title: Intra-Individual Response Variability Assessed by Ex-Gaussian Analysis may be a New Endophenotype for Attention-Deficit/Hyperactivity Disorder.
abstract: Intra-individual variability of response times (RTisv) is considered as potential endophenotype for attentional deficit/hyperactivity disorder (ADHD). Traditional methods for estimating 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 components 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 correlate for previously described genetic risk variants, VNTRs at DRD4 and SLC6A3 were identified in all sibling-pairs following standard protocols. Groups were compared adjusting 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.
authors: Department of Clinical Laboratories, Pontificia Universidad Católica de Chile , Santiago , Chile ; Cognitive Neurosciences Laboratory, Department of Psychiatry, Pontificia Universidad Católica de Chile , Santiago , Chile.
authors: Marcela Patricia
authors: MP
authors: Henríquez-Henríquez
authors: Cognitive Neurosciences Laboratory, Department of Psychiatry, Pontificia Universidad Católica de Chile , Santiago , Chile ; Centro de Investigación en Complejidad Social (CICS), Facultad de Gobierno, Universidad del Desarrollo , Santiago , Chile.
authors: Pablo
authors: P
authors: Billeke
authors: Medical Technology School, Universidad Mayor , Santiago , Chile.
authors: Hugo
authors: H
authors: Henríquez
authors: Cognitive Neurosciences Laboratory, Department of Psychiatry, Pontificia Universidad Católica de Chile , Santiago , Chile ; Centro de Investigación en Complejidad Social (CICS), Facultad de Gobierno, Universidad del Desarrollo , Santiago , Chile.
authors: Francisco Javier
authors: FJ
authors: Zamorano
authors: Instituto de Alta Investigación, Universidad de Tarapacá , Arica , Chile.
authors: Francisco
authors: F
authors: Rothhammer
authors: Cognitive Neurosciences Laboratory, Department of Psychiatry, Pontificia Universidad Católica de Chile , Santiago , Chile.
authors: Francisco
authors: F
authors: Aboitiz
keywords: ADHD; endophenotypes; ex-Gaussian analysis; intra-individual variability; response time
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