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Background:  Biomarkers for psychiatric disorders in children and adolescents are urgently needed. This cross-sectional pilot study investigated quantitative electroencephalogram (qEEG), a promising intermediate biomarker, in pediatric patients with major depressive disorder (MDD) compared with healthy controls (HCs). We hypothesized that youth with MDD would have increased coherence (connectivity) and absolute alpha power in the frontal cortex compared with HC.  Methods:  qEEG was obtained in adolescents aged 14-17 years with MDD ( n  = 25) and age- and gender-matched HCs ( n  = 14). The primary outcome was overall coherence on qEEG in the four frequency bands (alpha, beta, theta, and delta). Other outcomes included frontal-only coherence, overall and frontal-only qEEG power, and clinician-rated measures of anhedonia and anxiety.  Results:  Average coherence in the theta band was significantly lower in MDD patients versus HCs, and also lower in frontal cortex among MDD patients. Seven node pairs were significantly different or trending toward significance between MDD and HC; all had lower coherence in MDD patients. Average frontal delta power was significantly higher in MDD versus HCs.  Conclusions:  Brain connectivity measured by qEEG differs significantly between adolescents with MDD and HCs. Compared with HCs, youth with MDD showed decreased connectivity, yet no differences in power in any frequency bands. In the frontal cortex, youth with MDD showed decreased resting connectivity in the alpha and theta frequency bands. Impaired development of a resting-state brain network (e.g., default mode network) in adolescents with MDD may represent an intermediate phenotype that can be assessed with qEEG.

Resting-State Quantitative Electroencephalography Demonstrates Differential Connectivity in Adolescents with Major Depressive Disorder