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Neurohormones, Neurodevelopment, and Psychosis 269these findings. One investigation showed that schizophrenic twins, whether fromconcordant or discordant MZ pairs, had smaller whole brain volumes than controltwins; however, the ill twins from discordant pairs showed more hippocampalvolume reduction than their healthy co-twin or concordant twins (van Harenet al., 2004). The same pattern has been reported in at least two other studies ofdiscordant MZ twins (Baare et al., 2001; van Erp et al., 2004). These findingssuggest that genetic risk for schizophrenia is associated with generalized reductionsin brain volume, but that reductions in the hippocampus are most pronouncedin association with the clinical syndrome of schizophrenia. This is consistent withthe notion that the HPA axis-hippocampal system moderates the expression ofgenetically determined constitutional vulnerability for schizophrenia.Extending this further, it has been shown that the intraclass correlation for hippocampalvolume in healthy MZ twin pairs is larger than that for discordant MZpairs, and the estimate for the magnitude of genetic effects on hippocampal volumeis larger in healthy twins than in discordant twins (van Erp et al., 2004). Thus,hippocampal volume is largely affected by genetic factors in healthy twin pairs,and presumably other healthy individuals. But the smaller magnitude of geneticeffects on hippocampal volume in discordant pairs indicates that environmentalfactors are having a greater impact; in other words, environmental factors may beadversely affecting size of the hippocampus in the ill twin, and reducing the similaritywith the healthy co-twins. Similar findings have been reported for cortisollevels in healthy versus discordant MZ twin pairs; intraclass correlations for cortisolare high and significant for healthy twin pairs, but not for discordant twins(Walker, Bonsall, & Walder, 2002).At the cellular level, there is evidence of reductions in hippocampal glucocorticoidreceptors in schizophrenia (Ganguli, Singh, Brar, Carter, & Mintun, 2002).A postmortem study showed that GR mRNA levels were reduced in several regionsof the hippocampus (dentate gyrus, CA4, CA3, and CA1) in schizophreniapatients, but not depressives (Webster, Knable, O’Grady, Orthmann, & Weickert,2002). The dentate gyrus is a region that is especially sensitive to the affects ofstress-induced corticosteroids (Sousa & Almeida, 2002; van der Beek et al., 2004),as well as exposure to alcohol and nicotine (Jang et al., 2002). A reduction in GRreceptors in the hippocampus would be expected to compromise negative feedbackto the HPA axis and thus contribute to HPA dysregulation (Heuser, Deuschle,Weber, Stalla, & Holsboer, 2000).Adolescence Neurodevelopment:Hormones, Genes, and BrainAs noted, adolescent development is characterized by marked increases in neurohormonesecretion. In addition to rising gonadal hormones, there is now mounting