Stressful life events are associated with striatal dopamine receptor availability in alcohol dependence

Sebold, Miriam; Spitta, Gianna; Gleich, Tobias; Dembler-Stamm, Theresa; Butler, Oisín; Zacharias, Kristin; Aydın, Semiha; Garbusow, Maria; Rapp, Michael A.; Schubert, Florian; Buchert, Ralph; Gallinat, Jürgen; Heinz, Andreas

doi:10.1007/s00702-019-01985-2

Cited by 10 publications

(10 citation statements)

References 78 publications

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“…The results of this study demonstrate that DRD2/3 availability is reduced in the associative, sensorimotor, and limbic striatum of AUD patients compared to HCs. This supports our hypothesis and is in line with our previous finding of reduced striatal DRD2/3 availability in AUD patients compared to individuals at high risk of AUD and HCs [3,46]. Contrary to our hypothesis we did not find an association between the presence of the minor allele (risk allele) of the Taq1A polymorphism of the dopamine D2 receptor DRD2 gene and striatal DRD2/3 availability in AUD patients versus HCs.…”

Section: Discussionsupporting

confidence: 92%

Association between DRD2/ANKK1 TaqIA Allele Status and Striatal Dopamine D2/3 Receptor Availability in Alcohol Use Disorder

Spitta¹,

Fliedner²,

Gleich³

et al. 2022

J. Integr. Neurosci.

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Background:The association between blunted dopaminergic neurotransmission and alcohol use disorder (AUD) is well-known. In particular, the impairment of postsynaptic dopamine 2 and 3 receptors (DRD2/3) in the ventral and dorsal striatum during the development and maintenance of alcohol addiction has been investigated in several positron emission tomography (PET) studies. However, it is unclear whether these changes are the result of adaptation or genetic predisposition. Methods: Here we investigated the association between DRD2/ankyrin repeat and kinase domain-containing 1 (ANKK1) TaqIA allele (rs1800497) status and striatal DRD2/3 availability measured by 18F-fallypride PET in 12 AUD patients and 17 sex-matched healthy controls. Age and smoking status were included as covariates. Results: Contrary to our expectations, TaqIA allele status was not associated with striatal DRD2/3 availability in either group and there was no significant difference between groups, possibly due to the relatively small sample size (N = 29). Conclusions: Nonetheless, this is the first in vivo study investigating the relationship between dopamine receptor availability and genetic factors in AUD. The pitfalls of assessing such relationships in a relatively small sample are discussed. Clinical Trial Registration: The published analysis is an additional, post hoc analysis to the preregistered trial with clinical trial number NCT01679145 available on https://clinical -trials.gov/ct2/show/NCT01679145.

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Section: Discussionsupporting

confidence: 92%

Association between DRD2/ANKK1 TaqIA Allele Status and Striatal Dopamine D2/3 Receptor Availability in Alcohol Use Disorder

Spitta¹,

Fliedner²,

Gleich³

et al. 2022

J. Integr. Neurosci.

View full text Add to dashboard Cite

show abstract

“…The results of this study demonstrate that DRD2/3 availability is reduced in the associative, sensorimotor, and limbic striatum of AUD patients compared to HCs. This supports our hypothesis and is in line with our previous finding of reduced striatal DRD2/3 availability in AUD patients compared to individuals at high risk of AUD and HCs (Gleich et al, 2020;Sebold et al, 2019). On the other hand, contrary to our hypothesis we did not find any association between DRD2/ANKK1 TaqIA allele status and striatal DRD2/3 availability, although this result must be interpreted with caution because of the limited effect size and relatively small sample size.…”

Section: Discussionsupporting

confidence: 92%

Association between DRD2/ANKK1 TaqIA allele status and striatal dopamine D2/3 receptor availability in alcohol use disorder

Spitta¹,

Fliedner²,

Gleich³

et al. 2021

Preprint

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The association between blunted dopaminergic neurotransmission and alcohol use disorder (AUD) is well-known. In particular, the impairment of postsynaptic dopamine 2 and 3 receptors (DRD2/3) in the ventral and dorsal striatum during the development and maintenance of alcohol addiction has been investigated in several positron emission tomography (PET) studies. However, it is unclear whether these changes are the result of adaptation or genetic predisposition. Here we investigated the association between DRD2/ankyrin repeat and kinase domain-containing 1 (ANKK1) TaqIA allele (rs1800497) status and striatal DRD2/3 availability measured by 18F-fallypride PET in 13 AUD patients and 17 sex-matched healthy controls. Age and smoking status were included as covariates. Contrary to our expectations, TaqIA allele status was not associated with striatal DRD2/3 availability in either group and there was no significant difference between groups, possibly due to the relatively small sample size (N=30). Nonetheless, this is the first in vivo study investigating the relationship between dopamine receptor availability and genetic factors in AUD. The pitfalls of assessing such relationships in a relatively small sample are discussed.

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“…Interestingly, some previous studies have suggested that tonic dopamine might either increase ( 72 ) or decrease exploration ( 73 ). As AUDP show reduced availability of D2 receptors ( 59 , 74 , 75 ), putatively reflecting a downregulation of the dopaminergic system, future studies should apply appropriate tasks to further investigate the link between dopaminergic functioning and the exploration/exploitation trade-off in AUDP.…”

Section: Discussionmentioning

confidence: 99%

Computational analysis of probabilistic reversal learning deficits in male subjects with alcohol use disorder

et al. 2022

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BackgroundAlcohol use disorder is characterized by perseverative alcohol use despite negative consequences. This hallmark feature of addiction potentially relates to impairments in behavioral flexibility, which can be measured by probabilistic reversal learning (PRL) paradigms. We here aimed to examine the cognitive mechanisms underlying impaired PRL task performance in patients with alcohol use disorder (AUDP) using computational models of reinforcement learning.MethodsTwenty-eight early abstinent AUDP and 27 healthy controls (HC) performed an extensive PRL paradigm. We compared conventional behavioral variables of choices (perseveration; correct responses) between groups. Moreover, we fitted Bayesian computational models to the task data to compare differences in latent cognitive variables including reward and punishment learning and choice consistency between groups.ResultsAUDP and HC did not significantly differ with regard to direct perseveration rates after reversals. However, AUDP made overall less correct responses and specifically showed decreased win–stay behavior compared to HC. Interestingly, AUDP showed premature switching after no or little negative feedback but elevated proneness to stay when accumulation of negative feedback would make switching a more optimal option. Computational modeling revealed that AUDP compared to HC showed enhanced learning from punishment, a tendency to learn less from positive feedback and lower choice consistency.ConclusionOur data do not support the assumption that AUDP are characterized by increased perseveration behavior. Instead our findings provide evidence that enhanced negative reinforcement and decreased non-drug-related reward learning as well as diminished choice consistency underlie dysfunctional choice behavior in AUDP.

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Stressful life events are associated with striatal dopamine receptor availability in alcohol dependence

Cited by 10 publications

References 78 publications

Association between DRD2/ANKK1 TaqIA Allele Status and Striatal Dopamine D2/3 Receptor Availability in Alcohol Use Disorder

Association between DRD2/ANKK1 TaqIA Allele Status and Striatal Dopamine D2/3 Receptor Availability in Alcohol Use Disorder

Association between DRD2/ANKK1 TaqIA allele status and striatal dopamine D2/3 receptor availability in alcohol use disorder

Computational analysis of probabilistic reversal learning deficits in male subjects with alcohol use disorder

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