The role of lipids in neuromodulation for psychiatric disorders: A narrative review

Lipids are highly abundant in the brain and play key roles in membrane regulation, neurotransmission, neurogenesis, and inflammation. The same processes are involved in neuromodulation mechanisms. While neuromodulation therapies have shown promising outcomes for treatment-resistant psychiatric disorders, the factors determining individual variability in treatment response remain poorly understood. Furthermore, the potential impact of neurometabolic factors in predicting response has been largely overlooked. This narrative review aims to evaluate the role of lipids in psychiatric neuromodulation. Particularly glycerophospholipids, sphingolipids and polyunsaturated fatty acids (PUFAs) have been described as important mediators. Current evidence suggests a bidirectional relationship between lipids and neuromodulation therapies such as electroconvulsive therapy (ECT), and repetitive transcranial magnetic stimulation (rTMS). Neuromodulation effects are associated with lipid metabolism changes, including phospholipids, sphingolipids, and fatty acids. ECT is associated with an increase in lipid peroxidation and alterations of cholesterol and fatty acid levels, while rTMS is associated with normalization of sphingolipids and phospholipids levels. Solely one study investigated the relation between deep brain stimulation and lipids, showing an association with sphingolipid metabolism. To our knowledge, this is the first comprehensive review to consolidate findings on the relationship between lipids and neuromodulation. By mapping this emerging field, these findings might be a first step towards investigating whether lipids could be a potential biomarker for response prediction in the future. As most findings are preliminary, with variability across studies, further investigation is warranted and current findings should be interpreted in the context of their limitations.