title: Genetic analysis of reaction time variability: room for improvement?
abstract: BACKGROUND
  Increased reaction time variability (RTV) on cognitive tasks requiring a speeded response is characteristic of several psychiatric disorders. In attention deficit hyperactivity disorder (ADHD), the association with RTV is strong phenotypically and genetically, yet high RTV is not a stable impairment but shows ADHD-sensitive improvement under certain conditions, such as those with rewards. The state regulation theory proposed that the RTV difference score, which captures change from baseline to a rewarded or fast condition, specifically measures 'state regulation'. By contrast, the interpretation of RTV baseline (slow, unrewarded) scores is debated. We aimed to investigate directly the degree of phenotypic and etiological overlap between RTV baseline and RTV difference scores. Method We conducted genetic model fitting analyses on go/no-go and fast task RTV data, across task conditions manipulating rewards and event rate, from a population-based twin sample (n=1314) and an ADHD and control sibling-pair sample (n=1265).
  
  
  RESULTS
  Phenotypic and genetic/familial correlations were consistently high (0.72-0.98) between RTV baseline and difference scores, across tasks, manipulations and samples. By contrast, correlations were low between RTV in the manipulated condition and difference scores. A comparison across two different go/no-go task RTV difference scores (slow-fast/slow-incentive) showed high phenotypic and genetic/familial overlap (r = 0.75-0.83).
  
  
  CONCLUSIONS
  Our finding that RTV difference scores measure largely the same etiological process as RTV under baseline condition supports theories emphasizing the malleability of the observed high RTV. Given the statistical shortcomings of difference scores, we recommend the use of RTV baseline scores for most analyses, including genetic analyses.
authors.affiliation: King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, UK. jonna.kuntsi@kcl.ac.uk
authors.forename: J
authors.initials: J
authors.lastname: Kuntsi
authors.forename: A C
authors.initials: AC
authors.lastname: Frazier-Wood
authors.forename: T
authors.initials: T
authors.lastname: Banaschewski
authors.forename: M
authors.initials: M
authors.lastname: Gill
authors.forename: A
authors.initials: A
authors.lastname: Miranda
authors.forename: R D
authors.initials: RD
authors.lastname: Oades
authors.forename: H
authors.initials: H
authors.lastname: Roeyers
authors.forename: A
authors.initials: A
authors.lastname: Rothenberger
authors.forename: H-C
authors.initials: HC
authors.lastname: Steinhausen
authors.forename: J J
authors.initials: JJ
authors.lastname: van der Meere
authors.forename: S V
authors.initials: SV
authors.lastname: Faraone
authors.forename: P
authors.initials: P
authors.lastname: Asherson
authors.forename: F
authors.initials: F
authors.lastname: Rijsdijk
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000523:psychology; D016022:Case-Control Studies; D002648:Child; D005260:Female; D006801:Humans; D007266:Inhibition, Psychological; D008297:Male; D008957:Models, Genetic; D010641:Phenotype; D011930:Reaction Time / Q000235:genetics* / Q000502:physiology; D014427:Twins / Q000235:genetics* / Q000523:psychology; D014429:Twins, Dizygotic / Q000235:genetics / Q000523:psychology; D014430:Twins, Monozygotic / Q000235:genetics / Q000523:psychology