Association of aberrant gray matter neurite density with neurovegetative symptom in atypical depression

The heterogeneity of symptoms in major depressive disorder is impeding progress toward patient-specific treatment strategies and course trajectories. Origins of such differential clinical manifestations likely have dissociable pathophysiologies, but neural substrates associated with specific atypical depressive symptoms remain elusive.

The muti-shell diffusion MRI images were acquired from 50 patients with atypical depression (AD), 97 patients with non-atypical depression (non-AD), and 50 healthy controls (HCs). We used gray matter-specific multi-compartment diffusion models (cortical-neurite orientation dispersion and density imaging and free-water elimination model) to assess abnormalities of gray matter microstructure associated with AD. Superficial U-fibers analysis was performed to clarify short-range cortico-cortical connections.

Abnormalities in intracellular volume fraction (ICVF) and free-water fraction anisotropy were found in the superior frontal gyrus, middle frontal gyrus, inferior parietal gyrus, and superior parietal gyrus across three groups. Post-hoc pairwise comparative analysis yielded similar results. While adjusting for the effects of age, gender, education, and the ICVF mentioned above, AD patients showed significantly higher scores in reversed neurovegetative symptoms and leaden paralysis compared with non-AD patients. Moreover, diagnosis-related alterations in ICVF of right caudal middle frontal gyrus and education-related changes in ICVF of right superior frontal gyrus were significantly associated with hypersomnia. We also found that underlying superficial U-fibers reflected deficits in cortical-derived neurite density.

Cortical-derived neurite density abnormalities were significantly associated with atypical depressive symptoms, capturing interindividual etiological heterogeneity in patients with major depressive disorder. Cortical-derived neurite density within the medial prefrontal gyrus may be a robust biomarker for atypical depressive symptoms of AD.