The present study was a pilot study designed to investigate the utility of QbTest factor scores (i.e., technically assessed Hyperactivity, Inattention, and Impulsivity) as potential intermediate phenotype markers for ADHD. This is the first study to explore motion tracking-based motor activity in ADHD siblings. Moreover, we examined neuropsychological intermediate phenotypes for ADHD at the factor, rather than single variable, level for the first time. We hypothesized that ADHD children would show the greatest impairments in task performance and that their non-affected siblings would show intermediate impairments compared to a control group of children with no family history of ADHD.
Confirming our first hypothesis, children with ADHD showed substantially greater impairments compared to children from the control group across all three QbTest factors. They were more inattentive and impulsive, and showed higher levels of motor activity while performing the QbTest.
The Hyperactivity factor consisted of the following five QbTest variables: Time Active, Distance, Area, Microevents, and Motion Simplicity [22, 23]. ADHD children had significantly higher motor activity scores on all five QbTest variables, thus showing higher frequency of movement (indexed by a high percentage of Time Active) and larger body movement amplitudes (indicated by Distance, Area, Microevents, and Motion Simplicity scores) than controls. These findings are consistent with previous studies that used motion tracking-based measurement techniques and reported that ADHD children are more active than healthy control children during a CPT [11, 19].
The Inattention factor was composed of three QbTest variables: RT, RT variability, and Omission errors. ADHD children reacted more slowly and variably and they also committed more omission errors than did children in the control group. RT variability and omission errors have repeatedly been shown to be higher in children with ADHD compared to healthy controls [14, 15, 24]. Thus, our results are in line with the majority of studies comparing ADHD children and controls with respect to attention variables.
The Impulsivity factor consisted of three QbTest variables: Commission errors, Multiresponses, and Anticipatory responses. ADHD children committed more commission errors (false alarms), and had a higher percentage of multiresponse and anticipatory responses than controls. Commission errors have been defined as a measure of deficient response inhibition and have been shown to be substantially elevated in ADHD children compared to controls [13]. This is consistent with our Impulsivity factor score results.
We also hypothesized that children from the non-affected sibling group would show intermediate impairments—between ADHD and healthy control children—but would be significantly different from controls.
We found a strong linear trend across group means for the motion tracking-based Hyperactivity factor. As expected, non-affected siblings showed an intermediate level of motor activity between ADHD children (highest activity scores) and controls (lowest activity scores). Moreover, there was a significant difference between the non-affected sibling and control groups. Taken together, the presence of increased motor activity not only in ADHD children but also in their non-affected siblings indicates that the QbTest Hyperactivity factor fulfills two important criteria for an intermediate phenotype measure [24]: it co-occurred with the disorder and it was manifest in individuals who carry genes for ADHD but do not express the disorder itself.
We found a linear trend across groups, with ADHD children showing greatest, non-affected siblings showing intermediate, and control children showing the least impairment for the Inattention and Impulsivity factors. Group means for the non-affected sibling and control groups did not significantly differ for either the Inattention or Impulsivity factors. Note, however, that the present study may have been underpowered for detecting small to medium effects between non-affected siblings and control children (see power analyses in the method section), and hence subsequent studies should investigate whether QbTest factors are intermediate phenotypes using larger groups.
Results also showed that non-affected siblings performed very similarly to children from the control group with respect to the Inattention factor, which was supported by a significant quadratic trend. This contrasts with other findings suggesting that RT variability [14], omission errors [15], and commission errors [13] are in fact candidates for intermediate phenotypes in ADHD. However, these studies emphasized the relevance of motivational factors in ADHD, especially for RT variability. The influence of motivational factors on performance variation is beyond the scope of this paper, but further studies should assess motivational aspects because they might explain the discrepancy between our results and previous studies.
Furthermore, we explored whether group differences were independent of age and gender. Results clearly showed that none of the three QbTest factors were influenced by age or gender, indicating that adjusting by age and gender norms provided in the QbTest was successful. Finally, it should be noted that while intermediate phenotypes in ADHD can be assessed and established on different levels (neurophysiological, neuroanatomical, and neuropsychological levels), these lie on a continuum from the genetic underpinnings of the disorder to biologically rooted intermediate phenotypes to neuropsychological variables and factor scores to the observation of behavior representing the full heterogeneity of the ADHD phenotype. The QbTest factor scores are based on the neuropsychological level of the disorder and may represent a marker for ADHD that could ultimately help to improve phenotype definition.
Limitations
The following limitations of this study should be noted. First, as discussed above, age and gender distributions differed between the groups in our study. Boys were overrepresented in the ADHD group, and mean age was higher in the non-affected sibling than ADHD and control groups. However, analyses controlling for age and gender did not reveal significant influences of age and gender, and the higher number of boys in the ADHD group reflects the male to female ratio in ADHD [2–4].
Second, we did not administer the clinical interview to non-affected siblings and controls. Additionally, Conners’ Teacher Questionnaires were missing for some children in the non-affected sibling and control groups. However, known formal diagnosis of ADHD and other childhood disorders were assessed in the biographical parent questionnaire and participation in the control group was explicitly advertised as seeking children without any ADHD-related behavior problems. Nevertheless, five children in the non-affected sibling group and two children in the control group showed high Conners’ Parent ratings (T > 63). As parent ratings of ADHD behavior and QbTest factor scores were significantly correlated (Pearson’s Correlation: .24 < r > .44), it is likely that non-affected siblings and controls who show elevated QbTest scores also have higher ADHD behavior ratings than children with lower QbTest scores. As described above, we controlled classification and separability of the three groups by testing group means against our Conners’ Parent questionnaire cut-off score (T = 63). The ADHD group scored significantly higher, while the other two groups scored significantly lower, than the cut-off score. Thus, overall, the groups adequately differed with respect to parent ratings of ADHD-related behavior.
Finally, due to relatively small groups, the reported results are preliminary and need to be confirmed in larger samples. Future studies should further explore (1) the utility of technically assessed motor activity as an intermediate phenotype in ADHD, and (2) the advantage of neuropsychological factor scores over single variable scores.