Obtaining novel data-driven hypotheses from teaching activities: an
example assessing the role of the FKBP5 gene in major depression
Abstract
Many clinical and research efforts aim to develop antidepressant drugs
for those suffering from major depressive disorder (MDD). Yet even
today, the available treatments are suboptimal and unpredictable, with a
significant proportion of patients enduring multiple drug attempts and
adverse side effects before a successful response; and for many
patients, no response at all. Thus, a clearer understanding of the
mechanisms underlying MDD is necessary. In the “Brain Development and
Disease” class of our Master’s program in Cognitive Sciences, we ask
students to collect data about the expression of a gene whose altered
expression and/or function is related to a brain disorder. The students’
final exam assignment consists of writing a research article in which
the collected data are discussed in relation to the relevant disorder.
In the course of one of these assignments, we identified the FKBP5 gene
as a key player uniting two major hypotheses of MDD pathogenesis and
treatment response. FKBP5 controls biological processes including
immunoregulation and glucocorticoid function, both of which are
separately implicated in the development and prognosis of MDD. Gene
expression analyses from the human, non-human primate, and mouse Allen
Brain Atlases revealed that FKBP5 is expressed in brain regions involved
in MDD, particularly at ages susceptible to early-life stressors. Data
re-analysis from published studies confirmed that FKBP5 expression is
upregulated in relevant brain regions in human MDD and preclinical mouse
models of MDD. Our experience shows that classes engaging students in
data collection and analysis projects may effectively result in novel
data-driven hypotheses.