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Posts Tagged ‘Emotion’

Brain biomarkers in action

Posted in Uncategorized, tagged , , on September 13, 2008| Leave a Comment »

female reading emotionsImage by -kÇ- via Flickr Session 4 of our discussion group, “When Basic Neuroscience Meets Psych Rehab” will meet on Sept 25. This session will cover the topic of ‘affect labeling’ which is one strategy for managing one’s emotions. Did you know there are 3,000+ words you can choose from to describe your feelings ? How many can you name right off the bat ? The discussion seeks to flesh out the way in which basic brain mechanisms of emotional regulation work and how brain-based (and genetic) biomarkers might be used in a clinical therapy/rehabilitation setting. Slides and discussion highlights will be posted to the website.

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Benevolent dictators have longer AVPR1a promoters

Posted in AVPR1a, G-protein, OTR, tagged , on May 26, 2008| Leave a Comment »

The Great Dictator
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The small neuropeptides oxytocin (OT) and arginine-vasopressin (AVP) are well known for their influence on promoting warm-and-fuzzy social behaviors in mammals. The G-protein coupled OTR and AVPR1a receptors are also the subject of much research in this area – particularly AVPR1a – since it shows differences in brain expression in polygamous vs. monogamous vole species, and also shows genetic associations with dysfunction in human social affiliation. In a recent foray into this line of research, Richard Ebstein and colleagues examine whether an individual’s willingness to give away a cache of money is related to genetic variation in the promoter of the AVPR1a. In their paper, “Individual differences in allocation of funds in the dictator game associated with length of the arginine vasopressin 1a receptor RS3 promoter region and correlation between RS3 length and hippocampal mRNA“, the researchers asked 203 college students to play the “dictator game” where, simply, one person gets a sum of money and can choose to keep it or give some of it away to the other player. Thats it. Give some of it away if you like, or just walk away with all of it, no questions asked & no consequences (your identity and the identity of the other player are masked). Amazingly, individuals actually DO give some of the money away (15% gave none of it away, 35% gave half away and 7% gave all – yes, all of it – away) … and more amazing still … those with longer stretches of microsatellite repeats at the RS1 & RS3 promoter sites in the AVPR1a gene, gave away significantly more money than individuals with shorter version of the repeats.

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rs4675690 C-allele steers my left insula away from angry old farts

Posted in CREB, Insula, tagged , , , on May 14, 2008| Leave a Comment »

Angry face
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Indeed, learning how to manage one’s response to the negative emotions of others and stay out of trouble is an important life skill. At some point, most of us learn to just avoid angry, mean or melodramatically negative people and save ourselves the strife. Roy Perlis and colleagues, in their recent paper, “Association of a Polymorphism Near CREB1 With Differential Aversion Processing in the Insula of Healthy Participants“, show how the transcriptional regulator CREB might exert an influence on this learning process. By having subjects view images of various facial expressions, the investigators found that individuals with the TT genotype at rs4675690 (C/T) showed less negative activation in the left insula, a brain region that is known to activate when subjects feel disgust, but not happiness, desire or fear. Subjects with the TT genotype have been shown to require more effort in the management of negative emotions and are at greater risk for suicide when being treated for depression. In the Perlis et al., study, TT subjects showed less of an effort (as measured in key presses) to avoid viewing emotionally distressing pictures. The known role of CREB in neural plasticity suggests that this gene may facilitate neural changes associated with memory. Unfortunately, 23andMe does not cover this SNP, so I’ll just have to hope that (during the upcoming election) my insula keeps me on the path to enlightenment.

Update: Thanks so very much Brian for the info on rs7591784. This explains a lot – I’m a GG here, which means I’m a TT at rs4675690 – and have always had difficulty handling it when folks are rude to me.

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Nothing is so much to be feared as the proton sensor ASIC1a

Posted in Amygdala, ASIC1a, Cingulate cortex, Glutamate, Stria terminalis, tagged , , on December 14, 2007| Leave a Comment »

One of several versions of the painting Image via Wikipedia Many of the unpleasant feelings and physiological changes associated with fear and anxiety can be traced back to a tiny brain region known as the amygdala. Neuroimaging studies often find this region abnormally active in people having difficulty down-regulating negative emotions. It is no surprise then, that when genes that regulate innate fear and the reactivity of this brain region are identified there is much hope for future medications that might target these biochemical pathways and relieve emotional suffering. So it is that Coryell and colleagues identify such a gene, ASIC1a, the acid sensing ion channel 1a, and report in their paper, “Targeting ASIC1a Reduces Innate Fear and Alters Neuronal Activity in the Fear Circuit” (DOI) and report that more expression of this gene results in mice with more innate fear and, that less expression or blockade of this gene results in less innate fear. The gene appears expressed in a well-studied fear circuit including the cingulate cortex, the amygdala and the bed nucleus of the stria terminalis, so any type of pharmacologic manipulation would be predicted to affect the entire fear circuit. The normal function of ASIC1a – a proton sensor – is presumably to regulate pH within and/or across cell membranes. Such changes in pH are known to affect synaptic transmission in a manner such that lower pH inhibits NMDA channels and higher pH activates NMDA channels, so it is possible that the effects of ASIC1a on fear may be ultimately due to effects on synaptic plasticity. An exciting candidate not to be feared.

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rs6265 (A) is my bodyguard

Posted in BDNF, Nucleus accumbens, Striatum, Ventral tegmental area, tagged , , on November 19, 2007| Leave a Comment »

It’s generally not fun to be browbeaten, bullied, bulldozed or downright oppressed – by the schoolyard bully or perhaps the micromanaging boss – in any form. While we’ve all been there – sometimes with initial feelings of sorrow, mopiness, lethargy, etc. – all part of the normal adaptive response to just pack-it-in and withdraw, the effects of social stress in some individuals can be quite profound and serious. The recent paper, “Molecular Adaptations Underlying Susceptibility and Resistance to Social Defeat in Brain Reward Regions” by Krishnan and company (DOI) provides some insight into mechanisms of social stress and how several genetic factors are implicated in the regulation of activity of a particular synapse linking the ventral tegmental area (VTA) and nucleus accumbens (NAc). Of particular interest is the protective effect of a single G to A nucleotide change (rs6265) in the brain derived neurotrophic factor (BDNF) that leads to a valine to methionine amino acid substitution at position 66, a portion of the protein thought to play a role in cytoplasmic trafficking. As reported, transgenic mice that carry the human form of the poorly secreted Met/Met form of BDNF did not suffer a typical withdrawl, depression-like syndrome when subjected to a paradigm of chronic social defeat as compared to defeated Val/Val (highly secreted form) mice. In correspondence with this finding, higher levels of BDNF were found in the NAc in human cases of human depression. The authors’ work provides a new mechanistic model for regulation of VTA-NAc synaptic activity that makes testable predictions about complex behaviors and avenues for prevention and remediation of one of life’s unpleasant, but inevitable, tribulations.

…darn-it !  my 23andMe profile shws that I am a C/C valine/valine … how depressing 😦

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Neurobiology of Love: Is that AVPR1A postsynaptic excitation in your septum or are you just happy to see me ?

Posted in AVPR1a, Hypothalamus, Lateral septum, tagged , on October 29, 2007| Leave a Comment »

Woody Allen in concert in New York City.
Image via Wikipedia

“Love is the answer, but while you’re waiting for the answer, sex raises some pretty interesting questions” so says Woody Allen. Indeed, whether you’re in love or lust, the tiny neuropeptide arginine vasopressin (AVP) is your pal. Recently, Thompson et al., found that AVP increases the perception of friendliness in females exposed to unfamiliar faces (‘tend and befriend’ a stranger), while lowering the perception of friendliness in males (the more typical aggressive response to a stranger). The fascinating modulatory effects of AVP on social affiliation are now better understood in light of the work of Allaman-Exertier and colleagues who explored the relationship between the AVPR1A receptors and the neural circuitry that underlie complex behaviors and feelings of amour. The paper is focused on the lateral septal area which is rich in vasopressinergic axons and contains high amounts of AVPR1A receptors. Mice that lack a particular type of vasopressin receptor, AVPR1A, for example, are impaired in the recall and recognition of social encounters – but, replacing the receptor just in the lateral septum, is enough to restore social recognition. The AVPR1A receptors mediate both excitatory and inhibitory post-synaptic effects within the septal area and thus can modulate activity in downstream centers such as the hypothalamus.

Note: this tid bit of knowledge will not assist in the fulfillment of romantic endeavors !

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Genetic insights into “chicks dig smelly guys” hypothesis

Posted in MHC loci, tagged , , , on October 14, 2007| Leave a Comment »

Armpit
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“Hey, you with the smelly armpits, how about a date ?”

Ahhh, if only this were true ! Sadly, not. However, it would appear that females eschewing us slovenly males may doth protest too much. Recall the popular science lab where females rank their preference to the smell of sweaty t-shirts of unshowered male classmates. Typically, this lab involves the genotyping of a number of Major Histocompatibility (MHC) gene polymorphisms and comparisons that show females prefer the odor of dissimilar MHC genotype. There are, however, well known clusters of odorant receptor genes within the MHC gene super-clusters and these may provide a more direct link from odor to preference. Liza Gross describes related findings in her article, “A Genetic Basis for Hypersensitivity to “Sweaty” Odors in Humans,” where the dosage of an olfactory receptor gene OR11H7P correlated with sensitivity to the odorant isovaleric acid. Although OR11H7P is not located within the commonly assayed MHC super-cluster on human 6p, it is a sweet-smelling step toward understanding mechanisms of female choice.

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Genetics and emotional memory – a view from Rawanda

Posted in ADRA2A, Noradrenaline, tagged , , on June 2, 2007| Leave a Comment »

Map showing principal routes in RwandaImage via Wikipedia

Dominique JF de Quervain and colleagues provide an elegant example of how genetic differences can relate to complex traits such as the ability to recall emotionally laden experiences. In their recent Nature Neuroscience paper, they looked at a deletion of 3 glutamic acid residues (301–303) in the third intracellular loop of the alpha-2-adrenergic receptor and its relation to emotional memory. Since emotion-laden experience (fight-or-flight) is often accompanied by surges in noradrenaline, it makes sense that adrenergic receptors might facilitate such memories. In this case, the deletion genetic variant encodes a slightly less effective receptor whose carriers show enhanced recall of positive and negatively charged images – a memory effect that is similarly achieved when the receptor is blocked using the antagonist yohimbine.

Such genetic findings can lend themselves quickly to practical applications. One first step to begin to understand how the ADRA2B genetic influence might be used to help alleviate the sometimes debilitating effects of persistent emotional memory was an examination of individuals who fled from the Rwandan civil war and were living in the Nakivale refugee camp in Uganda at the time of investigation. Individuals who carry the deletion genetic variant were more likely to re-experience symptoms of traumatic events although, this particular variant is present at relatively low frequencies (about 1 in 8 individuals are carriers).

Readers may wish to learn more about the Rawandan Civi War and explore channels for aid including Rawanda-Aid and Genocide Intervention.

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