Imaging research has not yet delivered reliable psychiatric biomarkers. One challenge, particularly among youth, is high comorbidity. This challenge might be met through canonical correlation analysis (CCA) designed to model mutual dependencies between symptom dimensions and neural measures. We map the multivariate associations that intrinsic functional connectivity manifests with pediatric symptoms of anxiety, irritability, and attention-deficit/hyperactivity disorder (ADHD) as common, impactful, co-occurring problems. We evaluate the replicability of such latent dimensions in an independent sample.
We obtained ratings of anxiety, irritability, and ADHD, and 10 minutes of resting-state functional magnetic resonance imaging data, from two independent cohorts. Both cohorts (discovery: N=182; replication: N=326) included treatment-seeking youth with anxiety disorders, disruptive mood dysregulation disorder, ADHD, or without psychopathology. Functional connectivity was modeled as partial correlations among 216 brain areas. CCA, and independent-component analysis (ICA) jointly sought maximally-correlated, maximally-interpretable rsfMRI/clinical dimensions.
We identified seven canonical variates in the discovery and five in the replication cohort. Of these canonical variates, three exhibited similarities across datasets: two variates consistently captured shared aspects of irritability, ADHD, and anxiety, while the third was specific to anxiety. Across cohorts, canonical variates did not relate to specific resting-state networks but comprised edges interconnecting established networks within and across both hemispheres.
Findings revealed two replicable types of clinical variates, one related to multiple symptom dimensions and a second relatively specific to anxiety. Both types involved a multitude of broadly-distributed, weak brain connections as opposed to strong connections encompassing known resting-state networks.
Linke, J. O., Abend, R., Kircanski, K., Clayton, M., Stavish, C., Benson, B. E., Brotman, M. A., Renaud, O., Smith, S. M., Nichols, T. E., Leibenluft, E., Winkler, A. M., & Pine, D. S. (2021). Shared and Anxiety-Specific Pediatric Psychopathology Dimensions Manifest Distributed Neural Correlates. Biological psychiatry, 89(6), 579–587. https://doi.org/10.1016/j.biopsych.2020.10.018
Office of Human Genetics