Differential Impact of Anxious Misery Psychopathology on Multiple Representations of the Functional Connectome.

Background: One aim of characterizing dimensional psychopathology is associating different domains of affective dysfunction with brain circuitry. The functional connectome, as measured by functional magnetic resonance imaging, can be modeled and associated with psychopathology through multiple methods; some methods assess univariate relationships while others summarize broad patterns of activity. It remains unclear whether different dimensions of psychopathology require different representations of the connectome to generate reproducible associations. Methods: Patients experiencing anxious misery symptomology (depression, anxiety, and trauma; Results: Different modeling approaches varied in the extent to which they could model different symptom dimensions: seed-based correlation analysis failed to reproducibly model any symptoms, subsets of the connectome (edgewise regression) were sufficient to model insomnia and anxious arousal, and broad representations of the entire connectome (brain basis set modeling) were necessary to model negative affect and ruminative thought. Conclusions: These results indicate that different methods of representing the functional connectome differ in the degree that they can model different symptom dimensions, highlighting the potential sufficiency of subsets of connections for some dimensions and the necessity of connectome-wide approaches in others.