Low level of dopaminergic D2 receptor binding in obsessive-compulsive disorder

Denys, Damiaan; Wee, Nic van der; Janssen, Joost; Geus, Femke de; Westenberg, H.G.M.

doi:10.1016/j.biopsych.2004.01.023

Cited by 171 publications

(111 citation statements)

References 34 publications

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“…This observation is in line with the reduced D 2 receptors availability recently reported in drug-free OCD patients (Denys et al, 2004) and suggests that the increase in BP induced by fluvoxamine represents more a normalization than an increase of D 2 receptors availability.…”

Section: Discussionsupporting

confidence: 89%

“…However, other findings suggest a possible role also for dopamine and dopamine receptors. In particular, (a) dopamine regulates cortico-striatal-thalamo-cortical circuits through its activity on indirect and direct pathway (Alexander and Crutcher, 1990); (b) structural damages to the basal ganglia, a region particularly rich in dopamine receptors, promote OCD symptoms (Carmin et al, 2002); (c) a supersensitivity to cataleptic induction by the D 2 receptor antagonist sulpiride was observed in the D1CT mice, an animal model that shows symptoms of human compulsive disorders associated with cortical-limbic hyperactivity (Campbell et al, 1999); (d) differences in D 2 dopamine receptor binding in the head of the caudate nucleus predict phenotypic severity in monozygotic twins discordant for Tourette syndrome severity (Wolf et al, 1996); and (e) a reduced availability of D 2 receptors subtypes has been recently described in the left caudate nucleus of patients with OCD (Denys et al, 2004). In addition, preclinical studies on rodents indicated that the repeated administration of antidepressants affect dopamine D 2 receptors (Ainsworth et al, 1998a;Ainsworth et al, 1998b;Spyraki and Fibiger, 1981).…”

Section: Introductionmentioning

confidence: 99%

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Fluvoxamine Treatment and D2 Receptors: a Pet Study on OCD Drug-Naïve Patients

Moresco

Pietra

Henin

et al. 2006

Neuropsychopharmacol

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Changes in D 2 receptors during antidepressant therapy have been reported in patients with major depressive disorder using PET/SPET. The aim of this study was to evaluate modifications in D 2 receptors that might occur in patients affected by obsessive-compulsive disorder (OCD) during serotonin reuptake sites inhibitors (SSRIs). To this purpose, we measured the in vivo binding of [ 11 C]raclopride ([ 11 C]Rac)in the brain of a group of OCD naïve patients before and after the repeated administration of the inhibitor SSRI fluvoxamine. Eight patients with a Diagnostic and Statistical Manual of Mental Disorders IVth edition diagnosis of OCD completed the study undergoing a PET scan and a complete clinical evaluation before and during treatment with fluvoxamine. Patients have been compared also with a group of nine age-matched normal volunteers. Fluvoxamine treatment significantly improved clinical symptoms and increased [ 11 C]Rac binding potential (BP) in the basal ganglia of OCD patients (7.575.2, 6.976.9, and 9.979.3% in dorsal caudate, dorsal putamen, and ventral basal ganglia, respectively; po0.01) to values closer to those observed in the group of normal subjects. Chronic treatment with fluvoxamine induces a slight but significant increase in striatal [ 11 C]Rac BP of previously drug-naïve OCD patients. The modifications in D 2 receptor availability might be secondary to fluvoxamine effects on serotoninergic activity.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Fluvoxamine Treatment and D2 Receptors: a Pet Study on OCD Drug-Naïve Patients

Moresco

Pietra

Henin

et al. 2006

Neuropsychopharmacol

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“…For instance, neuroimaging studies have revealed abnormalities in brain regions densely endowed with dopaminergic terminals, such as the basal ganglia. In some studies, Dopamine D2 receptor binding potential is decreased 9 and dopamine transporter binding potential is up-regulated in the basal ganglia of OCD patients which is compatible with the hypothesis of an enhanced dopaminergic activity 10 . In addition, dopamine releasing agents and uptake inhibitors, such as metilfenidate, cocaine, bromocriptine, and bupoprion, exacerbate obsessive-compulsive symptoms (OCS) in OCD patients 11 .…”

supporting

confidence: 61%

Association analysis between a VNTR intron 8 polymorphism of the dopamine transporter gene (SLC6A3) and obsessive- compulsive disorder in a Brazilian sample

Miguita¹,

Cordeiro²,

Siqueira-Roberto³

et al. 2007

Arq. Neuro-Psiquiatr.

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-Family, twin and segregation analysis have provided evidences that genetic factors are implicated in the susceptibility for obsessive-compulsive disorder (OCD). Several lines of research suggest that the dopaminergic system may be involved in the pathophysiology of OCD. Thus, the aim of the present study was to investigate a possible association between a polymorphism located in intron 8 of the dopamine transporter gene (SLC6A3) and OCD in a Brazilian sample composed by 208 patients and 865 healthy controls. No statistically differences were observed in allelic and genotype distributions between cases and controls. No association was also observed when the sample was divided according to specific phenotypic features such as gender, presence of tic disorders co-morbidity and age at onset of obsessive-compulsive symptoms (OCS). Our results suggest that the intron 8 VNTR of the SLC6A3 investigated in this study is not related to the susceptibility for OCD in our Brazilian sample.KEY WORDS: dopamine, obsessive-compulsive disorder, genetic association, DAT1, allele, genotype. Análise de associação entre um polimorfismo VNTR no intron 8 do gene do transportador de dopamina (SLC6A3) e transtorno obsessivo-compulsivo em uma amostra brasileiraRESUMO -Estudos de família, gêmeos e de segregação têm demonstrado que fatores genéticos estão envolvidos na susceptibilidade para o desenvolvimento do transtorno obsessivo-compulsivo (TOC). Várias linhas de pesquisa sugerem que o sistema dopaminérgico possa estar envolvido na fisiopatologia do TOC. Assim, o objetivo do presente estudo foi investigar uma possível associação entre o polimorfismo localizado no intron 8 do gene do transportador da dopamina (SLC6A3) e o TOC em uma amostra brasileira composta por 208 pacientes e 865 controles sadios. Nenhuma diferença estatisticamente significante foi observada nas distribuições alélicas e genotípicas entre os grupos de pacientes e controles. Nenhuma associação também foi observada quando as amostras foram divididas de acordo com características fenotípicas específicas, tais como gênero, presença de co-morbidade com tiques e idade de início dos sintomas obsessivocompulsivo (SOC). Nossos resultados sugerem que o VNTR do intron 8 investigado neste estudo não está relacionado com o TOC na nossa amostra brasileira.

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“…In addition, evidence has accumulated that augmentation strategies with antipsychotics are beneficial for treatment-refractory OCD patients (Denys et al, 2002;McDougle et al, 1994McDougle et al, , 2000. Recently, SPECT studies provided evidence for higher dopamine transporter densities and lower dopamine D 2 binding ratios in patients with OCD relative to controls (Denys et al, 2003;Kim et al, 2003;van der Wee et al, 2001). The combined results of these receptor-binding studies provide circumstantial in vivo evidence for an increased dopaminergic activity in OCD patients.…”

Section: Introductionmentioning

confidence: 99%

Association between the dopamine D2 receptor TaqI A2 allele and low activity COMT allele with obsessive–compulsive disorder in males

Denys

Nieuwerburgh

Deforce

et al. 2006

European Neuropsychopharmacology

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Background: Mounting evidence suggests the involvement of the dopamine system in the pathophysiology of obsessive-compulsive disorder. Method: The relationship of the dopamine D 2 receptor (DRD2) TaqI A, and catechol-O-methyltransferase (COMT) NlaIII High/Low activity polymorphism to obsessive-compulsive disorder (OCD) was examined in a sample of 150 patients and 150 controls. Results: OCD patients did not show significant differences in genotype distribution and allele frequency for polymorphisms investigated relative to controls. However, when the sample was stratified by gender, there was a trend to a significant predominance of the DRD2 A2A2 genotype ( p = 0.049), and a higher frequency of the DRD2 A2 allele ( p = 0.020) and low-activity COMT allele ( p = 0.035) in male OCD patients compared to male controls. In addition, we observed an association of the DRD2 A2A2 genotype in patients with an early onset of disease (V15 years) ( p = 0.033). Conclusions: Our findings replicate previous reports and provide support for a potential role of the COMT and DRD2 locus in subgroup of male, early onset patients with OCD.

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Low level of dopaminergic D2 receptor binding in obsessive-compulsive disorder

Cited by 171 publications

References 34 publications

Fluvoxamine Treatment and D2 Receptors: a Pet Study on OCD Drug-Naïve Patients

Fluvoxamine Treatment and D2 Receptors: a Pet Study on OCD Drug-Naïve Patients

Association analysis between a VNTR intron 8 polymorphism of the dopamine transporter gene (SLC6A3) and obsessive- compulsive disorder in a Brazilian sample

Association between the dopamine D2 receptor TaqI A2 allele and low activity COMT allele with obsessive–compulsive disorder in males

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