Antidepressant Responsiveness to Sleep Deprivation Is Not a Fixed Phenotypic Trait

Sleep deprivation (SD) has long been known to produce a rapid antidepressant effect in approximately half of depressed patients, yet the underlying mechanisms and consistency of this response remain poorly understood. This study investigated whether the antidepressant response to SD reflects a stable, trait-like characteristic by analysing previously collected data from 76 depressed patients exposed repeatedly to SD over multiple separate sessions. Using intraclass correlation coefficient (ICC) analysis, we quantified the proportion of variance in SD responsiveness attributable to stable interindividual differences. Results revealed a low ICC value characterized as slight (< 0.2), indicating that most of the variance in the dataset was associated with variability within individuals across sessions. This finding challenges the assumption that SD responsiveness is a fixed phenotypic trait and instead supports a state-dependent model in which responsiveness fluctuates over time. This has important implications for clinical practice and research, indicating that the antidepressant response to SD is not reliably predictable from prior sessions and may be influenced by transient neurobiological states. Future work should focus on identifying dynamic biomarkers that can predict the potential for antidepressant responses in real time, possibly optimising the timing of SD interventions and shedding new light on the neurobiology of depression.