The goals of the Psychiatric Institute (PI), which is directed by Dr. Alessandro Guidotti, are to investigate the role of epigenetic mechanisms in regulating neuronal gene expression in the brain. The reversible modulation of gene function mediated through changes in DNA methylation and histone modifications is tightly regulated and is responsible for coordinating neuronal structure and function during development and in the adult. The programmatic focus is to examine DNA methylation marks and histone modifications as related to altered transcription profiles of sets of genes in the course of schizophrenia and autism. At a recent Society for Neuroscience Symposium lecture, Dr. Dennis R. Grayson, spoke about his ongoing efforts in studying DNA methylation and hydroxymethylation patterns in DNA from post-mortem cerebella from autism spectrum disorder subjects. In addition to the use of post-mortem brain specimens, researchers at the PI, including Drs. Erbo Dong and James Auta, are studying the effects of prenatal stress in animals as a means of modeling psychiatric behaviors in rodents. Collectively, we are investigating mechanisms by which psychiatrists may be able to reverse altered gene expression programs in the brain through the development of new pharmaceutical strategies. Another program being explored by Drs. Rajiv P. Sharma and John M. Davis involves examining DNA methylation of schizophrenia and non-psychiatric subjects for the presence of epigenetic biomarkers that may be useful in detecting schizophrenia at early stages of the disorder. The hope is to use this information for the development of hypothesis-designed pharmaceuticals aimed at altering chromatin structure.
In addition to the above studies, research at the PI includes studies of basic aspects of neuronal function and neuronal circuitry in vitro and in vivo. Dr. John Larson studies the cellular and molecular mechanisms of memory formation. Dr. Neil Smalheiser is examining endogenous siRNAs and noncoding RNA-derived small RNAs expressed in adult mouse hippocampus. Dr. Graziano Pinna investigates mouse models of post-traumatic stress disorder (PTSD); investigating the mechanism of action of antidepressants. Dr. Lech Kiedrowski studies intracellular zinc homeostasis in hippocampal neurons. Dr. Ghanshyam Pandey, Professor in the Department of Psychiatry and Director of Mood Disorders and Suicide Research, is also a member of the PI and he makes a significant contribution in research related to depression, bipolar illness, and suicide.