From genes to behaviour – Imaging genetics in Schizophrenia
Contact persons: Prof. Dr. S. Ehrlich, Dipl.-Ing. J. Hass, Dipl.-Inf. D. Geisler, E. Walton, M.Sc.
- Prof. R. Gollub, Massachusetts General Hospital/ Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging;
- Prof. V. Calhoun, Depts. of Electrical and Computer Engineering, Neurosciences, Psychiatry & Computer Science, University of New Mexico;
- Prof. J. A. Turner, Mind Research Network, New Mexico;
- Prof. Dr. A. Heinz, Klinik für Psychiatrie und Psychotherapie, Charité Universitätsmedizin Berlin
Approximately 0,7 % of the world population suffer from Schizophrenia (Saha et. al., 2005) and heritability of this disease is estimated at 80 % (Gottesman and Gould, 2003). Research results have already linked alterations in the dopamine- and glutamate-system to the emergence and course of this disease. However, the exact biochemical aberrations remain unidentified until now. This knowledge would be an important basis for the development of adequate pharmacological agentss and a more targeted pharmacotherapy.
Genetic association studies can help to understand underlying biological mechanisms. But research findings from conventional genetic association studies have shown inconsistencies concerning heritable mental disorders like Schizophrenia (O'Donovan et al., 2009).
These results may be caused by ill-defined clinical phenotypes in psychiatry. Hence scientific efforts have increased recently, aiming to link genetic polymorphisms with underlying physiological aspects of mental disorders (the so called intermediate phenotypes). This approach holds the promise of more reliable results (Gottesman and Gould, 2003).
Well-known characteristics and heritable intermediate phenotypes of Schizophrenia comprise prefrontal inefficiency during working memory tasks, a reduced hippocampal volume and a reduced cortical thickness (Ehrlich et al., 2011 in press). Our group and other scientists were already able to verify associations between candidate genes and some of the mentioned phenotypes (Ehrlich et al., 2010). Nevertheless, the exploration of new biological mechanisms possibly may be impeded as the candidate gene approach is based on known pathophysiological premises of Schizophrenia. Furthermore, well-established genetic variants, that have several times been associated to Schizophrenia, account only for a fraction of the variance.
Our group uses clinical, neurophysiological, genome-wide SNP and multi-modal imaging data from a large-scale multicenter study on Schizophrenia to test new concepts of data reduction and multivariate data analysis. We aim to identify associations between heritable risk-factors and biomarkers of Schizophrenia.
EHRLICH, S., MORROW, E. M., ROFFMAN, J. L., WALLACE, S. R., NAYLOR, M., BOCKHOLT, H. J., LUNDQUIST, A., YENDIKI, A., HO, B. C., WHITE, T., MANOACH, D. S., CLARK, V. P., CALHOUN, V. D., GOLLUB, R. L. & HOLT, D. J. 2010. The COMT Val108/158Met polymorphism and medial temporal lobe volumetry in patients with schizophrenia and healthy adults. Neuroimage, 53, 992-1000.
GOTTESMAN, II & GOULD, T. D. 2003. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry, 160, 636-45.
HALL, M. H. & RIJSDIJK, F. 2008. Validating endophenotypes for schizophrenia using statistical modeling of twin data. Clin EEG Neurosci, 39, 78-81.
O'DONOVAN, M. C., CRADDOCK, N. J. & OWEN, M. J. 2009. Genetics of psychosis; insights from views across the genome. Hum Genet, 126, 3-12.
SAHA, S., CHANT, D., WELHAM, J. & MCGRATH, J. 2005. A systematic review of the prevalence of schizophrenia. PLoS Med, 2, e141.