Publications by Year: 2015

2015
Cho-Yi Chen, Ryan Logan, Tianzhou Ma, David Lewis, George Tseng, Etienne Sibille, and Colleen McClung. 2015. “The Effects of Aging and Psychiatric Disease on Circadian Patterns of Gene Expression in the Human Prefrontal Cortex.” In Neuropsychopharmacology, 40: Pp. S199–S200. Hollywood, Florida, USA: Nature Publishing Group.Abstract

Background: With aging, significant changes in circadian rhythms occur, including a shift in phase toward a ‘‘morning’’ chronotype and a loss of rhythmicity in circulating hormones. There are also well documented disruptions to circadian rhythms that are associated with several psychiatric disorders. However, the effects of aging and psychiatric conditions on molecular rhythms in the human brain have remained elusive.
Methods: Here we employed a previously described time-ofdeath analyses to identify transcripts throughout the genome that have a significant circadian rhythm in expression in the human prefrontal cortex (Brodmann’s areas (BA) 11 and 47). Expression levels were determined by microarray analysis in 146 individuals.
Results: Rhythmicity in expression was found in B10% of detected transcripts (p<0.05). Using a meta-analysis across the two brain areas, we identified a core set of 235 genes (q<0.05) with significant circadian rhythms of expression. These 235 genes showed 92% concordance in the phase of expression between the two areas. In addition to the canonical core circadian genes, a number of other genes were found to exhibit rhythmic expression in the brain. Notably, we identified more than one thousand genes (1,186 in BA11; 1,591 in BA47) that exhibited age-dependent rhythmicity or alterations in rhythmicity patterns with aging. Interestingly, a set of transcripts gained rhythmicity in older individuals, which may represent a compensatory mechanism due to a loss of canonical clock function. We are currently analyzing samples from subjects with either bipolar disorder or schizophrenia and these data will also be presented.
Conclusions: We confirm that rhythmic gene expression can be reliably measured in human brain and identified for the first time significant changes in molecular rhythms with aging that may contribute to altered cognition, sleep and mood in later life.