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Emotional enhancement of memory is a widely accepted phenomenon that, in addition to its adaptive role, may play a role in the evolution of psychiatric disorders. Hence a comprehensive understanding of its neurobiological basis is imperative. Whilst the pharmacological and neural mechanisms are well known, the contribution of genetic variation is not. Research suggests that two qualitatively different processes (recollection and familiarity) contribute to recognition memory. In this study, we examined the relative contribution of two common genetic polymorphisms, the deletion variant of the ADRA2B gene that codes the α2b adrenergic receptor and the val158met polymorphism of the COMT gene that codes the catechol-O-methyltransferase enzyme, to emotional enhancement of these two memory processes in 97 healthy male volunteers. There was a significant interaction between COMT genotype and emotional arousal in relation to recollection, but not familiarity, with the former being significantly elevated for emotionally arousing versus neutral pictures in carriers of the val158 allele compared with met158 carriers. There were no main effects or interactions in relation to ADRA2B genotype. [ABSTRACT FROM PUBLISHER]

Background: Catechol-O-methyltransferase (COMT) metabolizes catecholamines in the prefrontal cortex (PFC). A common polymorphism in the COMT gene (COMT val158met) has pleiotropic effects on cognitive and emotional processing. The met allele has been associated with enhanced cognitive processing but impaired emotional processing relative to the val allele., Methods: We genotyped healthy, white men in relation to the COMT val158met polymorphism. They were given a single 4 mg dose of the selective noradrenaline reuptake inhibitor (NRI) reboxetine or placebo in a randomized, double-blind between-subjects model and then completed an emotional memory task 2 hours later., Results: We included 75 men in the study; 41 received reboxetine and 34 received placebo. In the placebo group, met/met carriers did not demonstrate the usual memory advantage for emotional stimuli that was observed in val carriers. Reboxetine restored this emotional enhancement of memory in met/met carriers, but had no significant effect in val carriers., Limitations: We studied only men, thus limiting the generalizability of our findings. We also relied on self-reported responses to screening questions to establish healthy volunteer status, and in spite of the double-blind design, participants were significantly better than chance at identifying their intervention allocation., Conclusion: Emotional memory is impaired in healthy met homozygotes and selectively improved in this group by reboxetine. This has potential translational implications for the use of reboxetine, which is currently licensed as an antidepressant in several countries, and edivoxetine, a new selective NRI currently in development.

Evidence suggests that emotional memory plays a role in the pathophysiology of depression/anxiety disorders. Noradrenaline crucially modulates emotional memory. Genetic variants involved in noradrenergic signaling contribute to individual differences in emotional memory and vulnerability to psychopathology. A functional deletion polymorphism in the α-2B adrenoceptor gene (ADRA2B) has been linked to emotional memory and post-traumatic stress disorder. The noradrenaline reuptake inhibitor reboxetine attenuates enhanced memory for negative stimuli in healthy and depressed individuals. We examined whether the effect of reboxetine on emotional memory in healthy individuals would be moderated by ADRA2B genotype. ADRA2B deletion carriers demonstrated enhanced emotional memory for negative stimuli compared with deletion noncarriers, consistent with prior studies. Reboxetine attenuated enhanced memory for negative stimuli in deletion noncarriers but had no significant effect in deletion carriers. This is the first demonstration of genetic variation influencing antidepressant drug effects on emotional processing in healthy humans.

Individual differences in emotional processing are likely to contribute to vulnerability and resilience to emotional disorders such as depression and anxiety. Genetic variation is known to contribute to these differences but they remain incompletely understood. The serotonin transporter (5-HTTLPR) and α2B-adrenergic autoreceptor (ADRA2B) insertion/deletion polymorphisms impact on two separate but interacting monaminergic signalling mechanisms that have been implicated in both emotional processing and emotional disorders. Recent studies suggest that the 5-HTTLPR s allele is associated with a negative attentional bias and an increased risk of emotional disorders. However, such complex behavioural traits are likely to exhibit polygenicity, including epistasis. This study examined the contribution of the 5-HTTLPR and ADRA2B insertion/deletion polymorphisms to attentional biases for aversive information in 94 healthy male volunteers and found evidence of a significant epistatic effect (p<0.001). Specifically, in the presence of the 5-HTTLPR s allele, the attentional bias for aversive information was attenuated by possession of the ADRA2B deletion variant whereas in the absence of the s allele, the bias was enhanced. These data identify a cognitive mechanism linking genotype-dependent serotonergic and noradrenergic signalling that is likely to have implications for the development of cognitive markers for depression/anxiety as well as therapeutic drug effects and personalized approaches to treatment.

The COMT val(158) variant has been associated with impaired cognitive function compared to the met(158) variant yet gene-gene interactions are not well described. In this study we demonstrate an interaction between this COMT polymorphism and a deletion variant of ADRA2B, the gene encoding the alpha2b-adrenergic receptor on episodic memory performance. Specifically, carriage of the ADRA2B deletion abolished the relative memory impairment in homozygous COMT val(158) carriers compared to met(158) carriers., (2009 Elsevier B.V. and ECNP. All rights reserved.)

Background: Few attempts have been made to examine the relationship between amygdala abnormalities and specific symptoms in psychosis. The present study explored the relationship between amygdala morphology and mood congruent and mood incongruent delusional beliefs., Methods: Amygdala volumes were measured in 43 patients presenting with delusional beliefs in the context of their first episode of psychosis and 43 healthy volunteers matched for age and gender., Results: Left-greater-than-right-asymmetry of the amygdala varied as a function of gender and mood congruence of delusional beliefs, due to asymmetrical enlargement of the left amygdala in women presenting with predominantly mood incongruent delusions. However, there was no difference in amygdala volumes across groups., Conclusions: Amygdala abnormalities in women may be associated with aberrant emotional processing that could contribute to the development of mood incongruent delusional beliefs. Sexually dimorphic changes in the amygdala may contribute to differential phenotypic illness expression in men and women.

Objective: Cognitive models suggest that biased processing of emotional information may play a role in the genesis and maintenance of psychotic symptoms. The role of dopamine and dopamine antagonists in the processing of such information remains unclear. The authors investigated the effect of a dopamine antagonist on perception of, and memory for, emotional information in healthy volunteers., Method: Thirty-three healthy male volunteers were randomly assigned to a single-blind intervention of either a single dose of the dopamine D(2)/D(3) antagonist amisulpride or placebo. An attentional blink task and an emotional memory task were then administered to assess the affective modulation of attention and memory, respectively., Results: A significant interaction was observed between stimulus valence and drug on recognition memory accuracy; further contrasts revealed enhanced memory for aversive-arousing compared with neutral stimuli in the placebo but not the amisulpride group. No effect of amisulpride was observed on the perception of emotional stimuli., Conclusions: Amisulpride abolished the enhanced memory for emotionally arousing stimuli seen in the placebo group but had no effect on the perception of such stimuli. These results suggests that dopamine plays a significant role in biasing memory toward emotionally salient information and that dopamine antagonists may act by attenuating this bias.

Unlabelled: Although there only have been a limited number of double-blind, placebo controlled trials, antipsychotics are considered to be effective drugs for the treatment of tics in Gilles de la Tourette syndrome (GTS). Evidence concerning the efficacy of olanzapine and other atypical antipsychotics in the treatment of tics in GTS is growing, but still limited. Little is known about the use of olanzapine in adult GTS patients and about its effect on comorbid behavioural problems. We report on the use of olanzapine in a 25-year old male GTS patient with comorbid obsessive-compulsive behaviours, who was treated with olanzapine. Tic severity was rated using the Yale Global Tic Severity Scale (Y-GTSS). Comorbid obsessive-compulsive symptoms were assessed with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Both scales were performed at admission and after 4 weeks of treatment with olanzapine. Treatment with olanzapine (20 mg) resulted not only in a fast reduction of tic severity and frequency, but also in a reduction of obsessive-compulsive behaviours., Conclusions: This case report further supports the available literature on the use of olanzapine as a therapeutic strategy for tics in GTS and draws attention to its possible use for comorbid behavioural disorders. Further research of antipsychotics in GTS should include measurements of comorbid behavioural symptom clusters.