HAMBURG 249the NIH to Stanford University in order to try to pursue a behavioral
endocrine-genetic approach to stress problems.
Many of the people involved in the NIMH-Walter Reed group on
stress and hormones went on to make important contributions at other
institutions in later years. They and other investigators in other coun
tries have elucidated the importance and much of the nature of the
hypothalamic-pituitary-adrenal axis in depressive disorders particularly.
Jack Barchas, who, for almost a decade, edited the Archives of Psychiatry,
has told me that there probably has not been anything more important
in psychiatric research in the past decade than the great elaboration–
and much greater depth, of course, than we had–of that work on the
hypothalamic-pituitary-adrenal axis, particularly in depressive and bipolar
disorders. These findings in depressed patients were counterintuitive.
When we made the initial discoveries, we were actually quite apprehen
sive that we must be wrong because it was assumed at the time that
a person sitting quietly, not communicating, and rather withdrawn
and despondent would not have physiological or biochemical alarm
responses, but that turned out not to be the case. Indeed, that work on
depression has turned out to be extremely interesting in many contexts.
The findings of consistent individual differences in adrenal cortical
response to environmental conditions touch on the important problem
of differential susceptibility to psychological stress. Clinicians have long
observed the precipitation and exacerbation of a variety of illnesses in
association with emotional crisis, not only psychiatric disorders, but also
clinical problems coming to the attention of other disciplines. Most of
the specialties of internal medicine, in one way or another, see that
phenomenon of stress-induced disorders or exacerbation.
Yet it is abundantly clear that many individuals undergo the common
stressful experiences of living without developing clinical disorders. A
number of genetic and environmental factors must contribute to these
individual differences in stress response and, hence, to the differential
susceptibility to illness.
One promising line of inquiry on this topic, which we began in a
rudimentary way, was based on human biochemical genetics, relating
genetically determined differences in metabolism of hormones to
behavior under stress. In pursuit of such questions, I formulated a