Aerobic Exercise and Subthreshold Depressive Symptoms in Adolescents: Secondary Analysis of a Randomized Clinical...

Adolescence is a high-risk period for subthreshold depression and a critical window for intervention. While aerobic exercise has shown efficacy in alleviating adult depressive symptoms, its efficacy and neural mechanisms in adolescents remain unclear.

To evaluate the association of aerobic exercise with reduced subthreshold depressive symptoms in adolescents and to identify potential neural mechanisms underpinning symptom improvement.

This was a prespecified secondary analysis of a 12-month, multicenter, cluster randomized clinical trial (RCT) conducted October 2021 to October 2022 among students aged 12 to 17 years in China. Data analysis took place between April and August 2024.

The 12-month aerobic exercise intervention consisted of a 6-month supervised phase followed by a 6-month unsupervised phase. The control group received 6 psychoeducation sessions (once every 2 months) focusing on mood regulation, depression awareness, and stress management.

At baseline and postintervention, participants reported depressive symptoms (Patient Health Questionnaire-9 [PHQ-9]) and underwent electroencephalography (EEG) recording. Group differences in symptom change were assessed using linear mixed models. Resting-state EEG data were analyzed for functional connectivity and both global and nodal network topology. Mediation analyses were conducted to test the neural processes mediating the exercise effect.

A total of 206 adolescents aged 12 to 17 years (110 males [53%]; median age, 13 years) with subthreshold depressive symptoms were included (111 in the exercise group and 95 in the psychoeducation group). The exercise group showed significantly greater reductions in subthreshold depressive symptoms than the control group (exercise: mean [SE] PHQ-9 score, 9.20 [0.05] points at baseline vs 7.33 [0.03] postintervention; t110, -4.49; P < .001; control: 7.74 [0.04] points at baseline vs 7.28 [0.04] postintervention; t94, -1.03; P = .30). The functional connectivity across 355 alpha-band, 127 beta-band, 30 theta-band, and 9 delta-band connections was reduced (all P < .05 after correction for false discovery rate), and global network efficiency, such as the clustering coefficient, was enhanced across all frequency bands after the exercise intervention (all P < .001 after correction for false discovery rate). Mediation analysis revealed 2 opposing neural pathways that represented depression-reduction (B, -2.28; P < .001) and depression-increase (B, 3.26; P < .001) processes.

In this secondary analysis of an RCT, the findings suggest that exercise reduced subthreshold depressive symptoms in adolescents by engaging opposing EEG-based neural network processes. These findings support exercise as a potential accessible intervention for adolescent subthreshold depression, highlighting neurophysiologic signatures that may inform individualized intervention strategies and outcome monitoring that need to be replicated in adolescents with clinical depression.

ClinicalTrials.gov Identifier: NCT04816617.