Fibroblast cell lines have been used to elucidate the pathophysiological mechanisms that may be relevant to central nervous system dysfunction in neuropsychiatric patients. In a preliminary study, we found growth parameters (initial growth and rate of growth) and morphology (size, shape and orientation) of the established fibroblasts of both schizophrenic and bipolar patients to markedly differ from normal subjects. Fibroblasts of patient grew at a much slower rate than fibroblasts of controls. We propose to conduct over a two year period, skin biopsies for obtaining fibroblast cell lines in 20 schizophrenic patients and 20 bipolar patients, both patient groups will be off neuroleptic treatment at the time of skin biopsies, and 20 normal controls matched for age, sex and ethnicity.
The specific aims will be: 1. To establish primary cell-lines of skin fibroblasts, and immortalize them by cell transformation with SV-40 to establish a fibroblast cell depository, which will be expanded in future years, for their long-term use. 2. To establish growth parameters (initial growth, rate of growth and morphology) of fibroblast primary cultures and immortalized cultures from schizophrenic patients and compare them to growth parameters in fibroblast cultures from bipolar patients and normal controls. The altered growth patterns of cells in culture may be indicative of possible genetic/metabolic alterations. 3. To identify the possible molecular mechanisms associated with abnormal growth parameters: the adhesiveness to plastic substratum, the levels of fibronectin and the growth response to growth factors, e.g. epidermal growth factor and fibroblast growth factor will be studied. Thus, these cultures would potentially be useful for the study of relevant biochemical variability in CNS that may be associated with specific neuropathological and/or possibly behavioral changes in schizophrenic patients.
