The following manuscript is mainly conceptual in nature. It should be read
with reservation. since the relevance of its suggestions have yet to be pro
ven. Basically it proposes two rules for the differentiation between primar
y illness related pathophysiological vs. secondary adaptational processes.
These rules may guide hypotheses generation for further research that is ai
med at understanding psychiatric disorders and their shared and unshared me
chanisms. For example, in the case of anxiety disorders and depression, it
may be of interest to learn if their shared properties are of primary patho
physiological or secondary adaptational significance. We first present some
historical observations on the development of the concept of secondary ada
ptational processes.'' We assume such adaptational processes are generated
by the organism in order to compensate for primary pathophysiological malfu
nction or impairment. Next, we propose rules that may enable the dissection
of secondary adaptational from primary pathophysiological processes. We al
so discuss the possible implications of designing studies to son out these
processes, suggesting that the understanding of adaptational processes, may
explain the effects of ''placebo treatment." Finally we illustrate the app
lication of these rules by two examples: a) amygdala activation, a biologic
al alteration shared by anxiety disorders and major depression and b) eleva
ted plasma soluble interleukin 2 receptor, an unshared property by anxiety
disorders and major depression. Also, the first example relates to a biolog
ical perturbation associated with a primary pathophysiological mechanism, w
hile the second represents a biological alteration associated with secondar
y adaptational processes. (C) 2001 Wiley-Liss, Inc.