CAS Key Laboratory of Brain Function and Diseases, Department of Neurobiology and Biophysics, School of Life Science, University of Science and Technology of China, Hefei 230027, China.
Department of Anatomy and Neurosciences, VU University Medical Center, Amsterdam 1081 HZ, the Netherlands.
Neurosci Biobehav Rev. 2020 May;112:376-391. doi: 10.1016/j.neubiorev.2020.02.013. Epub 2020 Feb 15.
The retinoid family members, including vitamin A and derivatives like 13-cis-retinoic acid (ITT) and all-trans retinoic acid (ATRA), are essential for normal functioning of the developing and adult brain. When vitamin A intake is excessive, however, or after ITT treatment, increased risks have been reported for depression and suicidal ideation. Here, we review pre-clinical and clinical evidences supporting association between retinoids and depressive disorders and discuss several possible underlying neurobiological mechanisms. Clinical evidences include case reports and studies from healthcare databases and government agency sources. Preclinical studies further confirmed that RA treatment induces hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis and typical depressive-like behaviors. Notably, the molecular components of the RA signaling are widely expressed throughout adult brain. We further discuss three most important brain systems, hippocampus, hypothalamus and orbitofrontal cortex, as major brain targets of RA. Finally, we highlight altered monoamine systems in the pathophysiology of RA-associated depression. A better understanding of the neurobiological mechanisms underlying RA-associated depression will provide new insights in its etiology and development of effective intervention strategies.
类视黄醇家族成员，包括维生素 A 及其衍生物，如 13-顺式视黄酸（ITT）和全反式视黄酸（ATRA），对发育中和成年期大脑的正常功能至关重要。然而，当维生素 A 摄入过多或接受 ITT 治疗后，抑郁和自杀意念的风险增加。在这里，我们回顾了支持类视黄醇与抑郁障碍之间关联的临床前和临床证据，并讨论了几个潜在的神经生物学机制。临床证据包括来自医疗保健数据库和政府机构来源的病例报告和研究。临床前研究进一步证实，RA 治疗会导致下丘脑-垂体-肾上腺 (HPA) 轴的过度活跃和典型的抑郁样行为。值得注意的是，RA 信号的分子成分在整个成年大脑中广泛表达。我们进一步讨论了三个最重要的大脑系统，即海马体、下丘脑和眶额皮质，作为 RA 的主要大脑靶标。最后，我们强调了单胺系统在 RA 相关抑郁的病理生理学中的改变。更好地了解 RA 相关抑郁的神经生物学机制将为其病因学和有效干预策略的发展提供新的见解。
