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Critical Reviews™ in Neurobiology

ISSN Print: 0892-0915

Archives: Volume 10, 1996 to Volume 20, 2008

Critical Reviews™ in Neurobiology

DOI: 10.1615/CritRevNeurobiol.v16.i12.190
pages 181-186

5-Lipoxygenase as a Putative Link Between Cardiovascular and Psychiatric Disorders

Radmila Manev
The Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA
Hari Manev
The Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA

ABSTRACT

There is evidence of an association between depression and anxiety and cardio— cerebro—vascular conditions, but the mechanisms of this association are unknown. Here we review a possible role for the 5-lipoxygenase (5-LOX) pathway. 5-LOX is an enzyme that, in association with 5-LOX-activating protein (FLAP), leads to the synthesis of leukotrienes from omega-6 arachidonic acid. Production of active leukotrienes can be reduced by dietary omega-3 fatty acids, which also are beneficial in cardiac and psychiatric (e.g., depression) pathologies. Human 5-LOX and FLAP gene polymorphisms are a risk factor in atherosclerosis and cardio—cerebro—vascular pathologies; an overactive 5-LOX pathway is found in these diseases. Studies with 5-LOX-deficient transgenic mice suggest that 5-LOX activity may contribute to anxiety- and depression-like behaviors. Future research should characterize the role of the 5-LOX pathway in comorbid cardio—cerebro—vascular and psychiatric disorders and in the therapeutic actions of dietary omega-3 fatty acids