Intra-individual response variability assessed by ex-Gaussian analysis may be a new endophenotype for attention-deficit/hyperactivity disorder

M. Henríquez, P. Billeke, H. Henríquez, F. Zamorano, F. Rothhammer and F. Aboitiz. PLoS One. DOI: 10.3389/fpsyt.2014.00197.


Intra-individual variability of response times (RTisv) is considered as potential endophe-notype for attentional deficit/hyperactivity disorder (ADHD). Traditional methods for esti-mating RTisv lose information regarding response times (RTs) distribution along the task, with eventual effects on statistical power. Ex-Gaussian analysis captures the dynamic nature of RTisv, estimating normal and exponential components for RT distribution, with specific phenomenological correlates. Here, we applied ex-Gaussian analysis to explore whether intra-individual variability of RTs agrees with criteria proposed by Gottesman and Gould for endophenotypes. Specifically, we evaluated if normal and/or exponential com-ponents of RTs may (a) present the stair-like distribution expected for endophenotypes (ADHD > siblings > typically developing children (TD) without familiar history of ADHD) and (b) represent a phenotypic correlate for previously described genetic risk variants. This is a pilot study including 55 subjects (20 ADHD-discordant sibling-pairs and 15 TD children), all aged between 8 and 13 years. Participants resolved a visual Go/Nogo with 10% Nogo probability. Ex-Gaussian distributions were fitted to individual RT data and compared among the three samples. In order to test whether intra-individual variability may represent a cor-relate for previously described genetic risk variants, VNTRs at DRD4 and SLC6A3 were identified in all sibling-pairs following standard protocols. Groups were compared adjust-ing independent general linear models for the exponential and normal components from the ex-Gaussian analysis. Identified trends were confirmed by the non-parametric Jonckheere– Terpstra test. Stair-like distributions were observed for µ (p = 0.036) and σ (p = 0.009). An additional “DRD4-genotype” × “clinical status” interaction was present for τ (p = 0.014) reflecting a possible severity factor. Thus, normal and exponential RTisv components are suitable as ADHD endophenotypes.


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