Impulsive behaviors

Another group of intermediate phenotypes in ADHD, the impulsivity-related behaviors are also associated with substance abuse, antisocial and borderline personality disorder, and impulse control disorders (e.g., kleptomania, trichotillomania, and pathological gambling). Impulsivity is a multidimensional trait, its various aspects are generally divided into two broad categories (cognitive/psychological and motor/behavioral). The cognitive aspects, such as impulsive decision making (the inability to withhold an action for the time needed to estimate consequences) or sensation seeking, are measured by self-report personality questionnaires; whereas the motor aspects, such as disinhibition (the inability to inhibit an unnecessary action) and delay aversion (see ADHD endophenotype paragraph) are assessed by behavioral inhibition and delayed reward tasks (Evenden, 1999). Behavioral inhibition can be measured with neurocognitive tests, such as the Go/NoGo or stop-signal tasks, which are used in endophenotype related genetic studies.

According to twin studies, self-reported impulsivity shows approximately 45% heritability (reviewed by Congdon and Canli, 2008), which prompted candidate gene research using personality questionnaires. The most consistent genetic findings in impulsivity-related studies are connected to the DRD2 gene. The results from studies conducted among healthy, young adults showed an association between the DRD2 A1-allele and impulsive behavior using a response inhibition test (White et al., 2008) or a delay discounting task (Eisenberg et al., 2007). A significant DRD2 A1-allele × DRD4 7-repeat allele interaction was observed for delay discounting in the latter study, and a trend towards an association with sensation seeking was also reported (Eisenberg et al., 2007). Our recent study in an at-risk, young adult population revealed an association between the DRD2 gene (A1- and B1-allele) and impulsive self-damaging behaviors that were assessed using borderline symptoms (Nemoda et al., 2010). Other DRD2 SNPs were also associated with impulsivity in healthy individuals. The C/C genotype of the DRD2 C957T polymorphism was associated with a higher reward responsiveness after a psychological stressor (White et al., 2009). In a neuroimaging study, the DRD2 -141C Del carriers exhibited higher reward-related ventral striatum reactivity, which was associated with self-reported impulsivity (Forbes et al., 2009). This neuroimaging study also reported a higher reactivity in the DRD4 7-repeat allele and the DAT1 9-repeat allele carriers. The authors suggested that a connection exists between greater ventral striatum reactivity and hypodopaminergic variants.

The DRD4 genetic effect on neurocognitive tasks is less clear than that of the DRD2 gene. As we mentioned earlier, the commission error rate findings in ADHD children were not in agreement with one another; the DRD4 7-repeat allele was linked to both higher and lower error rates (Manor et al., 2002a, Kieling et al., 2006). During a behavioral inhibition test that was conducted among healthy, young adults, the DRD4 7+ group had longer mean reaction times on the stop-signal task compared to the 7− group. In addition, a DRD4 × DAT1 interaction was observed: The longest reaction time was observed for the DRD4 7+ and DAT1 10/10 genotype group compared to other genotype combination groups (Congdon et al., 2008). This finding supports the conclusion found in the ADHD literature, namely that the DRD4 7-repeat allele and the DAT1 10-repeat allele are risk factors for ADHD. However, during a similar response inhibition test conducted in a healthy student population, the DRD4 7/7 genotype group performed better on the Go/NoGo task (Kramer et al., 2009). The opposing findings of the two studies might be explained by the observation that the attentional processes involved in detecting infrequent NoGo signals might be involved in the Go/NoGo task (Congdon and Canli, 2008), for which the DRD4 7-repeat allele might not be the risk allele (see the attentional performance section for more information). Further studies using brain activity measurements will hopefully elucidate the underlying processes, as event-related potential differences were also observed in the DRD4 7-repeat allele carriers during the Go/NoGo task (Kramer et al., 2009).

Dopamine synthesizing and catabolizing enzyme genes have not been frequently investigated in relation to behavioral inhibition (Congdon and Canli, 2008). A recent fMRI study conducted among healthy, young adults reported greater brain activity in the right inferior frontal gyrus of the COMT Met-allele carriers compared to the COMT Val/Val genotype group during a stop-signal task (Congdon et al., 2009). Similarly, higher activation was observed in the right supplementary motor area and in the right subthalamic nucleus of subjects with at least one DAT1 9-repeat allele compared to the 10/10 genotype group. According to the authors, the greater activation represented better inhibitory control, therefore, the DAT1 10/10 genotype and the COMT Val/Val genotype were associated with an impaired neural response during behavioral inhibition (Congdon et al., 2009), which is in agreement with ADHD findings (Thapar et al., 2007; Gizer et al., 2009).

Date: 2016-01-03; view: 810