Generational Association Studies of Dopaminergic Genes in Reward Deficiency Syndrome (RDS) Subjects: Selecting Appropriate Phenotypes for Reward Dependence Behaviors

Abnormal behaviors involving dopaminergic gene polymorphisms often reflect an insufficiency of usual feelings of satisfaction, or Reward Deficiency Syndrome (RDS). RDS results from a dysfunction in the “brain reward cascade,” a complex interaction among neurotransmitters (primarily dopaminergic and opioidergic). Individuals with a family history of alcoholism or other addictions may be born with a deficiency in the ability to produce or use these neurotransmitters. Exposure to prolonged periods of stress and alcohol or other substances also can lead to a corruption of the brain reward cascade function. We evaluated the potential association of four variants of dopaminergic candidate genes in RDS (dopamine D1 receptor gene [DRD1]; dopamine D2 receptor gene [DRD2]; dopamine transporter gene [DAT1]; dopamine beta-hydroxylase gene [DBH]). Methodology: We genotyped an experimental group of 55 subjects derived from up to five generations of two independent multiple-affected families compared to rigorously screened control subjects (e.g., N = 30 super controls for DRD2 gene polymorphisms). Data related to RDS behaviors were collected on these subjects plus 13 deceased family members. Results: Among the genotyped family members, the DRD2 Taq1 and the DAT1 10/10 alleles were significantly (at least p < 0.015) more often found in the RDS families vs. controls. The TaqA1 allele occurred in 100% of Family A individuals (N = 32) and 47.8% of Family B subjects (11 of 23). No significant differences were found between the experimental and control positive rates for the other variants. Conclusions: Although our sample size was limited, and linkage analysis is necessary, the results support the putative role of dopaminergic polymorphisms in RDS behaviors. This study shows the importance of a nonspecific RDS phenotype and informs an understanding of how evaluating single subset behaviors of RDS may lead to spurious results. Utilization of a nonspecific “reward” phenotype may be a paradigm shift in future association and linkage studies involving dopaminergic polymorphisms and other neurotransmitter gene candidates

Pharmacology of MDMA- and Amphetamine-Like New Psychoactive Substances

New psychoactive substances (NPS) with amphetamine-, aminoindan-, and benzofuran basic chemical structures have recently emerged for recreational drug use. Detailed information about their psychotropic effects and health risks is often limited. At the same time, it emerged that the pharmacological profiles of these NPS resemble those of amphetamine or 3,4-methylenedioxymethamphetamine (MDMA). Amphetamine-like NPS induce psychostimulation and euphoria mediated predominantly by norepinephrine (NE) and dopamine (DA) transporter (NET and DAT) inhibition and transporter-mediated release of NE and DA, thus showing a more catecholamine-selective profile. MDMA-like NPS frequently induce well-being, empathy, and prosocial effects and have only moderate psychostimulant properties. These MDMA-like substances primarily act by inhibiting the serotonin (5-HT) transporter (SERT) and NET, also inducing 5-HT and NE release. Monoamine receptor interactions vary considerably among amphetamine- and MDMA-like NPS. Clinically, amphetamine- and MDMA-like NPS can induce sympathomimetic toxicity. The aim of this chapter is to review the state of knowledge regarding these substances with a focus on the description of the in vitro pharmacology of selected amphetamine- and MDMA-like NPS. In addition, it is aimed to provide links between pharmacological profiles and in vivo effects and toxicity, which leads to the conclusion that abuse liability for amphetamine-like NPS may be higher than for MDMA-like NPS, but that the risk for developing the life-threatening serotonin syndrome may be increased for MDMA-like NPS

Screening for diabetic retinopathy in primary care with a mobile fundal camera - Evaluation of a South African pilot project

The original publication is available at http://www.samj.org.zaBackground and aims: In South Africa diabetes makes a significant contribution to the burden of disease. Diabetic retinopathy is a leading cause of adult blindness, and screening can reduce the incidence. This project aimed to implement and evaluate a new service for retinal screening that uses a non-mydriatic mobile fundal camera in primary care. This is the first time such a service has been evaluated in an African primary care context. Methods. The service was implemented as an operational research study at three community health centres and data were collected to evaluate the operational issues, screening, reporting and referral of patients. Results. Out of 400 patients screened 84% had a significantly reduced visual acuity, 63% had retinopathy (22% severe non-proliferative, 6% proliferative and 15% maculopathy), 2% of eyes could not be screened and 14% of patients required dilatation. Referral was necessary in 27% of cases for cataracts, in 7% for laser treatment and in 4% for other specialist services. Repeat photography was needed in 8% and urgent follow-up in 12%. A SWOT analysis of the pilot project was completed and recommendations were made on how to integrate it into the district health system. Conclusion. Screening with a fundal camera improved the quality of care for diabetic patients and is feasible in the South African public sector, primary care setting. A single technician should be able to photograph almost 10 000 patients a year.Publisher's versio

Screening for diabetic retinopathy in primary care with a mobile fundal camera - evaluation of a South African pilot project

Background and aims. In South Africa diabetes makes a significant contribution to the burden of disease. Diabetic retinopathy is a leading cause of adult blindness, and screening can reduce the incidence. This project aimed to implement and evaluate a new service for retinal screening that uses a non-mydriatic mobile fundal camera in primary care. This is the first time such a service has been evaluated in an African primary care context. Methods. The service was implemented as an operational research study at three community health centres and data were collected to evaluate the operational issues, screening, reporting and referral of patients. Results. Out of 400 patients screened 84% had a significantly reduced visual acuity, 63% had retinopathy (22% severe nonproliferative, 6% proliferative and 15% maculopathy), 2% of eyes could not be screened and 14% of patients required dilatation. Referral was necessary in 27% of cases for cataracts, in 7% for laser treatment and in 4% for other specialist services. Repeat photography was needed in 8% and urgent follow-up in 12%. A SWOT analysis of the pilot project was completed and recommendations were made on how to integrate it into the district health system. Conclusion. Screening with a fundal camera improved the quality of care for diabetic patients and is feasible in the South African public sector, primary care setting. A single technician should be able to photograph almost 10 000 patients a year