Are cognitive aspects of defense a core feature of anxiety and depression?

Anxiety and depression are highly prevalent behavior disorders, particularly in women. Recent preclinical work using animal models has been suboptimal in predicting the efficacy of drugs targeted at these conditions, suggesting a potential discrepancy between such models and the human disorders. Notably female animals tend to be equal to, or less responsive than, males in these tasks. A number of analyses suggest that mammalian defense patterns are complex: In addition to relatively discrete and immediate fight, flight, and freezing responses, a risk assessment pattern may occur in response to threat stimuli or situations with ambiguous elements. This pattern combines defensiveness with a number of cognition-linked behaviors such as sensory attention and orientation, approach, contact, and investigation of the potential threat. Studies measuring elements of this pattern suggest that female rats, and perhaps female mice, show higher levels than equivalent males. Higher female involvement may also occur in tasks involving learning/generalization/extinction of defensiveness to conditioned stimuli. Such findings are consonant with recent analyses of “female survival strategies” based on differential adaptiveness of cognitive components of defensiveness in females, due to the necessity of female care of offspring until they are independent. These data suggest the value of additional behavioral and functional analyses of cognitive aspects of defensive behavior; contributing to both an understanding of their underlying mechanisms, and providing more sensitive measures of drug responsivity for use with animal models.