Aperiodic Signatures of Stress Sensitivity and Depression Recurrence in Adolescents

Adolescence is a sensitive period for the emergence and refinement of cortical rhythms, which are shaped by excitatory-inhibitory (E/I) neurotransmission. However, stress-related disruptions in E/I balance may contribute to major depressive disorder (MDD). The aperiodic components of neurophysiological signals-slope and offset-index E/I dynamics and broadband power, respectively. Although altered E/I balance has been implicated in MDD and neurodevelopment more broadly, the role of aperiodic activity in predicting recurrence among adolescents remains unclear.

Resting-state electroencephalography and structured stress interviews were acquired from adolescents (N = 148; ages 13-18 years) with current (n = 42) or remitted (n = 106) MDD. Aperiodic slope and offset were parameterized across anterior, central, and posterior electrode clusters. In remitted youths, Cox proportional hazards models tested slope-by-stress and offset-by-stress interactions predicting MDD recurrence over the subsequent 12 months.

Adolescents with current MDD exhibited significantly flatter aperiodic slopes across anterior, central, and posterior clusters (range F_1,143 = 4.56-5.82, ps < .05) and lower offsets in anterior and central clusters (range F_1,143 = 5.38-7.25, ps < .023) compared with remitted adolescents. Among remitted youths, significant slope-by-stress interactions predicted recurrence, wherein flatter slopes were protective against recurrence under low stress but conferred elevated risk under high stress. This effect was strongest in the anterior cluster (hazard ratio = 2.13, p < .001). The aperiodic offset did not predict recurrence.

The aperiodic slope may function as a neurophysiological diathesis that amplifies stress-related risk for depression recurrence. Findings support a diathesis-stress model of adolescent MDD and highlight the aperiodic slope as a biomarker that may guide developmentally sensitive personalized prevention strategies.