Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Psychiatry
Published in: BMC Psychiatry 1/2017

Open Access 01-12-2017 | Study protocol

From the neurobiological basis of comorbid alcohol dependence and depression to psychological treatment strategies: study protocol of a randomized controlled trial

Authors: Alena Becker, Anna M. Ehret, Peter Kirsch

Published in: BMC Psychiatry | Issue 1/2017

Login to get access

Abstract

Background

Alcohol use disorder and depression occur commonly in the community. Even though this high-prevalence comorbidity is associated with poorer posttreatment outcomes and greater utilization of costly treatment services, existing treatment trials often exclude patients with comorbid depressive and alcohol use disorders. Past research suggests that symptoms such as craving and anhedonia might be associated with alterations within the reward circuit, while emotion regulation deficits are related to disruptions within the default mode network. The aim of this clinical neuroimaging study is to transfer previous research about the reward circuit and default mode network underlying alcohol use disorder and depression to achieve a better understanding of neural signatures characterizing their comorbidity. In addition, the neurobiological results will be used to test whether two psychotherapeutic intervention programs, mindfulness-based training and behavioral activation training, are able to positively influence the identified pathomechanisms.

Methods

By means of functional magnetic resonance imaging (fMRI), 60 comorbid alcohol dependent and depressed patients are compared to 30 patients with depression only, 30 patients with alcohol use disorder only and 30 healthy control participants. Comorbid patients are randomized to either receive a behavioral activation or mindfulness based training and asked to participate in a second fMRI session and 3 month follow-up assessment. Thereby, we plan to explore whether these brief group psychotherapeutic intervention programs are able to positively influence the identified neurobiological pathomechanisms. The primary outcomes are reward and default mode network activity and connectivity evoked by paradigms measuring different facets of reward and emotion processing. Secondary outcome measures include craving and depression scores, as well as relapse rates. Predictors include participants’ characteristics, personality traits and indicators of mental health.

Discussion

The objective of the project is to identify common and/or distinct neural signatures underlying the comorbidity of alcohol dependence and depression. If the neurobiological understanding of alcohol addiction and depression is improved, this could potentially serve as a key predictor of treatment response to specific types of behavioral or mindfulness therapies hypothesized to alter reward and resting state systems.

Trial registration

German Clinical Trial Register DRKS00010249. The trial was registered January 23th 2017.
Literature
1.
Bott K, Meyer C, Rumpf HJ, Hapke U, John U. Psychiatric disorders among at-risk consumers of alcohol in the general population. J Stud Alcohol. 2005;66(2):246–53.CrossRefPubMed
2.
Meyer C, Rumpf HJ, Hapke U, Dilling H, John U. Prevalence of alcohol consumption, abuse and dependence in a country with high per capita consumption: findings from the German TACOS study. Transitions in Alcohol Consumption and Smoking. Soc Psychiatry Psychiatr Epidemiol. 2000;35(12):539–47.CrossRefPubMed
3.
Grant BF, Hasin DS, Dawson DA. The relationship between DSM-IV alcohol use disorders and DSM-IV major depression: examination of the primary-secondary distinction in a general population sample. J Affect Disord. 1996;38(2–3):113–28.CrossRefPubMed
4.
Der-Avakian A, Markou A. The neurobiology of anhedonia and other reward-related deficits. Trends Neurosci. 2012;35(1):68–77.CrossRefPubMed
5.
Ubl B, Kuehner C, Kirsch P, Ruttorf M, Diener C, Flor H. Altered neural reward and loss processing and prediction error signalling in depression. Soc Cogn Affect Neurosci. 2015;
6.
Epstein J, Pan H, Kocsis JH, Yang Y, Butler T, Chusid J, Hochberg H, Murrough J, Strohmayer E, Stern E, et al. Lack of ventral striatal response to positive stimuli in depressed versus normal subjects. Am J Psychiatry. 2006;163(10):1784–90.CrossRefPubMed
7.
Keedwell PA, Andrew C, Williams SC, Brammer MJ, Phillips ML. The neural correlates of anhedonia in major depressive disorder. Biol Psychiatry. 2005;58(11):843–53.CrossRefPubMed
8.
Forbes EE, Dahl RE. Research Review: altered reward function in adolescent depression: what, when and how? J Child Psychol Psychiatry. 2012;53(1):3–15.CrossRefPubMed
9.
Smoski MJ, Felder J, Bizzell J, Green SR, Ernst M, Lynch TR, Dichter GS. fMRI of alterations in reward selection, anticipation, and feedback in major depressive disorder. J Affect Disord. 2009;118(1–3):69–78.CrossRefPubMedPubMedCentral
10.
Hagele C, Schlagenhauf F, Rapp M, Sterzer P, Beck A, Bermpohl F, Stoy M, Strohle A, Wittchen HU, Dolan RJ, et al. Dimensional psychiatry: reward dysfunction and depressive mood across psychiatric disorders. Psychopharmacology. 2015;232(2):331–41.CrossRefPubMed
11.
Dunlop BW, Nemeroff CB. The role of dopamine in the pathophysiology of depression. Arch Gen Psychiatry. 2007;64(3):327–37.CrossRefPubMed
12.
Hasler G, Drevets WC, Manji HK, Charney DS. Discovering endophenotypes for major depression. Neuropsychopharmacology. 2004;29(10):1765–81.CrossRefPubMed
13.
Knutson B, Bhanji JP, Cooney RE, Atlas LY, Gotlib IH. Neural responses to monetary incentives in major depression. Biol Psychiatry. 2008;63(7):686–92.CrossRefPubMed
14.
Stoy M, Schlagenhauf F, Sterzer P, Bermpohl F, Hagele C, Suchotzki K, Schmack K, Wrase J, Ricken R, Knutson B, et al. Hyporeactivity of ventral striatum towards incentive stimuli in unmedicated depressed patients normalizes after treatment with escitalopram. J Psychopharmacol. 2012;26(5):677–88.CrossRefPubMed
15.
Pizzagalli DA, Holmes AJ, Dillon DG, Goetz EL, Birk JL, Bogdan R, Dougherty DD, Iosifescu DV, Rauch SL, Fava M. Reduced caudate and nucleus accumbens response to rewards in unmedicated individuals with major depressive disorder. Am J Psychiatry. 2009;166(6):702–10.CrossRefPubMedPubMedCentral
16.
Knutson B, Cooper JC. Functional magnetic resonance imaging of reward prediction. Curr Opin Neurobiol. 2005;18(4):411–7.CrossRef
17.
McClure SM, York MK, Montague PR. The neural substrates of reward processing in humans: the modern role of FMRI. Neuroscientist. 2004;10(3):260–8.CrossRefPubMed
18.
19.
Schacht JP, Anton RF, Myrick H. Functional neuroimaging studies of alcohol cue reactivity: a quantitative meta-analysis and systematic review. Addict Biol. 2013;18(1):121–33.CrossRefPubMed
20.
Goldstein RZ, Volkow ND. Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications. Nat Rev Neurosci. 2011;12(11):652–69.CrossRefPubMedPubMedCentral
21.
Kirsch M, Gruber I, Ruf M, Kiefer F, Kirsch P. Real-time functional magnetic resonance imaging neurofeedback can reduce striatal cue-reactivity to alcohol stimuli. Addict Biol. 2015;
22.
Volkow ND, Wang GJ, Fowler JS, Tomasi D, Telang F, Baler R. Addiction: decreased reward sensitivity and increased expectation sensitivity conspire to overwhelm the brain's control circuit. BioEssays. 2010;32(9):748–55.CrossRefPubMedPubMedCentral
23.
Beck A, Schlagenhauf F, Wustenberg T, Hein J, Kienast T, Kahnt T, Schmack K, Hagele C, Knutson B, Heinz A, et al. Ventral striatal activation during reward anticipation correlates with impulsivity in alcoholics. Biol Psychiatry. 2009;66(8):734–42.CrossRefPubMed
24.
Wrase J, Schlagenhauf F, Kienast T, Wustenberg T, Bermpohl F, Kahnt T, Beck A, Strohle A, Juckel G, Knutson B, et al. Dysfunction of reward processing correlates with alcohol craving in detoxified alcoholics. NeuroImage. 2007;35(2):787–94.CrossRefPubMed
25.
Becker A, Kirsch M, Gerchen MF, Kiefer, F, Kirsch P. Striatal activation and frontostriatal connectivity during non-drug reward anticipation in alcohol dependence. Addict Biol. 2017;22:833–43. doi:10.1111/adb.12352.CrossRefPubMed
26.
Wang L, Hermens DF, Hickie IB, Lagopoulos J. A systematic review of resting-state functional-MRI studies in major depression. J Affect Disord. 2012;142(1–3):6–12.CrossRefPubMed
27.
Woodward ND, Cascio CJ. Resting-State Functional Connectivity in Psychiatric Disorders. JAMA Psychiat. 2015;72(8):743–4.CrossRef
28.
Berman MG, Peltier S, Nee DE, Kross E, Deldin PJ, Jonides J. Depression, rumination and the default network. Soc Cogn Affect Neurosci. 2011;6(5):548–55.CrossRefPubMed
29.
Hamilton JP, Furman DJ, Chang C, Thomason ME, Dennis E, Gotlib IH. Default-mode and task-positive network activity in major depressive disorder: implications for adaptive and maladaptive rumination. Biol Psychiatry. 2011;70(4):327–33.CrossRefPubMedPubMedCentral
30.
Nolen-Hoeksema S, Wisco BE, Lyubomirsky S. Rethinking Rumination. Perspect Psychol Sci. 2008;3(5):400–24.CrossRefPubMed
31.
Caselli G, Ferretti C, Leoni M, Rebecchi D, Rovetto F, Spada MM. Rumination as a predictor of drinking behaviour in alcohol abusers: a prospective study. Addiction. 2010;105(6):1041–8.CrossRefPubMed
32.
Zamoscik V, Huffziger S, Ebner-Priemer U, Kuehner C, Kirsch P. Increased involvement of the parahippocampal gyri in a sad mood predicts future depressive symptoms. Soc Cogn Affect Neurosci. 2014;9(12):2034–40.CrossRefPubMedPubMedCentral
33.
Zhu X, Cortes CR, Mathur K, Tomasi D, Momenan R. Model-free functional connectivity and impulsivity correlates of alcohol dependence: a resting-state study. Addict Biol. 2015;
34.
Camchong J, Stenger A, Fein G. Resting-state synchrony in long-term abstinent alcoholics. Alcohol Clin Exp Res. 2013;37(1):75–85.CrossRefPubMed
35.
Muller-Oehring EM, Jung YC, Pfefferbaum A, Sullivan EV, Schulte T. The Resting Brain of Alcoholics. Cereb Cortex. 2014;
36.
Chanraud S, Pitel AL, Pfefferbaum A, Sullivan EV. Disruption of functional connectivity of the default-mode network in alcoholism. Cereb Cortex. 2011;21(10):2272–81.CrossRefPubMedPubMedCentral
37.
Camchong J, Stenger A, Fein G. Resting-state synchrony during early alcohol abstinence can predict subsequent relapse. Cereb Cortex. 2013;23(9):2086–99.CrossRefPubMed
38.
Feldstein Ewing SW, Filbey FM, Sabbineni A, Chandler LD, Hutchison KE. How psychosocial alcohol interventions work: a preliminary look at what FMRI can tell us. Alcohol Clin Exp Res. 2011;35(4):643–51.CrossRefPubMedPubMedCentral
39.
Fu CH, Williams SC, Cleare AJ, Scott J, Mitterschiffthaler MT, Walsh ND, Donaldson C, Suckling J, Andrew C, Steiner H, et al. Neural responses to sad facial expressions in major depression following cognitive behavioral therapy. Biol Psychiatry. 2008;64(6):505–12.CrossRefPubMed
40.
Siegle GJ, Carter CS, Thase ME. Use of FMRI to predict recovery from unipolar depression with cognitive behavior therapy. Am J Psychiatry. 2006;163(4):735–8.CrossRefPubMed
41.
Dichter GS, Felder JN, Petty C, Bizzell J, Ernst M, Smoski MJ. The effects of psychotherapy on neural responses to rewards in major depression. Biol Psychiatry. 2009;66(9):886–97.CrossRefPubMedPubMedCentral
42.
Crowther A, Smoski MJ, Minkel J, Moore T, Gibbs D, Petty C, Bizzell J, Schiller CE, Sideris J, Carl H, et al. Resting-state connectivity predictors of response to psychotherapy in major depressive disorder. Neuropsychopharmacology. 2015;40(7):1659–73.CrossRefPubMedPubMedCentral
43.
Chiesa A, Brambilla P, Serretti A. Neuro-imaging of mindfulness meditations: implications for clinical practice. Epidemiol Psychiatr Sci. 2011;20(2):205–10.CrossRefPubMed
44.
Holzel BK, Carmody J, Evans KC, Hoge EA, Dusek JA, Morgan L, Pitman RK, Lazar SW. Stress reduction correlates with structural changes in the amygdala. Soc Cogn Affect Neurosci. 2010;5(1):11–7.CrossRefPubMed
45.
Kozasa EH, Radvany J, Barreiros MA, Leite JR, Amaro E Jr. Preliminary functional magnetic resonance imaging Stroop task results before and after a Zen meditation retreat. Psychiatry Clin Neurosci. 2008;62(3):366.CrossRefPubMed
46.
Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39(2):175–91.CrossRefPubMed
47.
Hopko DR, Lejuez CW, Ruggiero KJ, Eifert GH. Contemporary behavioral activation treatments for depression: procedures, principles, and progress. Clin Psychol Rev. 2003;23(5):699–717.CrossRefPubMed
48.
Lejuez CW, Hopko DR, Hopko SD. A brief behavioral activation treatment for depression. Treatment manual. Behav Modif. 2001;25(2):255–86.CrossRefPubMed
49.
Bowen S, Chawla N, Witkiewitz K. Mindfulness-based relapse prevention for addictive behaviors. Mindfulness-Based Treatment Approaches: Clinician's Guide to Evidence Base and Applications. 2014;141.
50.
Morgan D: Mindfulness-based cognitive therapy for depression: A new approach to preventing relapse. In.: Taylor & Francis; 2003.
51.
Deutsche Forschungsgemeinschaft (DFG). Sicherung guter wissenschaftlicher Praxis, in Sicherung Guter Wissenschaftlicher Praxis: Empfehlungen der Kommission “Selbstkontrolle in der Wissenschaft”. Weinheim: Wiley-VCH Verlag GmbH & Co. KGaA; 2013. doi:10.​1002/​9783527679188.​oth1.
52.
Kirsch P, Schienle A, Stark R, Sammer G, Blecker C, Walter B, Ott U, Burkart J, Vaitl D. Anticipation of reward in a nonaversive differential conditioning paradigm and the brain reward system: an event-related fMRI study. NeuroImage. 2003;20(2):1086–95.CrossRefPubMed
53.
Plichta MM, Schwarz AJ, Grimm O, Morgen K, Mier D, Haddad L, Gerdes AB, Sauer C, Tost H, Esslinger C, et al. Test-retest reliability of evoked BOLD signals from a cognitive-emotive fMRI test battery. NeuroImage. 2012;60(3):1746–58.CrossRefPubMed
54.
Wehrum-Osinsky S, Klucken T, Kagerer S, Walter B, Hermann A, Stark R. At the second glance: stability of neural responses toward visual sexual stimuli. J Sex Med. 2014;11(11):2720–37.CrossRefPubMed
55.
Power JD, Barnes KA, Snyder AZ, Schlaggar BL, Petersen SE. Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. NeuroImage. 2012;59(3):2142–54.CrossRefPubMed
56.
Gerchen MF, Bernal-Casas D, Kirsch P. Analyzing task-dependent brain network changes by whole-brain psychophysiological interactions: a comparison to conventional analysis. Hum Brain Mapp. 2014;35(10):5071–82.CrossRefPubMed
Metadata
Title
From the neurobiological basis of comorbid alcohol dependence and depression to psychological treatment strategies: study protocol of a randomized controlled trial
Authors
Alena Becker
Anna M. Ehret
Peter Kirsch
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Psychiatry / Issue 1/2017
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/s12888-017-1324-0

Other articles of this Issue 1/2017

BMC Psychiatry 1/2017 Go to the issue

Research article

Childhood neglect predicts the course of major depression in a tertiary care sample: a follow-up study

Research article

Suicide attempts in U.S. Army combat arms, special forces and combat medics

Research article

Prevalence of psychiatric morbidity in a community sample in Western Kenya

Research article

Perceptions of problem-drinker patients’ family members about their own hazardous-drinking behaviours in Chinese general hospitals: a qualitative study

Research article

Suicide risk among prisoners in French Guiana: prevalence and predictive factors

Research article

Lifetime prevalence of mental disorders among first and second generation individuals with Turkish migration backgrounds in Germany