Chunk #124 — 5. Implications for understanding gene-brain-behavior relationships in health and disease — 5.2. An example: P3 as intermediate phenotype for externalizing disorders
cognitive tasks by goal-relevant stimuli that require some sort of decision making and response. On the other hand, meta-analysis of functional neuroimaging studies indicated that diverse executive functions tend to engage a very similar set of brain regions, suggesting the existence of a common, super-ordinate fronto-cingulo-parietal cognitive control network (Niendam et al., 2012). Moreover, these regions show substantial overlap with regions identified as possible P3 generators (Eichele et al., 2005; Mantini et al., 2009; Mulert et al., 2004). It is therefore reasonable to hypothesize that P3 reflects the engagement of this frontopariatal cognitive control network (CCN), and reduced P3 indicates insufficient recruitment of this network, perhaps due to poor integration of its components. Due to non-specificity of CCN, it is more likely to act as a moderator, rather than mediator of more specific risk factors, such that high level of CCN functioning will suppress the manifestation of specific predisposing factors, while low level of CCN functioning will facilitate the development of abnormal behavior by reducing threshold for the expression of disease-specific liability. This proposed model can explain why P3 amplitude reduction is observed across diverse psychiatric disorders.
