Phospholipid and eicosanoid signaling disturbances in schizophrenia

Abstract

A variety of biochemical, clinical and genetic evidence suggests that phospholipid metabolism may play an aetiological role in schizophrenia. A key piece of evidence is the reduced vasodilatory response of patients with schizophrenia to nicotinic acid (NA). NA causes vasodilation via the activation of phospholipase A₂ (PLA₂) leading to the release of free fatty acids from membrane phospholipids and the subsequent production of prostaglandins. Insensitivity to NA may be due to a ‘block’ in the downstream signaling pathway used by the drug to evoke its response. It can be argued that if such an abnormality occurs in neurons, impaired PLA₂-dependent signaling could result in altered glutamateric and dopaminergic transmission in such a way as to produce or exacerbate psychotic symptoms. The complimentary finding of increased PLA₂ activity in schizophrenia may be an attempt to overcome the signaling block. It is suggested that intervention aimed at increasing the activity of PLA₂-dependent signaling systems may be therapeutically useful in the treatment of the illness.