Epigenomics of Major Psychiatric Disorders

Since the genetic make-up, along with functional genetic polymorphisms are insufficient by themselves to provide a molecular basis for the pathogenesis of the majority of individuals with major psychiatric disorders such as schizophrenia (SCZ) and bipolar disorder (BD), we decided to focus on the epigenetic basis of the major psychiatric disorders. Pioneering studies performed by Drs. Thiagalingam and Abdolmaleky provided the first conclusive evidence for DNA hypermethylation silencing of reelin (RELN) and hypomethylation associated overexpression of the membrane-bound catechol-O-methyltransferase (MB-COMT) gene in the SCZ and BD patients. Our more recent and ongoing studies using post-mortem brain samples from controls and patients with SCZ, found asymmetric expression of many genes involved in the TGFB super family signaling pathways and epigenetic alterations may play critical roles in determining the nature of left-right asymmetry in the brain of patients. Furthermore, because of the practical difficulties in designing controlled experiments using genuinely fresh brain tissue samples for performing molecular psychiatry research, in collaboration with clinicians, we are using surrogate samples such as saliva and blood for the accurate diagnosis and prognosis of SCZ and BD.