[Frontiers in Bioscience S3, 298-330, January 1, 2011]

Cognition, dopamine and bioactive lipids in schizophrenia

Ruth Condray1,2, ">Jeffrey K. Yao1,2,3

1 Department 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


1. Abstract
2. Introduction
3. Cognition, neurotransmission, and membrane phospholipids in schizophrenia
3.1. Memory impairment in schizophrenia
3.1.1. Systems of memory
3.1.2. Memory deficits in schizophrenia patients Verbal declarative memory Semantic memory
3.1.3. Memory deficits in nonaffected family members of patients
3.2. Association between cognition and neurochemistry
3.2.1. Cognition and the dopamine hypothesis
3.2.2. Possible roles of polyunsaturated fatty acids (PUFAs) in cognition n-3 PUFAs Animal studies Human studies n-6 PUFAs Eicosanoids (Arachidonic acid cascade)
3.3. Phospholipids signaling and schizophrenia
3.4. Interactions between monoaminergic neurotransmission and PUFAs: A model for neurocognitive deficits in schizophrenia
3.5. Hypothesis: The relationship between cognition and membrane phospholipids in schizophrenia is moderated by dopaminergic neurotransmission
3.5.1. Association between arachidonic acid and semantic memory, reading, and intelligence Semantic memory
3.5.2. Association between semantic memory and dopamine turnover
3.5.3. Association between membrane phospholipids and dopamine turnover
4. Summary and perspective
5. Acknowledgements
6. References


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.