Cellular and Molecular Neuropathology

Steven Arnold, M.D. - CELLULAR & MOLECULAR NEUROPATHOLOGY

Associate Professor Director, Laboratory for Cellular and Molecular Neuropathology Center for Neurobiology and Behavior Department of Psychiatry 415 Curie Boulevard, 142 Clinical Research Building Philadelphia, PA 19104 phone: (215) 573-3258 fax: (215) 573-2041 alveus@mail.med.upenn.edu
EDUCATION: 1989-90: University of Iowa Hospitals, Iowa City, IA - Behavioral Neurology Fellowship 1987-90, University of Iowa, Iowa City, IA - Neuroanatomy Post-Doctoral Studies 1987-90: University of Iowa Hospitals, Iowa City, IA - Neurology Residency 1984-87: New York State Psychiatric Institute, NY, NY - Psychiatry Residency 1983: Boston University School of Medicine, Boston, MA - M.D.

RESEARCH OVERVIEW: Our laboratory investigates the cellular and molecular neuropathologic substrates of neuropsychiatric illness with a focus on schizophrenia, neurodegenerative disorders, and late life depression. A brain bank with tissues from patients who have been clinically well-characterized with antemortem assessments represents a unique resource for clinicopathological correlation studies. Neuroanatomic and biochemical methods include immunohistochemistry, in situ hybridization, Western and Northern blotting, and quantitative microscopic analysis using stereology, cellular morphometry and densitometry, and spatial point pattern analysis.

Research in schizophrenia includes studies of neurodegeneration and neural injury, quantitative cytoarchitecture of molecularly distinct neuronal subpopulations, neuronal cytoskeletal protein expression, synapse-related protein expression, and signal transduction pathways. To complement studies exploring neurodevelopmental aspects of schizophrenia, we have conducted parallel studies of fetal hippocampal development. Ongoing neurodegenerative disease research includes quantitative molecular neuroanatomic correlative studies of cognition and behavioral disturbances (e.g., depression, psychosis, agitation) in Alzheimer’s disease, Lewy body diseases, frontal lobe dementias, and mild cognitive impairment in the elderly. A brain collection for studies of late-life depression is currently in development which will be used for studies of microvascular disease and selective neurodegenerative vulnerability of aminergic neurotransmitter systems. We also collaborate with neuroanatomic analyses in studies of mice with mutations which result in behavioral abnormalities as animal models of human neuropsychiatric disease.

Representative recent publications:

Arnold, S.E., Lee, V.M.-Y., Gur, R.E., Trojanowski, J.Q.: The expression of two microtubule-associated proteins (MAP2 and MAP5) is disturbed in specific subfields of the hippocampal formation in schizophrenia. Proc. Natl. Acad. Sci. (USA), 88:10850-10854, 1991.

Arnold, S.E., Gur, R.E., Shapiro, R.M., Fisher, K.R., Moberg, P.J., Gibney, M.R., Blackwell, P., Trojanowski, J.Q.: Prospective clinicopathologic studies of schizophrenia: accrual and assessment. Am. J. Psychiatry, 152:731-737, 1995.

Arnold, S.E., Franz, B.R., Gur, R.C., Gur, R.E., Shapiro, R.M., Moberg, P.J., Trojanowski, J.Q.: Smaller neuron size in hippocampal subfields that mediate cortical-hippocampal interactions in schizophrenia. Am. J. Psychiatry, 152:738-748, 1995.

Arnold, S.E., Trojanowski, J.Q.: Human fetal hippocampal development. II: The neuronal cytoskeleton. J. Comp. Neurol., 367:293-307, 1996.

Arnold, S.E., Trojanowski, J.Q., Gur, R.E., Blackwell, P., Han, L.-Y., Choi, C.H.: Investigations of neurodegeneration and neural injury in elderly patients with schizophrenia. Arch Gen Psychiatry, in press.