Sleep Biomarkers for Stress-Induced Vulnerability to Depression.

Stress can push individuals close to the threshold to depression. An individual's intrinsic vulnerability before a stressful event determines how close they come to the threshold of depression. Identification of vulnerability biomarkers at early (before the stressful event) and late (close to the threshold after the stressful event) stages would allow for corrective actions. Social defeat is a stressful event that triggers vulnerability to depression in half of exposed rats. We analyzed the sleep properties of rats before (baseline) and after (recovery) social defeat by telemetry electroencephalogram recordings. Using Gaussian partitioning, we identified three non-Rapid Eye Movement (NREM) stages (N-S1, N-S2, and N-S3) in rats based on a sleep-depth index (relative δ power) and a cortical activity index (fractal dimension). We found (i) that, at baseline, N-S3 lability and high-θ relative power in wake identified, with 82% accuracy, the population of rats that will become vulnerable to depression after social defeat, and (ii) that, at recovery, N-S1 instability identified vulnerable rats with 83% accuracy. Thus, our study identified early and late sleep biomarkers of vulnerability to depression, opening the way to the development of treatments at a prodromal stage for high sensitivity to stress, and for stress-induced vulnerability to depression.