Test-Retest Reliability of Functional Connectivity in Adolescents With Depression

The test-retest reliability of functional magnetic resonance imaging is critical to identifying reproducible biomarkers for psychiatric illness. Recent work has shown how reliability limits the observable effect size of brain-behavior associations, hindering detection of these effects. However, while a fast-growing literature has explored both univariate and multivariate reliability in healthy individuals, relatively few studies have explored reliability in populations with psychiatric illnesses or how this interacts with age.

Here, we investigated functional connectivity reliability over the course of 1 year in a longitudinal cohort of 88 adolescents (age at baseline = 15.63 ± 1.29 years; 64 female) with major depressive disorder (MDD) and without MDD (healthy volunteers [HVs]). We compared a univariate metric, intraclass correlation coefficient, and 2 multivariate metrics, fingerprinting and discriminability.

Adolescents with MDD had marginally higher mean intraclass correlation coefficient (μ_MDD = 0.34, 95% CI, 0.12-0.54; μ_HV = 0.27, 95% CI, 0.05-0.52), but both groups had poor average intraclass correlation coefficients (<0.4). Fingerprinting index was greater than chance and did not differ between groups (fingerprinting index_MDD = 0.75; fingerprinting index_HV = 0.91; Poisson tests p < .001). Discriminability indicated high multivariate reliability in both groups (discriminability_MDD = 0.80; discriminability_HV = 0.82; permutation tests p < .01). Neither univariate nor multivariate reliability was associated with symptom severity or edge-level effect size of group differences.

Overall, we found little evidence for a relationship between depression and reliability of functional connectivity during adolescence. These findings suggest that biomarker identification in depression is not limited due to reliability compared with healthy samples and support the shift toward multivariate analysis for improved power and reliability.