Identification of Longitudinal Associations Between Depressive Symptoms and EEG Functional Connectivity in Adolescents Receiving Antidepressant Treatment

Major depressive disorder (MDD) is the most common mood disorder in adolescents, affecting up to 20% of adolescents in the US. Identifying neurophysiological functional connectivity biomarkers that track treatment response and provide mechanistic insights could inform early interventions and improve depression outcomes in adolescents. Resting-state quantitative electroencephalography (qEEG) provides a low-cost, non-invasive method to examine functional connectivity and link connectivity dynamics to symptom changes during treatment. We utilized qEEG to identify associations between functional connectivity measures and depressive symptom severity over time by analyzing longitudinal data from 21 adolescents with moderate-to-severe MDD (85.7% female) recruited at University Hospitals Cleveland Medical Center, Ohio. Participants completed EEG recordings and depressive symptom assessments using the Children’s Depression Rating Scale-Revised (CDRS-R) at baseline (pre-treatment), week 4, and week 16. Participants received fluoxetine or escitalopram alongside evidence-based therapy (EBT). We computed baseline functional connectivity measures for selected channel pairs across five canonical EEG frequency bands. Principal component analysis (PCA) reduced the dimensionality of baseline functional connectivity metrics to seven components, which were projected onto subsequent time points. Longitudinal associations between PCs and CDRS-R Total and subscale scores were inspected with a linear mixed effects model (LMEM). We observed robust clinical improvement over time. PC2 and PC3 showed significant time-dependent interactions with CDRS total, while PC3 revealed a significant interaction with CDRS Morbidity over time. These findings suggest that fronto-parietal and fronto-temporal connectivity features, especially involving Weighted Pairwise Phase Consistency (WPPC) and Coherence, longitudinally track treatment response in adolescents undergoing antidepressant treatment.