Objectives: To review the evidence of the involvement of the Wnt signalling pathway in mood disorders and in
the action of drugs used to treat these disorders.
Methods: We performed a careful PubMed search using as keywords all possible terms relevant to the Wnt pathway and
crossing them with each of four areas, i.e., developmental effects, behavioural effects, mood disorders, and drugs used in
their treatment. Papers were selected on the basis of their content and their data used for discussion.
Results: Neurodevelopmental and behavioural data point to the possibility of involvement of the Wnt pathway in the
pathophysiology of mood disorders. Clinical and post-mortem data are not sufficient to corroborate a definite role for Wnt
alterations in any mood disorder. Combining genetic and pharmacological data, we may state that glycogen synthase
kinase is the key molecule in bipolar disorder, as it is connected with many other signalling pathways that were shown to
be involved in mood disorders, while Wnt molecules in the hippocampus appear to be mainly involved in depressive
Conclusions: Altered Wnt signalling may play a role in the pathophysiology of mood disorders, although not a central
one. It is premature to draw conclusions regarding the possible usefulness of Wnt manipulations in the treatment of mood