Background: Human dermal fibroblasts (HDF) can be used as a cellular model relatively
easily and without genetic engineering. Therefore, HDF represent an interesting tool to study several
human diseases including psychiatric disorders. Despite major depressive disorder (MDD)
being the second cause of disability in the world, the efficacy of antidepressant drug (AD) treatment
is not sufficient and the underlying mechanisms of MDD and the mechanisms of action of AD are
Objective: The aim of this review is to highlight the potential of HDF in the study of cellular
mechanisms involved in MDD pathophysiology and in the action of AD response.
Methods: The first part is a systematic review following PRISMA guidelines on the use of HDF in
MDD research. The second part reports the mechanisms and molecules both present in HDF and
relevant regarding MDD pathophysiology and AD mechanisms of action.
Results: HDFs from MDD patients have been investigated in a relatively small number of works
and most of them focused on the adrenergic pathway and metabolism-related gene expression as
compared to HDF from healthy controls. The second part listed an important number of papers
demonstrating the presence of many molecular processes in HDF, involved in MDD and AD
mechanisms of action.
Conclusion: The imbalance in the number of papers between the two parts highlights the great and
still underused potential of HDF, which stands out as a very promising tool in our understanding of
MDD and AD mechanisms of action.