Phenotype of spontaneous orofacial dyskinesia in neuregulin-1 'knockout' mice.

Studies in antipsychotic-naïve patients with schizophrenia indicate a baseline level of spontaneous involuntary movements, particularly orofacial dyskinesia. Neuregulin-1 is associated with risk for schizophrenia and its functional role can be studied in 'knockout' mice. We have shown previously that neuregulin-1 'knockouts' evidence disruption in social behaviour. Neuregulin-1 'knockouts' were assessed for four topographies of orofacial movement, both spontaneously and under challenge with the D(1)-like dopamine receptor agonist SKF 83959. Neuregulin-1 'knockouts' evidenced an increase in spontaneous incisor chattering, particularly among males. SKF 83959 induced incisor chattering, vertical jaw movements and tongue protrusions; the level of horizontal jaw movements was increased and that of tongue protrusions decreased in neuregulin-1 'knockouts'. These findings indicate that the schizophrenia risk gene neuregulin-1 is involved in the regulation of not only social behaviour but also orofacial dyskinesia. Orofacial dyskinesia in neuregulin-1 mutants may indicate some modest genetic relationship between risk for schizophrenia and vulnerability to spontaneous movement disorder.