A Single Gene Controls Emotional Recall!

And the neurotransmitter norepinephrine (NE), which has been in the news lately, plays a key role in the overstated headline of the day:

Emotional recall is in your genes
18:00 29 July 2007
Paul Marks

Image from Fig. 1A of Depue et al. (2007)

Your ability to recall emotional events – such as meeting the love of your life, or the trauma of a painful car crash – is governed by a common variation in a single gene, according to a new study. [NOTE: As if variations in many other genes were tested.]

. . .

Highly emotive incidents trigger the brain to release the hormone and neurotransmitter noradrenaline. This stimulates the amygdala – part of the brain involved with processing emotional reactions – to store memories in the hippocampus and other parts of the brain, says Dominique de Quervain, a neuroscientist at the University of Zurich in Switzerland.

Yet for some reason, recall of emotional events varies a great deal from person to person. So de Quervain wondered if common variations in a gene called ADRA2B, which codes for [one of the subtypes of the alpha-2] noradrenaline receptor, could be responsible. Some 30 per cent of Caucasians and 12 per cent of Africans possess this variant, he says.

So this is the alpha-2 receptor, which responds to clonidine (agonist) and yohimbine (antagonist), rather than the beta-2 receptor, which is antagonized by our old friend, propranolol. According to the NCBI Sequence Viewer v2.0 Summary on ADRA2B adrenergic, alpha-2B-, receptor [Homo sapiens]:

Alpha-2-adrenergic receptors are members of the G protein-coupled receptor superfamily. They include 3 highly homologous subtypes: alpha2A, alpha2B, and alpha2C. These receptors have a critical role in regulating neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system. This gene encodes the alpha2B subtype, which was observed to associate with eIF-2B, a guanine nucleotide exchange protein that functions in regulation of translation. A polymorphic variant of the alpha2B subtype, which lacks 3 glutamic acids from a glutamic acid repeat element, was identified to have decreased G protein-coupled receptor kinase-mediated phosphorylation and desensitization; this polymorphic form is also associated with reduced basal metabolic rate in obese subjects and may therefore contribute to the pathogenesis of obesity. This gene contains no introns in either its coding or untranslated sequences.

Let's return to the New Scientist article.

One group comprised healthy Swiss citizens and the other comprised traumatised survivors of the Rwandan genocide – who were living in a refugee camp in Uganda.

The researchers found that, in both groups, people carrying the ADRA2B gene variant were "substantially more likely" to remember both positive and negative pictures than people with other forms of the gene. Neutral images were recalled to the same degree by people with and without the variant.

However, Rwandans with the variant had far higher recall of negative emotional events than the Europeans who carried it – and this was unrelated to whether or not they suffered from post traumatic stress disorder.

"The genetic variant is related to enhanced emotional memory," concludes de Quervain. "But it also appears to predispose people to stronger traumatic memories when something terrible happens."

Is that the same as saying that a single gene governs your ability to recall emotional events? It certainly appears to influence one's ability to recall emotional events, whether pleasant, unpleasant, or traumatic. That's not to say, however, that other genes do not have any influence over such complicated cognitive and affective processes.

In the paper (de Quervain et al., 2007), a large group of normal Swiss participants (n=435) was shown a series of photographs from the International Affective Picture Set (10 each positive, negative, and neutral in emotional content) and asked to rate them on valence and arousal. Ten minutes later, they were asked to recall the words. Overall, the participants showed an advantage in recalling emotional words relative to neutral words: 57% better for positive and 55% for negative. The breakdown for carriers and noncarriers of the variant are shown in the table below, which illustrates that the carriers showed a significantly greater enhancement in emotional recall.

SWISS
All emotional pictures
carriers (N = 214)	78% +/- 7%
noncarriers (N = 221)	43% +/- 6%
Positive
carriers	77% +/- 8%
noncarriers	43% +/- 7%
Negative
carriers	79% +/- 7%
noncarriers	43% +/- 6%

The second group of participants had survived one of the most horrific events of the 20th century: the 1994 genocide of 1,000,000 human beings in Rwanda over the course of only 100 days (Survivors Fund, SURF). These individuals were in a refugee camp and were recruited to participate not in the trivial picture recall task, but to report their experiences in a clinical setting. At this point, it's best to quote the paper directly:

We hypothesized that deletion carriers would have increased emotional memory for traumatic events reflected in increased re-experiencing symptoms. We tested this hypothesis in 202 refugees who had fled from the Rwandan civil war and were living in the Nakivale refugee camp in Uganda at the time of investigation (100 females, 102 males; median age, 34 years...). All subjects had experienced multiple, highly aversive situations and were examined by trained experts with a structured interview based on the Post-traumatic Diagnostic Scale with the help of trained interviewers chosen from the refugee community. Traumatic events were assessed using a checklist of 31 war- and nonwar-related traumatic-event types (for example, injury by a weapon, rape, accidents). The population consisted of 133 subjects fulfilling the diagnostic criteria of DSM-IV for post-traumatic stress disorder (PTSD) and 69 subjects without PTSD or a history of PTSD. Deletion carriers had a significantly higher score for re-experiencing symptoms per traumatic-event type than did noncarriers (carriers, N=42, 0.47 +/- 0.05; noncarriers, N=160, 0.31 +/- 0.03), whereas the deletion was not significantly associated with hyperarousal or avoidance symptoms. The association of the deletion with increased traumatic memory was independent of the presence of PTSD ... and the genotype was equally distributed across the diagnostic groups. Correcting for gender did not influence the genotype effect on traumatic memory.

Fig. 3 (de Quervain et al., 2007)

The authors' conclusion:

Taken together, we show that a genetically anchored alteration in the noradrenergic system is related to enhanced emotional memory in healthy young Swiss subjects. Furthermore, we found that the same genetic alteration is related to increased traumatic memory in a Sub-Saharan African population of civil war refugees who experienced multiple and highly aversive emotional situations. The present findings suggest that the price for the deletion-related enhancement of emotional memory may be enhanced intrusive and distressing emotional memory for traumatic events.

Reference

de Quervain DJ, Kolassa IT, Ertl V, Onyut PL, Neuner F, Elbert T, Papassotiropoulos A. (2007). A deletion variant of the alpha 2b-adrenoceptor is related to emotional memory in Europeans and Africans. Nature Neurosci. Published online: 29 July 2007.

Emotionally arousing events are recalled better than neutral events. This phenomenon, which helps us to remember important and potentially vital information, depends on the activation of noradrenergic transmission in the brain. Here we show that a deletion variant of ADRA2B, the gene encoding the alpha2b-adrenergic receptor, is related to enhanced emotional memory in healthy Swiss subjects and in survivors of the Rwandan civil war who experienced highly aversive emotional situations.

Symbol Report: ADRA2B