Brain membrane lipids in major depression and anxiety disorders

Abstract

Major depression and anxiety disorders have high prevalence rates and are frequently comorbid. The neurobiological bases for these disorders are not fully understood, and available treatments are not always effective. Current models assume that dysfunctions in neuronal proteins and peptide activities are the primary causes of these disorders. Brain lipids determine the localization and function of proteins in the cell membrane and in doing so regulate synaptic throughput in neurons. Lipids may also leave the membrane as transmitters and relay signals from the membrane to intracellular compartments or to other cells. Here we review how membrane lipids, which play roles in the membrane's function as a barrier and a signaling medium for classical transmitter signaling, contribute to depression and anxiety disorders and how this role may provide targets for lipid-based treatment approaches. Preclinical findings have suggested a crucial role for the membrane-forming n-3 polyunsaturated fatty acids, glycerolipids, glycerophospholipids, and sphingolipids in the induction of depression- and anxiety-related behaviors. These polyunsaturated fatty acids also offer new treatment options such as targeted dietary supplementation or pharmacological interference with lipid-regulating enzymes. While clinical trials support this view, effective lipid-based therapies may need more individualized approaches. Altogether, accumulating evidence suggests a crucial role for membrane lipids in the pathogenesis of depression and anxiety disorders; these lipids could be exploited for improved prevention and treatment. This article is part of a Special Issue entitled Brain Lipids.

Focus on fatty acids in the neurometabolic pathophysiology of psychiatric disorders

“…More recent hypotheses suggest broader metabolic alterations that extend beyond monoamine metabolism (Su 2008;Maes et al 2009;Assies et al 2014;Naviaux 2014;Rosenblat et al 2014;Muller et al 2015;Mocking et al 2016a). Complex interacting metabolic pathways are being hypothesized to partly underlie -and be connected with -observed coexistent biological (oxidative) stress, inflammatory, and brain network alterations.…”

Plasma sphingolipids and depressive symptoms in coronary artery disease

“…Sphingolipids are a diverse class of lipids containing a sphingoid base attached to an acyl group such as a fatty acid (Merrill, Sullards, Allegood, Kelly, & Wang, 2005). They are the most common form of lipid in brain cell membranes (Merrill et al., 2005; Muller et al., 2015). Lipid families in the sphingolipid class include sphingomyelins, ceramides, sphingosines, cerebrosides, and gangliosides (Merrill et al., 2005).…”

Direct affinity of dopamine to lipid membranes investigated by Nuclear Magnetic Resonance spectroscopy

“…Extensive research highlights the importance of brain lipid composition interaction with neurotransmitters for a properly functioning depolarization and its effect. Without a proper interaction among the two, certain neuropsychiatric disorders can arise [9]. The aim of this paper is to understand the interaction and affinity of dopamine to PS and PC lipid vesicles using NMR and Ultraviolet/Visible (UV/Vis) Spectroscopy.…”