Differential patterns of axonal loss associated with threat-related adversity in atypical depression and non-atypical...

Major depressive disorder (MDD) encompasses a broad spectrum of heterogeneous symptoms arising from distinct etiological mechanisms. Phenotypic markers of psychopathology are most likely influenced by exposure to childhood maltreatment, yielding distinct subtypes within conventional diagnostic boundaries. However, the biological interactions between MDD subtypes and types of childhood trauma remain unclear.

50 atypical depression (AD) patients, 97 non-AD patients and 50 healthy controls were included to complete multi-shell diffusion MRI scans and clinical assessments. Differential tractography was performed to clarify the axonal injury between the AD and non-AD groups. Moreover, correlational tractography was employed to individually assess the relationship between quantitative anisotropy (QA) and all types of childhood trauma in each depressed subgroup.

Our study found that AD and non-AD patients had differential axonal loss primarily involving the bilateral superior longitudinal fasciculus, arcuate fasciculus, inferior longitudinal fasciculus, parietal aslant tract, and corpus callosum. Furthermore, AD patients showed significantly negative associations between QA values, childhood trauma total scores, and threat-related adversity, while significantly positive associations were observed in non-AD patients. However, similar phenomena were not observed for deprivation-related adversities.

Our findings indicate differential spatial patterns of axonal alterations associated with threat-related adversity in atypical depression and non-atypical depression. Efforts to attenuate the consequences of childhood maltreatment for MDD should consider the associations between specific patterns of adversity and specific clinical manifestations.