Dietary fat intake and the brain: a developing frontier in biological psychiatry.

Some ideas are many years ahead of their time. In the last quarter of the nineteenth century, Thudichum, one of the founding fathers of neurochemistry, studied the composition of the brain. (For reviews of Thudichum’s work and his contributions to the development of neurochemistry, see Sourkes). His aim was to determine the composition of the brain, as far as was possible, in order to discover what changes occur in brain disorders, including mental illness. The major part of his work concerned lipids, the main constituent of the brain after water. The idea that brain lipid content may be important in the etiology or treatment of psychiatric disorders lay dormant until relatively recently, but it is growing in importance. Lipid is an important constituent of the brain, not only because of myelin, but also because of the large surface-to-volume ratio of neurons — neurons contain a higher proportion of lipid than other cells because lipid is the main constituent of the neuronal cell membrane. The precise characteristics of this lipid bilayer may affect not only the electrical properties of the membrane, but also the properties of proteins embedded in it, such as receptors. However, the extent to which the lipid content of the brain can be altered and the implications this has, both for variations in normal behaviour and for psychopathology, remain uncertain. Reports of altered plasma, red cell or brain lipid profiles in certain psychiatric disorders, including depression and schizophrenia, have led some investigators to postulate that impaired fatty acid and phospholipid metabolism may play a major role in the etiology of psychiatric disorders. Specifically reported are lower levels and altered ratios of the omega-6 and omega-3 essential fatty acids. Whether these changes are secondary to other behavioural attributes of patients (e.g., altered food intake, smoking or alcohol use) or a primary metabolic event associated with the disease has not been unequivocally answered. However, increasing evidence is pointing to altered membrane turnover and release of fatty acids from phospholipids via phospholipase A2 in individuals with depression or schizophrenia. These released fatty acids, which are ultimately converted to omega-6 or omega-3 series eicosanoids, contribute to a wide variety of cellular responses, thus implicating genetic disturbances in lipid metabolizing enzymes in the psychopathology of these disorders. Although genetic disturbances in brain lipid metabolism may be associated with psychopathologic disorders, an important question is whether dietary fat can play a contributory role, a therapeutic role or both. At one time, the lipid content of the brain was considered