Chunk #150 — 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
Of course, we ultimately want to trace the path from endophenotype to specific genes. Research that provides a more detailed understanding of the endophenotype nevertheless is also potentially informative about the nature of unobserved, latent genetic risk reflected in the endophenotype. For instance, administering ketamine, an antagonist of the NMDA receptor for glutamate, to healthy subjects results in mean reduced MMN amplitude and performance on the CPT-AX task that resembles that of patients with schizophrenia (Umbricht et al., 2000). This suggests that compromised NMDAR function may be a characteristic of the disorder. Reduction of the amplitude of the P300 ERP potential is a robust endophenotype for externalizing disorders (W. G. Iacono & Malone, 2011; W. G. Iacono et al., 2008). However, “the” P300 is not a unitary phenomenon, as we have discussed in an earlier section. Although we argued that 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
