Neuropharmacology

Biography

Biography: Marcela Henríquez-Henríquez

Abstract

In 1972, Gottesman and Shield introduced the concept of “endophenotypes” in behavioral genetics as a response to the pressing need for a construct able to bridge the explanatory gap in the genes-to-behavior pathway. They conceived endophenotypes as markers of genetic liability that lie in-between the gene and the clinical disorder. In being more proximal to primary gene products, they would have a less complex genetic architecture and allow for an easier identification of the genetic factors underling pathology. Additionally, endophenotypes would aid to elucidate the specific domains of brain function influenced by genetic risk variants. Intra-individual variability (moment to moment fluctuations in task performance) has been suggested as candidate endophenotype for ADHD. Traditional approaches to estimate intra-individual variability collapse responses across the entire task. Alternatively, more accurate statistics approaches like ex-gaussian and FFT analysis and mixed effect models allow for a better phenomenological description of moment-to-moment fluctuations in performance. Using a highly demanding Go-NoGo task and mixed-model analysis, we found that carriers of at least one copy of 2R or 7R-DRD4 alleles present faster deterioration in performance, independently of ADHD status. Ex-Gaussian analysis, on the other hand, allowed us to identify a geneX diagnosis interaction for the same allelic variants on the tau component of the ex-Gaussian distribution of response times, suggesting that attentional lapses (accepted phenomenological correlate for tau component in this case) may be predominantly expressed in ADHD patients carrying 2R or 7R-DRD4 alleles. Both approaches allowed us to unravel net genotype effects previously masked by traditional non-dynamic analysis.