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Neurohormones, Neurodevelopment, and Psychosis 271significant organizational changes during this period. There are rapidly accumulatingdata on the postnatal development of the human brain, and they demonstratethat the maturational process extends through adolescence, and probablyinto early adulthood (Gogtay et al., 2004). Notable among these developments isan increase in the volume of the hippocampus (Suzuki, 2005). Using MRI, strongage-related increases are observed in the subiculum and CA1-CA3 (CAS) regionsof the hippocampus (Saitoh, Karns, & Courchesne, 2001).Adolescent Stress SensitivityAdolescence is a period of heightened stress sensitivity and vulnerability to theonset of major mental disorder (Arnsten & Shansky, 2004; Compas, Connor-Smith,& Jaser, 2004; Cunningham et al., 2002; Spear, 2000; Walker, 2002). Heightenedstress sensitivity has been shown repeatedly in animal models of adolescent development,and recent studies of human subjects also suggest this (Chambers,Taylor, & Potenza, 2003). For example, rodents typically show hippocampalvolume increases during the peri/postpubertal period (Isgor, Kabbaj, Akil, &Watson, 2004). But exposure to physical stress in early postpuberty reduces hippocampalgrowth, especially in the CA1 and CA3 pyramidal cell layers, and inthe dentate gyrus. Exposure to chronic stress resulted in hippocampal volumedeficits that were first observable 3 weeks later, but not 24 hours after exposure.Moreover, these volume deficits were associated with impairments in water-mazenavigation, sustained downregulation in hippocampal GR gene expression, andgreater acute stress-induced corticosterone. Thus, exposure of adolescents tochronic stress may lead to significant alterations in the HPA axis, as well as changesin hippocampal structure and cognitive function, that persist into adulthood. Atthe receptor level, there is evidence that glucocorticoids have differential effectson the regional expression of mRNA NMDA receptor subunits in the hippocampus,which would be expected to change the sensitivity of hippocampal neuronsto the excitatory neurotransmitter, glutamate. Studies of rodents indicate that theremay be window during adolescence in which the receptor genes are especiallyresponsive to glucocorticoids (Lee, Brady, & Koenig, 2003).In human adolescents, there are also data indicating increased sensitivity of thehippocampus. In subjects with a history of alcohol abuse, earlier age and longerduration of abuse was associated with reduced volume of the hippocampus (De Belliset al., 2000). The volume of other brain regions was not associated with alcoholabuse. These findings were interpreted to suggest that during adolescence, the hippocampusmay be particularly susceptible to the adverse effects of alcohol.In summary, postpubertal neuromaturation entails significant changes in theHPA axis and the hippocampus. These changes may result in greater sensitivityof the HPA axis to external stress and increased sensitivity of the hippocampus to