Mania-like behavior induced by disruption of CLOCK.

Circadian rhythms and the genes that make up the molecular clock have long been implicated in bipolar disorder. Genetic evidence in bipolar patients suggests that the central transcriptional activator of molecular rhythms, CLOCK, may be particularly important. However, the exact role of this gene in the development of this disorder remains unclear.

Brain-derived neurotrophic factor conditional knockouts show gender differences in depression-related behaviors.

Background: Indirect evidence suggests that loss of brain-derived neurotrophic factor (BDNF) from forebrain regions contributes to an individual's vulnerability for depression, whereas upregulation of BDNF in these regions is suggested to mediate the therapeutic effect of antidepressants.

Methods: We have tested this hypothesis by generating two independent lines of conditional BDNF knockout mice in which the BDNF gene is deleted selectively in forebrain.

Results: We show that male conditional knockouts exhibit hyperactivity but normal depression-related behaviors.