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Mindfulness-based focused attention training versus progressive muscle relaxation in remitted depressed patients: Effects on salivary cortisol and associations with subjective improvements in daily life
Journal Pre-proof Mindfulness-based focused attention training versus progressive muscle relaxation in remitted depressed patients: effects on salivary cortisol and associations with subjective improvements in daily life Theresa Beddig, Christina Timm, Bettina Ubl-Rachota, Vera Zamoscik, Ulrich Ebner-Priemer, Iris Reinhard, Peter Kirsch, Christine Kuehner
PII:
S0306-4530(19)31296-X
DOI:
https://doi.org/10.1016/j.psyneuen.2019.104555
Reference:
PNEC 104555
To appear in:
Psychoneuroendocrinology
Received Date:
6 May 2019
Revised Date:
12 October 2019
Accepted Date:
13 December 2019
Please cite this article as: Beddig T, Timm C, Ubl-Rachota B, Zamoscik V, Ebner-Priemer U, Reinhard I, Kirsch P, Kuehner C, Mindfulness-based focused attention training versus progressive muscle relaxation in remitted depressed patients: effects on salivary cortisol and associations with subjective improvements in daily life, Psychoneuroendocrinology (2019), doi: https://doi.org/10.1016/j.psyneuen.2019.104555
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier.
Mindfulness-based focused attention training versus progressive muscle relaxation in remitted depressed patients: effects on salivary cortisol and associations with subjective improvements in daily life
Theresa Beddigae, Christina Timmae, Bettina Ubl-Rachotaa, Vera Zamoscikb, Ulrich Ebner-Priemerc, Iris Reinhardd, Peter Kirschb, and Christine Kuehnera*
a
Research Group Longitudinal and Intervention Research, Department of Psychiatry and
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Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/ Heidelberg University, Germany b
Department of Clinical Psychology, Central Institute of Mental Health, Medical Faculty Mannheim/
Chair of Applied Psychology, Karlsruhe Institute of Technology, Germany
d
Department of Biostatistics, Central Institute of Mental Health, Medical Faculty Mannheim/
Heidelberg University, Germany these authors contributed equally to this work
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e
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Corresponding author: Christine Kuehner, PhD, Research Group Longitudinal and Intervention
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*
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c
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Heidelberg University, Germany
Research, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical
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Faculty Mannheim/ Heidelberg University, J5, 68159 Mannheim, Germany, Tel.: +49-621-1703-6058,
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Email: [email protected]
Highlights:
no intervention-related effects on CAR and diurnal slopes for MBAT and PMR increase in total cortisol in both conditions cortisol change linked to decreases in daily life negative affect and rumination for MBAT only
Abstract
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Major Depression is a stress-related disorder characterized by altered hypothalamic-pituitary-adrenal axis function. Mindfulness-based interventions have shown to improve subjective parameters of stress and to reduce relapse rates in depressed patients. However, research on their effects on diurnal patterns of cortisol and associations with subjective outcomes is lacking. The present Ambulatory Assessment study investigated possible changes in daily rhythm cortisol parameters (cortisol awakening response (CAR), daily slope, total cortisol) in currently remitted individuals with recurrent depression who were randomized to a four-week mindfulness-based focused attention training (MBAT, n=39) or a progressive muscle relaxation training (PMR, n=39). A second
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aim was to investigate whether changes in cortisol were linked to improvements in affective and cognitive daily life states. On three weekdays before and after the intervention, seven saliva cortisol samples per day were collected. For analysis, multilevel models were applied. Results revealed no
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group-specific or general change in CAR and daily slopes from pre- to postintervention. In contrast, total cortisol increased across groups, which was however moderated by group and subjective
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improvement status. While cortisol increased irrespective of subjective improvement in PMR participants, MBAT participants with larger reductions in negative affect and rumination maintained
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their initial cortisol levels, whereas those with lower improvement paralleled the PMR group. Thereby, MBAT appeared to buffer an increase in overall cortisol secretion over time, but only in patients
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showing marked improvements in those affective and cognitive states that constitute core elements for
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depressive relapses in the vulnerability model of mindfulness-based cognitive therapy.
Key words: HPA axis, mindfulness-based intervention, Ambulatory Assessment, rumination, negative
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affect, cortisol
1. Introduction
Major Depression is considered a stress-related disorder of the brain characterized by altered hypothalamic-pituitary-adrenal axis (HPAA) function (Gold, 2015). In addition to altered reactivity to acute stressors, depression-related changes in the circadian regulation of cortisol secretion have been noted in recent research. Key diurnal cortisol parameters, which can be assessed by non-invasive 2
saliva probes during ambulatory assessment, are the cortisol awakening response (CAR), the diurnal cortisol slope, and the total cortisol output over the day. HPAA dysregulation in depression has been linked to an abnormally large or small CAR (Dedovic & Ngram, 2015), a flattened slope (Adam et al., 2017), and high total cortisol (Hinkelmann et al., 2009). Mindfulness-based interventions have been consistently associated with subjective indicators of stress reduction (O’Leary et al., 2016), and Mindfulness-Based Cognitive Therapy (MBCT, Segal et al., 2013) has shown to be highly effective in reducing relapse rates in recurrently depressed patients (Kuyken et al., 2016). Research on effects of mindfulness interventions on diurnal cortisol patterns in
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depression is still extremely rare but is important to identify possible physiological pathways through which these interventions might affect recurrence risk. One small systematic review on saliva-related outcomes with diagnostically heterogeneous samples (n=6) has been published so far, in which two
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methodologically weak studies reported opposed results (CAR increase vs. decrease) and four randomized controlled trials (RCTs) identified no effects on CAR or diurnal slope (O’Leary et al.,
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2015). One of these RCTs compared MBCT with treatment as usual in 56 recurrently depressed remitted patients: Gex-Fabry et al. (2012) conducted single day assessments of CAR, daily slopes, and
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total cortisol six times from pretest to up to 12 months after termination of the eight-week program. While MBCT delayed the risk for relapse, the intervention showed no effect regarding CAR and daily
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slope. In contrast, total cortisol increased in both groups over time, which the authors attributed to seasonal variations of the cortisol secretion (follow-ups with higher cortisol levels were mainly
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conducted during autumn months). Furthermore, the authors suggested that future studies should investigate cortisol outcomes together with proposed MBCT mechanisms of change. In this context,
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MBCT assumes increased reactivation of ruminative thoughts in response to even mild negative affect in recurrently depressed patients and proposes MBCT to be specifically effective in stopping the vicious circle between rumination and negative affect, thereby eventually preventing depressive relapses (Segal et al., 2013). The present investigation was part of a randomized controlled trial (RCT) examining effects of a four-week mindfulness-based focused attention training (MBAT) compared to an active control condition (progressive muscle relaxation, PMR) on affective, cognitive and physiological states during 3
daily life in recurrently depressed remitted patients. Our study aims were based on previous observations showing that mindfulness interventions involving focused attention improved selective and executive attention processes (Chiesa et al., 2011). These processes are particularly impaired in depression and appear to be linked to self-focused rumination during daily life (cf. Timm et al., 2018). We previously reported from this study that MBAT was clearly superior to PMR regarding improvements in momentary negative affect, rumination, and other subjective states during daily life (Timm et al., 2018). The first aim of the present investigation was to examine possible effects of MBAT versus PMR on changes in CAR, daily slope, and total cortisol during treatment. A second aim
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was to examine whether decreases in negative affect and rumination predicted changes in these cortisol parameters and whether this was specific for MBAT. We focused on negative affect and rumination because their interplay is a proposed core mechanism for relapse in the MBCT model (see
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above). We hypothesized MBAT compared to PMR to be linked to a) a steeper daily slope, and b) a reduction in total cortisol, and in addition tested for c) a possible intervention-specific change in the
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CAR. We did not have a directed hypothesis regarding the latter because both over- and underactivation of the CAR have been reported for depression (Dedovic & Ngram, 2015).
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Furthermore, we expected larger decreases in negative affect and rumination to be linked to larger changes in respective cortisol outcomes, especially for MBAT.
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Our study expands previous cortisol-related mindfulness research in depression by assessing diurnal standard cortisol patterns repeatedly at pre- and postintervention, thereby increasing
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measurement reliability. Another innovative feature is that we for the first time investigated possible links between changes in the circadian rhythm of cortisol and changes in relevant subjective indicators
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of improvement.
2. Method
Trial design The investigation was part of an open-label randomized controlled trial (RCT, German Clinical Trails Register: DRKS00005222) in remitted depressed individuals (rMDD) which compared effects of a four-week mindfulness-based focused attention training (MBAT) versus progressive muscle relaxation 4
(PMR) on changes in daily life subjective (affect, cognition) and physiological (cortisol) states. The trial was approved by the local ethics committee of the Medical Faculty Mannheim of the University of Heidelberg (2009-299N-MA, 7.3.2013) and met all ethical standards specified in the Declaration of Helsinki. All participants provided written informed consent. Participants Participants were recruited through different sources: newspapers, local family doctors, homepage of the Central Institute of Mental Health (CIMH) and social networks. Individuals were eligible for the study if they were aged between 25 and 55, were currently remitted from an episode of
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Major Depression (DSM-IV), i.e., did not meet the criteria of an episode during the last two months, and fulfilled the criteria for at least two previous episodes of Major Depression in the past. Exclusion criteria were severe psychiatric comorbid disorders (lifetime bipolar or psychotic disorders, substance
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dependence, obsessive-compulsive disorder, eating disorder), medication intake affecting cortisol secretion, and mindfulness and/or relaxation practice during the last three months prior to study entry.
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Diagnostic in- and exclusion criteria were assessed by a trained research psychologist with the Structured Clinical Interview for DSM-IV (Wittchen et al., 1997). Recruitment took place between
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July 2014 and February 2017. Assessment of the last participant was completed in May 2017. Sample size
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A sample size of 2*35 was regarded as sufficient to identify medium effect sizes in a repeated measurement design (f=0.25) with α=0.05 (two-tailed) and a power (1-ß) of >.90.
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Randomization
Seventy-eight eligible participants were individually randomly assigned to either MBAT (n=39)
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or PMR (n=39), stratified according to age and gender (allocation 1:1 by number list). Allocation concealment was retained for all participants. Due to the nature of the interventions, it was not possible to blind either participants or trainers, as they notified to which of the conditions they had been assigned to. Interventions Both interventions were manual-based interventions delivered by video-based supervised trainers (supervision by CK). MBAT trainings were provided by mindfulness-based stress reduction 5
trainers (n=2) and cognitive behavioral therapists regularly applying mindfulness-based interventions (n=3), and PMR was provided by cognitive behavior therapists regularly applying PMR (n=5). Interventions took place during five weekly sessions of 50 min each provided individually by the assigned trainer. Sessions in both training conditions followed the same formal schedule (1. psychoeducational introduction, 2. review of homework (from session 2), 3. introduction and practice of elements, 4. debriefing, 5. homework assignment) and were strictly matched regarding practice duration. MBAT training included psychoeducational elements (e.g., mindful awareness and automatic pilot, coping with difficulties during practice), practice of focused attention mindfulness elements
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(mindfulness of the breath and body scan), and demonstration and practicing of short mindfulness exercises for application during daily life. PMR training also included psychoeducational elements (e.g., how PMR works, coping with difficulties during practice), practice of relaxation elements with
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muscle tension for different body regions for about 5-7 sec followed by relaxation for about 35 sec and demonstration and practicing of short PMR exercises for application during daily life.
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Additionally, during the intersession weekdays, participants were asked to perform audioguided home practice (with instructions provided by recordings of their trainer) of 20 min per day and
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to record time of homework practicing and how they felt during practicing (bipolar scales, Wilhelm & Schoebi, 2007).
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Ambulatory Assessment of subjective data and cortisol Ambulatory Assessment (AA) was conducted using Motorola Moto G1 smartphones with the
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software movisensXS, 1.1.1 (movisens GmbH Karlsruhe, Germany). Subjective outcomes were measured over three consecutive weekdays before and after the training with 10 assessments per day.
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The average time between the last AA preintervention day and the first training session was 13.1 days (SD=13.4), and between the last training session and the first AA postintervention day was 8.7 days (SD=6.1).
Subjective ratings were given on 7-point Likert scales which were provided during randomized time points at least 30 min apart between 8:00 am and 10:00 pm. Participants rated their momentary negative affect with six items balanced on activation (angry, irritated, nervous, listless, down, bored), and rumination was rated with the item “at the moment, I am stuck on negative thoughts and cannot 6
disengage from them”. Assessments were announced by beeps. Responses could be delayed up to 15 min, otherwise the assessment was rated as missing. During the six study days, seven saliva samples per day were collected. Participants were requested to wake no later than at 7:00 am and to immediately start with the first sample before getting up, followed by a second sample 30 min later. They were instructed to refrain from eating, drinking (except water), smoking, physically exertion and teeth brushing during the CAR assessment period. Participants recorded their individual wake-up and sampling times for the CAR. Sample 1 had to be collected within 15 min of awakening, and sample 2 30±10 min after awakening. Samples extending
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these periods were treated as missing. Further five samples were collected after the 1 st, 3rd, 5th, 7th, and 9th subjective assessment with a 20 min delay during which participants were asked not to eat, drink, smoke, or physically exert themselves. Exact sampling times for these samples were recorded via
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smartphone. Participants were informed extensively about the procedure and were handed out detailed instructions on how to collect, store, and return the samples. Cortisol samples were stored in the
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participant's fridge and subsequently frozen at −20 °C at the CIMH laboratory until biochemical analysis at the TU Dresden laboratory (Prof. C. Kirschbaum). Saliva cortisol concentrations were
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measured using commercially available chemiluminescence-immunoassay with high sensitivity (IBL International, Hamburg, Germany). Intra- and interassay coefficients were <8%.
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Statistical analyses
Cortisol outcome data were log-transformed to adjust for skewness, and log values exceeding 3 SDs
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from the mean were winsorized (cf. Schlotz, 2019). Samples 1 and 2 determined the CAR, and samples 1 and 3 to 7 the daily slope and total cortisol (cf. Adam et al., 2009). Data were analyzed with
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multilevel models. For all dependent variables the two- and three-level model had similar fits (AIC and BIC; Hox et al., 2017). Therefore, the more parsimonious 2-level model was applied for all outcomes with AA (level 1) nested within persons (level 2). Cortisol values were entered in three separate models as dependent variables to estimate CAR, slope and total cortisol. In all models, time was centered at the waking sample. For daily slope and total cortisol we checked whether time 2 was significant and if so retained it in the models, if not, time was only included as a linear effect. All models included random intercepts at level 2 and were checked for potential confounders (age, sex, 7
antidepressants, other medication, awakening time, sleep duration, sleep quality, average number of cigarettes per day, number of previous episodes). Only confounders at p≤0.05 were retained in the respective models (sleep duration, sleep quality and habitual smoking for CAR, sex and antidepressant use for DCS, age and previous episodes for total cortisol). Preparatory analyses revealed that groups differed significantly in their overall log-cortisol levels at baseline (MBAT 2.63 (SE 0.05), PMR 2.50 (SE 0.05), F(1,75)=4.3, p=0.042), therefore we further controlled for person-level aggregated preintervention cortisol levels in all analyses. Multilevel models were estimated with Restricted Maximum Likelihood (REML). Therefore, analyses are based on the total sample (n=78). Data were
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analyzed using IBM SPSS version 23. 3. Results
Participant flow is displayed in the Consort flowchart (Supplementum S1). Of 243 screened
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individuals, n=165 did not meet the inclusion criteria, and n=55 declined to participate before randomization, mainly due to anticipated temporal overload linked to study participation. Therefore,
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n=78 remitted depressed participants (MBAT: n=39, PMR: n=39) were enrolled. Three patients per condition (7.7%) dropped out prematurely (see S1).
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Adherence to individual sessions was high in both groups. Among those who dropped out prematurely (n=6), three dropped out after session 1, one after session 3, and two after session 4.
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Among those who completed the trainings (n=72), two participants missed one session each. In total (including drop outs), 16 of 390 sessions were missed (4.1%). The high adherence rate was
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substantially attributable to the one-to-one session format that allowed to offer flexible alternative appointments if a participant was indisposed on short notice. Homework compliance, defined as the
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percentage of filled in diaries of a maximum of 24 practice days in total, reached 92.1%. As a limitation, there was no external validation of the number of sessions performed by participants. The overall AA-response rate for the subjective ratings was 82.2% (cf. Timm et al., 2018). The
overall compliance for cortisol assessments reached 87.5% (2867 of possible 3276 (7*6*78) probes were delivered). Table 1 displays baseline characteristics of participants. MBAT and PMR participants did not differ significantly on any of these baseline variables. 8
To examine treatment effects on CAR, slope and total cortisol, three separate models were performed estimating fixed effects of group, prepost status and time (for CAR) or time and time 2 (for slope and total cortisol) adjusted for confounders and for aggregated pre-intervention cortisol levels. In all models, interactions including group and prepost status were nonsignificant (CAR: group*prepost*time F(1,551)=0.06, p=0.808; slope: group*prepost*time2 F(1,2014)=2.25, p=0.133; total cortisol: group*prepost F(1,2053)=0.93, p=0.335). After removal of group status, prepost status was nonsignificant regarding CAR (prepost*time F(1,555)=1.23, p=0.269) and slope (prepost*time 2 F(1,2020)=1.57, p=0.211), whereas a significant prepost effect was identified for total cortisol
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(F(1,2053)=11.99, B=0.09, SE=0.03, p<0.001) indicating an increase from pre to post. A posthoc-test revealed that seasonality did not significantly affect total cortisol values (F(1,324)=0.23, p=0.634).
To examine whether changes in cortisol parameters were related to changes in subjective AA-
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variables, pre-post difference scores of aggregated means were calculated for negative affect and rumination, which were entered as level 2 predictors in the respective models. In the models for CAR
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and slope, the interactions including group, prepost status and change scores of negative affect and rumination were non-significant (CAR: group*prepost*time*negative affect change F(1,546)=0.58,
group*prepost*time2*negative
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p=0.448; CAR: group*prepost*time*rumination change F(1,546)=1.00, p=0.320; daily slope: affect
change
F(1,2009)=0.61,
p=0.436;
daily
slope:
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group*prepost*time2*rumination change F(1,2017)=0.14, p=0.705). In contrast, the models for total cortisol revealed significant interactions (group*prepost*negative affect change F(1,2012)=4.53,
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p=0.033; group*prepost*rumination change F(1,2025)=6.03, p=0.014). Figure 1A and 1B show these estimated interactions. Posthoc analyses per group revealed a marginally significant effect of negative
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affect change on change in cortisol for MBAT (prepost*negative affect change, F(1,1064)=3.03, p=0.082) indicating higher cortisol increase in participants with smaller decreases in negative affect compared to those with larger decreases while no such interaction was found for PMR (F(1,942)=1.65, p=0.200, see Fig. 1A). Furthermore, a significant effect of rumination change on cortisol change was observed for MBAT (prepost*rumination change, F(1,1071)=7.63, p=0.006). MBAT participants with larger decreases in rumination in contrast to those with smaller decreases showed no increase in
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cortisol from pre to post. No such interaction was found for PMR (F(1,952)=0.49, p=0.485, see Fig.1B).1 4. Discussion Consistent with previous research (Gex-Fabry et al., 2012) our study revealed no treatmentspecific or general change in CAR and daily cortisol slopes over the course of a 4-week MBAT versus PMR training. This may imply that these dynamic components of diurnal cortisol are quite stable and not responsive to the short intervention phase implemented in this study. In contrast, and contrary to our hypothesis, total cortisol increased from pre to post across
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groups. High levels of total cortisol output regularly indicate stressful periods, and total cortisol reflecting the average level of cortisol across the day has been found to be more responsive towards daily stressors than CAR and daily slope (Stawski et al., 2013). Notably, the only related study with
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recurrently depressed patients we are aware of (Gex-Fabry et al., 2012) showed exactly the same results. While these authors attributed the temporal cortisol increase to variations in seasonality, there
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was no seasonality effect on total cortisol in the present sample. Therefore, alternative explanations are conceivable. One possibility is that recurrent depression may per se be linked to increasing total
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cortisol levels over time, thereby reflecting accumulating stress levels that eventually could result in further relapses/recurrences. This idea is supported by our confounder analysis showing that the
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number of previous episodes positively predicted total cortisol (but not CAR and daily slope) and was therefore controlled in the respective model (see S1). However, these considerations are still
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speculative and require more systematic research in this high-risk group. Importantly, however, change in total cortisol was moderated by group and subjective
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improvement status in the present study. While total cortisol increased in PMR participants irrespective of subjective improvements, MBAT participants with larger decreases in negative affect and rumination maintained their initial cortisol levels, whereas those with lower improvement paralleled the PMR group by showing increased total cortisol from pre to post. Hence, MBAT appeared to buffer an increase in overall cortisol secretion over time, but only in those patients with 1
Including mean rumination change scores as a possible confounder in the model for negative affect and vice versa did not change the significance levels of respective models (group*prepost*negative affect changeF(1,1958)=4.58, p=0.032, group*prepost*rumination change F(1,1972)=5.96, p=0.015), indicating that both variables independently drove the relationship with cortisol.
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marked improvements in affective and cognitive daily life experiences constituting core elements for depressive relapses in the MBCT vulnerability model (Segal et al., 2013). Generally, these results point to a closer connection between psychological and physiological changes in MBAT, which is in line with theoretical assumptions of mindfulness interventions (e.g. Segal et al., 2013). The study has strengths and limitations. Strengths include the implementation of a randomized controlled trial and the application of PMR as an active control condition against MBAT, the repeated assessment of standard cortisol parameters (CAR, daily slope, and total cortisol) at pre- and postintervention, as recommended in the literature (cf. Adam & Kumari, 2009, Ryan et al., 2016), and
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the linking of cortisol outcomes to subjective daily life experiences. Limitations include the lack of electronic monitoring of the morning cortisol values, which we however tried to minimize through detailed instructions, as well as the lack of an objective measure for homework compliance. Further,
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the sample size was too small to further subdivide into subgroups with possible heterogeneous activation of the HPAA (cf. Gold, 2015).
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To conclude, this is the first RCT investigating effects of a short mindfulness-based versus active control treatment on changes in key diurnal cortisol parameters. Moreover, this is the first study
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investigating whether improvements in relevant subjective outcomes - as proposed by mindfulnessbased theory - predicted changes in respective cortisol outcomes. Our negative results regarding CAR
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and daily slopes warrant further research that should aim at identifying optimal treatment length of mindfulness-based interventions to enable beneficial effects on changes in dynamic components of
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diurnal cortisol to occur, but also to investigate whether these parameters are possibly more responsive to other components of mindfulness interventions not investigated in our study, such as meta-cognitive
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awareness or decentering. Observed increasing total cortisol levels in both training groups were unexpected and should be interpreted with care. However, since both Gex-Fabry et al. (2012) and the present study demonstrated such an increase in samples of recurrently depressed patients it appears worthwhile to address this issue more systematically in future longitudinal research. Finally, future research is required to replicate our findings on the buffering effect of MBAT on total cortisol increase in those patients who improved in relevant subjective outcomes. To our opinion, this will constitute an important step to increase knowledge on possible multiple but interconnected paths through which 11
mindfulness-based interventions might work. Generally, our study points to the relevance of including diurnal cortisol parameters as biomarkers in RCTs on mindfulness-based and other psychosocial interventions for recurrently depressed patients to be able to identify possible multi-faceted mechanisms involved in effective relapse prevention for this high-risk population. Role of the funding source This study was supported by the German Research Foundation (DFG, KU1464/4-2, KI576/12-2). The sponsor had no involvement in study design, data collection, analysis and interpretation of data, writing of the report, and in the decision to submit the article for publication.
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Declaration of interest None Conflict of Interest
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None
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Acknowledgement
The authors wish to thank all study participants and the trainers for delivering the interventions
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(Dr. M.Sc.Psych. A. Becker, M.Sc.Psych. S. Fenske, Dr. Dipl.-Psych. D. Mier, Dr. M.Sc.Psych. K.
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MBSR-trainer).
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Muszer, Dr. Dipl.-Psych. C. Paul, A. Rossa, MBSR-trainer, Dr. M.Sc.Psych. C. Sauer, J. Stern,
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version. Hogrefe, Göttingen.
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Figure 1. Estimated cortisol scores (ln nmol/l) during three days before (pre) and after (post) intervention (MBAT (n=39) vs. PMR (n=39)) in participants with high (+ 1 SD) versus low (- 1 SD) improvement in NA (Fig. 1A) and in participants with high (+ 1 SD) versus low (- 1 SD) improvement in RUM (Fig. 1B). Note. MBAT = Mindfulness Based Attention Training; PMR = Progressive Muscle Relaxation. NA_DIFF = difference score of aggregated negative affect prescore minus postscore; RUM_DIFF = difference score of aggregated rumination prescore minus postscore. Error bars represent standard error of the mean. Models include age, number of previous depressive episodes, time of assesments, time² of assesments and aggregated pre-intervention cortisol levels as covariates.
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Fig. 1A.
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Fig. 1B.
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Table 1. Baseline Characteristics of Participants. MBAT1 (n=39) PMR2 (n=39) Test statistic % / mean (SD) % / mean (SD)
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Demographic variables Age 36.7 (10.3) 39.8 (11.8) t=-1.23 .223 2 Gender (% women) 69.2% 71.8% Chi =.06 .804 2 Education (% > 10 years) 65.8% 82.1% Chi =2.65 .104 Clinical variables Duration of illness (years, 16.4 (10.1) 15.5 (11.8) t=0.41 .681 3 SCID-I ) Number of previous MDE4 4.6 (2.6) 4.2 (2.7) t=0.51 .612 (SCID-I3) Previous inpatient treatment 38.5% 41.0% Chi2=0.54 .817 2 Previous psychotherapy 66.7% 66.7% Chi =0.00 >.999 5 BDI-II at baseline 6.2 (6.9) 9.2 (10.8) t=-1.48 .143 Antidepressant medication at 12.8% 23.7% Chi2=1.53 .217 baseline 1 MBAT = Mindfulness-based attention training, 2PMR = Progressive muscle relaxation, 3SCID-I = Structured Clinical Interview for DSM-IV, 4MDE = Major Depression Episodes (DSM-IV, SKID-I), 5 BDI-II = Beck Depression Inventory-Revised.
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PII:
S0306-4530(19)31296-X
DOI:
https://doi.org/10.1016/j.psyneuen.2019.104555
Reference:
PNEC 104555
To appear in:
Psychoneuroendocrinology
Received Date:
6 May 2019
Revised Date:
12 October 2019
Accepted Date:
13 December 2019
Please cite this article as: Beddig T, Timm C, Ubl-Rachota B, Zamoscik V, Ebner-Priemer U, Reinhard I, Kirsch P, Kuehner C, Mindfulness-based focused attention training versus progressive muscle relaxation in remitted depressed patients: effects on salivary cortisol and associations with subjective improvements in daily life, Psychoneuroendocrinology (2019), doi: https://doi.org/10.1016/j.psyneuen.2019.104555
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier.
Mindfulness-based focused attention training versus progressive muscle relaxation in remitted depressed patients: effects on salivary cortisol and associations with subjective improvements in daily life
Theresa Beddigae, Christina Timmae, Bettina Ubl-Rachotaa, Vera Zamoscikb, Ulrich Ebner-Priemerc, Iris Reinhardd, Peter Kirschb, and Christine Kuehnera*
a
Research Group Longitudinal and Intervention Research, Department of Psychiatry and
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Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/ Heidelberg University, Germany b
Department of Clinical Psychology, Central Institute of Mental Health, Medical Faculty Mannheim/
Chair of Applied Psychology, Karlsruhe Institute of Technology, Germany
d
Department of Biostatistics, Central Institute of Mental Health, Medical Faculty Mannheim/
Heidelberg University, Germany these authors contributed equally to this work
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Corresponding author: Christine Kuehner, PhD, Research Group Longitudinal and Intervention
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*
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c
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Heidelberg University, Germany
Research, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical
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Faculty Mannheim/ Heidelberg University, J5, 68159 Mannheim, Germany, Tel.: +49-621-1703-6058,
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Email: [email protected]
Highlights:
no intervention-related effects on CAR and diurnal slopes for MBAT and PMR increase in total cortisol in both conditions cortisol change linked to decreases in daily life negative affect and rumination for MBAT only
Abstract
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Major Depression is a stress-related disorder characterized by altered hypothalamic-pituitary-adrenal axis function. Mindfulness-based interventions have shown to improve subjective parameters of stress and to reduce relapse rates in depressed patients. However, research on their effects on diurnal patterns of cortisol and associations with subjective outcomes is lacking. The present Ambulatory Assessment study investigated possible changes in daily rhythm cortisol parameters (cortisol awakening response (CAR), daily slope, total cortisol) in currently remitted individuals with recurrent depression who were randomized to a four-week mindfulness-based focused attention training (MBAT, n=39) or a progressive muscle relaxation training (PMR, n=39). A second
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aim was to investigate whether changes in cortisol were linked to improvements in affective and cognitive daily life states. On three weekdays before and after the intervention, seven saliva cortisol samples per day were collected. For analysis, multilevel models were applied. Results revealed no
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group-specific or general change in CAR and daily slopes from pre- to postintervention. In contrast, total cortisol increased across groups, which was however moderated by group and subjective
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improvement status. While cortisol increased irrespective of subjective improvement in PMR participants, MBAT participants with larger reductions in negative affect and rumination maintained
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their initial cortisol levels, whereas those with lower improvement paralleled the PMR group. Thereby, MBAT appeared to buffer an increase in overall cortisol secretion over time, but only in patients
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showing marked improvements in those affective and cognitive states that constitute core elements for
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depressive relapses in the vulnerability model of mindfulness-based cognitive therapy.
Key words: HPA axis, mindfulness-based intervention, Ambulatory Assessment, rumination, negative
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affect, cortisol
1. Introduction
Major Depression is considered a stress-related disorder of the brain characterized by altered hypothalamic-pituitary-adrenal axis (HPAA) function (Gold, 2015). In addition to altered reactivity to acute stressors, depression-related changes in the circadian regulation of cortisol secretion have been noted in recent research. Key diurnal cortisol parameters, which can be assessed by non-invasive 2
saliva probes during ambulatory assessment, are the cortisol awakening response (CAR), the diurnal cortisol slope, and the total cortisol output over the day. HPAA dysregulation in depression has been linked to an abnormally large or small CAR (Dedovic & Ngram, 2015), a flattened slope (Adam et al., 2017), and high total cortisol (Hinkelmann et al., 2009). Mindfulness-based interventions have been consistently associated with subjective indicators of stress reduction (O’Leary et al., 2016), and Mindfulness-Based Cognitive Therapy (MBCT, Segal et al., 2013) has shown to be highly effective in reducing relapse rates in recurrently depressed patients (Kuyken et al., 2016). Research on effects of mindfulness interventions on diurnal cortisol patterns in
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depression is still extremely rare but is important to identify possible physiological pathways through which these interventions might affect recurrence risk. One small systematic review on saliva-related outcomes with diagnostically heterogeneous samples (n=6) has been published so far, in which two
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methodologically weak studies reported opposed results (CAR increase vs. decrease) and four randomized controlled trials (RCTs) identified no effects on CAR or diurnal slope (O’Leary et al.,
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2015). One of these RCTs compared MBCT with treatment as usual in 56 recurrently depressed remitted patients: Gex-Fabry et al. (2012) conducted single day assessments of CAR, daily slopes, and
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total cortisol six times from pretest to up to 12 months after termination of the eight-week program. While MBCT delayed the risk for relapse, the intervention showed no effect regarding CAR and daily
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slope. In contrast, total cortisol increased in both groups over time, which the authors attributed to seasonal variations of the cortisol secretion (follow-ups with higher cortisol levels were mainly
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conducted during autumn months). Furthermore, the authors suggested that future studies should investigate cortisol outcomes together with proposed MBCT mechanisms of change. In this context,
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MBCT assumes increased reactivation of ruminative thoughts in response to even mild negative affect in recurrently depressed patients and proposes MBCT to be specifically effective in stopping the vicious circle between rumination and negative affect, thereby eventually preventing depressive relapses (Segal et al., 2013). The present investigation was part of a randomized controlled trial (RCT) examining effects of a four-week mindfulness-based focused attention training (MBAT) compared to an active control condition (progressive muscle relaxation, PMR) on affective, cognitive and physiological states during 3
daily life in recurrently depressed remitted patients. Our study aims were based on previous observations showing that mindfulness interventions involving focused attention improved selective and executive attention processes (Chiesa et al., 2011). These processes are particularly impaired in depression and appear to be linked to self-focused rumination during daily life (cf. Timm et al., 2018). We previously reported from this study that MBAT was clearly superior to PMR regarding improvements in momentary negative affect, rumination, and other subjective states during daily life (Timm et al., 2018). The first aim of the present investigation was to examine possible effects of MBAT versus PMR on changes in CAR, daily slope, and total cortisol during treatment. A second aim
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was to examine whether decreases in negative affect and rumination predicted changes in these cortisol parameters and whether this was specific for MBAT. We focused on negative affect and rumination because their interplay is a proposed core mechanism for relapse in the MBCT model (see
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above). We hypothesized MBAT compared to PMR to be linked to a) a steeper daily slope, and b) a reduction in total cortisol, and in addition tested for c) a possible intervention-specific change in the
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CAR. We did not have a directed hypothesis regarding the latter because both over- and underactivation of the CAR have been reported for depression (Dedovic & Ngram, 2015).
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Furthermore, we expected larger decreases in negative affect and rumination to be linked to larger changes in respective cortisol outcomes, especially for MBAT.
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Our study expands previous cortisol-related mindfulness research in depression by assessing diurnal standard cortisol patterns repeatedly at pre- and postintervention, thereby increasing
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measurement reliability. Another innovative feature is that we for the first time investigated possible links between changes in the circadian rhythm of cortisol and changes in relevant subjective indicators
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of improvement.
2. Method
Trial design The investigation was part of an open-label randomized controlled trial (RCT, German Clinical Trails Register: DRKS00005222) in remitted depressed individuals (rMDD) which compared effects of a four-week mindfulness-based focused attention training (MBAT) versus progressive muscle relaxation 4
(PMR) on changes in daily life subjective (affect, cognition) and physiological (cortisol) states. The trial was approved by the local ethics committee of the Medical Faculty Mannheim of the University of Heidelberg (2009-299N-MA, 7.3.2013) and met all ethical standards specified in the Declaration of Helsinki. All participants provided written informed consent. Participants Participants were recruited through different sources: newspapers, local family doctors, homepage of the Central Institute of Mental Health (CIMH) and social networks. Individuals were eligible for the study if they were aged between 25 and 55, were currently remitted from an episode of
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Major Depression (DSM-IV), i.e., did not meet the criteria of an episode during the last two months, and fulfilled the criteria for at least two previous episodes of Major Depression in the past. Exclusion criteria were severe psychiatric comorbid disorders (lifetime bipolar or psychotic disorders, substance
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dependence, obsessive-compulsive disorder, eating disorder), medication intake affecting cortisol secretion, and mindfulness and/or relaxation practice during the last three months prior to study entry.
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Diagnostic in- and exclusion criteria were assessed by a trained research psychologist with the Structured Clinical Interview for DSM-IV (Wittchen et al., 1997). Recruitment took place between
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July 2014 and February 2017. Assessment of the last participant was completed in May 2017. Sample size
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A sample size of 2*35 was regarded as sufficient to identify medium effect sizes in a repeated measurement design (f=0.25) with α=0.05 (two-tailed) and a power (1-ß) of >.90.
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Randomization
Seventy-eight eligible participants were individually randomly assigned to either MBAT (n=39)
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or PMR (n=39), stratified according to age and gender (allocation 1:1 by number list). Allocation concealment was retained for all participants. Due to the nature of the interventions, it was not possible to blind either participants or trainers, as they notified to which of the conditions they had been assigned to. Interventions Both interventions were manual-based interventions delivered by video-based supervised trainers (supervision by CK). MBAT trainings were provided by mindfulness-based stress reduction 5
trainers (n=2) and cognitive behavioral therapists regularly applying mindfulness-based interventions (n=3), and PMR was provided by cognitive behavior therapists regularly applying PMR (n=5). Interventions took place during five weekly sessions of 50 min each provided individually by the assigned trainer. Sessions in both training conditions followed the same formal schedule (1. psychoeducational introduction, 2. review of homework (from session 2), 3. introduction and practice of elements, 4. debriefing, 5. homework assignment) and were strictly matched regarding practice duration. MBAT training included psychoeducational elements (e.g., mindful awareness and automatic pilot, coping with difficulties during practice), practice of focused attention mindfulness elements
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(mindfulness of the breath and body scan), and demonstration and practicing of short mindfulness exercises for application during daily life. PMR training also included psychoeducational elements (e.g., how PMR works, coping with difficulties during practice), practice of relaxation elements with
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muscle tension for different body regions for about 5-7 sec followed by relaxation for about 35 sec and demonstration and practicing of short PMR exercises for application during daily life.
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Additionally, during the intersession weekdays, participants were asked to perform audioguided home practice (with instructions provided by recordings of their trainer) of 20 min per day and
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to record time of homework practicing and how they felt during practicing (bipolar scales, Wilhelm & Schoebi, 2007).
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Ambulatory Assessment of subjective data and cortisol Ambulatory Assessment (AA) was conducted using Motorola Moto G1 smartphones with the
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software movisensXS, 1.1.1 (movisens GmbH Karlsruhe, Germany). Subjective outcomes were measured over three consecutive weekdays before and after the training with 10 assessments per day.
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The average time between the last AA preintervention day and the first training session was 13.1 days (SD=13.4), and between the last training session and the first AA postintervention day was 8.7 days (SD=6.1).
Subjective ratings were given on 7-point Likert scales which were provided during randomized time points at least 30 min apart between 8:00 am and 10:00 pm. Participants rated their momentary negative affect with six items balanced on activation (angry, irritated, nervous, listless, down, bored), and rumination was rated with the item “at the moment, I am stuck on negative thoughts and cannot 6
disengage from them”. Assessments were announced by beeps. Responses could be delayed up to 15 min, otherwise the assessment was rated as missing. During the six study days, seven saliva samples per day were collected. Participants were requested to wake no later than at 7:00 am and to immediately start with the first sample before getting up, followed by a second sample 30 min later. They were instructed to refrain from eating, drinking (except water), smoking, physically exertion and teeth brushing during the CAR assessment period. Participants recorded their individual wake-up and sampling times for the CAR. Sample 1 had to be collected within 15 min of awakening, and sample 2 30±10 min after awakening. Samples extending
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these periods were treated as missing. Further five samples were collected after the 1 st, 3rd, 5th, 7th, and 9th subjective assessment with a 20 min delay during which participants were asked not to eat, drink, smoke, or physically exert themselves. Exact sampling times for these samples were recorded via
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smartphone. Participants were informed extensively about the procedure and were handed out detailed instructions on how to collect, store, and return the samples. Cortisol samples were stored in the
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participant's fridge and subsequently frozen at −20 °C at the CIMH laboratory until biochemical analysis at the TU Dresden laboratory (Prof. C. Kirschbaum). Saliva cortisol concentrations were
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measured using commercially available chemiluminescence-immunoassay with high sensitivity (IBL International, Hamburg, Germany). Intra- and interassay coefficients were <8%.
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Statistical analyses
Cortisol outcome data were log-transformed to adjust for skewness, and log values exceeding 3 SDs
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from the mean were winsorized (cf. Schlotz, 2019). Samples 1 and 2 determined the CAR, and samples 1 and 3 to 7 the daily slope and total cortisol (cf. Adam et al., 2009). Data were analyzed with
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multilevel models. For all dependent variables the two- and three-level model had similar fits (AIC and BIC; Hox et al., 2017). Therefore, the more parsimonious 2-level model was applied for all outcomes with AA (level 1) nested within persons (level 2). Cortisol values were entered in three separate models as dependent variables to estimate CAR, slope and total cortisol. In all models, time was centered at the waking sample. For daily slope and total cortisol we checked whether time 2 was significant and if so retained it in the models, if not, time was only included as a linear effect. All models included random intercepts at level 2 and were checked for potential confounders (age, sex, 7
antidepressants, other medication, awakening time, sleep duration, sleep quality, average number of cigarettes per day, number of previous episodes). Only confounders at p≤0.05 were retained in the respective models (sleep duration, sleep quality and habitual smoking for CAR, sex and antidepressant use for DCS, age and previous episodes for total cortisol). Preparatory analyses revealed that groups differed significantly in their overall log-cortisol levels at baseline (MBAT 2.63 (SE 0.05), PMR 2.50 (SE 0.05), F(1,75)=4.3, p=0.042), therefore we further controlled for person-level aggregated preintervention cortisol levels in all analyses. Multilevel models were estimated with Restricted Maximum Likelihood (REML). Therefore, analyses are based on the total sample (n=78). Data were
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analyzed using IBM SPSS version 23. 3. Results
Participant flow is displayed in the Consort flowchart (Supplementum S1). Of 243 screened
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individuals, n=165 did not meet the inclusion criteria, and n=55 declined to participate before randomization, mainly due to anticipated temporal overload linked to study participation. Therefore,
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n=78 remitted depressed participants (MBAT: n=39, PMR: n=39) were enrolled. Three patients per condition (7.7%) dropped out prematurely (see S1).
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Adherence to individual sessions was high in both groups. Among those who dropped out prematurely (n=6), three dropped out after session 1, one after session 3, and two after session 4.
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Among those who completed the trainings (n=72), two participants missed one session each. In total (including drop outs), 16 of 390 sessions were missed (4.1%). The high adherence rate was
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substantially attributable to the one-to-one session format that allowed to offer flexible alternative appointments if a participant was indisposed on short notice. Homework compliance, defined as the
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percentage of filled in diaries of a maximum of 24 practice days in total, reached 92.1%. As a limitation, there was no external validation of the number of sessions performed by participants. The overall AA-response rate for the subjective ratings was 82.2% (cf. Timm et al., 2018). The
overall compliance for cortisol assessments reached 87.5% (2867 of possible 3276 (7*6*78) probes were delivered). Table 1 displays baseline characteristics of participants. MBAT and PMR participants did not differ significantly on any of these baseline variables. 8
To examine treatment effects on CAR, slope and total cortisol, three separate models were performed estimating fixed effects of group, prepost status and time (for CAR) or time and time 2 (for slope and total cortisol) adjusted for confounders and for aggregated pre-intervention cortisol levels. In all models, interactions including group and prepost status were nonsignificant (CAR: group*prepost*time F(1,551)=0.06, p=0.808; slope: group*prepost*time2 F(1,2014)=2.25, p=0.133; total cortisol: group*prepost F(1,2053)=0.93, p=0.335). After removal of group status, prepost status was nonsignificant regarding CAR (prepost*time F(1,555)=1.23, p=0.269) and slope (prepost*time 2 F(1,2020)=1.57, p=0.211), whereas a significant prepost effect was identified for total cortisol
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(F(1,2053)=11.99, B=0.09, SE=0.03, p<0.001) indicating an increase from pre to post. A posthoc-test revealed that seasonality did not significantly affect total cortisol values (F(1,324)=0.23, p=0.634).
To examine whether changes in cortisol parameters were related to changes in subjective AA-
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variables, pre-post difference scores of aggregated means were calculated for negative affect and rumination, which were entered as level 2 predictors in the respective models. In the models for CAR
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and slope, the interactions including group, prepost status and change scores of negative affect and rumination were non-significant (CAR: group*prepost*time*negative affect change F(1,546)=0.58,
group*prepost*time2*negative
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p=0.448; CAR: group*prepost*time*rumination change F(1,546)=1.00, p=0.320; daily slope: affect
change
F(1,2009)=0.61,
p=0.436;
daily
slope:
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group*prepost*time2*rumination change F(1,2017)=0.14, p=0.705). In contrast, the models for total cortisol revealed significant interactions (group*prepost*negative affect change F(1,2012)=4.53,
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p=0.033; group*prepost*rumination change F(1,2025)=6.03, p=0.014). Figure 1A and 1B show these estimated interactions. Posthoc analyses per group revealed a marginally significant effect of negative
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affect change on change in cortisol for MBAT (prepost*negative affect change, F(1,1064)=3.03, p=0.082) indicating higher cortisol increase in participants with smaller decreases in negative affect compared to those with larger decreases while no such interaction was found for PMR (F(1,942)=1.65, p=0.200, see Fig. 1A). Furthermore, a significant effect of rumination change on cortisol change was observed for MBAT (prepost*rumination change, F(1,1071)=7.63, p=0.006). MBAT participants with larger decreases in rumination in contrast to those with smaller decreases showed no increase in
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cortisol from pre to post. No such interaction was found for PMR (F(1,952)=0.49, p=0.485, see Fig.1B).1 4. Discussion Consistent with previous research (Gex-Fabry et al., 2012) our study revealed no treatmentspecific or general change in CAR and daily cortisol slopes over the course of a 4-week MBAT versus PMR training. This may imply that these dynamic components of diurnal cortisol are quite stable and not responsive to the short intervention phase implemented in this study. In contrast, and contrary to our hypothesis, total cortisol increased from pre to post across
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groups. High levels of total cortisol output regularly indicate stressful periods, and total cortisol reflecting the average level of cortisol across the day has been found to be more responsive towards daily stressors than CAR and daily slope (Stawski et al., 2013). Notably, the only related study with
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recurrently depressed patients we are aware of (Gex-Fabry et al., 2012) showed exactly the same results. While these authors attributed the temporal cortisol increase to variations in seasonality, there
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was no seasonality effect on total cortisol in the present sample. Therefore, alternative explanations are conceivable. One possibility is that recurrent depression may per se be linked to increasing total
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cortisol levels over time, thereby reflecting accumulating stress levels that eventually could result in further relapses/recurrences. This idea is supported by our confounder analysis showing that the
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number of previous episodes positively predicted total cortisol (but not CAR and daily slope) and was therefore controlled in the respective model (see S1). However, these considerations are still
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speculative and require more systematic research in this high-risk group. Importantly, however, change in total cortisol was moderated by group and subjective
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improvement status in the present study. While total cortisol increased in PMR participants irrespective of subjective improvements, MBAT participants with larger decreases in negative affect and rumination maintained their initial cortisol levels, whereas those with lower improvement paralleled the PMR group by showing increased total cortisol from pre to post. Hence, MBAT appeared to buffer an increase in overall cortisol secretion over time, but only in those patients with 1
Including mean rumination change scores as a possible confounder in the model for negative affect and vice versa did not change the significance levels of respective models (group*prepost*negative affect changeF(1,1958)=4.58, p=0.032, group*prepost*rumination change F(1,1972)=5.96, p=0.015), indicating that both variables independently drove the relationship with cortisol.
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marked improvements in affective and cognitive daily life experiences constituting core elements for depressive relapses in the MBCT vulnerability model (Segal et al., 2013). Generally, these results point to a closer connection between psychological and physiological changes in MBAT, which is in line with theoretical assumptions of mindfulness interventions (e.g. Segal et al., 2013). The study has strengths and limitations. Strengths include the implementation of a randomized controlled trial and the application of PMR as an active control condition against MBAT, the repeated assessment of standard cortisol parameters (CAR, daily slope, and total cortisol) at pre- and postintervention, as recommended in the literature (cf. Adam & Kumari, 2009, Ryan et al., 2016), and
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the linking of cortisol outcomes to subjective daily life experiences. Limitations include the lack of electronic monitoring of the morning cortisol values, which we however tried to minimize through detailed instructions, as well as the lack of an objective measure for homework compliance. Further,
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the sample size was too small to further subdivide into subgroups with possible heterogeneous activation of the HPAA (cf. Gold, 2015).
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To conclude, this is the first RCT investigating effects of a short mindfulness-based versus active control treatment on changes in key diurnal cortisol parameters. Moreover, this is the first study
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investigating whether improvements in relevant subjective outcomes - as proposed by mindfulnessbased theory - predicted changes in respective cortisol outcomes. Our negative results regarding CAR
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and daily slopes warrant further research that should aim at identifying optimal treatment length of mindfulness-based interventions to enable beneficial effects on changes in dynamic components of
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diurnal cortisol to occur, but also to investigate whether these parameters are possibly more responsive to other components of mindfulness interventions not investigated in our study, such as meta-cognitive
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awareness or decentering. Observed increasing total cortisol levels in both training groups were unexpected and should be interpreted with care. However, since both Gex-Fabry et al. (2012) and the present study demonstrated such an increase in samples of recurrently depressed patients it appears worthwhile to address this issue more systematically in future longitudinal research. Finally, future research is required to replicate our findings on the buffering effect of MBAT on total cortisol increase in those patients who improved in relevant subjective outcomes. To our opinion, this will constitute an important step to increase knowledge on possible multiple but interconnected paths through which 11
mindfulness-based interventions might work. Generally, our study points to the relevance of including diurnal cortisol parameters as biomarkers in RCTs on mindfulness-based and other psychosocial interventions for recurrently depressed patients to be able to identify possible multi-faceted mechanisms involved in effective relapse prevention for this high-risk population. Role of the funding source This study was supported by the German Research Foundation (DFG, KU1464/4-2, KI576/12-2). The sponsor had no involvement in study design, data collection, analysis and interpretation of data, writing of the report, and in the decision to submit the article for publication.
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Declaration of interest None Conflict of Interest
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None
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Acknowledgement
The authors wish to thank all study participants and the trainers for delivering the interventions
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(Dr. M.Sc.Psych. A. Becker, M.Sc.Psych. S. Fenske, Dr. Dipl.-Psych. D. Mier, Dr. M.Sc.Psych. K.
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MBSR-trainer).
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Muszer, Dr. Dipl.-Psych. C. Paul, A. Rossa, MBSR-trainer, Dr. M.Sc.Psych. C. Sauer, J. Stern,
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Timm, C., Rachota-Ubl, B., Beddig, T., Zamoscik, V.E., Ebner-Priemer, U., Reinhard, I., Kirsch, P., Kuehner, C., 2018. Mindfulness-based attention training improves cognitive and affective
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processes in daily life in remitted patients with recurrent depression: a randomized controlled trial. Psychother Psychosom 87, 184-186. doi:10.1159/000488862
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Psychological Assessment 23, 258-267.. Wittchen, H., Zaudig, M., Fydrich, T., 1997. Structured clinical interview for DSM-IV - German
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version. Hogrefe, Göttingen.
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Figure 1. Estimated cortisol scores (ln nmol/l) during three days before (pre) and after (post) intervention (MBAT (n=39) vs. PMR (n=39)) in participants with high (+ 1 SD) versus low (- 1 SD) improvement in NA (Fig. 1A) and in participants with high (+ 1 SD) versus low (- 1 SD) improvement in RUM (Fig. 1B). Note. MBAT = Mindfulness Based Attention Training; PMR = Progressive Muscle Relaxation. NA_DIFF = difference score of aggregated negative affect prescore minus postscore; RUM_DIFF = difference score of aggregated rumination prescore minus postscore. Error bars represent standard error of the mean. Models include age, number of previous depressive episodes, time of assesments, time² of assesments and aggregated pre-intervention cortisol levels as covariates.
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Table 1. Baseline Characteristics of Participants. MBAT1 (n=39) PMR2 (n=39) Test statistic % / mean (SD) % / mean (SD)
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Demographic variables Age 36.7 (10.3) 39.8 (11.8) t=-1.23 .223 2 Gender (% women) 69.2% 71.8% Chi =.06 .804 2 Education (% > 10 years) 65.8% 82.1% Chi =2.65 .104 Clinical variables Duration of illness (years, 16.4 (10.1) 15.5 (11.8) t=0.41 .681 3 SCID-I ) Number of previous MDE4 4.6 (2.6) 4.2 (2.7) t=0.51 .612 (SCID-I3) Previous inpatient treatment 38.5% 41.0% Chi2=0.54 .817 2 Previous psychotherapy 66.7% 66.7% Chi =0.00 >.999 5 BDI-II at baseline 6.2 (6.9) 9.2 (10.8) t=-1.48 .143 Antidepressant medication at 12.8% 23.7% Chi2=1.53 .217 baseline 1 MBAT = Mindfulness-based attention training, 2PMR = Progressive muscle relaxation, 3SCID-I = Structured Clinical Interview for DSM-IV, 4MDE = Major Depression Episodes (DSM-IV, SKID-I), 5 BDI-II = Beck Depression Inventory-Revised.
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