Schizophrenia is a heterogeneous chronic and debilitating disorder that affects approximately 24 million individuals worldwide. Current treatments for schizophrenia are characterized by only moderate success and relatively high side effect profiles. Accordingly, investigations of the underlying neurobiology of the disorder are essential. This dissertation reviews the evidence for a link between an early environmental disruption, prenatal stress (PNS), and an increased likelihood of developing schizophrenia in PNS offspring. Further, it reviews a biological outcome of PNS, impairment of the adult neurogenic system. Evidence in support of a link between impairment of the adult neurogenic system and schizophrenia is also reviewed. Given that alteration to the adult neurogenic system appears to be a converging factor between PNS and in schizophrenia, it is hypothesized that this system is a critical mediatior of the disproportionate occurrence of schizophrenia in PNS offspring.

Presented here are empirical studies which clarify the functional link between glucocorticoid hormones released during PNS, the adult neurogenic system, and schizophrenia. The broad aims were to determine whether: 1) Glucocorticoid stress hormones mediate PNS induced impairment of the adult neurogenic system and some PNS induced behavioral deficits, 2) Ablation of the adult neurogenic system alters behaviors on tests relevant to partial animal models of psychoses, and 3) Ablation of the neurogenic system leads to an increased susceptibility to the effects of stress in these behavioral measures. These studies found that prenatal glucocorticoid administration is sufficient to impair the adult neurogenic system and alter behaviors relevant to some partial animal models of psychoses.

Further, it was found that selective ablation of the adult neurogenic system leads to increased behavioral despair in the Porsolt swim test but does not alter behavior on other tests relevant to partial animal models of psychoses chosen for these experiments. Further, it was found that stress exposure does not interact with ablation of the adult neurogenic system to potentiate the increase in behavioral despair following ablation alone, or lead to alterations in any of the other behavioral measures employed. Finally, the use of selective ablation of the adult neurogenic system as a potential animal model of the positive, negative, sensorimotor gating, and cognitive symptoms of schizophrenia is discussed in the context of the present findings and current literature.