Neurolipidomics in schizophrenia: A not so well-oiled machine

Abstract

Most patients with schizophrenia (SCZ) do not exhibit violent behaviors and are more likely to be victims rather than perpetrators of violent acts. However, a subgroup of forensic detainees with SCZ exhibit tendencies to engage in criminal violations. Although numerous models have been proposed, ranging from substance use, serotonin transporter gene, and cognitive dysfunction, the molecular underpinnings of violence in SCZ patients remains elusive. Lithium and clozapine have established anti-aggression properties and recent studies have linked low cholesterol levels and ultraviolet (UV) radiation with human aggression, while vitamin D3 reduces violent behaviors. A recent study found that vitamin D3, omega-3 fatty acids, magnesium, and zinc lower aggression in forensic population. In this review article, we take a closer look at aryl hydrocarbon receptor (AhR) and the dysfunctional lipidome in neuronal membranes, with emphasis on cholesterol and vitamin D3 depletion, as sources of aggressive behavior. We also discuss modalities to increase the fluidity of neuronal double layer via membrane lipid replacement (MLR) and natural or synthetic compounds.