Subcortical resting state functional connectivity as a neural marker of first onset internalizing disorder in high-risk youth.

Background: Research has linked individual differences in resting state functional connectivity (RSFC) of subcortical brain regions to internalizing disorders, but little research has examined if these changes are pre-morbid risk factors. This study examined individual differences in subcortical RSFC as risk factors for the first lifetime onset of an internalizing disorder in youth at familial risk. Methods: Participants (n = 93) were adolescents with a parental history of internalizing disorders, but with no such history themselves. Youth completed resting state fMRI scans, as well as the MINI-Kid and the Youth Self Report internalizing symptoms scale at baseline. The MINI-Kid was completed again at 9 or 18-month follow-up to assess onset of internalizing disorders. Seed-to-whole brain analyses consisted of a multiple regression models controlling for sex, age, in scanner motion, and baseline symptoms. Results: First onsets at follow-up were associated with increased baseline RSFC between the left caudate and the bilateral SMA (pFDR = .002), and between the right nucleus accumbens and the right superior parietal lobule (pFDR = .0003). Conclusion: Altered RSFC of subcortical regions may represent a pre-morbid risk factor for developing a first onset of an internalizing disorder. Results may have implications for understanding the neural bases of internalizing disorders and for early identification and prevention efforts.