Clock gene rhythm disruption: Comparison of major depressive disorder (mdd), bipolar (bp), and schizophrenia

Hagenauer MH, Li JZ, Bunney B, Walsh D, Turner C, Absher D, Meng F, Vawter M, Evans S, Barchas JD, Schatzberg AF, Myers RM, Bunney W, Watson S, Akil H
Society for Neuroscience. 2015.


One of the cardinal characteristics of many mood disorders, including Major Depressive Disorder (MDD) and Bipolar Disorder (BP), is the disruption of daily rhythms in sleep and activity. Recently we discovered that a similar disruption occurs in daily rhythms of clock gene expression in the brains of individuals with MDD. To perform this analysis, we organized microarray data from high-quality post-mortem brain tissue by the time of death of the subjects. As a group, the clock gene data from non-psychiatric control subjects showed a clear daily rhythm, and the molecular “time stamp” for any particular individual matched the time that the individual had died. In contrast, as a group the clock gene data from MDD subjects had either a dampened or non-existent rhythm, and the molecular “time stamp” for MDD individuals differed widely from the time that they had died, suggesting that the MDD subjects were internally “jet lagged” from the rest of the population. We have now extended these analyses to include individuals with BP and Schizophrenia. As a group, we find that BP subjects exhibit disrupted clock gene rhythms in the brain similar to MDD subjects, whereas the disruptions present in Schizophrenia are not as severe. We also find that these patterns hold true even after controlling for other potential confounding factors, including age and gender. This work indicates that psychiatric interventions to improve patient sleep are likely to be enhanced if they simultaneously address the presence of severe circadian disturbance.