Neurobiology of Depression

Abstract

The link between antidepressants and lipid in depression is the basis of this study. Changes in lipid profiles in various regions of the mouse brain after antidepressant therapy was examined using lipidomics. Results showed a drop in phospholipids with a corresponding increase in lysophospholipids in the prefrontal cortex, evidencing the presence of enhanced phospholipase A2 enzyme activity with resultant endogenous release of fatty acids. Hypothesizing that iPLA2 played an important role, the subsequent study used antisense oligonucleotides to iPLA2, along with forced swim test and lipidomics to investigate its role. It was found that iPLA2 was essential in the reduction of stress-related behavioural despair brought about by maprotiline. The final study used rTMS to investigate if similar trends in lipid changes indicating PLA2 activity would be observed, thereby supporting the evidence for a common downstream effect amongst various treatment modalities of depression. Indeed, there were similar alterations in phospholipid species.