A linkage study of candidate loci in familial Parkinson's Disease

BACKGROUND: Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease. Most cases are sporadic, however familial cases do exist. We examined 12 families with familial Parkinson's disease ascertained at the Movement Disorder clinic at the Oregon Health Sciences University for genetic linkage to a number of candidate loci. These loci have been implicated in familial Parkinson's disease or in syndromes with a clinical presentation that overlaps with parkinsonism, as well as potentially in the pathogenesis of the disease. METHODS: The examined loci were PARK3, Parkin, DRD (dopa-responsive dystonia), FET1 (familial essential tremor), BDNF (brain-derived neurotrophic factor), GDNF (glial cell line-derived neurotrophic factor), Ret, DAT1 (the dopamine transporter), Nurr1 and Synphilin-1. Linkage to the α-synuclein gene and the Frontotemporal dementia with parkinsonism locus on chromosome 17 had previously been excluded in the families included in this study. Using Fastlink, Genehunter and Simwalk both parametric and model-free non-parametric linkage analyses were performed. RESULTS: In the multipoint parametric linkage analysis lod scores were below -2 for all loci except FET1 and Synphilin-1 under an autosomal dominant model with incomplete penetrance. Using non-parametric linkage analysis there was no evidence for linkage, although linkage could not be excluded. A few families showed positive parametric and non-parametric lod scores indicating possible genetic heterogeneity between families, although these scores did not reach any degree of statistical significance. CONCLUSIONS: We conclude that in these families there was no evidence for linkage to any of the loci tested, although we were unable to exclude linkage with both parametric and non-parametric methods

Values determine the (in)effectiveness of informational interventions in promoting pro-environmental behavior

Informational interventions (e.g., awareness campaigns, carbon footprint calculators) are built on the assumption that informing the public about the environmental consequences of their actions should result in increased pro-environmental intentions and behavior. However, empirical support for this reasoning is mixed. In this paper, we argue that informational interventions may succeed in improving people's knowledge about the negative environmental consequences of one's actions, but this knowledge will not gain motivational force if people do not consider protecting the environment an important personal value. In an experiment, we measured individual differences in value priorities, and either presented participants a movie clip that portrayed the negative environmental consequences of using bottled water, or a control movie. As predicted, we found that the environmental movie improved recipients' knowledge of the negative environmental impact of bottled water, but this knowledge only resulted in concomitant changes in intentions and acceptability of related policies among participants who strongly endorsed biospheric (i.e. environmental) values, while having no effect on those who care less about the environment. Interestingly, the results suggest that although informational interventions are perhaps not always successful in directly affecting less environmentally-conscious recipients, they could still have beneficial effects, because they make those who strongly care about the environment more inclined to act on their values

Custom genotyping for substance addiction susceptibility genes in Jordanians of Arab descent

<p>Abstract</p> <p>Background</p> <p>Both environmental and genetic factors contribute to individual susceptibility to initiation of substance use and vulnerability to addiction. Determining genetic risk factors can make an important contribution to understanding the processes leading to addiction. In order to identify gene(s) and mechanisms associated with substance addiction, a custom platform array search for a genetic association in a case/control of homogenous Jordanian Arab population was undertaken. Patients meeting the DSM-VI criteria for substance dependence (<it>n</it> = 220) and entering eight week treatment program at two Jordanian Drug Rehabilitation Centres were genotyped. In addition, 240 healthy controls were also genotyped. The sequenom MassARRAY system (iPLEX GOLD) was used to genotype 49 single nucleotide polymorphisms (SNPs) within 8 genes (<it>DRD1</it>, <it>DRD2</it>, <it>DRD3</it>, <it>DRD4</it>, <it>DRD5</it>, <it>BDNF</it>, <it>SLC6A3</it> and <it>COMT</it>).</p> <p>Results</p> <p>This study revealed six new associations involving SNPs within <it>DRD2</it> gene on chromosome 11. These six SNPs within the <it>DRD2</it> were found to be most strongly associated with substance addiction in the Jordanian Arabic sample. The strongest statistical evidence for these new association signals were from rs1799732 in the C/−C promoter and rs1125394 in A/G intron 1 regions of <it>DRD2</it>, with the overall estimate of effects returning an odds ratio of 3.37 (<it>χ2</it> (2, <it>N</it> = 460) = 21, <it>p-value</it> = 0.000026) and 1.78 (<it>χ2</it> (2, <it>N</it> = 460) = 8, <it>p-value</it> = 0.001), respectively. It has been suggested that <it>DRD2</it>, dopamine receptor D2, plays an important role in dopamine secretion and the signal pathways of dopaminergic reward and drug addiction.</p> <p>Conclusion</p> <p>This study is the first to show a genetic link to substance addiction in a Jordanian population of Arab descent. These findings may contribute to our understanding of drug addiction mechanisms in Middle Eastern populations and how to manage or dictate therapy for individuals. Comparative analysis with different ethnic groups could assist further improving our understanding of these mechanisms.</p

Dopamine and Working Memory: Genetic Variation, Stress and Implications for Mental Health

At the molecular level, the neurotransmitter dopamine (DA) is a key regulatory component of executive function in the prefrontal cortex (PFC) and dysfunction in dopaminergic (DAergic) circuitry has been shown to result in impaired working memory (WM). Research has identified multiple common genetic variants suggested to impact on the DA system functionally and also behaviourally to alter WM task performance. In addition, environmental stressors impact on DAergic tone, and this may be one mechanism by which stressors confer vulnerability to the development of neuropsychiatric conditions. This chapter aims to evaluate the impact of key DAergic gene variants suggested to impact on both synaptic DA levels (COMT, DAT1, DBH, MAOA) and DA receptor function (ANKK1, DRD2, DRD4) in terms of their influence on visuospatial WM. The role of stressors and interaction with the genetic background is discussed in addition to discussion around some of the implications for precision psychiatry. This and future work in this area aim to disentangle the neural mechanisms underlying susceptibility to stress and their impact and relationship with cognitive processes known to influence mental health vulnerability