Epigenetics of TrkB in Suicide

Abstract

Suicide is a major public health concern, yet the little is known of the neurobiology.  Astrocyte dysfunction has been suggested to have a role in suicide, but it is unclear exactly how this cell-type may be involved.  Using whole genome expression analysis, we found that expression of the astrocyte-related variant of TrkB, TrkB.T1, is reduced in frontal cortex of suicide completers.  To understand why the expression of TrkB.T1 is decreased, we assessed the methylation state of the TrkB promoter, the methylation state of histone 3 at the TrkB locus, and performed a genome wide analysis of microRNA expression levels in frontal cortex.  DNA methylation, histone methylation, and microRNA are all potential factors that could affect the expression of TrkB.T1.  We found an association between both the methylation state of the TrkB promoter and methylation lysine 27 on histone 3, and reduced expression of TrkB.T1 in suicide completers.  Three microRNA molecules were also found to have a role in TrkB.T1 expression.  These results suggest that reduced expression of a neurotrophin receptor in astrocytes may be due to epigenetic mechanisms and further implicate astrocyte dysfunction in suicide.