Preventive Antimigraine Drugs

peer reviewe

A Novel Interaction between Tryptophan Hydroxylase 2 (TPH2) Gene Polymorphism (rs4570625) and BDNF Val66Met Predicts a High-Risk Emotional Phenotype in Healthy Subjects.

Poor inhibitory processing of negative emotional content is central to many psychiatric disorders, including depression and anxiety. Moreover, increasing evidence suggests that core aspects of emotion-inhibitory processing are largely inherited and as such may represent a key intermediate or risk-related phenotype for common affective diseases (e.g., unipolar depressive, anxiety disorders). The current study employed a candidate-gene approach in order to most effectively examine this complex behavioral phenotype. We examined the novel interaction between BDNF (Val66Met) and TPH2 (rs4570625) polymorphisms and their influence on behavioral inhibition of negative emotion in two independent investigations of healthy adults. BDNF Met carriers consistently report greater symptoms of affective disease and display corresponding behavioral rigidity, while TPH2 T carriers display poor inhibitory processing. These genotypes are traditionally perceived as 'risk' genotypes when compared to their respective major Val and G homozygous genotypes, but evidence is mixed. Recent studies in humans and mutant mouse models suggest biological epistasis between BDNF and genes involved in serotonin regulation. Moreover, polymorphisms in the TPH2 gene may have greater influence on serotonergic function than other more commonly studied polymorphisms (e.g., 5-HTTLPR). We observed consistent evidence across two different emotion-inhibition paradigms, one with high internal validity (Study 1, n = 119) and one with high ecological validity (Study 2, n = 115) that the combination of Val/Val and G/G genotypes was clearly associated with impaired inhibition of negative emotional content. This was followed by individuals carrying the BDNF-Met allele (including Met/Val and Met/Met) when combined with the TPH2-T allele (including T/G and T/T combinations). The consistency of these results across tasks and studies suggests that these two groups may be particularly vulnerable to the most common psychiatric disorders and should be targets for future clinical investigation

Reaction time to negative words in the Emotion-word Stroop task.

<p>Subjects from Study 1 that were Val/Val–G/G had significantly increased reaction times to negative words compared to Val/Val–T Carriers (F(1,80) = 10.87, p<0.001) and Met Carrier–G/Gs (F(1,68) = 13.28, p<0.001). There was also a trend for an increased reaction time of Val/Val–G/Gs compared to Met Carrier–T Carriers (F(1,55) = 2.72, p = 0.11). Met Carrier–G/Gs were not significantly different from Val/Val–T Carriers (F(1,56) = 0.11, p = 0.74) nor from Met Carrier–T Carriers (F(1,31) = 0.70, p = 0.41). Val/Val–T Carriers were also not significantly different from Met Carrier–T Carriers (F(1,43) = 0.22, p = 0.64). All data are presented as mean ± SEM.</p

A Novel Interaction between Tryptophan Hydroxylase 2 (TPH2) Gene Polymorphism (rs4570625) and BDNF Val⁶⁶Met Predicts a High-Risk Emotional Phenotype in Healthy Subjects - Table 1

A Novel Interaction between Tryptophan Hydroxylase 2 (TPH2) Gene Polymorphism (rs4570625) and BDNF Val⁶⁶Met Predicts a High-Risk Emotional Phenotype in Healthy Subjects - Table