Robert Keers, Inti Pedroso, Gerome Breen, Kathy J. Aitchison, Patrick M. Nolan, Sven Cichon, Markus M. Nöthen, Marcella Rietschel, Leonard C. Schalkwyk, Cathy Fernandes

Disruption of the circadian rhythm is a key feature of bipolar disorder. Variation in genes encoding components of the molecular circadian clock has been associated with increased risk of the disorder in clinical populations. Similarly in animal models, disruption of the circadian clock can result in altered mood and anxiety which resemble features of human mania; including hyperactivity, reduced anxiety and reduced depression-like behaviour. One such mutant, after hours (Afh), an ENU-derived mutant with a mutation in a recently identified circadian clock gene Fbxl3, results in a disturbed (long) circadian rhythm of approximately 27 hours.