Neuroimaging the infant: the application of modern neurobiological methods to the neurodevelopmental hypothesis of schizophrenia.

1017 " Identifying ways to conduct neuro-imaging with a population that is unable to respond to requests to 'lie still' is an important advance. " In the study reported in this issue, Gilmore et al. (1) demonstrated that neuroimaging the brain in infants at risk for schizophrenia is feasible. This work may lead to advances in understanding the neurobiological underpinnings of the neurodevelopmental hypothesis of schizophrenia. This hypothesis proposes that the onset of psychotic symptoms is the end result of decades of interaction between genetic and environmental factors. Two critical windows have been suggested: a fetal and early infancy period, during which vulnerability is established, and a later, often adolescent or young adult period, during which conversion from vulnerability to psychosis occurs. Brain changes during the perinatal window are not deterministic in that the majority of individuals born with vulnerability will never develop the full clinical disorder. Similarly, in less vulnerable individuals, genetic and environmental factors present during the second critical window appear to have minimal effect and are not associated with an increased risk for psychosis. The adolescent/young adult critical development period received a signifi cant amount of scientifi c attention for over 120 years (2). The last two decades have seen a focus on subjects with early signs of psy-chosis, a group that appears to have about a 30% risk for developing a psychotic illness. A number of techniques , including neuroimaging (3), physiological measures (4), and neuropsychological tests (5), have been used to explore the neural underpinnings of the conversion to psychosis as well as the impact of prevention strategies. Although larger randomized trials have not yet identifi ed any clearly successful prevention strategies, early efforts are suggesting strategies for future evaluation (6). Although a signifi cant amount of work remains to be completed, there is a clear ongoing effort to analyze individuals during the adolescent/young adult critical window and to use that information to rationally design and test prevention efforts. The concept of an earlier, perinatal critical window was fi rst suggested by Laura Bender in the 1950s (7). The idea was initially based on peripheral motor and behavioral assessments of infants (see review by Watt [8]) and later supported by neurobiological studies of adults (see review by Weinberger [9]) and epidemiological studies that identi-fi ed correlations between adult disease state and perinatal environmental risk factors (10, 11). These results have provided strong but very indirect …