A Meta-Analysis of Electroencephalographic Sleep in Depression: Evidence for Genetic Biomarkers

Background Research on whether any electroencephalographic (EEG) sleep abnormalities observed among individuals with major depressive disorder (MDD) represent genetic biomarkers remains inconclusive. We aimed to identify EEG-based biomarkers of MDD through a review of studies from three populations: individuals with MDD, individuals with MDD under remission, and never depressed high-risk probands (HRPs) of individuals with MDD. Methods We searched databases such as MEDLINE and PsycINFO for EEG studies published since 1970. Of the 886 records, our selection criteria identified 56 studies that employed standardized EEG scoring procedures and addressed confounds such as participant reactivity and drug effects. We then used fixed-effects models to calculate average weighted mean differences in EEG parameters between clinical groups across these studies. Results Individuals with MDD differed significantly from control subjects on several EEG variables. However, remitted individuals showed normalization of all affected EEG parameters except rapid eye movement (REM) density and slow-wave sleep (SWS). Surprisingly, proportion of SWS was significantly shorter during remission than depression. Never-depressed HRPs also exhibited significantly elevated REM density and reduced SWS. Finally, these parameters constituted the only two EEG variables that were not moderated by depression severity. Conclusions Individuals experiencing MDD and those in remission exhibit increased REM density and shortened SWS, as do HRPs with no history of MDD. Thus, this combination of EEG features may represent a genetic biomarker of MDD. Further, SWS appears to be shorter during remission than depression, suggesting its role as both a genetic marker as well as a biological scar of the disorder. Research on whether any electroencephalographic (EEG) sleep abnormalities observed among individuals with major depressive disorder (MDD) represent genetic biomarkers remains inconclusive. We aimed to identify EEG-based biomarkers of MDD through a review of studies from three populations: individuals with MDD, individuals with MDD under remission, and never depressed high-risk probands (HRPs) of individuals with MDD. We searched databases such as MEDLINE and PsycINFO for EEG studies published since 1970. Of the 886 records, our selection criteria identified 56 studies that employed standardized EEG scoring procedures and addressed confounds such as participant reactivity and drug effects. We then used fixed-effects models to calculate average weighted mean differences in EEG parameters between clinical groups across these studies. Individuals with MDD differed significantly from control subjects on several EEG variables. However, remitted individuals showed normalization of all affected EEG parameters except rapid eye movement (REM) density and slow-wave sleep (SWS). Surprisingly, proportion of SWS was significantly shorter during remission than depression. Never-depressed HRPs also exhibited significantly elevated REM density and reduced SWS. Finally, these parameters constituted the only two EEG variables that were not moderated by depression severity. Individuals experiencing MDD and those in remission exhibit increased REM density and shortened SWS, as do HRPs with no history of MDD. Thus, this combination of EEG features may represent a genetic biomarker of MDD. Further, SWS appears to be shorter during remission than depression, suggesting its role as both a genetic marker as well as a biological scar of the disorder.