Marcel A Pawlowski1, Mary Gazea2, Bastian Wollweber1, Martin Dresler3, Florian Holsboer1, Martin E Keck1, Axel Steiger1, Marek Adamczyk4, Thorsten Mikoteit5. 1. Max Planck Institute of Psychiatry, Munich, Germany. 2. Max Planck Institute of Psychiatry, Munich, Germany; University of Bern, Inselspital University Hospital, Department of Neurology, Bern, Switzerland. 3. Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands. 4. Psychiatric Clinics of the University of Basel, Center for Affective, Stress and Sleep Disorders, Basel, Switzerland. 5. Max Planck Institute of Psychiatry, Munich, Germany; Psychiatric Clinics of the University of Basel, Center for Affective, Stress and Sleep Disorders, Basel, Switzerland. Electronic address: thorsten.mikoteit@upkbs.ch.
Abstract
OBJECTIVES: The relevance of rapid eye movement (REM) sleep in affective disorders originates from its well-known abnormalities in depressed patients, who display disinhibition of REM sleep reflected by increased frequency of rapid eye movements (REM density). In this study we examined whether heart rate variability (HRV) and prefrontal theta cordance, both derived from REM sleep, could represent biomarkers of antidepressant treatment response. METHODS: In an open-label, case-control design, thirty-three in-patients (21 females) with a depressive episode were treated with various antidepressants for four weeks. Response to treatment was defined as a ≥50% reduction of HAM-D score at the end of the fourth week. Sleep EEG was recorded after the first and the fourth week of medication. HRV was derived from 3-min artifact-free electrocardiogram segments during REM sleep. Cordance was computed for prefrontal EEG channels in the theta frequency band during tonic REM sleep. RESULTS: HRV during REM sleep was decreased in depressed patients at week four as compared to controls (high effect size; Cohen's d > 1), and showed a negative correlation with REM density in both, healthy subjects and patients at week four. Further, the fourteen responders had significantly higher prefrontal theta cordance as compared to the nineteen non-responders after the first week of antidepressant medication; in contrast, HRV at week one did not discriminate between responders and non-responders. CONCLUSIONS: Our data suggest that HRV in REM sleep categorizes healthy subjects and depressed patients, whereas REM sleep-derived prefrontal cordance may predict the response to antidepressant treatment in depressed patients.
OBJECTIVES: The relevance of rapid eye movement (REM) sleep in affective disorders originates from its well-known abnormalities in depressedpatients, who display disinhibition of REM sleep reflected by increased frequency of rapid eye movements (REM density). In this study we examined whether heart rate variability (HRV) and prefrontal theta cordance, both derived from REM sleep, could represent biomarkers of antidepressant treatment response. METHODS: In an open-label, case-control design, thirty-three in-patients (21 females) with a depressive episode were treated with various antidepressants for four weeks. Response to treatment was defined as a ≥50% reduction of HAM-D score at the end of the fourth week. Sleep EEG was recorded after the first and the fourth week of medication. HRV was derived from 3-min artifact-free electrocardiogram segments during REM sleep. Cordance was computed for prefrontal EEG channels in the theta frequency band during tonic REM sleep. RESULTS: HRV during REM sleep was decreased in depressedpatients at week four as compared to controls (high effect size; Cohen's d > 1), and showed a negative correlation with REM density in both, healthy subjects and patients at week four. Further, the fourteen responders had significantly higher prefrontal theta cordance as compared to the nineteen non-responders after the first week of antidepressant medication; in contrast, HRV at week one did not discriminate between responders and non-responders. CONCLUSIONS: Our data suggest that HRV in REM sleep categorizes healthy subjects and depressedpatients, whereas REM sleep-derived prefrontal cordance may predict the response to antidepressant treatment in depressedpatients.
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