Major depressive disorder (MDD) is a clinically and biologically heterogeneous syndrome. Identifying discrete subtypes of illness with distinguishing neurobiological substrates and clinical features is a promising strategy for guiding personalised therapeutics.

This study aimed to identify depression subtypes with correlated patterns of functional network connectivity and clinical symptoms by clustering patients according to a weighted linear combination of both features in a relatively large, medication-naïve depression sample.

We recruited 115 medication-naïve adults with MDD and 129 matched healthy controls, and evaluated all participants with magnetic resonance imaging. We used regularised canonical correlation analysis to identify component mapping relationships between functional network connectivity and symptom profiles, and K-means clustering was used to define distinct subtypes of patients.

Two subtypes of MDD were identified: insomnia-dominated subtype 1 and anhedonia-dominated subtype 2. Subtype 1 was characterised by abnormal hyperconnectivity within the ventral attention network and sleep maintenance insomnia. Subtype 2 was characterised by abnormal hypoconnectivity in the subcortical and dorsal attention networks, and prominent anhedonia symptoms.

Our study identified two distinct subtypes of patients with specific neurobiological and clinical symptom profiles. These findings advance understanding of the biological and clinical heterogeneity of MDD, offering a pathway for defining categorical subtypes of illness via consideration of both biological and clinical features.

重度抑郁症（MDD）是一种临床和生物学异质性综合征。通过区分神经生物学底物和临床特征来识别疾病的离散亚型是指导个性化治疗的有前途的策略。

本研究旨在通过在一个相对较大的、未经药物治疗的抑郁症样本中根据这两种特征的加权线性组合对患者进行聚类，从而确定具有功能网络连接和临床症状相关模式的抑郁症亚型。

我们招募了 115 名未接受药物治疗的 MDD 成人和 129 名匹配的健康对照，并通过磁共振成像评估了所有参与者。我们使用正则化典型相关分析来识别功能网络连接和症状特征之间的组件映射关系，并使用K均值聚类来定义不同的患者亚型。

确定了 MDD 的两种亚型：失眠为主的亚型 1 和快感缺乏为主的亚型 2。亚型 1 的特征是腹侧注意网络内的异常超连接和睡眠维持性失眠。亚型 2 的特点是皮质下和背侧注意网络异常低连接，以及明显的快感缺失症状。

我们的研究确定了具有特定神经生物学和临床症状特征的两种不同亚型患者。这些发现促进了对 MDD 的生物学和临床异质性的理解，提供了通过考虑生物学和临床特征来定义疾病分类亚型的途径。