Many of the biochemical alterations observed in people suffering from major depression are changes in the concentrations and activity of components of the generalized stress response. These include the principal hypothalamic stimulus of pituitary-adrenal activation (corticotropin releasing hormone) and the locus ceruleus/norepinephrine system. The current study attempts to provide a clearer picture of the stability of changes during the acute illness, the treatment phase and the recovery process. We particularly wish to determine whether abnormalities in HPA axis perturbability in the well-state can be demonstrated, and if so how these are related to the acutely-ill state, since this information could provide a quantifiable phenotypic marker for depression.