Parsing Clinical and Neurobiological Sources of Heterogeneity in Depression

Patients with depression vary from one another in their clinical and neuroimaging presentation, but the relationship between clinical and neuroimaging sources of variation is poorly understood. Determining sources of heterogeneity in depression is important to gain insights into its diverse and complex neural etiology. In this study, we aimed to test whether depression heterogeneity is characterized by subgroups that differ both clinically and neurobiologically and/or whether multiple neuroimaging profiles give rise to the same clinical presentation.

This study utilized population-based data from the UK Biobank over multiple imaging sites. Clinically dissociated groups were selected to isolate clinical characteristics of depression (symptoms of anhedonia, depressed mood, and somatic disturbance; severity indices of lifetime chronicity and acute impairment; and late onset). Residual neuroimaging heterogeneity within each group was assessed using neuroimaging-driven clustering.

The clinically dissociated subgroups had significantly larger neuroimaging normative deviations than a comparison heterogeneous group and had distinct neuroimaging profiles from each other. Imaging-driven clustering within each clinically dissociated group identified 2 stable subtypes within the acute impairment group that differed significantly in cognitive ability despite identical clinical profiles.

The study identified distinct neuroimaging profiles related to particular clinical depression features that may explain inconsistencies in the literature and subclusters within the acute impairment group with cognitive differences that were only differentiable by neuroimaging. Our results provide evidence that multiple neuroimaging profiles may give rise to the same clinical presentation, emphasizing the presence of complex interactions between clinical and neuroimaging sources of heterogeneity.