[Frontiers in Bioscience S3, 298-330, January 1, 2011]
Cognition, dopamine and bioactive lipids in schizophrenia
Ruth Condray1,2, ">Jeffrey K. Yao1,2,3
1Department of Psychiatry and Western Psychiatric Institute and Clinic University of Pittsburgh School of Medicine, 3811 O'Hara Street, Pittsburgh, PA 15213,U.S.A.2VA Pittsburgh Healthcare System,7180 Highland Drive, Pittsburgh, PA 15206,
3Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA 15213
TABLE OF CONTENTS
Schizophrenia is a remarkably complex disorder with a multitude of behavioral and biological perturbations. Cognitive deficits are a core feature of this disorder, and involve abnormalities across multiple domains, including memory, attention, and perception. The complexity of this debilitating illness has led to a view that the key to unraveling its pathophysiology lies in deconstructing the clinically-defined syndrome into pathophysiologically distinct intermediate phenotypes. Accumulating evidence suggests that one of these intermediate phenotypes may involve phospholipid signaling abnormalities, particularly in relation to arachidonic acid (AA). Our data show relationships between levels of AA and performance on tests of cognition for schizophrenia patients, with defects in AA signaling associated with deficits in cognition. Moreover, dopamine may moderate these relationships between AA and cognition. Taken together, cognitive deficits, dopaminergic neurotransmission, and bioactive lipids have emerged as related features of schizophrenia. Existing treatment options for cognitive deficits in schizophrenia do not specifically target lipid-derived signaling pathways; understanding these processes could inform efforts to identify novel targets for treatment innovation.