Affective disorders (AD, including bipolar disorder, BD, and major depressive disorder) are severe recurrent illnesses. Identifying neural markers of processes underlying AD development in at-risk youth can provide objective, “early-warning” signs that may predate onset or worsening of symptoms. Using data (n = 34) from the Bipolar Offspring Study, we examined relationships between neural response in regions supporting executive function, and those supporting self-monitoring, during an emotional n-back task (focusing on the 2-back face distractor versus the 0-back no-face control conditions) and future depressive and hypo/manic symptoms across two groups of youth at familial risk for AD: Offspring of parents with BD (n = 15, age = 14.15) and offspring of parents with non-BD psychopathology (n = 19, age = 13.62). Participants were scanned and assessed twice, approximately 4 years apart. Across groups, less deactivation in the mid-cingulate cortex during emotional regulation (Rate Ratio = 3.07(95% CI:1.09–8.66), χ2(1) = 4.48, p = 0.03) at Time-1, and increases in functional connectivity from Time-1 to 2 (Rate Ratio = 1.45(95% CI:1.15–1.84), χ2(1) = 8.69, p = 0.003) between regions that showed deactivation during emotional regulation and the right caudate, predicted higher depression severity at Time-2. Both effects were robust to sensitivity analyses controlling for clinical characteristics. Decreases in deactivation between Times 1 and 2 in the right putamen tail were associated with increases in hypo/mania at Time-2, but this effect was not robust to sensitivity analyses. Our findings reflect neural mechanisms of risk for worsening affective symptoms, particularly depression, in youth across a range of familial risk for affective disorders. They may serve as potential objective, early-warning signs of AD in youth.
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Two individuals had higher KDRS scores than the rest of the cohort. When removed from the larger models, the associations remained significant: BOLD response in the mid-cingulate continued to predict Time-2 KDRS (RR = 9.15, χ2 (1) = 6.34, p = 0.01), as did change in connectivity between the task-negative seeds and the right caudate between Time-1 and Time-2 (RR = 1.51, χ2 (1) = 6.47, p = 0.01).
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Fournier, J.C., Bertocci, M., Ladouceur, C.D. et al. Neural function during emotion regulation and future depressive symptoms in youth at risk for affective disorders. Neuropsychopharmacol. (2021). https://doi.org/10.1038/s41386-021-01001-w