Clinical trial NCT02801513: Maintaining Mechanisms of Chronic Depression and Their Changeability
Official title: Maintaining Mechanisms of Chronic Depression and Their Changeability: the Role of Discrepancy-based Processing
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Major Depressive Disorder
Keywords: mindfulness
EEG
error-related negativity
late positive potential
long-range temporal correlations
Lead sponsor: Freie Universität Berlin
Sponsor class: OTHER
Collaborators: name: Charite University, Berlin, Germany
First posted: 2016-06-16
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Error-related negativity
timeFrame: Two weeks
measure: Long-range temporal correlations of theta oscillations in resting EEG
timeFrame: Two weeks
measure: Late positive potentials
timeFrame: Two weeks
Secondary outcomes:
measure: Levels of state mindfulness
timeFrame: Two weeks
measure: Interoceptive awareness
timeFrame: Two weeks
measure: Levels of depressive symptoms
timeFrame: Two weeks
measure: Ruminative tendencies
timeFrame: Two weeks
Other outcomes:
Locations:
Study officials:
affiliation: Freie Universität Berlin
name: Thorsten Barnhofer, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.