Contrary to what was found for the DRD4 gene, the 10-repeat allele of the DAT gene has at most a minor role in the genetic susceptibility of ADHD. The different biases detected herein probably explain the initial impression of a significant impact of the DAT gene on hyperactivity.

Anatomical, pharmacological and human post-mortem studies suggest the dopamine D 3 receptor (DRD3) gene as a candidate for drug dependence. We thus performed an association study of the Bal I polymorphism at the DRD3 gene, including 54 opiate addicts and 70 controls. Opiate addicts had a higher sensation-seeking score (on the Zü ckerman scale) than controls (P = 0.001), particularly a subgroup (70%) who had a distinctly higher score, exceeding 24. There were no marked differences in genotypes between patients as a whole and controls. However, patients with a sensation-seeking score above 24 were more frequently homozygotes for both alleles than patients with a sensation-seeking score under 24 (P = 0.038) or controls (P = 0.034). Although obtained in a sample of limited size, these results suggest that the DRD3 gene may have a role in drug dependence susceptibility in individuals with high sensation-seeking scores. This hypothesis is consistent with the role of DRD3 in mediating responses to drugs of abuse in animals and the association of homozygosity at the Bal I polymorphism with drug abuse in schizophrenic patients (see companion article by Krebs et al).Addiction to substances, including drugs and alcohol, probably arises from a combination of environmental and genetic factors. 1-3 Alcohol, opiates and psychostimulants share the ability in animals to enhance the activity of mesolimbic-mesocortical dopaminergic neurons, thought to be involved in drug reward and reinforcement. 4 The dopamine D 3 receptor (DRD3) is selectively expressed in the projection field of dopaminergic mesolimbic-mesocortical neurons. 5 Stimulation of DRD3 enhances the reinforcing properties of cocaine in rats 6 and monkeys; 7,8 behavioral sensitization occurring after repeated administration of an indirect dopamine agonist, a process also observed after repeated administration of opiates and psychostimulants, is accompanied by a selective induction of DRD3 gene expression. 9 Furthermore, DRD3 binding 10 and gene transcripts 11 are elevated in the ventral striatum of cocaine fatalities. These experimental and clinical observations suggest the DRD3 gene as a candidate for susceptibility to drug dependence.We recruited 54 patients with opiate dependence and without schizophrenia, both according to DSM-III-R criteria (mean age ± s.d. 32.3 ± 6.1 yrs), and 70 controls without drug use or any psychiatric disease (mean age 42.2 ± 7 yrs), all white males of French ancestry. The older age of controls minimises the risk of including not yet revealed addicts. Twenty-nine patients had less than three life-time comorbid substance dependences, and 25 more than three comorbid dependences. The age of first opiate use was 18.6 ± 2.9 yrs.The sensation-seeking score, as assessed using the Zü ckerman scale, was significantly higher in patients (26 ± 5) than in controls (17 ± 6, P = 0.001). The sensation-seeking score in patients was found inversely correlated with age (r = −0.37, P = 0.005), as it is in the general population. 12 However, testing for normali...

Pharmacogenetic studies investigating the 40-bp VNTR polymorphism at SLC6A3 and methylphenidate response have shown conflicting results and large differences in study design and efficacy endpoints. Our objective was to investigate the relation between the 3'-VNTR at SLC6A3 and variability in methylphenidate response in a sample of 141 ADHD children and adolescents, assessed before and after methylphenidate treatment with both clinical and neuropsychological outcome measures. 10-R homozygotes were significantly overrepresented in the low response group, but no genotype effect was shown in cognitive variables improvement. A meta-analysis of pharmacogenetic studies with comparable data (responders vs. non-responders) on a total of 475 subjects showed a significant association between the 10-10 genotype and low rates of methylphenidate response (mean Odds Ratio = 0.46; 95% CI [0.28-0.76]). Heterogeneity between these studies did not reach a significant level but, as publications with different endpoints were excluded from this meta-analysis, our results do not rule out a possible influence of study design.

Background.Compulsory admission procedures of patients with mental disorders vary between countries in Europe. The Ethics Committee of the European Psychiatric Association (EPA) launched a survey on involuntary admission procedures of patients with mental disorders in 40 countries to gather information from all National Psychiatric Associations that are members of the EPA to develop recommendations for improving involuntary admission processes and promote voluntary care.Methods.The survey focused on legislation of involuntary admissions and key actors involved in the admission procedure as well as most common reasons for involuntary admissions.Results.We analyzed the survey categorical data in themes, which highlight that both medical and legal actors are involved in involuntary admission procedures.Conclusions.We conclude that legal reasons for compulsory admission should be reworded in order to remove stigmatization of the patient, that raising awareness about involuntary admission procedures and patient rights with both patients and family advocacy groups is paramount, that communication about procedures should be widely available in lay-language for the general population, and that training sessions and guidance should be available for legal and medical practitioners. Finally, people working in the field need to be constantly aware about the ethical challenges surrounding compulsory admissions.