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

Front Neuroendocrinol. 2019 Oct:55:100791. doi: 10.1016/j.yfrne.2019.100791. Epub 2019 Sep 19.


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.

Keywords: Adolescence; Amygdala; Anxiety; Myelination; Orbitofrontal cortex; Puberty; Sex differences; Testosterone; Uncinate fasciculus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adolescent
  • Adult
  • Affective Symptoms* / metabolism
  • Affective Symptoms* / physiopathology
  • Amygdala* / growth & development
  • Amygdala* / metabolism
  • Amygdala* / physiopathology
  • Animals
  • Anxiety Disorders* / metabolism
  • Anxiety Disorders* / physiopathology
  • Female
  • Humans
  • Male
  • Nerve Net* / growth & development
  • Nerve Net* / metabolism
  • Nerve Net* / physiopathology
  • Neurosecretory Systems / metabolism*
  • Prefrontal Cortex* / growth & development
  • Prefrontal Cortex* / metabolism
  • Prefrontal Cortex* / physiopathology
  • Puberty / metabolism*
  • Sex Characteristics*
  • Testosterone / metabolism*
  • Young Adult


  • Testosterone