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Posts Tagged ‘Addiction’

Deep-fried onion rings arranged in a line on a...Image via Wikipedia To go out tonight or stay home? Hillary or Barack? Curly fries or onion rings? How do I make these important choices and why will others decide differently? Although there are many reasons for not stressing-out and over-thinking one’s decisions (except for really important choices like curly fry vs. onion ring), it turns out that variation in your genome, in particular, 3 dopaminergic genes (DARPP-32, DRD2 and COMT: rs907094, rs1800496, rs4680) are influencing your tendency to ‘go for it’ or not to go for it. Frank and colleagues, in their paper, “Genetic triple dissociation reveals multiple roles for dopamine in reinforcement learning“, give an in-depth treatment of the neurobiology underlying decision making and reinforcement learning. After carefully reviewing the basic biology of dopaminergic synapses and selecting 3 candidate genetic variants, they find that each is associated with an independent aspect of decision making in a learning paradigm. The paper is an excellent example of how genetic variation can be linked to specific neural processes. Now bring on the curly fries – no wait – the onion rings.

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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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I much enjoyed Helen Mayberg’s October 13th podcast, “Paths to Recovery in Major Depression: Insights from Functional Neuroimaging” hosted by Science & the City, the webzine of the NY Academy of Science. One comment that stuck with me was her mention of ‘brain-based algorithms’ for the diagnosis and treatment of mental illness. Indeed, from her talk, there are many brain regions involved in the regulation of mood and that individuals who experience depression may show poor activity in any or all of these brain regions. Also, Dr. Mayberg shows that these various brain regions may be more or less responsive to drug- vs. talk-based therapies. This seems like a major step forward in personalized medicine in psychiatry and perhaps might be augmented by other biomarkers. Presently, scanning is somewhat cumbersome relative to current drug-trial-and-error regimens, but the benefits of recovery far, far outweigh the costs of a lifetime of chronic illness.

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