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.

中文翻译：

---

维甲酸和抑郁症：证据和可能的神经生物学机制。

类维生素A家族成员，包括维生素A及其衍生物，如13-顺-视黄酸（ITT）和全反式视黄酸（ATRA），对于发育中和成年大脑的正常功能至关重要。然而，当维生素A摄入过多时或在ITT治疗后，据报道抑郁症和自杀意念的风险增加。在这里，我们审查支持类视黄醇和抑郁症之间的关联的临床前和临床证据，并讨论几种可能的潜在神经生物学机制。临床证据包括病例报告以及来自医疗保健数据库和政府机构来源的研究。临床前研究进一步证实，RA治疗可诱发下丘脑-垂体-肾上腺（HPA）轴功能亢进和典型的抑郁样行为。值得注意的是 RA信号传导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，下丘脑和眶额皮质，它们是RA的主要大脑目标。最后，我们重点介绍了与RA相关的抑郁症的病理生理变化中的单胺系统。对RA相关性抑郁症潜在的神经生物学机制的更好理解将为其病因和有效干预策略的发展提供新的见解。