M22 - GENOME-WIDE METHYLOME AND TRANSCRIPTOME PROFILES OF MANIC EPISODE IN BIPOLAR DISORDER

Abstract

Background Bipolar Disorder (BD) is a highly heritable psychiatric disorder. More than two thirds of BD patients have recurrent episodes throughout lifetime. To explore the underlying biological mechanisms of manic episode in BD, the current study adopted two experimental platforms to capture the episodic dynamic feature. We compared the differences of methylome and transcriptome between acute manic episode and remission, which were influenced by both inheritant genetic sequence and environmental stimuli. Methods We enrolled 12 BD patients with collected biological samples and clinical data at two time points, the acute manic state and remission in at least two-months follow-up for intra-individual comparisons. Young Mania Rating Scale (YMRS) score and Hamilton Depression Rating Scale (HAMD-21) were used to evaluate symptom severity. The manic state was defined as having YMRS score ≥21 and HAM-D ≤8; the remission was defined as having YMRS score Results The average reads number for RRBS and RNA-Seq were 38 and 30 millions, respectively. No significant global methylation changes were found across the whole-genome with adjustment of multiple testing, while 337 DMGs had nominal p-values Discussion With comprehensive genomic data obtained by high-throughput technologies at the genome-wide level, we identify potential biomarkers underlying BD manic state. The overlapping results of DEGs and DMGs are relevant to transcriptional regulation, such as PAX8 and FOXD2. Their functions are found to be related to mitochondrial dysfunction and brain development through transcriptional regulation. Further experimental studies are needed to validate these results. In conclusion, methylomic and transcriptomic biomarkers are identified for regulating BD manic episode, which could provide novel insights for the pathogenesis of manic illness, and facilitating to allocate better therapeutic targets for BD.