Subscribe to RSS
DOI: 10.1055/s-2001-15184
Psychopathological Correlates of Reduced Dopamine Receptor Sensitivity in Depression, Schizophrenia, and Opiate and Alcohol Dependence[1] [2]
Publication History
Publication Date:
31 December 2001 (online)
A dysfunction of central dopaminergic neurotransmission has been found in various neuropsychiatric diseases, and may be associated with a common psychopathological correlate. One hypothesis suggests that dopaminergic stimulation of the brain reward system reinforces behavior because it is experienced as pleasurable, and that dopaminergic dysfunction leads to anhedonia, the inability to experience pleasure. An alternative hypothesis assumes that dopaminergic stimulation does not promote pleasure or “liking” of a reward but rather mediates “wanting” of a reward, and suggests that dopaminergic dysfunction is associated with a failure to be motivated by stimuli that indicate reward. We measured negative symptoms, psychomotor slowing and dopamine receptor sensitivity in twelve drug-free patients with major depression, seventeen alcohol-dependent and sixteen opiate-dependent patients, ten schizophrenics with neuroleptic medication, and ten healthy controls. The sensitivity of central dopamine receptors was assessed with the growth hormone response to apomorphine application. Psychomotor slowing was measured in a reaction-time test and anhedonia and other negative symptoms were assessed with self-rating scales [7] and the Scale for the Assessment of Negative Symptoms. Patients with major depression, alcohol dependence and neuroleptic medication displayed a reduced sensitivity of central dopamine receptors compared to control subjects. Anhedonia was not a common correlate of dopamine receptor dysfunction. Instead, affective flattening was associated with both dopamine receptor sensitivity and psychomotor slowing. Our findings thus do not support the anhedonia hypothesis of central dopaminergic dysfunction. Rather, affective flattening may result from the lack of an emotional response towards reward-indicating stimuli. These findings indicate that patients with dopaminergic dysfunction are not unable to experience pleasure, but may fail to be motivated by environmental stimuli to seek reward.
1 Supported in part by the DFG (Az He: 2597/1-1) and by a research grant of Wander Pharma
2 Assessment of the psychopathological correlates of dopamine receptor sensitivity among patients with schizophrenia and major depression is part of a doctoral thesis by J. Patzer; among patients with alcohol- and opiate-dependence by B. Nolte-Zenker.
References
- 1 Alexander G E, DeLong M R, Strick P L. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Ann Rev Neurosci. 1986; 9 357-381
- 2 Andreason N C. Negative symptoms in schizophrenia. Definition and reliability. Arch Gen Psychiat. 1982; 39 784-788
- 3 Ansseau M, Von Freckell R, Cerfontaine J L, Papart P, Franck G, Timsit-Berthier M, Geenen V, Legros J J. Blunted response of growth hormone to clonidine and apomorphine in endogenous depression. Br J Psychiat. 1988; 153 65-71
- 4 Balldin J I, Berggren U C, Lindsted G. Neuroendocrine evidence for reduced dopamine receptor sensitivity in alcoholism. Alc Clin Exp Res. 1992; 16 71-74
- 5 Bermanzohn P C, Siris S G. Akinesia: a syndrome common to parkinsonism, retarded depression, and negative symptoms of schizophrenia. Compr Psychiat. 1992; 33 221-232
- 6 Berridge K C, Robinson T E. What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience?. Brain Res Rev. 1998; 28 309-369
- 7 Chapman L J, Edell W S, Chapman J P. Physical anhedonia, perceptual aberration, and psychosis proneness. Schiz Bull. 1980; 6 639-653
-
8 Chapman L J, Chapman J P.
Psychosis proneness. In: Alpert M (ed) Controversies in schizophrenia. New York; Guilford Press 1985: 157-174 - 9 Dettling M, Heinz A, Dufeu P, Rommelspacher H, Graf K J, Schmidt L G. Dopaminergic responsitivity in alcoholism - trait, state or residual marker?. Am J Psychiat. 1995; 152 1317-1321
- 10 D’Haenen H, Bossuyt A. Dopamine D2 receptors in depression measured with SPECT. Biol Psychiatry. 1994; 35 128-132
- 11 Di Chiara G, Imperato A. Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci. 1988; 85 5274-5278
- 12 Di C hiara. The role of dopamine in drug-abuse viewed from the perspective of its role in motivation. Drug Alc Dependence. 1995; 38 95-137
- 13 Ebert D, Feistel H, Barocka A, Kaschka W, Pirner A. Dopamine and depression - D2 receptor SPECT before and after antidepressant therapy. Psychopharmacology. 1996; 126 91-94
- 14 Farde F, Wiesel F A, Halldin C, Sedvall G. Central D2-dopamine receptor occupancy in patients treated with antipsychotic drugs. Arch Gen Psychiat. 1988; 45 71-76
- 15 Farde L, Nordstrom A L, Wiesel F A, Pauli S, Halldin C, Sedvall G. Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine: relation to extrapyramidal side effects. Arch Gen Psychiat. 1992; 49 538-544
- 16 Ferrier I N, Johnstone E C, Crow T J. Hormonal effects of apomorphine in schizophrenia. Br J Psychiat. 1984; 144 349-357
- 17 Guy W, Ban T A. The AMDP-System. Manual for the Assessment and Documentation of Psychopathology. Berlin, Heidelberg, New York; Springer 1982
- 18 Hamilton M A. A rating scale for depression. J Neurol Neurosurgery Psychiat. 1960; 23 56-62
- 19 Harrow M, Yonan C A, Sands J R, Marengo J. Depression in schizophrenia: are neuroleptics, akinesia, or anhedonia involved?. Schiz Bull. 1994; 20 327-338
- 20 Heinz A, Schmidt L G, Reischies F M. Anhedonia in schizophrenic, depressed, or alcohol-dependent patients: neurobiological correlates. Pharmacopsychiatry. 1994; 27 (suppl) 7-10
- 21 Heinz A, Lichtenberg-Kraag B, Sällström Baum S, Gräf K, Krüger F, Dettling M, Rommelspacher H. Evidence for prolonged recovery of dopaminergic transmission in alcoholics with poor treatment outcome. J Neural Transm. 1995; 102 149-158
- 22 Heinz A, Dufeu P, Kuhn S, Dettling M, Graef K J, Kuerten I, Rommelspacher H, Schmidt L G. Psychopathological and behavioral correlates of dopaminergic sensitivity in alcohol-dependent patients. Arch Gen Psychiat. 1996; 53 1123-1128
- 23 Heinz A, Knable M B, Coppola R, Gorey J G, Jones D W, Lee K S, Weinberger D R. Psychomotor slowing, negative symptoms and dopamine receptor availability - an IBZM SPECT study in neuroleptic-treated and drug-free schizophrenic patients. Schizophr Res. 1998; 31 9-26
- 24 Koob G F, Le Moal M. Drug abuse: hedonic homeostatic dysregulation. Science. 1997; 278 52-58
- 25 Lal S, Nair N PV, Thavundayil J X, Tawar V, Tesfaye Y, Dastoor D, Gauthier S, Guyda H. Growth hormone response to apomorphine, a dopamine receptor agonist, in normal aging and in dementia of the Alzheimer type. Neurobiol Aging. 1989; 10 227-231
- 26 Malas K L, van Kammen D P, de Fraites E A, Brown G M, Gold P W. Reduced growth hormone response to apomorphine in schizophrenic patients with poor premorbid social functioning. J Neural Transm. 1987; 69 319-324
- 27 Meltzer H Y, Kolakowska T, Fang V S, Fogg L, Robertson A, Lewine R, Strahilevitz M, Busch D. Growth hormone and prolactin response to apomorphine in schizophrenia and the major affective disorders. Arch Gen Psychiat. 1984; 14 512-519
- 28 Oldfield R C. The assessment and analysis of handedness: the Edinburgh Inventory. Neuropsychol. 1979; 9 97-113
- 29 Palsson A. The efficacy of early chlormethiazole medication in the prevention of delirium tremens. A retrospective study of the outcome of different drug treatment strategies at the Halsingborg psychiatric clinics. Acta Psychiat Scand. 1986; 73 (Suppl. 329) 140-145
- 30 Pitchot W, Ansseau M, Moreno A G, Hansenne M, Von Freckell R. Dopaminergic function in panic disorder: comparison with major and minor depression. Biol Psychiat. 1992; 32 1004-1011
- 31 Robbins T W, Everitt B J. Neurobehavioral mechanisms of reward and motivation. Curr Opinion Neurobiol. 1996; 6 228-236
- 32 Robinson T E, Berridge K C. The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Rev. 1993; 18 247-291
- 33 Schultz W, Apicella P, Ljungberg T. Responses of monkey dopamine neurons to reward and conditioned stimuli during successive steps of learning a delayed response task. J Neurosc. 1993; 13 900-913
- 34 Sullivan J T, Sykora K, Schneiderman J, Narkanjo C A, Sellers E M. Assessment of alcohol withdrawal: the revised Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar). Br J Addiction. 1989; 84 535-544
- 35 van Praag H M. Significance of biochemical parameters in the diagnosis, treatment and prevention of depressive disorders. Biol Psychiat. 1977; 12 101-131
- 36 Volkow N D, Wang G J, Fowler J S, Logan J, Hitzemann R, Ding Y S, Pappas N, Shea C, Piscani K. Decreases in dopamine receptors but not in dopamine transporters in alcoholics. Alc Clin Exp Res. 1996; 20 1594-1598
- 37 Wiesbeck G A, Müller T, Wodarz N, Davids E, Kraus T, Thome J, Weijers H G, Boening J. Growth hormone response to placebo, apomorphine and growth hormone releasing hormone in abstinent alcoholics and control subjects. Drug Alc Dep. 1998; 52 53-56
- 38 Wise R A. Neuroleptics and operant behavior: the anhedonia hypothesis. Behav Brain Sci. 1982; 5 39-87
- 39 Wise R A. The neurobiology of craving: Implications for the understanding of addiction. J Abnorm Psychol. 1988; 97 118-132
-
40 World Health Organization .
Tenth revision of the International Classification of Diseases, chapter V (F). Mental and behavioral disorders. Göttingen; Huber 1991
1 Supported in part by the DFG (Az He: 2597/1-1) and by a research grant of Wander Pharma
2 Assessment of the psychopathological correlates of dopamine receptor sensitivity among patients with schizophrenia and major depression is part of a doctoral thesis by J. Patzer; among patients with alcohol- and opiate-dependence by B. Nolte-Zenker.
PD Dr. A. Heinz
Department of Addictive Behavior and Addiction Research
Central Institute of Mental Health
J5
68159 Mannheim
Germany