Altered Reward Functions in Patients on Atypical Antipsychotic Medication in Line with the Revised Dopamine Hypothesis of Schizophrenia

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 2009 Jun 13

PMID 19521678

Citations 59

Authors

Henrik Walter

Hannes Kammerer

Karel Frasch

Manfred Spitzer

Birgit Abler

Affiliations

Soon will be listed here.

Abstract

Objective: To study the mesolimbic dopamine system during expectation and receipt or omission of rewards in partially remitted patients with schizophrenia treated with the atypical antipsychotic olanzapine.

Methods: We studied 16 patients with a current episode of schizophrenia, all treated with the atypical drug olanzapine, and 16 healthy subjects using functional magnetic resonance imaging. Subjects performed a delayed incentive paradigm with monetary rewards.

Results: During reward expectation, both, patients with schizophrenia and healthy control subjects, showed activation of the ventral striatum and midbrain in the vicinity of the ventral tegmental area. Significant categorical group differences emerged in the anterior cingulate cortex with only healthy controls showing increasing activation with increasing reward. In the patients, activation of this region was inversely correlated with positive symptoms. During outcome, both, patients with schizophrenia and healthy controls, showed activation of the ventral striatum and the mesial prefrontal cortex. Significant categorical group differences emerged in the right ventrolateral prefrontal cortex for the salience contrast with healthy controls showing a U-shaped activation curve, i.e., higher activation for either omission or receipt of reward compared to no reward.

Conclusions: Our findings partially support the current concept of dopaminergic dysfunction in schizophrenia, suggesting a rather hyperactive mesolimbic dopamine system and reduced prefrontal activation, at least in partially remitted patients treated with atypical antipsychotics.

Citing Articles

The role of glial cells in mental illness: a systematic review on astroglia and microglia as potential players in schizophrenia and its cognitive and emotional aspects.

Laricchiuta D, Papi M, Decandia D, Panuccio A, Cutuli D, Peciccia M Front Cell Neurosci. 2024; 18:1358450.

PMID: 38419655 PMC: 10899480. DOI: 10.3389/fncel.2024.1358450.

Gm527 deficiency in dentate gyrus improves memory through upregulating dopamine D1 receptor pathway.

Jia J, Peng H, Tian R, Zhou H, Zheng H, Liu B CNS Neurosci Ther. 2023; 29(11):3290-3306.

PMID: 37248637 PMC: 10580352. DOI: 10.1111/cns.14259.

Insular and Striatal Correlates of Uncertain Risky Reward Pursuit in Schizophrenia.

Purcell J, Brown J, Tullar R, Bloomer B, Kim D, Moussa-Tooks A Schizophr Bull. 2023; 49(3):726-737.

PMID: 36869757 PMC: 10154703. DOI: 10.1093/schbul/sbac206.

Microglia sequelae: brain signature of innate immunity in schizophrenia.

Rodrigues-Neves A, Ambrosio A, Gomes C Transl Psychiatry. 2022; 12(1):493.

PMID: 36443303 PMC: 9705537. DOI: 10.1038/s41398-022-02197-1.

Neural substrates of reward anticipation and outcome in schizophrenia: a meta-analysis of fMRI findings in the monetary incentive delay task.

Zeng J, Yan J, Cao H, Su Y, Song Y, Luo Y Transl Psychiatry. 2022; 12(1):448.

PMID: 36244990 PMC: 9573872. DOI: 10.1038/s41398-022-02201-8.

References

Abi-Dargham A . Probing cortical dopamine function in schizophrenia: what can D1 receptors tell us?. World Psychiatry. 2006; 2(3):166-71. PMC: 1525099. View

Wolf R, Vasic N, Walter H . Differential activation of ventrolateral prefrontal cortex during working memory retrieval. Neuropsychologia. 2006; 44(12):2558-63. DOI: 10.1016/j.neuropsychologia.2006.05.015. View

Kapur S . Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. Am J Psychiatry. 2002; 160(1):13-23. DOI: 10.1176/appi.ajp.160.1.13. View

Abler B, Walter H, Erk S, Kammerer H, Spitzer M . Prediction error as a linear function of reward probability is coded in human nucleus accumbens. Neuroimage. 2006; 31(2):790-5. DOI: 10.1016/j.neuroimage.2006.01.001. View

da Silva Alves F, Figee M, van Amelsvoort T, Veltman D, de Haan L . The revised dopamine hypothesis of schizophrenia: evidence from pharmacological MRI studies with atypical antipsychotic medication. Psychopharmacol Bull. 2008; 41(1):121-32. View

Koo M, Levitt J, Salisbury D, Nakamura M, Shenton M, McCarley R . A cross-sectional and longitudinal magnetic resonance imaging study of cingulate gyrus gray matter volume abnormalities in first-episode schizophrenia and first-episode affective psychosis. Arch Gen Psychiatry. 2008; 65(7):746-60. PMC: 2793338. DOI: 10.1001/archpsyc.65.7.746. View

Jensen J, Willeit M, Zipursky R, Savina I, Smith A, Menon M . The formation of abnormal associations in schizophrenia: neural and behavioral evidence. Neuropsychopharmacology. 2007; 33(3):473-9. DOI: 10.1038/sj.npp.1301437. View

Carlsson A, Lindqvist M . EFFECT OF CHLORPROMAZINE OR HALOPERIDOL ON FORMATION OF 3METHOXYTYRAMINE AND NORMETANEPHRINE IN MOUSE BRAIN. Acta Pharmacol Toxicol (Copenh). 1963; 20:140-4. DOI: 10.1111/j.1600-0773.1963.tb01730.x. View

Abler B, Walter H, Erk S . Neural correlates of frustration. Neuroreport. 2005; 16(7):669-72. DOI: 10.1097/00001756-200505120-00003. View

10.

Knutson B, Cooper J . Functional magnetic resonance imaging of reward prediction. Curr Opin Neurol. 2005; 18(4):411-7. DOI: 10.1097/01.wco.0000173463.24758.f6. View

11.

Waltz J, Gold J . Probabilistic reversal learning impairments in schizophrenia: further evidence of orbitofrontal dysfunction. Schizophr Res. 2007; 93(1-3):296-303. PMC: 2063592. DOI: 10.1016/j.schres.2007.03.010. View

12.

Szeszko P, Bilder R, Lencz T, Ashtari M, Goldman R, Reiter G . Reduced anterior cingulate gyrus volume correlates with executive dysfunction in men with first-episode schizophrenia. Schizophr Res. 2000; 43(2-3):97-108. DOI: 10.1016/s0920-9964(99)00155-3. View

13.

Burgdorfer G, Hautzinger M . [Psychological and social anhedonia. Evaluation of a research instrument for measuring a basic psychopathologic disorder]. Eur Arch Psychiatry Neurol Sci. 1987; 236(4):223-9. DOI: 10.1007/BF00383852. View

14.

Cools R, Clark L, Owen A, Robbins T . Defining the neural mechanisms of probabilistic reversal learning using event-related functional magnetic resonance imaging. J Neurosci. 2002; 22(11):4563-7. PMC: 6758810. DOI: 20026435. View

15.

Murray G, Corlett P, Clark L, Pessiglione M, Blackwell A, Honey G . Substantia nigra/ventral tegmental reward prediction error disruption in psychosis. Mol Psychiatry. 2007; 13(3):239, 267-76. PMC: 2564111. DOI: 10.1038/sj.mp.4002058. View

16.

Abler B, Greenhouse I, Ongur D, Walter H, Heckers S . Abnormal reward system activation in mania. Neuropsychopharmacology. 2007; 33(9):2217-27. PMC: 2574988. DOI: 10.1038/sj.npp.1301620. View

17.

Abler B, Erk S, Walter H . Human reward system activation is modulated by a single dose of olanzapine in healthy subjects in an event-related, double-blind, placebo-controlled fMRI study. Psychopharmacology (Berl). 2007; 191(3):823-33. DOI: 10.1007/s00213-006-0690-y. View

18.

Ritter L, Meador-Woodruff J, Dalack G . Neurocognitive measures of prefrontal cortical dysfunction in schizophrenia. Schizophr Res. 2004; 68(1):65-73. DOI: 10.1016/S0920-9964(03)00086-0. View

19.

Kollias C, Kontaxakis V, Havaki-Kontaxaki B, Stamouli S, Margariti M, Petridou E . Association of physical and social anhedonia with depression in the acute phase of schizophrenia. Psychopathology. 2008; 41(6):365-70. DOI: 10.1159/000152378. View

20.

Goel V, Vartanian O . Dissociating the roles of right ventral lateral and dorsal lateral prefrontal cortex in generation and maintenance of hypotheses in set-shift problems. Cereb Cortex. 2004; 15(8):1170-7. DOI: 10.1093/cercor/bhh217. View