The picture is consistent with a fairly undifferentiated phenotype emerging as the final common outcome of diverse processes, a process called equifinality in the development literature. The list of possible pathways is large: in addition to long-running favorites such as abnormalities of monoamine metabolism (including postreceptor components of the downstream cAMP signaling pathway [Duman et al., 1997]) and impaired corticosteroid receptor signaling (Holsboer, 2000), more recent hypotheses include the involvement of neurotrophins (Samuels and Hen, 2011), fibroblast growth factors (both ligands and receptors) (Turner et al., 2012), GABAergic deficits (Luscher et al., 2011), and epigenetic changes, specifically alterations in methylation and acetylation profiles at the promoters of glucocorticoid receptors and brain-derived neurotrophic factor (McGowan et al., 2009). Genetics does not support the primacy of one theory over another; indeed as our Review of the candidate gene literature indicates, genetics does not support any of the biological theories put forward to date.
