Phospholipid metabolism and depression: The possible roles of phospholipase A₂ and coenzyme A-independent transacylase

Phospholipids make up 60 per cent of the dry weight of the brain. They are essential for neuronal and especially for synaptic structure and play key roles in the signal transduction responses to dopamine, serotonin, glutamate and acetyl choline. The unsaturated fatty acid components of phospholipids are abnormal in depression, with deficits of eicosapentaenoic acid and other omega-3 fatty acids and excesses of the omega-6 fatty acid arachidonic acid. Correction of this abnormality by treatment with eicosapentaenoic acid improves depression. The fatty acid abnormalities provide a rational explanation for the associations of depression with cardiovascular disease, immunological activation, cancer, diabetic complications and osteoporosis. The abnormalities cannot be explained by diet, although diet may attenuate or exacerbate their consequences. A number of enzyme abnormalities could explain the phenomena: phospholipase A₂, and coenzyme A-independent transacylase are strong candidates.