PsyLab Work and Prospects Hong CJ, Jul 10, 2006
Disturbances of brain functioning may be presented as various psychiatric disorders, such as schizophrenia, anxiety, depression, mania, dementia, autism, etc. These disorders are thought with some heritability, however, variable therapeutic responses and adverse effects in the patients with the same diagnosis are not uncommon. We use psychiatric methods to assess human thought, mood, cognition, behavior, and use molecular techniques to analyze genetic variations. In the past decade, we have conducted genetic and pharmacogenetic studies of schizophrenia and mood disorders and have the following positive findings: (1) Genetic variant of tryptophan hydroxylase gene and PICK1 gene are related to schizophrenic susceptibility (Schizophr Res 2001;49:59-63, NeuroReport 2004;15:1965-7); (2) Serotonin-6 receptor genetic variant affect antipsychotic treatment response in schizophrenia (NeuroReport 1999;10:1231-3); (3) Genetic variant of α7 nicotinic acetylcholine receptor gene is related to bipolar disorder susceptibility (Neurosci Lett 2004;355:69-72); (4) Serotonin-1A receptor genetic variant may affect antidepressant treatment response in major depression (Pharmacogenomics J 2006;6:27-33); (5) Genetic variant of brain-derived neurotrophic-factor gene is related to major depression and schizophrenia susceptibility (Neurobiol Aging 2006; Neurosci Lett 2003;349:206-8). These findings have been replicated by other research groups from other countries.
In order to gain insights into the biological basis of psychiatric disorders, we established methods to assess rodent behavior and developed devices to standardize the procedures, of which some have obtained patent protection from the USA: (1) Method and system for measuring motility of a tested animal (US 6,799,535 B2); (2) Tail suspension test apparatus (US 6,955,139 B2); (3) Apparatus and Method to Evaluate the Interest of an Animal (approved). We are now applying these behavioral methods to carry out the following studies: (1) screening inheritable patterns of behavior in the ENU-mutagenized mice, wherein genetic animal models of psychiatric disorders can be obtained and related genes are expected to be cloned; (2) combining the use quantitative trait locus analysis to map the chromosomal loci related to antidepressant response; (3) combing the technology of gene expression array to identify transcription elements associated with antipsychotics-induced tardive dyskinesia and (4) combining the technologies of neuroanatomy, immunohistochemistry and gene expression assay, to test drugs or regimens with potential therapeutic effects on schizophrenia or mood disorders. As convincing evidences accumulate, we with good clinical experiences and resources will be able to launch clinical trials. We expect the results of our research will not only clarify the etiology and pathophysiology of mental disorders but also be clinically useful and helpful.
2006/09/30 10:47 下午