There is growing evidence to suggest that schizophrenia is a neurobehavioral disorder that affects fronto-temporal areas of the brain. A relatively neglected, but in many ways ideal, probe of the fronto-limbic system is olfaction. Olfactory processing is mediated by limbic structures implicated in the pathophysiology of schizophrenia. Patients with schizophrenia have significant olfactory deficits, which occur at the first onset of illness. Unlike the relatively static pattern of cognitive deficits seen over the course of illness, though, olfactory abilities appear to decline in a linear fashion, independent of normal aging and gender effects. Family studies, however, have also demonstrated significant deficits in olfactory identification in unaffected first-degree relatives of schizophrenic probands. It would seem, therefore, that olfactory brain regions are affected by genetically-mediated developmental, as well as neurodegenerative processes. Unfortunately, little is known about the developmental course, scope and laterality of olfactory processing deficits in schizophrenia, how these deficits interact, and the manner in which they are moderated by age and gender. In this project, we will investigate the psychophysical correlates of olfactory dysfunction and decline, cross-sectionally, in patients with schizophrenia and healthy controls. A reliable and well-validated psychophysical battery assessing the domains of odor identification, detection threshold sensitivity, memory and intensity/hedonics will be given so differential deficits/decline can be detected. All olfactory measures will be administered unilaterally so laterality effects can be detailed. Neuropsychological and emotional measures will be obtained to investigate interactions with olfactory functions as well as assess whether any decline over the lifespan is specific to olfaction. These measures will be investigated in men and women with schizophrenia (n=96) and healthy controls (n=96) age 18-57, with a sufficient number of individuals in each decade band to yield a cross-sectional estimate of developmental trajectory. In order to assess whether any declines in olfactory function are due to antipsychotic use, cumulative antipsychotic burden will be assessed across decade bands and acute effects will be assessed in a subsample of 48 neuroleptic-naive and previously-medicated patients in a pre- post-medication design using a standard medication.
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