So it's not "all in her head," or maybe it is! A team of researchers led by NIMH grantee Rita Valentino PhD, and Debra Bangasser, PhD., reported on their study—the first to uncover sex differences in response to stressors at the level of receptor molecules—in the journal Molecular Psychiatry. In females, certain brain cells are more sensitive to Corticotropin Releasing Factor or CRF, both a hormone and a neurotransmitter than is released during stress. In addition, the female brain cells were less able to adapt to too much CRF. The greater coupling of CRF receptors to relay proteins and their inability to internalize could translate into a lower threshold for stress-induced activation of the alarm system. This could increase risk for chronic activation and impair the brain's ability to cope with high levels of CRF, as occurs in depression and PTSD. Males, with their less stress-reactive brain, could conceivably help females perceive stressors in a different way. Saying "It's no big deal; just let it go" is likely to be unhelpful and could even create additional stress to the female brain.