PII: S0952-3278(03)00159-5

Abstract

Schizophrenia is a complex psychiatric disorder that is associated with a wide range of cognitive, emotional, and social disabilities. The cause and pathophysiology of this devastating illness have not been clearly identified. A multiplicity of theories have been proposed over the years that aim to conceptualize the pathophysiology of schizophrenia, including neuronal maldevelopment, impaired neurotransmission, intrauterine viral infections, autoimmune dysfunction, and many others. Although the dopamine hypothesis remains the most widely studied conceptualization, none of the above hypotheses can fully explain the etiology and manifold manifestations of schizophrenia. There are a large variety of seemingly disparate biological findings, possibly due to etiologic heterogeneity. This would suggest that there are one or more (but very few) common pathogenetic pathways that lead to the syndromes of schizophrenia. Over a quarter of a century ago, Feldberg (1976) and Horrobin (1977) postulated that schizophrenia is associated in part with phospholipid/fatty acid abnormalities since a point of convergence for many theoretical models occurs at the level of the neuronal membrane. Evidence to date shows defects in phospholipid metabolism and cell signaling for schizophrenia patients. Specifically, low levels of arachidonic acid (AA)-enriched phospholipids have been observed in both central and peripheral tissues from patients with chronic schizophrenia, and a relative paucity of such evidence in early schizophrenia. Since AA has many key roles in neural functioning, understanding its significance for the pathophysiology of schizophrenia may lead to novel approaches to improving treatment approaches to schizophrenia.