Altered signal transduction in fibroblasts from first-episode schizophrenic patients

A specific functional consequence of the lower levels of plasma membrane phospholipids and their esterified polyunsaturated essential fatty acids (EPUFAs) reported in red blood cells, brain and in cultured skin fibroblasts from schizophrenic patients is unclear. It is well established that the metabolic products (e.g., diacylglycerol, arachidonic acid, and inositol phosphates) of phospholipids generated following membrane receptor-mediated processes contribute to cell signal transduction, which is suggested to be altered in schizophrenia. Since cultured skin fibroblasts from schizophrenic patients contain lower levels of membrane phospholipids and their esterified EPUFAs, and they express receptors to several neurotransmitters, we studied the release of phospholipid-arachidonic acid induced by muscarinic agonist. Fibroblasts from 5 patients at the first-episode of psychosis and 5 matched normal controls were grown in log phase, and phospholipids were prelabeled with 1-14C-AA by continuing growth for 24 hrs. Labeled cells were washed with medium containing fatty acid free albumin, suspended in phosphate buffered saline containing fatty acid free albumin and with or without 5 uM carbacol for 5 minutes. Medium was collected, centrifuged and radioactivity was determined. There was a significantly lower level of AA released from fibroblasts of patients as compared with that released from normal controls (92.8 ± 25.0 vs 151.2 ± 13.8 pmoles AA released/hr/mg cell protein, respectively; P = <0.01, Mann-Whitney Test). These studies indicate that fibroblasts may be suitable for investigating the mechanisms of possible altered neurotransmitter receptor mediated signal transduction in schizophrenia.