Abnormal growth of skin fibroblasts from schizophrenic patients

Abstract

Fibroblast cultures were established from skin biopsies of 18 schizophrenic patients (14 on drug and 4 off drug) and 13 normal subjects, and growth parameters (initial growth and rate of growth) and morphology were studied. Fibroblasts from patients took significantly longer to grow than did normal fibroblasts. Cell lines were established within 2 weeks for all normal controls, but for only 6 (33%) of 18 schizophrenic patients. The rate of growth (doubling time) was also significantly longer for fibroblasts from patients than from normals. Neither time to establishment of initial growth nor doubling time was related to age, sex, age at onset, duration of illness, or medication status in the patients. Fibroblasts from normals showed uniform, long (slender), characteristic spindlelike, bipolar appearance, with unidirectional orientation, both while growing from explant as well as after subculturing. By contrast, fibroblasts from patients generally showed random size (shorter and flatter), mostly spiny, multipolar cells with short stubby projections, and an irregular orientation resulting in a criss-cross pattern, and often exhibited poor attachment. Fibroblasts from skin biopsies of patients who were drug free at the time of biopsy showed similar initial growth, doubling time, and morphology to those from patients who were receiving neuroleptic treatment. In vitro challenge of skin biopsies of normal subjects with haloperidol in culture resulted in slight delay in initial growth and marginal increase in doubling time. However, the morphology remained normal. Possible molecular mechanisms that may be associated with abnormal growth of fibroblasts in schizophrenia are discussed.