Behavioural Addiction and Genetics in Parkinson's Disease

Overview

The " Behavioural Addiction and Genetics in Parkinson's Disease " study (BADGE-PD) is a national (France), multicenter, genetic association, case-control study to identify genetic factors associated with behavioural addiction (or Impulse Control Disorders, ICD) related to dopamine agonists treatment in Parkinson's disease (PD). Polymorphisms of candidate genes supposed to be involved in this adverse effect will be compared in 200 PD patients with ICD (n=200) and 200 matched PD patients without ICD (n=200).

Objective: To identify susceptibility genes to impulse control disorders in Parkinson's Disease. Study design: Genetic association study. Primary objective: To identify the susceptibility genes in behavior addiction in Parkinson's Disease Secondary endpoints: * To compare the clinical, neurological and psychiatric features of parkinsonian patients with behavior addiction compared to the control population. In case of differences between these groups, interaction will be studied with genetic factors * Identify a psychometric profile from the TCI-R scale corresponding to the "hyperdopaminergic" subjects with AC personality Patient selection: Cases: patients with Parkinson's disease (PD) and impulse control disorder (ICD) as defined by a score greater than or equal to 2 or 3 scores greater than or equal to 2 at the "Evaluation Comportementale de la Maladie de Parkinson" scale (ECMP, Ardouin et al. 2009) for hyperdopaminergic items. Controls: PD patients without impulse control disorder (ICD) as defined by a score of 0 or 1 at each hyperdopaminergic items AND no more than 2 items with a score of 1. Controls must have been treated with at least 300 mg of Levodopa equivalent daily dose for more than 12 months. Controls will be matched for sex, age, and age at onset of PD. Number of subjects: 200 cases and 200 controls. Clinical assessment: motor score (UPDRS), neuropsychological assessment, diagnostic criteria for addiction and ICD (MINI), self-administered psychometric questionnaire (TCI-R), treatment history, ICD history. Genetic analysis: A blood sample will be taken for extraction and storage of DNA (DNA bank and Pitie-Salpetriere cells). Candidate genes\* and polymorphisms will be selected from the literature data (receptors, transporters and metabolizing enzymes monoamine) and the molecular signature induced by L-DOPA in the striatum of a mice model of PD. Statistical analysis: A two-step analysis will be performed. For the first step, a training set (36% of subjects) will be analyzed with a logistic regression model considering an additive genetic effect. For the second step, the top 27% of the more significant genetic markers will be analyzed by using the left over replication set (64% of patients). Finally, a pooled analysis will be performed. Sample Size: 200 patients per group to study 50 candidate markers with a power of 83% for genotype effect of 2.0, an additive genetic model, each allele frequency of 0.5. \* candidate genes list: 20 genes from the literature : DRD1, ANKK1, DRD2, DRD3, DRD4, DAT1, MAOA, COMT, HTR2A, HTR1B, TPH1, TPH2, 5HTT, GRIN2B, DBH, SCL6A2, BDNF, OPMR1, OPRK1, PDYN 8 genes from the experimentation: FosB, Arc, Nptx2, Ccrn4l, Car12, C8b, Mocs1, Mef2c

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