Response to therapeutic sleep deprivation: a naturalistic study of clinical and genetic factors and post-treatment depressive symptom trajectory

Major Depressive Disorder Working Group Of The Psychiatric Genomics Consortium ,Jens Treutlein,Andreas J. Forstner,Steffen Conrad von Heydendorff,Stephanie H. Witt,Ulrich Ebner-Priemer,Jerome C. Foo,Maria Gilles,Josef Frank,Marcella Rietschel,Nina Trautmann,Markus M. Nöthen,Fabian Streit,Michael Deuschle

doi:10.1038/s41386-018-0092-y

Abstract

Research has shown that therapeutic sleep deprivation (SD) has rapid antidepressant effects in the majority of depressed patients. Investigation of factors preceding and accompanying these effects may facilitate the identification of the underlying biological mechanisms. This exploratory study aimed to examine clinical and genetic factors predicting response to SD and determine the impact of SD on illness course. Mood during SD was also assessed via visual analogue scale. Depressed inpatients (n = 78) and healthy controls (n = 15) underwent ~36 h of SD. Response to SD was defined as a score of ≤ 2 on the Clinical Global Impression Scale for Global Improvement. Depressive symptom trajectories were evaluated for up to a month using self/expert ratings. Impact of genetic burden was calculated using polygenic risk scores for major depressive disorder. In total, 72% of patients responded to SD. Responders and non-responders did not differ in baseline self/expert depression symptom ratings, but mood differed. Response was associated with lower age (p = 0.007) and later age at life-time disease onset (p = 0.003). Higher genetic burden of depression was observed in non-responders than healthy controls. Up to a month post SD, depressive symptoms decreased in both patients groups, but more in responders, in whom effects were sustained. The present findings suggest that re-examining SD with a greater focus on biological mechanisms will lead to better understanding of mechanisms of depression.

Highlights

Therapeutic sleep deprivation (SD) reliably induces rapid and substantial antidepressant effects in the majority of patients with a major depressive episode [1,2,3,4]
Beck Depression Inventory-II (BDI-II) scores decreased significantly on all measurement days compared with baseline (Fig. 4b, Table S4c) and significantly higher in spring compared with all other seasons
The finding that responders and nonresponders did not differ in terms of baseline depressive symptom scores is consistent with reports of depression severity not influencing SD response [11, 17, 19, 42]

Summary

INTRODUCTION

Therapeutic sleep deprivation (SD) reliably induces rapid and substantial antidepressant effects in the majority of patients with a major depressive episode [1,2,3,4]. 1234567890();,: polymorphisms in a single risk score offer the ability to associate burden of disease with clinical and phenotypic factors, and have been successfully applied to explore the genetic architecture of complex disorders [29, 31,32,33,34]. In this naturalistic exploratory study, we assessed clinical and genetic factors associated with response to SD, going beyond the study of individual candidate genes for the first time, using allgenomic information in the form of PRS. We evaluated mood longitudinally during SD, and the impact of SD on the further trajectory of depressive symptoms

MATERIALS AND METHODS

RESULTS

DISCUSSION