Dopamine D2 receptor binding is reduced in Wilson's disease: Correlation of neurological deficits with striatal123I-Iodobenzamide binding

Oder, W.; Brücke, Thomas; Kollegger, H.; Spatt, J.; Asenbaum, S.; Deecke, Lüder

doi:10.1007/bf01291794

Cited by 28 publications

(20 citation statements)

References 23 publications

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“…In WD, most neuropsychiatric symptoms are due to basal ganglia copper accumulation and the secondary damage to affected structures (dystonia, parkinsonism, and others) or prefrontal cortex disturbances (Magalhes et al 1994;Schlaug et al 1994;Nyberg et al 1982;Oder et al 1993;Seniow et al 2002), as both of these areas involve the dopaminergic system (Vallone et al 2000). Autopsies and radiological and laboratory investigations of WD cases have found reduced striatal dopamine and hydroxylase tyrosine levels (Nyberg et al 1982), as well as reduced dopamine D2 receptor density (Oder et al 1996;Schlaug et al 1994). However, treatment with dopamine agonists or levodopa had no effect, probably due to the presence of both pre-and postsynaptic dopaminergic damage (Frankel et al 1989;Jeon et al 1998).…”

Section: Discussionmentioning

confidence: 99%

“…According to some studies (Jonsson et al 1999;Zhang et al 2010) Del + carriers may have higher numbers of DRD2 receptors in the striatum. A decrease of postsynaptic DRD2 is usually observed during WD (Oder et al 1996;Schlaug et al 1994), and increase is observed during chelating treatment (Schlaug et al 1994). According to these observations, we should have found a protective effect of the Del + allele on neuropsychiatric presentation (increased number of DRD2) in WD, but we did not.…”

Section: Drd2 Ex 8 (A/a Vs A/g and G/g)mentioning

confidence: 99%

“…Pathology studies in WD revealed reduced striatal dopamine and hydroxylase tyrosine levels (Vallone et al 2000;Nyberg et al 1982;Mousseau et al 1993) and animal studies have indicated decreased dopamine receptor 2 (DRD2) during copper overloading (de Vries et al 1986). Single photon emission computerized tomography (SPECT) and positron emission tomography (PET) studies have shown postsynaptic dopaminergic deficit (loss of D2 receptors in striatum) in WD patients (Oder et al 1996;Westermark et al 1995) as well as presynaptic nigrostratial dopaminergic damage (Jeon et al 1998). WD patients also exhibit reduced bindings of dopamine ligands to dopamine receptors on lymphocytes probably due to dopamine receptors damage during copper intoxication (Członkowski and Członkowska 1984;Członkowska et al 1987).…”

Section: Introductionmentioning

confidence: 99%

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Association of Dopamine Receptor Gene Polymorphisms with the Clinical Course of Wilson Disease

et al. 2012

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Section: Discussionmentioning

confidence: 99%

Section: Drd2 Ex 8 (A/a Vs A/g and G/g)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association of Dopamine Receptor Gene Polymorphisms with the Clinical Course of Wilson Disease

et al. 2012

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“…Thus, the in vivo approximation of specific binding (Bmax/Kd) in each individual was obtained by the ratio index -mean basal ganglia:frontal cortex (BG:FC) ratio over 120 to 180 minutes after injection. This method has been shown to provide accurate and reliable data and to be sensitive to changes in dopaminergic function (Goyette et al 1978, Brücke et al 1991, Oertel et al 1992, Costa et al 1993, Oder et al 1996, Ichise et al 1998). Furthermore, subregional D2 receptor availability was also measured by drawing anatomical regions of interest on four brain areas rich in dopamine (head of the caudate and putamen on the right and left side) and again the in vivo approximation of regional specific binding in each participant was obtained by the ratio index.…”

Section: Discussionmentioning

confidence: 99%

“…In order to assess the significance of baseline D2 levels, one sample t-test was performed (two tailed, 95% confidence interval) with a hypothetical specific D2 level of 1.80 derived from previously published data obtained from healthy young adults (Goyette et al 1978, Oertel et al 1992, Costa et al 1993, Oder et al 1996, Ichise et al 1998. Correlation between specific binding and symptoms were performed initially with the Pearson product moment correlation and subsequently by simple linear regression.…”

Section: Discussionmentioning

confidence: 99%

Is increased D2 receptor availability associated with response to stimulant medication in ADHD

Ilgin

Şenol

Gücüyener

et al. 2001

Develop Med Child Neuro

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The purpose of this study was to estimate striatal dopamine (D2) receptor availability in non-drug treated children with attention-deficit-hyperactivity disorder (ADHD) before and after methylphenidate therapy, and to examine correlations between severity of symptoms and response rates to stimulant medication with levels of striatal D2 receptor binding. Nine children (six males, three females; mean age 9.8 years, SD 2.3 years) with ADHD participated. All underwent iodobenzamide (123I IBZM) brain SPECT within 2 hours following intravenous injection of 123I IBZM before and 3 months after methylphenidate therapy. A semiquantitative approach was used to generate indices of specific D2 receptor binding in the basal ganglia. Specific binding ratios at baseline were higher than the previously reported specific binding values obtained in studies using young healthy adults. D2 availability reduced significantly (paired t-test, p<0.05) as a function of methylphenidate therapy in patients with ADHD in all four regions of the striatum. When the relation between therapy response and D2 availability was investigated, we observed that the higher the baseline D2 levels were, the higher the response rate was (detected as the percentage reduction of hyperactivity scores and Conners Teacher Rating Scale scores), while no such trend was observed between the initial D2 binding levels and the response in attention-deficit scores. Results indicate that in non-drug treated children with ADHD, higher D2 receptor availability is observed at baseline which is down-regulated back to reported near-normal values after methylphenidate therapy. The effect of methylphenidate on D2 receptor levels in patients with ADHD is similar to that observed in healthy adults; a down-regulation phenomenon within 0 to 30%. In addition, initially higher values of D2 availability seem to indicate better response to methylphenidate therapy in ADHD.

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Extrapyramidal symptoms in Wilson's disease are associated with olfactory dysfunction

Mueller¹,

Reuner²,

Landis

et al. 2006

Movement Disorders

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Wilson's disease is a rare autosomal recessive disorder characterized by the accumulation of copper, mainly in the liver and the brain. As copper accumulation in the brain leads to disturbances in basal ganglia function, neurological-type patients typically present with hypo- and hyperkinetic extrapyramidal symptoms, with Parkinsonism being very common. Although there are numerous reports on olfactory deficits in primary neurodegenerative disorders, olfactory function has not been investigated in metabolic disorders presenting with extrapyramidal features. Twenty-four patients with Wilson's disease participated in the investigation. All patients were treated pharmacologically. They comprised patients with liver disease alone (including mild enzyme elevation in asymptomatic individuals; n = 11) and/or neurological symptoms (n = 13) at the time of testing. Twenty-one patients underwent both [18F]fluoro-2-deoxy-D-glucose positron emission tomography ([18F]FDG-PET) and magnetic resonance imaging (MRI). The severity of extrapyramidal symptoms was judged using a clinical score system ranging from 0 (no symptoms) to 3 (severe symptoms). In all patients, psychophysical testing was performed using the Sniffin' Sticks, which involved tests for odor threshold, discrimination, and identification. Results from the present study revealed that Wilson's disease patients with neurological symptoms show a significant olfactory dysfunction compared to hepatic-type patients. Individuals who are more severely neurologically affected also present with a more pronounced olfactory deficit. Of interest, there was no significant effect of long-term treatment with penicillamine on olfactory function. Olfactory function did not correlate significantly with the presence of MRI visible lesions in the basal ganglia or with any regional glucose metabolism as measured by [18]F-FDG-PET. In conclusion, these findings indicate that the underlying pathological alterations with degeneration in the basal ganglia and neuronal loss in association with a marked increase of the copper content in this brain region play a role in the olfactory deficit.

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Dopamine D2 receptor binding is reduced in Wilson's disease: Correlation of neurological deficits with striatal123I-Iodobenzamide binding

Cited by 28 publications

References 23 publications

Association of Dopamine Receptor Gene Polymorphisms with the Clinical Course of Wilson Disease

Association of Dopamine Receptor Gene Polymorphisms with the Clinical Course of Wilson Disease

Is increased D2 receptor availability associated with response to stimulant medication in ADHD

Extrapyramidal symptoms in Wilson's disease are associated with olfactory dysfunction

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