Maintaining Mechanisms of Chronic Depression and Their Changeability (GetWell)

Maintaining Mechanisms of Chronic Depression and Their Changeability: the Role of Discrepancy-based Processing

Despite considerable progress in the understanding of depression, the treatment of those who have entered a chronic course of the disorder still represents a major challenge. In order to develop more effective interventions it is important to learn more about maintaining mechanisms and the ways in which these can be addressed. Recent research has outlined aberrations in neurophysiological parameters that may serve as risk factors underlying tendencies to engage in maladaptive responses to negative mood, and that may be particularly pronounced in patients with chronic depression. Initial evidence suggests that such deficits may not be easily amenable through established treatments. The current study investigated whether mental training using mindfulness mediation, as compared to an active control training, could alter these parameters in chronically depressed patients.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Behavioral: Brief Mindfulness Training; Behavioral: Resting Control Training

Detailed Description

Persistent engagement in maladaptive patterns of thinking is a hallmark of depression. In those who suffer from a chronic course of the disorders, tendencies towards engagement in such patterns of thinking are likely to have become habitual and automatic in nature. Recent research has begun to elucidate potential cognitive and neurophysiological bases of such persistence. There is evidence that depressed patients show significant deficits in performance monitoring (Weinberg, Dieterich, & Riesel, 2015). Research on error-related negativity (ERN), a signal that occurs briefly after commission of an error, has reported significant aberrations in depressed suggesting deficits at the early stages of processing discrepancies. Deficits in ERN have been suggested to serve as an endophenotype for depression and psychopathology more generally (Manoach & Agam, 2013). Preliminary findings suggest that deficits remain even when symptoms are reduced following established treatments. Similarly, there is evidence for increased tendencies to elaborate negative information as evidenced by stronger late positive potentials (LPP; Auerbach, Stanton, Proudfit, & Pizzagalli, 2015) and an increased rigidity of spontaneous activity of the brain during rest as indicated by increased long-range temporal correlations of spontaneous brain oscillations (LRTC; Bornas et al., 2013).

Interventions using mental training may be particularly suited to address these aberrations. Indeed even brief training in mindfulness has been found to have significant neuroplastic effects (Tang et al., 2010) The aim of the current study was therefore to investigate the effects of a brief intervention using training in mindfulness meditation on the above listed parameters. Chronically depressed patients were randomly allocated to receive either a two-week mindfulness training or a resting control training. EEG was measured before and after the intervention along with self-reports of current symptoms and resilience/vulnerability factors. We expected the mindfulness training to have significantly stronger effects on ERN, LPP, and LRTC than the resting control training.

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• a current diagnosis of Major Depression as assessed by Structured Clinical Interview for DSM IV (First, Spitzer, Gibbon, & Williams, 2002)
• a lifetime history of depression with onset before age 19 and either chronic persistence of symptoms or a history of at least three previous episodes of depression, two of which needed to have occurred during the last two years
• self-reported severity of current symptoms on a clinical level as indicated by Beck Depression Inventory-II (Beck, Steer, & Brown, 1996) scores above 19
• age 25 to 60 thus excluding cases of late-onset depression, and e) fluency in spoken and written German.

Exclusion Criteria:

• history of psychosis or mania, current eating disorder, OCD, current self-harm, current substance abuse or dependence
• history of traumatic brain injury
• current treatment with CBT
• We allowed patients who were currently taking antidepressants into the study provided that the medication had not been changed during the last four weeks before entry into the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brief Mindfulness Training; The brief mindfulness training comprised of three 1.5-hour weekly individual sessions and included intensive daily home practice. Participants were asked to engage in formal meditation practice for about 25 minutes twice per day on six out of seven days of each week using recorded guided meditations. Practices were shorter in duration than the practices in Mindfulness-Based Cognitive Therapy (MBCT, Segal et al., 2002) in order to allow for more flexibility in scheduling the practices, but followed the standard sequence of mindfulness-based interventions.	Behavioral: Brief Mindfulness Training; Brief mindfulness training comprising of three weekly individual sessions and daily guided meditation home practice; Other Names: Mindfulness Intervention
Active Comparator: Resting Control Training; The resting control training comprised of three 1.5-hour weekly individual sessions and included intensive daily home practice. Participants were asked to schedule regular rest periods as a means of deliberately retreating from the activities of the day. Length and frequency of the rest periods mirrored the time demands of the meditation training. Participants received a plausible rationale for the control training that linked acute depression to stress and suggested rest, relaxation, and disengagement from negative thinking as an initial and preliminary step towards recovery.	Behavioral: Resting Control Training; Brief resting control training comprising of three weekly individual sessions and daily home practice consisting of resting periods; Other Names: Resting Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Error-related negativity	Event-related potential (EEG)	Two weeks
Long-range temporal correlations of theta oscillations in resting EEG	Resting EEG	Two weeks
Late positive potentials	Event-related potential (EEG)	Two weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of state mindfulness	Self-report	Two weeks
Interoceptive awareness	Self-report	Two weeks
Levels of depressive symptoms	Self-report	Two weeks
Ruminative tendencies	Self-report	Two weeks

Collaborators and Investigators

• Sponsor: Freie Universität Berlin
• Collaborators: Charite University, Berlin, Germany
• Investigators: Principal Investigator: Thorsten Barnhofer, PhD, Freie Universität Berlin

Publications and helpful links

General Publications

• Auerbach RP, Stanton CH, Proudfit GH, Pizzagalli DA. Self-referential processing in depressed adolescents: A high-density event-related potential study. J Abnorm Psychol. 2015 May;124(2):233-45. doi: 10.1037/abn0000023. Epub 2015 Feb 2.
• Bornas, X., Noguera, M., Balle, M., Morillas-Romero, A., Aguayo-Siquier, B., Tortella-Feliu, M., & Llabrés, J. (2013). Long-Range Temporal Correlations in Resting EEG. Journal of Psychophysiology, 27(2), 60-66. doi:10.1027/0269-8803/a000087
• Manoach DS, Agam Y. Neural markers of errors as endophenotypes in neuropsychiatric disorders. Front Hum Neurosci. 2013 Jul 18;7:350. doi: 10.3389/fnhum.2013.00350. eCollection 2013.
• Tang YY, Lu Q, Geng X, Stein EA, Yang Y, Posner MI. Short-term meditation induces white matter changes in the anterior cingulate. Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15649-52. doi: 10.1073/pnas.1011043107. Epub 2010 Aug 16.
• Weinberg A, Dieterich R, Riesel A. Error-related brain activity in the age of RDoC: A review of the literature. Int J Psychophysiol. 2015 Nov;98(2 Pt 2):276-299. doi: 10.1016/j.ijpsycho.2015.02.029. Epub 2015 Mar 4.
• Fissler, M. Winnebeck, E., Schroeter, T. A., Gummersbach, M., Huntexburg, J. M., Gaertner, M., & Barnhofer, T. (in press). An Investigation of the Effects of Brief Mindfulness Training on Self-Reported Interoceptive Awareness, the Ability to Decenter, and Their Role in the Reduction of Depressive Symptoms. Mindfulness.
• Barnhofer T, Reess TJ, Fissler M, Winnebeck E, Grimm S, Gartner M, Fan Y, Huntenburg JM, Schroeter TA, Gummersbach M, Bajbouj M, Holzel BK. Effects of Mindfulness Training on Emotion Regulation in Patients With Depression: Reduced Dorsolateral Prefrontal Cortex Activation Indexes Early Beneficial Changes. Psychosom Med. 2021 Jul-Aug 01;83(6):579-591. doi: 10.1097/PSY.0000000000000955.

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: June 11, 2016
• First Submitted That Met QC Criteria: June 15, 2016
• First Posted (Estimate): June 16, 2016

Study Record Updates

• Last Update Posted (Estimate): June 16, 2016
• Last Update Submitted That Met QC Criteria: June 15, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: mindfulness; EEG; error-related negativity; late positive potential; long-range temporal correlations
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: BA2255/3-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO