Association of Serotonin Transporter (SERT) Polymorphisms with Opioid Dependence and Dimensional Aspects of Cocaine Use in a Caucasian Cohort of Opioid Users.

Introduction: A functional tandem repeat polymorphism in the promoter of the serotonin transporter (SERT) gene (SLC6A4) has been studied for association to neuropsychiatric conditions, including substance use disorders. Short (S) forms of this repeat result in reduced transcription, and presumably greater synaptic levels of serotonin, which are involved in opioid and cocaine-induced reward. Dual exposure to heroin and cocaine is a common pattern of poly-drug use and is associated with considerable morbidity.

Further evidence for the association of , and variants with opioid dependence.

Heroin addiction is a chronic, relapsing disease that has genetic and environmental, including drug-induced, contributions. Stress influences the development of addictions. This study was conducted to determine if variants in stress-related genes are associated with opioid dependence (OD).

VMAT2 gene () variants associated with a greater risk for developing opioid dependence.

To determine if selected serotonergic and noradrenergic gene variants are associated with heroin addiction. A total of 126 variants in 19 genes in subjects with Dutch European ancestry from The Netherlands. Subjects included 281 opioid-dependent volunteers in methadone maintenance or heroin-assisted treatment, 163 opioid-exposed but not opioid-dependent volunteers who have been using illicit opioids but never became opioid-dependent and 153 healthy controls.

Association of variants of prodynorphin promoter 68-bp repeats in caucasians with opioid dependence diagnosis: Effect on age trajectory of heroin use.

The dynorphin/kappa opioid receptor (Dyn/KOR) system is involved in reward processing and dysphoria/anhedonia. Exposure to mu-opioid receptor agonists such as heroin increases expression of the prodynorphin gene (PDYN) in the brain. In this study in a Caucasian cohort, we examined the association of the functional PDYN 68-bp repeat polymorphism with opioid use disorders.

Dopamine gene variants in opioid addiction: comparison of dependent patients, nondependent users and healthy controls.

Aim: To determine whether specific dopaminergic system gene variants are associated with opioid dependence.

Patients & Methods: Subjects included 153 healthy controls, 163 opioid exposed, but not dependent and 281 opioid dependent. Genotypes of 90 variants in 13 genes were examined.

Variants of opioid system genes are associated with non-dependent opioid use and heroin dependence.

Background: Heroin addiction is a chronic, relapsing brain disease. Genetic factors are involved in the development of drug addiction. The aim of this study was to determine whether specific variants in genes of the opioid system are associated with non-dependent opioid use and heroin dependence.

Efficacy of cocaine contingency management in heroin-assisted treatment: Results of a randomized controlled trial.

Aims: To determine the efficacy of contingency management (CM), targeting cocaine use, as an add-on intervention for heroin dependent patients in supervised heroin-assisted treatment (HAT) with frequent cocaine use.

Design: Multi-center, open-label, parallel group, randomized controlled trial.

Setting: Twelve specialized addiction treatment centers for HAT in The Netherlands; April 2006-January 2011.

Personality as a risk factor for illicit opioid use and a protective factor for illicit opioid dependence.

Background: Most studies investigating the role of personality as a risk factor for the development of opioid dependence compare dependent opioid users with healthy controls who never used heroin. In order to understand the potential protective role of personality, it is crucial to compare illicit opioid users who never became dependent with dependent opioid users.

Aims: This study aims to examine the role of personality as a risk factor for opioid use and as a protective factor for the development of opioid dependence.

Sensory handedness is not reflected in cortical responses after basic nerve stimulation: a MEG study.

Motor dominance is well established, but sensory dominance is much less clear. We therefore studied the cortical evoked magnetic fields using magnetoencephalography (MEG) in a group of 20 healthy right handed subjects in order to examine whether standard electrical stimulation of the median and ulnar nerve demonstrated sensory lateralization. The global field power (GFP) curves, as an indication of cortical activation, did not depict sensory lateralization to the dominant left hemisphere.

Effects of a brief cardiovascular prevention program by a health advisor in primary care; the 'Hartslag Limburg' project, a cluster randomized trial.

Objective: To determine in primary care patients at high risk for a cardiovascular event, the effects on biomedical risk factors for and incidence of cardiovascular events, of a brief cardiovascular prevention program executed by a health advisor.

Design: cluster randomized controlled trial with 1275 patients (24 general practices) in and around Maastricht, the Netherlands (1999-2004).

Intervention: health advisors were to complete computerized cardiovascular risk profiles, provide multi-factorial tailored health education and advice, and communicate with GP's to optimize treatment.

Craving and illicit heroin use among patients in heroin-assisted treatment.

Aims: To investigate in heroin-assisted treatment (HAT) compared to methadone maintenance treatment (MMT): the course of heroin craving and illicit heroin use, their mutual association, and their association with multi-domain treatment response.

Design: RCTs on the efficacy of 12 months co-prescribed injectable or inhalable HAT compared to 12 months continued oral MMT.

Setting: Outpatient treatment in MMT- or specialized HAT-centers in the Netherlands.

Anesthetic block of pain-related cortical activity in patients with peripheral nerve injury measured by magnetoencephalography.

Background: This study examined whether chronic neuropathic pain, modulated by a local anesthetic block, is associated with cortical magnetic field changes.

Methods: In a group of 20 patients with pain caused by unilateral traumatic peripheral nerve injury, a local block with lidocaine 1% was administered and the cortical effects were measured and compared with a control group. The global field power (GFP), describing distribution of cortical activation after median and ulnar nerve stimulation, was plotted and calculated.

Experiences of doctors and nurses implementing nurse-delivered cardiovascular prevention in primary care: a qualitative study.

Aim: This paper reports on a study of the experiences of general practitioners and practice nurses implementing nurse-delivered cardiovascular prevention to high risk patients in primary care.

Background: Difficulties may arise when innovations are introduced into routine daily practice. Whether or not implementation is successful is determined by different factors related to caregivers, patients, type of innovation and context.

Adherence to a guideline on cardiovascular prevention: a comparison between general practitioners and practice nurses.

Background: Patient non-compliance with prescribed treatment is an important factor in the lack of success in cardiovascular prevention. Another important cause is non-adherence of caregivers to the guidelines. It is not known how doctors and nurses differ in the application of guidelines.

Heroin-assisted treatment in the Netherlands: History, findings, and international context.

This monograph describes the history, findings and international context of heroin-assisted treatment (HAT) in the Netherlands. The monograph consists of (1) a short introduction and seven paragraphs describing the following aspects of HAT in the Netherlands: (2) history of HAT studies and implementation of routine HAT in the Netherlands; (3) main findings on efficacy, safety and cost-effectiveness from the two randomized controlled HAT trials in the Netherlands; (4) new findings from a large cohort study on the effectiveness of HAT in routine clinical practice in the Netherlands; (5) unique data on the patient's perspective of HAT; (6) data on the pharmacological and pharmaceutical basis for HAT in the Netherlands; (7) description of the registration process; and (8) account of the international context of HAT. Together, these data show that HAT can now be considered a safe and proven-effective intervention for the treatment of chronic, treatment-resistant heroin dependent patients.

Patient perceptions of nurse-delivered cardiovascular prevention: cross-sectional survey within a randomised trial.

Background: Studies have shown that in general patients are positive about cardiovascular prevention delivered by general practitioners. Further, it has been found that care by nurses for the chronically ill leads to even greater patient satisfaction.

Objective: The aim of this survey was to answer the following questions: How do patients perceive cardiovascular prevention delivered by the practice nurse? Are patient characteristics and personal health status associated with experiences of received nurse-led care?

Design: A cross-sectional survey after completion of a randomised trial.

Effectiveness of nurse-delivered cardiovascular risk management in primary care: a randomised trial.

Background: A substantial part of cardiovascular disease prevention is delivered in primary care. Special attention should be paid to the assessment of cardiovascular risk factors. According to the Dutch guideline for cardiovascular risk management, the heavy workload of cardiovascular risk management for GPs could be shared with advanced practice nurses.

Outcome of long-term heroin-assisted treatment offered to chronic, treatment-resistant heroin addicts in the Netherlands.

Aims: To describe 4-year treatment retention and treatment response among chronic, treatment-resistant heroin-dependent patients offered long-term heroin-assisted treatment (HAT) in the Netherlands.

Design: Observational cohort study.

Setting And Intervention: Out-patient treatment in specialized heroin treatment centres in six cities in the Netherlands, with methadone plus injectable or inhalable heroin offered 7 days per week, three times per day.

Lifestyle factors of a five-year community-intervention program: the Hartslag Limburg intervention.

Background: Community-based health promotion is a widely advocated strategy in public health to favorably alter lifestyle. The aim of this study was to investigate the net effect of a cardiovascular disease-prevention program (Hartslag Limburg) on lifestyle factors after 5 years of intervention (1998-2003).

Methods: In a cohort study, 5-year mean changes in lifestyle factors (energy intake; fat intake; time spent on leisure-time physical activity; walking, bicycling, and sports; and smoking behavior) between subjects from the intervention area (n=2356) and the control area (n=758) were compared for men and women and for those with a low (less than intermediate secondary education) and a moderate (intermediate vocational or higher secondary education) or high (higher vocational education or university) educational level.

A common variant in DRD3 receptor is associated with autism spectrum disorder.

Background: The presence of specific and common genetic etiologies for autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) was investigated for 132 candidate genes in a two-stage design-association study.

Methods: 1,536 single nucleotide polymorphisms (SNPs) covering these candidate genes were tested in ASD (n = 144) and ADHD (n = 110) patients and control subjects (n = 404) from The Netherlands. A second stage was performed with those SNPs from Stage I reaching a significance threshold for association of p < .

Differential genetic regulation of motor activity and anxiety-related behaviors in mice using an automated home cage task.

Traditional behavioral tests, such as the open field test, measure an animal's responsiveness to a novel environment. However, it is generally difficult to assess whether the behavioral response obtained from these tests relates to the expression level of motor activity and/or to avoidance of anxiogenic areas. Here, an automated home cage environment for mice was designed to obtain independent measures of motor activity levels and of sheltered feeding preference during three consecutive days.

Pharmacokinetics and pharmacokinetic variability of heroin and its metabolites: review of the literature.

This article reviews the pharmacokinetics of heroin after intravenous, oral, intranasal, intramuscular and rectal application and after inhalation in humans, with a special focus on heroin maintenance therapy in heroin dependent patients. In heroin maintenance therapy high doses pharmaceutically prepared heroin (up to 1000 mg/day) are prescribed to chronic heroin dependents, who do not respond to conventional interventions such as methadone maintenance treatment. Possible drug-drug interactions with the hydrolysis of heroin into 6-monoacetylmorphine and morphine, the glucuronidation of morphine and interactions with drug transporting proteins are described.

Incidental use of ecstasy: no evidence for harmful effects on cognitive brain function in a prospective fMRI study.

Rationale: Heavy ecstasy use in humans has been associated with cognitive impairments and changes in cognitive brain function supposedly due to damage to the serotonin system. There is concern that even a single dose of 3,4-methylenedioxymethamphetamine may be neurotoxic, but very little is known about the consequences of a low dose of ecstasy for cognitive brain function.

Objectives: The objective of the study was to assess the effects of a low dose of ecstasy on human cognitive brain function using functional magnetic resonance imaging (fMRI).