Abstract：
Major depressive disorder is one of the most prevalent psychiatric diseases, and up to 30-40% of patients remain symptomatic despite treatment. Novel therapies are sorely needed, and animal models may be used to elucidate fundamental neurobiological processes that contribute to human disease states. We conducted a systematic review of current preclinical approaches to investigating treatment resistance with the goal of describing a path forward for improving our understanding of treatment resistant depression. We conducted a broad literature search to identify studies relevant to the preclinical investigation of treatment resistant depression. We followed PRISMA (Preferred Reporting Items for Systemic Reviews and Meta-Analyses) guidelines and included all relevant studies. We identified 467 studies in our initial search. Of these studies, we included 69 in our systematic review after applying our inclusion/exclusion criteria. We identified 10 broad strategies for investigating treatment resistance in animal models. Stress hormone administration was the most commonly used model, and the most common behavioral test was the forced swim test. We systematically identified and reviewed current approaches for gaining insight into the neurobiology underlying treatment resistant depression using animal models. Each approach has its advantages and disadvantages, but all require careful consideration of their potential limitations regarding therapeutic translation. An enhanced understanding of treatment resistant depression is sorely needed given the burden of disease and lack of effective therapies.
摘要：
重度抑郁障碍是最常见的精神疾病之一。尽管接受了治疗，但仍有30-40％的患者仍有症状。迫切需要新的疗法，和动物模型可用于阐明导致人类疾病状态的基本神经生物学过程。我们对当前研究治疗耐药性的临床前方法进行了系统回顾，目的是描述一条改善我们对治疗耐药性抑郁症的理解的前进道路。我们进行了广泛的文献检索，以确定与治疗难治性抑郁症的临床前研究相关的研究。我们遵循PRISMA（系统评价和荟萃分析的首选报告项目）指南，并纳入所有相关研究。我们在最初的搜索中确定了467项研究。在这些研究中,在应用纳入/排除标准后,我们在系统综述中纳入了69项.我们确定了10种用于研究动物模型中治疗抗性的广泛策略。应激激素管理是最常用的模型，最常见的行为测试是强迫游泳测试。我们系统地确定和回顾了目前的方法，以了解使用动物模型治疗难治性抑郁症的神经生物学基础。每种方法都有其优点和缺点，但所有这些都需要仔细考虑它们在治疗性翻译方面的潜在局限性。鉴于疾病负担和缺乏有效的治疗方法，迫切需要对难治性抑郁症的理解。
