Stress may cause anxiety in adolescents due to an atypical response to a neurosteroid, reports a paper to be published online in Nature Neuroscience. Tetrahydropregnanalone (THP) is produced in response to stress and normally acts to reduce anxiety, but in adolescent mice, THP acts on an unusual type of inhibitory receptor to increase it. If a similar mechanism occurs in humans, this may explain why stress causes so much anxiety in teenagers.
In adult mice, THP enhances inhibition through GABA receptors that contain the delta subunit, calming neural activity to reduce anxiety. Sheryl Smith and colleagues discovered that expression of a subtype of GABA receptor containing both delta and alpha4 subunits is markedly higher in adolescent mice. They also found that THP has the opposite effect on this type of receptor, reducing inhibition and thus making the brain more excitable. Thus, the release of THP triggered by stress made adolescent mice more anxious instead of more calm.
In many species, puberty is the time to leave the home environment and make one's way among strangers. Anxiety under stressful circumstances during adolescence could contribute to caution, increasing the odds of survival. In humans, THP levels increase during adolescence, as does the risk of anxiety disorders, which often occur in response to stress. Further research is needed to determine whether THP has similar effects on GABA receptors and anxiety in human teenagers as in adolescent mice.
Sheryl Smith (SUNY Downstate Medical Center, Brooklyn, NY, USA)
Additional contact for comment on paper:
Margaret McCarthy (University of Maryland, Baltimore, MD, USA)
Abstract available online.
(C) Nature Neuroscience press release.
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