[Identification of multidimensional symptom subgroups in parents who lost their only child and its neurostructural...

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.