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Posts Tagged ‘Nicotine’

It has been reported that cigarettes can impart some calm and clarity from racing thoughts and mental fog. Patients with schizophrenia, who often experience cognitive disorganization, are 2-4 times more likely than the general population to smoke, and also seem to prefer stronger brands of cigarettes. This is not surprising since nicotine can raise levels of dopamine indirectly via stimulation of alpha4/beta2 high affinity nicotinic acetyl choline receptors (nAChR) expressed widely in the parietal cortex of the human brain. In an open access article entitled, “Association of attentional network function with exon 5 variations of the CHRNA4 gene“, Georg Winterer and colleagues demostrate that individuals who vary in a synonymous G/A variant (rs1044396) in the CHRNA4 gene – an snp which has previously been associated with nicotine dependence – show differential brain activity in the parietal cortex. When asked to remain alert and respond to rare visual “oddball” stimuli (visual oddball detection task), subjects with the AA genotype showed robust brain activity in the parietal cortex while subjects with the GG genotype showed very little change in activity. This finding reveals where in the brain – circuits connecting to the parietal cortex – may be especially important in mediating self-medication and even in the management of side-effects in psychiatric pharmacotherapy. Although rs1044396 is not measured in my 23andMe profile, the neighboring rs3787138 showing tight LD is measured and reveals that I am a boring, middle of the road heterozygote. As such, I do admit that I could use some mind-clearing relief from time to time – but, the yellow teeth are not quite worth it.

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In a recent free and open BMC report on gene expression in non-smokers vs. current smokers vs. quitters, Chari and colleagues identify a class of genes whose expression “appears to be permanently altered despite prolonged smoking cessation.” Frighteningly, a number of genes encoding DNA repair enzymes are irreversibly altered … definitely not good to mutagenize your genome and then knock out the repairman. Worse yet, another gene that popped up was calcium binding tyrosine-(Y) phosphorylation regulated (CABYR) a gene that is found in the sperm flagellum, lung and brain (these are all tissues with cells that are rich in microtubules and dynein motors – so perhaps CABYR plays a smoking-related role in the lung in ciliary clearance of mucous). Wait a minute, did someone say sperm cell ? Ouch – no more cigarettes please. Although, the effects of smoking on CABYR expression were reversible, I don’t need a direct mutagenic hit there to make me wince, just thinking about that is enough.

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A 21 mg patch applied to the left arm
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Uhl and colleagues present a genome-wide search for SNPs that distinguish smokers (nicotine dependence) – and perhaps more importantly – successful smoking quitters, in their recent article in the free and open-access journal BioMed Central. As pointed out in the article, this work is a step closer to personalized “efforts to match vulnerable individuals with the prevention and treatment strategies most likely to work for them.” A set of genetic variants that distinguish nicotine dependence from a control population with no personal history of smoking or substance abuse was identified and a novel set of variants that distinguish folks who’ve had success after using the patch and other self-help methods are exciting new tools that were produced by the study.

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