Addiction Rehab: Effects of APOE on Brain White Matter Microstructure in Healthy Adults.

Effects of APOE on brain white matter microstructure in healthy adults.

Filed under: Addiction Rehab

Neurology. 2012 Oct 24;
Westlye LT, Reinvang I, Rootwelt H, Espeseth T

OBJECTIVES: APOE is related to cholesterol transport and clearance and brain white matter (WM) properties involving myelin, of which cholesterol is a major component. Diffusion tensor imaging enables in vivo investigations of brain WM, and could increase our understanding of the pathways leading to Alzheimer disease. The main objective was to investigate the association between APOE and diffusion tensor imaging-derived indices of WM microstructure. METHODS: Healthy participants were assessed on a range of neuropsychological measures, genotyped, and underwent MRI. A total of 203 volunteers (aged 21.1-69.9 years, mean = 47.6, SD = 14.9) with APOE genotypes ?2/?3 (n = 30), ?3/?3 (n = 113), and ?3/?4 (n = 60) were included. RESULTS: There were widespread increases in mean and radial diffusion in carriers of the ?3/?4 alleles compared with ?3/?3 with medium to strong effect sizes (Cohen’s d = 0.77-0.79). No interactions between genotype and age were observed, indicating relatively stable differences from early adulthood. The results were independent of presence of dementia in close family. We also observed increased mean and radial diffusion and decreased fractional anisotropy in carriers of the ?2/?3 alleles compared with ?3/?3 carriers. No significant differences were found between ?2/?3 and ?3/?4. CONCLUSIONS: APOE affects microstructural properties of the brain WM from early adulthood, but the specific allelic effects do not directly reflect the associated risk of developing Alzheimer disease. The role of APOE in cholesterol transport, the high density of cholesterol in myelin, and the specific effects on radial diffusivity support a putative functional role of APOE in modulating myelin-related processes in the brain.
HubMed – addiction


A Multi-Route Model of Nicotine-Cotinine Pharmacokinetics, Pharmacodynamics and Brain Nicotinic Acetylcholine Receptor Binding in Humans.

Filed under: Addiction Rehab

Regul Toxicol Pharmacol. 2012 Oct 22;
Teeguarden JG, Housand C, Smith JN, Hinderliter PM, Gunawan R, Timchalk C

The pharmacokinetics of nicotine, the pharmacologically active alkaloid in tobacco responsible for addiction, are well characterized in humans. We developed a physiologically based pharmacokinetic/pharmacodynamic model of nicotine pharmacokinetics, brain dosimetry and brain nicotinic acetylcholine receptor (nAChRs) occupancy. A Bayesian framework was applied to optimize model parameters against multiple human data sets. The resulting model was consistent with both calibration and test data sets, but in general underestimated variability. A pharmacodynamic model relating nicotine levels to increases in heart rate as a proxy for the pharmacological effects of nicotine accurately described the nicotine related changes in heart rate and the development and decay of tolerance to nicotine. The PBPK model was utilized to quantitatively capture the combined impact of variation in physiological and metabolic parameters, nicotine availability and smoking compensation on the change in number of cigarettes smoked and toxicant exposure in a population of 10,000 people presented with a reduced toxicant (50%), reduced nicotine (50%) cigarette Across the population, toxicant exposure is reduced in some but not all smokers. Reductions are not in proportion to reductions in toxicant yields, largely due to partial compensation in response to reduced nicotine yields. This framework can be used as a key element of a dosimetry-driven risk assessment strategy for cigarette smoke constituents.
HubMed – addiction


The Neurobiological Underpinnings of Obesity and Binge Eating: A Rationale for Adopting the Food Addiction Model.

Filed under: Addiction Rehab

Biol Psychiatry. 2012 Oct 22;
Smith DG, Robbins TW

The food addiction model of overeating has been proposed to help explain the widespread advancement of obesity over the last 30 years. Parallels in neural substrates and neurochemistry, as well as corresponding motivational and behavioral traits, are increasingly coming to light; however, there are still key differences between the two disorders that must be acknowledged. We critically examine these common and divergent characteristics using the theoretical framework of prominent drug addiction models, investigating the neurobiological underpinnings of both behaviors in an attempt to justify whether classification of obesity and binge eating as an addictive disorder is merited.
HubMed – addiction



REHAB-My Addiction HD – REHAB on the Kid Rock’s Chillin the most Cruise 05/02/10. Shot by LoudMouth


Related Addiction Rehab Information…