysregulation and related pathologies normatively decline during the transition into adulthood, this does not occur for a sizable minority of individuals. Finally, sex differences in anxiety emerge during adolescence, with females developing a 2-fold increase in risk relative to males. Unfortunately, a neurobiological model of the mechanisms that cause these changes during adolescence has yet to be proposed. In the present work, we first provide brief reviews of relevant literature. Next, we outline a dual-mechanism model focused on (i) the influence of pubertal testosterone on key emotion-regulation circuitry (i.e., orbitofrontal cortex-amygdala coupling) and (ii) myelination of the fiber bundles connecting such circuitry (i.e., uncinate fasciculus). The proposed model offers a set of specific, testable hypotheses that will hopefully spur much needed cross-disciplinary research.