Inflammation and Depression: Is Immunometabolism the Missing Link?

Abstract

Converging clinical and preclinical evidence points to the existence of a subtype of depression associated with low-grade inflammation. This form of depression is characterized by a predominance of somatic symptoms over cognitive and affective symptoms of depression. The possibility of a causal role of inflammation in these symptoms has been investigated mainly in terms of interaction between inflammatory mediators and brain neurotransmitter metabolism, release, and action. More recently, another possibility has emerged in the form of a competition between the energy requirements of the cellular and organismic metabolic reprogramming that is necessary for immune cell activation and those of brain metabolism. In this chapter we will present what has been learned from the progress in immunometabolism, this field of research that examines how the energetic requirements of the proliferation of immune cells and their production of immune communication signals influence their function. We will then examine how this metabolic reprogramming taking place at the periphery and in the brain because of the propagation of the immune response from the periphery to the brain might interfere with brain metabolism, and discuss whether it accounts for the alterations in mitochondrial functions that have been described in preclinical studies of stress and inflammation-induced depression-like behavior and in clinical studies of depressed individuals. We will also present what is known about the sensitivity of the brain dopaminergic neurons to metabolic influences and discuss whether this sensitivity could account for the development of somatic symptoms of depression.