Intra-individual variability in genetic and environmental models of attention-deficit/hyperactivity disorder.

The frequent observation of intra-individual variability (IIV) in the expression of ADHD symptoms suggest that IIV is an integral component of the disorder. We tested IIV in ADHD-like phenotype from five different studies of rodent models of ADHD, including studies with Spontaneous Hypertensive Rats (SHR/NCrl and SHR/N), Wistar-Kyoto Hyperactive Rats (WKHA/N), Wistar-Kyoto Hypertensive rat (WKHT), PCB-126 and -153-treated Lewis rats and behaviorally normal Wistar/Mol, Wistar-Kyoto (WKY/N and WKY/NMol), and untreated Lewis rats. Averages of the absolute residual deviation of ADHD-like behavior from individual means ("individual phenotypic dispersion," PD(i)) were used to represent IIV in the fixed-interval (FI) and extinction (EXT) phases of operant behavioral activity. Across all studies, SHR rats had higher PD(i) than WKY rats (P < 0.0001) for all ADHD-like traits, and higher PD(i) for hyperactivity than WKHT and WKHA/N rats. Male SHR rats in particular had higher PD(i) for hyperactivity than male or female WKYs, SHR females for EXT hyperactivity, and higher dispersion for inattention than WKY females. These findings strongly suggest the genetic control of IIV, and suggest that the SHR may be a useful model for the identification of genes for IIV in human ADHD. These findings also obliquely support the SHR as a useful model for ADHD overall.