Abstract
AbstractThe 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.
Funder
Studienstiftung des Deutschen Volkes
Deutsche Forschungsgemeinschaft
Publisher
Springer Science and Business Media LLC
Subject
Biological Psychiatry,Cellular and Molecular Neuroscience,Psychiatry and Mental health
Reference62 articles.
1. Bloom DE, Cafiero E, Jané-Llopis E, Abrahams-Gessel S, Bloom LR, Fathima S, et al. The Global Economic Burden of Noncommunicable Diseases. 2011;(September). Available from: http://www3.weforum.org/docs/WEF_Harvard_HE_GlobalEconomicBurdenNonCommunicableDiseases_2011.pdf.
2. Krishnan V, Nestler EJ. The molecular neurobiology of depression. Nature 2008;455:894–902.
3. Workman ER, Niere F, Raab-Graham KF. Engaging homeostatic plasticity to treat depression. Mol Psychiatry. 2018;23:26–35.
4. Dean J, Keshavan M. The neurobiology of depression: an integrated review. Asian J Psychiatr. 2017;27:101–11.
5. Otte C, Gold SM, Penninx BW, Pariante CM, Etkin A, Fava M, et al. Major depressive disorder. Nat Rev Dis Prim. 2016;2:1–20.
Cited by
5 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献