This is an application for an ADAMHA Scientist Development Award for Clinicians. My overall career goal is to gain expertise in the molecular neuroanatomic and neuropathologic investigation of neuropsychiatric illness, with an emphasis on schizophrenia. During the tenure of the requested award I expect to: 1) acquire further skills in basic neuropathologic diagnosis; 2) develop technical expertise with qualitative and quantitative immunohistochemical methods for characterizing brains of patients with schizophrenia and controls; 3) learn techniques for biochemical analysis of brain tissue and for generating monoclonal antibodies; and 4) expand skills in data analysis and the integration of postmortem and antemortem findings. These goals will be accomplished in the course of a research plan whose aims are to: 1) investigate the cytoarchitecture and molecular character of neurons in limbic temporal structures in schizophrenia; and 2) characterize normal human fetal molecular development of these brain regions by determining the timing of cytoskeletal and synaptic protein expression and establishment of neuronal polarity and laminar position. By this research I hope to extend and clarify the abnormalities that have been suggested by studies using traditional neuropathologic methods and to explore the thesis of schizophrenia as a neurodevelopmental disorder.

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National Institute of Mental Health (NIMH)
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Research Scientist Development Review Committee (MHK)
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University of Pennsylvania
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Rioux, Lise; Arnold, Steven Edward (2005) The expression of retinoic acid receptor alpha is increased in the granule cells of the dentate gyrus in schizophrenia. Psychiatry Res 133:13-21
Rioux, Lise; Gelber, Edward Isaac; Parand, Leila et al. (2005) Characterization of olfactory bulb glomeruli in schizophrenia. Schizophr Res 77:229-39
Rioux, Lise; Ruscheinsky, Delta; Arnold, Steven Edward (2004) Microtubule-associated protein MAP2 expression in olfactory bulb in schizophrenia. Psychiatry Res 128:1-7
Rioux, Lise; Nissanov, Jonathan; Lauber, Katherine et al. (2003) Distribution of microtubule-associated protein MAP2-immunoreactive interstitial neurons in the parahippocampal white matter in subjects with schizophrenia. Am J Psychiatry 160:149-55
Arnold, S E (1999) Neurodevelopmental abnormalities in schizophrenia: insights from neuropathology. Dev Psychopathol 11:439-56
Arnold, S E; Ruscheinsky, D D; Han, L Y (1997) Further evidence of abnormal cytoarchitecture of the entorhinal cortex in schizophrenia using spatial point pattern analyses. Biol Psychiatry 42:639-47
Arnold, S E; Franz, B R; Trojanowski, J Q et al. (1996) Glial fibrillary acidic protein-immunoreactive astrocytosis in elderly patients with schizophrenia and dementia. Acta Neuropathol (Berl) 91:269-77
Arnold, S E; Trojanowski, J Q (1996) Cognitive impairment in elderly schizophrenia: a dementia (still) lacking distinctive histopathology. Schizophr Bull 22:5-9
Arnold, S E; Franz, B R; Gur, R C et al. (1995) Smaller neuron size in schizophrenia in hippocampal subfields that mediate cortical-hippocampal interactions. Am J Psychiatry 152:738-48
Arnold, S E; Gur, R E; Shapiro, R M et al. (1995) Prospective clinicopathologic studies of schizophrenia: accrual and assessment of patients. Am J Psychiatry 152:731-7

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