Retinoid homeostasis in major depressive disorder

Abstract

The small, hormone-like molecule retinoic acid (RA) is a vital regulator in several neurobiological processes that are affected in depression. Next to its involvement in dopaminergic signal transduction, neuroinflammation, and neuroendocrine regulation, recent studies highlight the role of RA in homeostatic synaptic plasticity and its link to neuropsychiatric disorders. Furthermore, experimental studies and epidemiological evidence point to the dysregulation of retinoid homeostasis in depression. Based on this evidence, the present study investigated the putative link between retinoid homeostasis and depression in a cohort of 109 patients with major depressive disorder (MDD) and healthy controls. Retinoid homeostasis was defined by several parameters. Serum concentrations of the biologically most active Vitamin A metabolite, all-trans RA (at-RA), and its precursor retinol (ROL) were quantified and the individual in vitro at-RA synthesis and degradation activity was assessed in microsomes of peripheral blood-derived mononuclear cells (PBMC). Additionally, the mRNA expression of enzymes relevant to retinoid signaling, transport, and metabolism were assessed. Patients with MDD had significantly higher ROL serum levels and greater at-RA synthesis activity than healthy controls providing evidence of altered retinoid homeostasis in MDD. Furthermore, MDD-associated alterations in retinoid homeostasis differed between men and women. This study is the first to investigate peripheral retinoid homeostasis in a well-matched cohort of MDD patients and healthy controls, complementing a wealth of preclinical and epidemiological findings that point to a central role of the retinoid system in depression.

Serum Vitamin Levels, Cardiovascular Disease Risk Factors, and Their Association with Depression in Korean Women: A Cross-Sectional Study of a Nationally Representative Sample

“…Vitamin A is activated in a form called retinoic acid (RA). RA is a vital regulator in several neurobiological processes that are affected in depression [31]. There are a few possible explanations for the link between low serum vitamin A levels and depression.…”

“…Another possibility is that low serum vitamin A levels are a marker of inflammation. Inflammation is thought to play a role in the development of depression [31]. However, when vitamin A is supplied in excess, the beta-cis form of retinoic acid can be produced [32].…”

Food and Food Waste Antioxidants: Could They Be a Potent Defence against Parkinson’s Disease?

“…Vitamin A and its active derivatives seem to have antioxidant and neuroprotective properties in many animal studies, and this is confirmed even by the important role of vitamin A and carotenoids during the development of the central nervous system and neuronal differentiation [ 35 ]. Some authors state that retinoic acid is essential in many signalling pathways and has also been implicated in the pathophysiology of Alzheimer’s disease and neurological diseases [ 36 ]. Retinoic acid-synthesizing enzymes are abundant in the mesotelencephalic dopamine system because dopaminergic neurotransmission is controlled by retinoid signal transduction, where retinoic acid is a crucial component.…”

The Role and Mechanism of Retinol and Its Transformation Product, Retinoic Acid, in Modulating Oxidative Stress-Induced Damage to the Duck Intestinal Epithelial Barrier In Vitro

“…The term "vitamin A" encompasses a group of chemically related organic compounds that includes retinol, retinal, and retinoic acid (RA) [13]. The concentration of vitamin A in the blood can be disturbed under pathological or physiological conditions [14,15]. In addition to dietary levels that can change vitamin A concentration, key tissues in the animal body, such as the liver, use retinol dehydrogenase and retinaldehyde dehydrogenase to irreversibly convert retinol into retinoic acid through enzymatic reactions [16].…”