The synapsin family of neuronal phosphoproteins is composed of three genes (SYN1, SYN2 and SYN3) with alternative splicing resulting in a number of variants with various levels of homology. These genes have been postulated to play significant roles in several neuropsychiatric disorders, including bipolar disorder, schizophrenia and epilepsy. Epigenetic regulatory mechanisms, such as histone modifications in gene regulatory regions, have also been proposed to play a role in a number of psychiatric disorders, including bipolar disorder and major depressive disorder. One of the best characterized histone modifications is histone 3 lysine 4 tri-methylation (H3K4me3), an epigenetic mark shown to be highly enriched at transcriptional start sites and associated with active transcription. In the present study we have quantified the expression of transcript variants of the three synapsin genes and investigated their relationship to H3K4me3 promoter enrichment in post-mortem brain samples. We found that histone modification marks were significantly increased in bipolar disorder and major depression and this effect was correlated with significant increases in gene expression. Our findings suggest that synapsin dysregulation in mood disorders is mediated in part by epigenetic regulatory mechanisms.