Depression is a highly heterogeneous syndrome that bears only modest correlations with its biological substrates, motivating a renewed interest in rethinking our approach to diagnosing depression for research purposes and new efforts to discover subtypes of depression anchored in biology. Here, we review the major causes of diagnostic heterogeneity in depression, with consideration of both clinical symptoms and behaviors (symptomatology and trajectory of depressive episodes) and biology (genetics and sexually dimorphic factors). Next, we discuss the promise of using data-driven strategies to discover novel subtypes of depression based on functional neuroimaging measures, including dimensional, categorical, and hybrid approaches to parsing diagnostic heterogeneity and understanding its biological basis. The merits of using resting-state functional magnetic resonance imaging functional connectivity techniques for subtyping are considered along with a set of technical challenges and potential solutions. We conclude by identifying promising future directions for defining neurobiologically informed depression subtypes and leveraging them in the future for predicting treatment outcomes and informing clinical decision making.

中文翻译：

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抑郁症诊断异质性的原因和后果：发现新型生物学抑郁症亚型的途径

抑郁症是一种高度异质性的综合征，与其生物基质仅具有适度的相关性，这激发了人们重新思考我们为研究目的诊断抑郁症的方法的新兴趣，以及为发现以生物学为基础的抑郁症亚型的新努力。在这里，我们回顾了抑郁症诊断异质性的主要原因，同时考虑了临床症状和行为（抑郁发作的症状学和轨迹）和生物学（遗传学和性二态因素）。接下来，我们讨论了使用数据驱动策略发现基于功能性神经影像学测量的新型抑郁症亚型的前景，包括维度、分类和混合方法来解析诊断异质性和理解其生物学基础。考虑使用静息状态功能磁共振成像功能连接技术进行子分型的优点以及一系列技术挑战和潜在解决方案。最后，我们确定了有希望的未来方向，用于定义神经生物学告知的抑郁症亚型，并在未来利用它们来预测治疗结果和为临床决策提供信息。