As a big fan of black and white photography, I’m intrigued by the concept of “Splitting” or so-called “black and white” thinking. It’s something we all do to different degrees … when we avoid dealing with the “shades of gray” and group things in our life into “all good” or “all bad” groups.
Psychologists have considered this cognitive tendency to be a normal part of cognitive development (eg. good guys vs. bad guys), a response to stress, and also a part of various psychopathologies (funny, how psychiatrists have a tendency to group us into the “normal” and “abnormal”, huh?).
Is there anything wrong with seeing the world in black and white? Perhaps, if you label mildly annoying people as “bad”, you’ll soon have no friends … but otherwise, I’m not sure. Simplicity can be soothing.
I mean, our brains have a strong tendency to work at the extremes … for example, when it comes to cognition and movement. We’re wired with so-called striatonigral (Go) and striatopallidal (NoGo) neural pathways that are engaged when cognition is transduced into action. In the primal world of our ancestors, we didn’t survive very long if we danced around fretfully pondering the costs and benefits of running, or not running, from saber tooth tigers! So, it’s no surprise, that we’re inherently uncomfortable in the wishy-washy, indecisive, muddling middle ground when making a decision. We want to “go” or “freeze”, “do it” or “don’t”, “good” or “bad” … just make a f**king decision already.
Here’s a link to some current research on the “Go” and “NoGo” brain systems … and their genetic underpinnings (eg. the DRD2 protein is active when we are flummoxed with uncertainty which keeps us lingering in the NoGo state). Hey, our genome got us here … in one piece … it helped us stay alive … that’s not necessarily a bad thing.
thanks for the pic amadeus
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Posted in ADORA2A, DRD2, Uncategorized, tagged 23andMe, Anxiety, Brain, Caffeine, Coffee, Cognition, Disorders, DNA, evolution, Genetic testing, Genetics, Mental disorder, Mental health, panic disorder, Personalized medicine, Psychoactive drug, Starbucks, Stress on March 4, 2010 |
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If you’re a coffee drinker, you may have noticed the new super-sized portions available at Starbucks. On this note, it may be worth noting that caffeine is a potent psychoactive substance of which – too much – can turn your buzz into a full-blown panic disorder. The Diagnostic and Statistical Manual for psychiatry outlines a number of caffeine-related conditions mostly involving anxieties that can arise when the natural alertness-promoting effects are pushed to extremes. Some researchers have begun to explore the way the genome interacts with caffeine and it is likely that many genetic markers will surface to explain some of the individual differences in caffeine tolerance.
Here’s a great paper, “Association between ADORA2A and DRD2 Polymorphisms and Caffeine-Induced Anxiety” [doi: 10.1038/npp.2008.17] wherein polymorphisms in the adenosine A2A receptor (ADORA2A encodes the protein that caffeine binds to and antagonizes) – as well as the dopamine D2 receptor (DRD2 encodes a protein whose downstream signals are normally counteracted by A2A receptors) — show associations with anxiety after the consumption of 150mg of caffeine (about an average cup of coffee – much less than the super-size, super-rich cups that Starbucks sells). The variants, rs5751876 (T-allele), rs2298383 (T-allele) and rs4822492 (G-allele) from the ADORA2A gene as well as rs1110976 (-/G genotype) from the DRD2 gene showed significant increases in anxiety in a test population of 102 otherwise-healthy light-moderate regular coffee drinkers.
My own 23andMe data only provides a drop of information suggesting I’m protected from the anxiety-promoting effects. Nevertheless, I’ll avoid the super-sizes.
rs5751876 (T-allele) C/C – less anxiety
rs2298383 (T-allele) – not covered
rs4822492 (G-allele) – not covered
rs1110976 (-/G genotype) – not covered
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Posted in DRD2, tagged advertisement, Art, meme-art on December 8, 2009 |
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Posted in COMT, DARPP32, DRD2, Uncategorized, tagged Artificial Intelligence, Basal Ganglia, Brown University, Cognition, Cognitive science, Dopamine, economics, interviews, podcasts, Working memory on August 18, 2009 |
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If you’re interested in the neurobiology of learning and decision making, then you might be interested in this brief interview with Professor Michael Frank who runs the Laboratory of Neural Computation and Cognition at Brown University.
From his lab’s website: “Our research combines computational modeling and experimental work to understand the neural mechanisms underlying reinforcement learning, decision making and working memory. We develop biologically-based neural models that simulate systems-level interactions between multiple brain areas (primarily basal ganglia and frontal cortex and their modulation by dopamine). We test theoretical predictions of the models using various neuropsychological, pharmacological, genetic, and neuroimaging techniques.”
In this interview, Dr. Frank provides some overviews on how genetics fits into this research program and the genetic results in his recent research article “Prefrontal and striatal dopaminergic genes predict individual differences in exploration and exploitation”. Lastly, some lighthearted, informal thoughts on the wider implications and future uses of genetic information in decision making.
To my mind, there is no one else in the literature who so seamlessly and elegantly interrelates genetics with the modern tools of cognitive science and computational neurobiology. His work really allows one to cast genetic variation in terms of its influence on neural computation – which is the ultimate way of understanding how the brain works. It was a treat to host this interview!
Click here for the podcast and here, here, here for previous blog posts on Dr. Frank’s work.
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The selection and dosing of medication in psychiatry is far from scientific – even though a great deal of hard science goes into the preclinical design and clinical development. One reason, among many, has to do with the so-called ‘inverted-U-shaped’ relationship between the dose of a psychoactive compound and an individuals’ performance. Some folks show dramatic improvement with a given dose (their system may be functioning down at the low side of the inverted U mountain and hence, and added boost from medication may send their system up in performance), while others may actually get worse (those who are already at the peak of the inverted U mountaintop). How can a psychiatrist know where the patient is on this curve – will the medication boost raise or topple their patient’s functioning ? Some insight comes in the form of a genetic marker closely linked to the DRD2 gene, that as been shown to predict response to a dopaminergic drug.
Michael Cohen and colleagues, in their European Journal of Neuroscience paper (DOI: 10.1111/j.1460-9568.2007.05947.x) entitled, “Dopamine gene predicts the brain‘s response to dopaminergic drug” began with a polymorphism linked to the DRD2 gene wherein one allele (TaqA1+) is associated with fewer DRD2 receptors in the striatum (these folks should show improvement when given a DRD2 agonist) while folks with the alternate allele (TaqA1-) were predicted to show a falling off of their DRD2 function in response to additional DRD2 stimulation. The research team then asked participants to perform a cognitive task – a learning task where subjects use feedback to choose between a ‘win’ or ‘not win’ stimulus – that is well known to rely on proper functioning of DRD2-rich frontal and striatal brain regions.
Typically, DRD2 agonists impair reversal learning and, as expected, subjects in the low DRD2 level TaqA1+ genetic group actually got “more” impaired – or perseverated longer on rewarding stimuli and required more trials to switch on the go and figure out which stimulus was the “win” stimulus. Similarly, when differences in brain activity between baseline and positive “you win” feedback was measured, subjects in the drug treated, TaqA1+ genetic group showed an increase in activity in the putamen and the medial orbitofrontal cortex while subjects in the TaqA1- showed decreases in brain actiity in these regions. The authors suggest that the TaqA1+ group generally has a somewhat blunted response to positive feedback (sore winners) but that the medication enhanced the frontal-striatal reaction to positive feedback. Functional connectivity analyses showed that connectivity between the frontal cortex and striatum was worsened by the DRD2 agonist in the TaqA1+ genetic group and improved in the TaqA1- group.
Although the interpretations of these data are limited by the complexity of the systems, it seems clear that the TaqA1 genetic marker has provided a sort of index of baseline DRD2 function that can be useful in predicting an individual’s relative location on the theoretical inverted-U-shaped curve.
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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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