Applying dimensional psychopathology: transdiagnostic prediction of executive cognition using brain connectivity and
Yange Wei1,2, Fay Y Womer3, Kaijin Sun1
1Early Intervention Unit, Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Background:
The association between executive dysfunction, brain dysconnectivity, and inflammation is a prominent feature across major psychiatric disorders (MPDs), schizophrenia, bipolar disorder, and major depressive disorder. A dimensional approach is warranted to delineate their mechanistic interplay across MPDs.
Methods:
This single site study included a total of 1543 participants (1058 patients and 485 controls). In total, 1169 participants underwent diffusion tensor and resting-state functional magnetic resonance imaging (745 patients and 379 controls completed the Wisconsin Card Sorting Test). Fractional anisotropy (FA) and regional homogeneity (ReHo) assessed structural and functional connectivity, respectively. Pro-inflammatory cytokine levels [interleukin (IL)-1β, IL-6, and tumor necrosis factor-α] were obtained in 325 participants using blood samples collected with 24 h of scanning. Group differences were determined for main measures, and correlation and mediation analyses and machine learning prediction modeling were performed.
Results:
Executive deficits were associated with decreased FA, increased ReHo, and elevated IL-1β and IL-6 levels across MPDs, compared to controls. FA and ReHo alterations in fronto-limbic-striatal regions contributed to executive deficits. IL-1β mediated the association between FA and cognition, and IL-6 mediated the relationship between ReHo and cognition. Executive cognition was better predicted by both brain connectivity and cytokine measures than either one alone for FA-IL-1β and ReHo-IL-6.
Conclusions:
Transdiagnostic associations among brain connectivity, inflammation, and executive cognition exist across MPDs, implicating common neurobiological substrates and mechanisms for executive deficits in MPDs. Further, inflammation-related brain dysconnectivity within fronto-limbic-striatal regions may represent a transdiagnostic dimension underlying executive dysfunction that could be leveraged to advance treatment.
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