Third, many patients with depression do not exhibit an increase in anxiety and instead exhibit blunted responses to emotional stimuli, including anxiogenic stimuli. Likewise, anxiety does not co-occur with depression in many other families. While such subtypes of hyperreactive and hyporeactive depression have been described for decades, very little information has been available concerning the underlying neurobiological mechanisms involved. Our studies of BDNF conditional KOs may provide unique insight into the phenotypic variations seen among depressed individuals and specifically implicate forebrain BDNF in a syndrome of depression found in women who are hyporesponsive to environmental stimuli. Further work is needed to study the validity of this and alternative explanations