Download Toward the Identification of Peripheral Epigenetic Biomarkersof

UNIVERSITY OF ILLINOIS AT CHICAGO
Department of Psychiatry
Fifth Annual Research Forum – Extravaganza 2014
POSTER TITLE
Toward the Identification of Peripheral Epigenetic
Biomarkersof Schizophrenia
DISEASE/KEY
WORDS:
AUTHORS:
MENTEE
CATEGORY:
BACKGROUND:
Auta J, Zhubi A, Davis JM, Dong E, Gavin DP, Grayson DR, Sharma RP, Smith
RC, Tueting P, Gudotti A
RESEARCH MENTOR:
Schizophrenia (SZ) is a heritable, non-Mendelian, neurodevelopmental disorder in
which epigenetic dysregulation of the brain genome plays a fundamental role in
mediating the clinical manifestations and course of the disease. We have reported that
two enzymes that belong to the dynamic DNA-methylation/demethylation networkDNMT (DNA-methyltransferase) and TET (5-hydroxycytosine translocator)-are
abnormally increased in cortico-limbic structures of the SZ post-mortem brain. This
suggests a causal relationship between the clinical manifestations of SZ and changes
in DNA methylation and in the expression of SZ candidate genes (e.g., brain derived
neutrophic factor [BDNF], glucocorticoid receptor [GCR], glutamic acid
decarboxylase67 [GAD7] and reelin). Because the clinical manifestations of SZ
typically begin with a prodrome followed by a first episode in adolescence with
subsequent deterioration, it is obvious that the natural history of this disease cannot be
studied in post-mortem brain.
METHODS:
RESULTS:
The focus is currently shifting towards the feasibility of studying epigenetic molecular
signatures of SZ in blood cells. Initial studies show a significant enrichment of
epigenetic changes in lymphocytes in gene networks directly relevant to psychiatric
disorders. Furthermore, the expression of DNA-methylating/demethylating enzymes
and SZ candidate genes such as BDNF and GCR are altered in the same direction in
both brain and blood lymphocytes.
UNIVERSITY OF ILLINOIS AT CHICAGO
Department of Psychiatry
CONCLUSIONS:
The coincidence of these changes in lymphocytes and brain supports the hypothesis
that common environmental or genetic risk factors are operative in altering the
epigenetic components involved in orchestrating transcription of specific genes in
brain and peripheral tissues. The identification of DNA-methylation signatures for SZ
in peripheral blood cells of subjects with genetic and clinical high risk would clearly
have potential for diagnosis of SZ early in its course and would be invaluable for
initiating early intervention and individualized treatment plans.