A Connectome-wide Functional Signature of Transdiagnostic Risk for Mental Illness

Abstract

Background: High rates of comorbidity, shared risk, and overlapping therapeutic mechanisms have led psychopathology research toward transdiagnostic dimensional investigations of clustered symptoms. One influential framework accounts for these transdiagnostic phenomena through a single general factor, sometimes referred to as the p factor, associated with risk for all common forms of mental illness.

Methods: We build on previous research identifying unique structural neural correlates of the p factor by conducting a data-driven analysis of connectome-wide intrinsic functional connectivity (n = 605).

Results: We demonstrate that higher p factor scores and associated risk for common mental illness maps onto hyperconnectivity between visual association cortex and both frontoparietal and default mode networks.

Conclusions: These results provide initial evidence that the transdiagnostic risk for common forms of mental illness is associated with patterns of inefficient connectome-wide intrinsic connectivity between visual association cortex and networks supporting executive control and self-referential processes, networks that are often impaired across categorical disorders.

Keywords: Connectivity; Psychopathology; Resting state; Transdiagnostic; fMRI; p factor.

Figure 1

Data driven multi-dimensional matrix regression (MDMR) analysis revealed four regions with whole-brain connectivity patterns significantly associated with p factor scores: two adjacent parcels of the left middle occipital gyrus (left panel), left lingual gyrus (middle panel), and right middle occipital gyrus (right panel). These four clusters are projected onto a surface volume for visualization.

Figure 2

Follow-up connectivity analyses of the four seeds identified through MDMR revealed a highly-conserved pattern of altered connectivity between visual association cortex and both frontoparietal and default mode networks as a function of p factor scores. All results were projected from the volume onto a surface to aid visualization. Left panel: MDMR-derived seed regions. Middle panel: average intrinsic connectivity for each seed. Right panel: connectome wide intrinsic connectivity patterns for each seed as a function of p factor scores.

Figure 3

Mean pattern of intrinsic connectivity as a function of p factor scores across the networks associated with each of the four MDMR-derived seeds in visual association cortex (left panel). The relative contributions of seven canonical intrinsic cerebral networks(47) to this mean pattern of connectivity (right panel).