Genetic Marker for Wishful Thinking? James Dillon, Michigan Department of Community Health and University of Michigan School of Medicine Department of Psychiatry 24 June 2010 In this study of methylphenidate treatment of ADHD the authors found a genotype by treatment interaction leading them to conclude that the "...5-HTTLPR polymorphism of the SLC6A4 gene in children with ADHD... appears to modulate the behavioral response to methylphenidate in children with ADHD as assessed in the home environment by parents." Figure one and the article's narrative suggest that this difference is attributable almost entirely to a robust placebo response among children of the s's' genotype. On its face, then, this tells us very little about response to methylphenidate. But why would a placebo-response occur in a sub-group of subjects? One possibility is that a particular species of ADHD characterized by this genotype is predisposed to greater variablity, though this seems unlikely, because these children look like all the others on teacher ratings. Another possibility is that the ratings are a reflection of the raters or the relationship between the raters and their children, giving rise to a quasi-placebo effect best characterized as "wishful thinking." This is consistent with the discrepant responses between parent ratings and teacher ratings and is plausible in light of the genetic bias that must exist in raters who are biological parents. For biological parents conducting ratings, none of those rating s's' children can be l'l' themselves, nor can any of the parents of l'l' children have s's' genotypes. The polymorphism plausibly could underly personality traits associated with rating biases and distorted observations. If such traits exist, we can hypothesize that at least one s' allele is required for their expression. Perhaps the investigators have discovered the gene for wishful thinking! Competing interests No competing interests or conflicts.