Chunk #151 — 10.0 Where Do We Go From Here? — 10.4 More research on the utility of an endophenotype — 10.4.2 Enhancing our understanding of brain mechanisms
decomposing it into supposedly simpler elements is not likely to lead to significant genetic discovery, this type of effort can nevertheless lead to an increasingly elaborated understanding of the genetic risk for externalizing. For instance, Ford, Mathalon, and colleagues found that the consistency of inter-trial phase locking (ITPC) of gamma activity during the peak of the P300 response was correlated with P300 amplitude in control subjects but not patients with schizophrenia, suggesting a breakdown of the normal (partial) dependence of P300 amplitude on gamma synchrony in schizophrenia (J. M. Ford, Roach, Hoffman, & Mathalon, 2008). We have similarly found that ITPC of theta activity is reduced in externalizing disorders, and in fact partially mediates P300 amplitude reduction (Burwell, Malone, Bernat, & Iacono, 2014). To be clear, we are not advocating ITPC as yet another candidate endophenotype; we are suggesting that endophenotypes can lead to further understanding of the neurobehavioral mechanisms contributing to a clinical outcome as well as new targets for genetic association analysis.
