Aperiodic brain activity in major depression: Increased inhibition and developmental effects of childhood maltreatment

The aperiodic exponent of EEG-power spectra is emerging as a non-oscillatory marker of cortical excitation-inhibition balance (E/I balance). Altered E/I balance has been proposed in major depressive disorder (MDD), but evidence from clinical cohorts remains limited and inconsistent, and the impact of developmental risk factors is unknown. We analysed resting-state EEG from 91 unmedicated MDD patients and 35 healthy controls enrolled in the NeuroPharm-1 study. Patients received 10–20 mg of escitalopram treatment for 8 weeks, with 39 undergoing follow-up EEG. Before treatment, MDD patients showed significantly greater frontal aperiodic exponents compared to healthy controls (Cohen's d  = 0.44, p  = 0.03), consistent with increased cortical inhibition in depression. Importantly, pretreatment frontal aperiodic exponent showed a strong negative association with childhood trauma severity ( p  < 0.001), independent of current depressive symptoms and familial predisposition for depression, suggesting that early adversity leaves a lasting imprint on cortical dynamics. No associations were found with treatment, and aperiodic exponents remained unchanged during SSRI treatment. These findings demonstrate that aperiodic EEG activity captures state-related alterations in unmedicated depression and highlight long-term developmental signatures of childhood trauma. This underscores the potential of aperiodic measures as translational markers of environmentally shaped vulnerability in psychiatric disorders.