Polyunsaturated fatty acids (PUFAs) are essential for normal brain development and function and alterations in their metabolism may be involved in the development of mental illnesses. To understand this interaction we are utilising an endophenotype for lipid metabolism, the Niacin Skin Patch test.

There are a range of models of how genetic and environmental processes may alter central nervous system function in a way that results in schizophrenia. Neurodevelopmental hypotheses of schizophrenia proposes that normal brain development, which involved period of growth in cell numbers followed by removal of excess cells (sculpting), is altered (Murray et al 1987; Weinberger 1987). Neurotransmitter based theories implicate a range of signalling pathways (i.e. dopamine) based on the targets of antipsychotics and conversely chemicals that induce psychotic-like symptoms (Creese et al., 1976).

The metabolism of the polyunsaturated fatty acids, in particular arachidonic acid (AA) is involved in brain development. Neurotransmitters implicated in schizophrenia can mediate signals by the release of AA from cell membranes (Piomelli et al., 1991). AA itself is a potent signalling molecule, and also the precursor for a range of messenger eicosanoids (signalling molecules) necessary for normal neuronal function (Fink et al., 1998; Kurrasch-Orbaugh et al., 2003; Shimizu and Wolfe, 1990).

Many, but not all previous studies have reported that patients with schizophrenia present a decreased or absent vasodilation (skin blush) response to vitamin nicotinic acid (niacin). Depending on the method or definitions used, 40-80% of patients with psychotic disorders and 10% of controls show an impaired sensitivity to niacin (Glen et al., 1996; Hudson et al., 1997; Hudson et al., 1999; Maclean et al., 2003; Peet et al., 1998; Shah et al., 2000; Tavares et al., 2003; Ward et al., 1998). Niacin induces the production of inflammatory eicosanoids from AA (Morrow et al., 1992) . Interruption of AA metabolism abolishes the ability to produce those inflammatory messengers induced by niacin, and niacin insensitivity is associated with reduced AA levels in schizophrenia (Fujishima et al., 1999; Glen et al., 1996; Nakatani et al., 2000).  Critically, reduced sensitivity is present in early onset drug naïve patients and remains associated with schizophrenia after exclusion of environmental factors modifying inflammation such as smoking (Ross, 2003; Smesny et al., 2003; Smesny et al., 2004; Turenne et al., 2001). Niacin sensitivity is also impaired in healthy first degree relatives of patients with schizophrenia suggesting it is a marker for underlying genetic risk (Waldo, 1999). Niacin sensitivity may detect a subgroup of schizophrenia that arises from alterations in fatty acid metabolism.