Early and late neurodevelopmental influences in the prodrome to XXXX : contributions of genes, environment, and their interactions.

@entity1 @entity245 @entity161 @entity716 @entity221
Both early (i.e., pre- and perinatal periods) and late (i.e., adolescent period) neurodevelopmental processes are thought to participate in the etiology and pathophysiology of @entity161 . However, whether markers of these processes would be expected to predict an imminent onset of @entity716 , as is hoped in the current generation of prodromal research programs, depends on whether their disruptions result from genetic factors shared by @entity1 and some of their unaffected relatives, nongenetic factors specific to those who manifest the @entity221 phenotype, or combinations of these sets of influences. Here we present recent work deriving primarily from high-risk and family-study (i.e., "genetic high-risk") designs, which provide a framework for investigating the neural changes that may occur proximally to the initial onset of @entity716 . This work indicates that some of the alterations in brain function and structure in @entity161 are primarily genetically mediated and also appear in some of @entity1 ' unaffected first degree relatives, while other alterations are present in individuals who manifest the @entity221 phenotype but not in relatives at genetic risk (Cannon et al. 2002a, 2002c; Van Erp et al. 2002). Whereas the primarily genetically mediated deficits shared by at-risk but nonsymptomatic relatives are not likely to show differential change in the premorbid period and may be necessary but clearly not sufficient for the development of @entity716 , the deficits specific to @entity1 who manifest the @entity221 phenotype are good candidates for marking the neurobiological processes associated with the emergence of @entity716 at the time of @entity161 onset. Preliminary results from longitudinal studies of individuals ascertained initially in a prodromal (i.e., "clinical high-risk") state appear to be interpretable within this framework. A number of questions arising from this line of inquiry need to be addressed in the current generation of prodromal research programs: To what extent do the neural systems affected by early and late neurodevelopmental influences overlap? Is there likely to be a @entity161 -related disturbance in the processes associated with adolescent brain maturation, or are these maturational processes themselves intact, participating in @entity716 onset only indirectly, by promoting a neurobiological context in which the early @entity245 can be expressed in @entity716 ? What pattern of changes observable from in vivo imaging studies is consistent with a reduction in neuropil volume? We develop a framework for addressing these questions and evaluating their implications for understanding the roles of early and late neurodevelopmental influences in the etiology and pathophysiology of @entity161 .
