Dopamine-Modulated Aversive Emotion Processing Fails in Alcohol-Dependent Patients

T. Kienast; F. Schlagenhauf; M. A. Rapp; J. Wrase; I. Daig; H.-G. Buchholz; M. N. Smolka; G. Gründer; Y. Kumakura; P. Cumming; K. Charlet; P. Bartenstein; A. R. Hariri; A. Heinz

doi:10.1055/s-0032-1331747

Pharmacopsychiatry, Table of Contents

Pharmacopsychiatry 2013; 46(04): 130-136
DOI: 10.1055/s-0032-1331747

Original Paper

Dopamine-Modulated Aversive Emotion Processing Fails in Alcohol-Dependent Patients

T. Kienast

¹Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité – Universitätsmedizin Berlin, Berlin, Germany

¹⁰Equal contributions

,

F. Schlagenhauf

¹Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité – Universitätsmedizin Berlin, Berlin, Germany

²Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany

¹⁰Equal contributions

,

M. A. Rapp

¹Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité – Universitätsmedizin Berlin, Berlin, Germany

,

J. Wrase

¹Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité – Universitätsmedizin Berlin, Berlin, Germany

,

I. Daig

³Institute of Medical Psychology, Charité – Universitätsmedizin Berlin, Berlin, Germany

,

H.-G. Buchholz

⁴Department of Nuclear Medicine, Johannes Gutenberg University of Mainz, Mainz, Germany

,

M. N. Smolka

⁵Section of Systems Neuroscience, Department of Psychiatry and Psychotherapy, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

,

G. Gründer

⁶Department of Psychiatry and Psychotherapy, RWTH Aachen University, Aachen, Germany

,

Y. Kumakura

⁷Department of Nuclear Medicine and Research Center for Advanced Science and Technology, Tokyo University, Tokyo, Japan

,

P. Cumming

⁸Department of Nuclear Medicine, Ludwig Maximilian University, Campus Gro hadern, Munich, Germany

,

K. Charlet

¹Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité – Universitätsmedizin Berlin, Berlin, Germany

,

P. Bartenstein

⁸Department of Nuclear Medicine, Ludwig Maximilian University, Campus Gro hadern, Munich, Germany

,

A. R. Hariri

⁹Department of Psychology and Neuroscience, Duke University, Durham, NC, USA

,

A. Heinz

¹Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité – Universitätsmedizin Berlin, Berlin, Germany

› Author Affiliations

Abstract

Introduction:

Negative mood states after alcohol detoxification may enhance the relapse risk. As recently shown in healthy volunteers, dopamine storage capacity (V _d) in the left amygdala was positively correlated with functional activation in the left amygdala and anterior cingulate cortex (ACC) during an emotional task; high functional connectivity between the amygdala and the ACC, a region important for emotion regulation, was associated with low trait anxiety. Based on these findings, we now tested whether detoxified alcohol-dependent patients have a disrupted modulation of the anterior cingulate cortex activation in response to aversive stimuli by amygdala dopamine. Furthermore, we asked whether disrupted functional coupling between amygdala and ACC during aversive processing is related to trait anxiety.

Methods:

We used combined 6-[¹⁸F]-fluoro-l-DOPA positron emission tomography (PET), functional magnetic resonance imaging (fMRI) and Spielberger’s state-trait anxiety questionnaire (STAI) in 11 male detoxified alcohol-dependent patients compared to 13 matched healthy controls.

Results:

Unlike healthy controls, patients showed no significant correlation between our PET metric for dopamine storage capacity (FDOPA V _d), in left amygdala and activation in left ACC. Moreover, the functional connectivity between amygdala and ACC during processing of aversive emotional stimuli was reduced in patients. Voxel-based morphometry did not reveal any discernible group differences in amygdala volume.

Discussion:

These results suggest that dopamine-modulated corticolimbic circuit function is important for responding to emotional information such that apparent functional deficits in this neuromodulatory circuitry may contribute to trait anxiety in alcohol-dependent patients.

Key words

alcoholism - amygdale - emotion - functional connectivity - neuroimaging

Full Text

References

References
1 Hartka E, Johnstone B, Leino E et al. A meta-analysis of depressive symptomatology and alcohol consumption over time. Br J Addict 1991; 86: 1283-1298
2 Heinz A, Mann K, Weinberger D. Serotonergic dysfunction, negative mood states, and response to alcohol. Alcohol Clin Exp Res 2001; 25: 487-495
3 Heinz A, Wrase J, Kahnt T et al. Brain activation elicited by affectively positive stimuli is associated with a lower risk of relapse in detoxified alcoholic subjects. Alcohol Clin Exp Res 2007; 31: 1138-1147
4 Kienast T, Hariri A, Schlagenhauf F et al. Dopamine in amygdala gates limbic processing of aversive stimuli in humans. Nat Neurosci 2008; 11: 1381-1382
5 Phelps E, LeDoux J. Contributions of the amygdala to emotion processing: from animal models to human behavior. Neuron 2005; 48: 175-187
6 Volkow N, Fowler J, Wang G-J et al. Role of dopamine, the frontal cortex and memory circuits in drug addiction: insight from imaging studies. Neurobiol Learning Memory 2002; 78: 610-624
7 Alcaro A, Huber R, Panksepp J. Behavioral functions of the mesolimbic dopaminergic system: an affective neuroethological perspective. Brain Res Rev 2007; 56: 283-321
8 Hyman S. Addiction: a disease of learning and memory. Am J Psychiatry 2005; 162: 1414-1422
9 Wrase J, Makris N, Braus D et al. Amygdala volume associated with alcohol abuse relapse and craving. Am J Psychiatry 2008; 165: 1179-1184
10 Skinner H, Sheu W. Reliability of alcohol use indices: the lifetime drinking history and the MAST. J Stud Alcohol 1982; 43: 1157-1170
11 Fagerström K. Measuring degree of physical dependence to tobacco smoking with reference to individualization of treatment. Addict Behav 1978; 3: 235-241
12 Cloninger C, Przybeck T, Svrakic D et al. The temperament and character inventory (TCI): a guide to its development and use. Washington University, St Louis, Missouri: Center for Psychobiology of Personality 1994;
13 First M, Spitzer R, Gibbon M et al. Structured clinical interview for DSM-IV personality disorders, (SCID-II). Washington, DC: American Psychiatric Press; 1997
14 First M, Spitzer R, Gibbon M et al. Structured clinical interview for DSM-IV-TR axis I disorders, research version, patient edition with psychotic screen (SCID-I/P W/PSY SCREEN). New York: New York State Psychiatric Institute. NY: Biometrics Research; 2001
15 Spielberger C, Gorsuch R, Lushene P et al. Manual for the State-Trait Anxiety Inventory (form Y). Paolo Alto, USA: Consulting Psychologists Press; 1983
16 Kumakura Y, Cumming P, Vernaleken I et al. Elevated [¹⁸F]-fluorodopamine turnover in brain of patients with schizophrenia: an [¹⁸F]-fluorodopa/positron emission tomography study. J Neurosci 2007; 27: 8080-8087
17 Martin W, Palmer M, Patlak C et al. Nigrostriatal function in humans studied with positron emission tomography. Ann Neurol 1989; 26: 535-542
18 Maldjian J, Laurienti P, Kraft R. et al. An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fmri data sets. NeuroImage 2003; 19: 1233-1239 (WFU Pickatlas, version 3.0.3)
19 Tzourio-Mazoyer N, Landeau B, Papathanassiou D et al. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage 2002; 15: 273-289
20 Heinz A, Braus D, Smolka M et al. Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter. Nat Neurosc 2005; 8: 20-21
21 Smolka M, Schumann G, Wrase J et al. Catechol-O-methyltransferase val158met genotype affects processing of emotional stimuli in the amygdala and prefrontal cortex. J Neurosci 2005; 25: 836-842
22 Taylor S, Phan K, Decker L et al. Subjective rating of emotionally salient stimuli modulates neural activity. NeuroImage 2003; 18: 650-659
23 Bradley M, Lang P. Measuring emotion: the Self-Assessment Manikin and the Semantic Differential. J Behav Ther Exp Psychiatry 1994; 25: 49-59
24 Friston K, Holmes A, Worsley K et al. Statistical parametric maps in functional imaging: a general linear approach. Human Brain Mapping 1995; 2: 189-210
25 Friston K, Buechel C, Fink G et al. Psychophysiological and modulatory interactions in neuroimaging. NeuroImage 1997; 6: 218-229
26 Gitelman D, Penny W, Ashburner J et al. Modeling regional and psychophysiologic interactions in fMRI: the importance of hemodynamic deconvolution. NeuroImage 2003; 19: 200-207
27 O’Reilly JX, Woolrich MW, Behrens TE et al. Tools of the trade: psychophysiological interactions and functional connectivity. Soc Cogn Affect Neurosci 2012; 7: 604-609
28 Good C, Johnsrude I, Ashburner J et al. A voxel-based morphometric study of ageing in 465 normal adult human brains. NeuroImage 2001; 14: 21-36
29 Pezawas L, Meyer-Lindenberg A, Drabant E et al. 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nat Neurosc 2005; 8: 828-834
30 Friedel E, Schlagenhauf F, Sterzer P et al. 5-HTT genotype effect on prefrontal-amygdala coupling differs between major depression and controls. Psychopharmacology 2009; 205: 261-271
31 Heinz A, Lichtenberg-Kraag B, Baum S et al. Evidence for prolonged recovery of dopaminergic transmission after detoxification in alcoholics with poor treatment outcome. J Neural Transm Gen 1995; 102: 149-157
32 Cumming P, Ljubic-Thibal V, Laliberté C et al. The effect of unilateral neurotoxic lesions to serotonin fibres in the medial forebrain bundle on the metabolism of [³H]DOPA in the telencephalon of the living rat. Brain Res 1997; 747: 60-69