Abstract
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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Notes
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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JCF, MB, and MLP conceived the analytic plan, conducted or interpreted the statistical analyses, and drafted the manuscript. MLP and BB were the principal investigators and oversaw the project. Additionally, CDL, AV, JPLS, SI aided substantially in elements of the design or interpretation of the results. LB, KM, and HA-W made substantial contributions to the acquisition of the data. All authors made significant contributions to the manuscript, and all approved the final version.
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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. 46, 1340–1347 (2021). https://doi.org/10.1038/s41386-021-01001-w
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DOI: https://doi.org/10.1038/s41386-021-01001-w
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