Objective: To identify potential clinical subgroups among parents who lost their only child and compare inter-subgroup differences in brain structure and function. Methods: Parents who lost their only child and participated in a psychological assistance program organized by the local civil affairs department in Southern Jiangsu, China, between April 2021 and June 2022 were retrospectively recruited. They were randomly divided into a discovery set and a validation set in a 1∶1 ratio using a random number table. Assessments included the Clinician Administered Post-Traumatic Stress Disorder Scale (CAPS), the 24-item Hamilton Depression Rating Scale (HAMD-24), and the Hamilton Anxiety Rating Scale (HAMA). Seven symptom dimension factors were extracted: re-experiencing, avoidance, hyperarousal, depressive mood, somatic/anxiety, psychic anxiety, and somatic anxiety. Hierarchical clustering was applied in the discovery set to identify clinical subgroups. The stability of this classification was verified in the validation set. Cranial MRI scans were conducted to compare differences in fractional anisotropy (FA) from diffusion tensor imaging, as well as degree centrality (DC) and regional homogeneity (ReHo) from functional MRI among the different subgroups. Pearson correlation analysis was used to assess the correlations between neuroimaging metrics and scale scores. Results: A total of 154 parents who lost their only child were enrolled, with an average age of (57.6±5.2) years, including 68 males (44.2%), and a mean trauma duration of (15.1±5.1) months. The discovery set and the validation set each comprised 77 participants. Hierarchical clustering and cross-validation consistently identified two stable subgroups. Subgroup A was characterized by core features of traumatic re-experiencing, cognitive avoidance, and depressive mood, while subgroup B was dominated by somatization symptoms and anxiety. Neuroimaging results showed that compared with subgroup B, subgroup A exhibited significantly higher FA values in multiple white matter tracts closely associated with emotion regulation and cognitive processing (P<0.05, corrected with threshold-free cluster enhancement). Compared with subgroup A, subgroup B demonstrated higher DC in the left precentral gyrus (t=-3.02, Gaussian random field-corrected P=0.003) and lower ReHo in the left middle frontal gyrus (t=3.90, Gaussian random field-corrected P=0.001). Correlation analyses indicated that FA values in white matter tracts were positively correlated with total CAPS score, total HAMD-24 score, and specific CAPS factors (avoidance, re-experiencing) (r=0.30-0.36, false discovery rate-corrected P<0.05). DC values in the left precentral gyrus were positively correlated with total HAMA score and the somatic anxiety factor (r=0.32-0.37, false discovery rate-corrected P<0.05). Conclusions: Parents who lost their only child can be categorized into two clinical subgroups: one dominated by emotional disturbances and the other by somatic anxiety. The observed differences in brain structure and function provide neurobiological evidence for this subgroup classification and may suggest potential targets for precise neuromodulation interventions. 目的： 识别失独人群的多维度症状亚群特征，并分析不同亚群在脑结构与功能上的差异。 方法： 回顾性纳入2021年4月至2022年6月参加中国江苏省苏南地区地方民政部门心理援助项目的失独父母，通过随机数字表按1∶1随机分为发现集与验证集。在受试者中评估临床用创伤后应激障碍诊断量表（CAPS）、24项汉密尔顿抑郁量表（HAMD-24）及汉密尔顿焦虑量表（HAMA），提取重现、回避、警觉、抑郁情绪、躯体/焦虑、焦虑心理、焦虑躯体这7个症状维度因子，在发现集中采用层次聚类法识别症状亚群，并通过验证集重复聚类验证亚群划分的稳定性。进行头颅MRI检查，比较不同亚群的扩散张量成像的各向异性分数（FA）及功能MRI的度中心度（DC）与局部一致性（ReHo）差异。采用Pearson相关分析评估影像学指标与各量表评分的相关性。 结果： 共纳入失独父母154位，年龄（57.6±5.2）岁，男性68位（44.2%），创伤持续时间（15.1±5.1）个月。验证集和发现集各77位，层次聚类分析与跨组验证稳定识别出两类亚群，A类亚群以创伤重现、认知回避及抑郁情绪为核心特征，B类亚群以躯体化症状及焦虑为主。A类亚群与情绪调节及认知加工密切相关的白质纤维束FA值高于B类亚群（P<0.05，无阈值簇类增强法校正）；与A类亚群相比，B类亚群在左侧中央前回DC更高（t=-3.02，高斯随机场校正P=0.003），左侧额中回ReHo更低（t=3.90，高斯随机场校正P=0.001）。Pearson相关分析表明，白质纤维束FA值与CAPS总分、HAMD-24总分及部分CAPS因子（回避、重现）呈正相关（r=0.30~0.36，错误发现率校正P<0.05）；左侧中央前回DC与HAMA总分及焦虑躯体因子呈正相关（r=0.32~0.37，错误发现率校正P<0.05）。 结论： 失独人群存在以情绪障碍为主和以躯体化焦虑为主的两类临床亚群。其脑结构与功能差异为亚群划分提供了神经生物学证据，并可能为精准神经调控干预提供潜在靶点。.
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