Phospholipid and eicosanoid signaling disturbances in schizophrenia.
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.
Ross
Brian M
BM
Ness Foundation, UNI Millennium Institute, Ness House, Dochgarroch, IV3 8GY, Inverness, Scotland, UK. brain@hprf.org.uk
D002118:Calcium / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism*; D006801:Humans; D009525:Niacin / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism*; D012559:Schizophrenia / Q000201:enzymology / Q000378:metabolism*; D015398:Signal Transduction
D015777:Eicosanoids; D010743:Phospholipids; D009525:Niacin; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium