SCHIZOPHRENIA: FUNCTIONAL AND STRUCTURAL STUDIES
Laboratory of Neuroscience, Department of Psychiatry, VA Boston Healthcare System
Robert W. McCarley, M.D., Martha E. Shenton, Ph.D., Paul G. Nestor, Ph.D., Margaret Niznikiwicz, Ph.D., Dean Salisbury, Ph.D., Cynthia Wible, Ph.D., Yoshio Hirayasu, M.D., Ph.D., James J. Levitt, M.D., Larry J. Seidman, Ph.D., Martina Voglmaier, Ph.D., Chandlee Dickey, M.D., Melissa Frumin, M.D. Kevin Spencer, Ph.D., Kiyoto Kasai, M.D. Toshiaki Onitsuka, M.D., and XiangyangLi, M.D., Ph.D.
This project seeks to link biological and clinical features of schizophrenia and schizotypal personality disorder by conjoint use of neurophysiological, MRI, neuropsychological, and clinical measures. A major focus of the work is on measures related to temporal lobe, an emphasis that began with our 1983 finding of a left temporal scalp region deficit in the P300 evoked potential. This abnormality has now been linked to the presence of gray matter tissue loss in the left posterior superior temporal gyrus (STG) in quantitative volumetric MRI studies in both chronic and first episode schizophrenic patients. The extent of both of these abnormalities is strongly correlated with the degree of thought disorder, and neuropsychological impairments. Moreover, there is now evidence for progressive gray matter loss in left STG in first episode schizophrenia, a finding that may be indexed by the mismatch negativity evoked potential. fMRI work has localized the mismatch abnormality to the STG. These deficits appear to be selective for schizophrenic psychosis as contrasted with first psychotic episode bipolar patients. Recent work indicates fusiform gyrus gray matter volume reduction in both first episode and chronic schizophrenia that is associated with decreased memory for faces. Individuals with schizotypal personality disorder have been found to have left STG gray matter volume reduction, suggesting this may be basic to the schizophrenia spectrum. Schizotypal individuals also have left temporal P300 and neuropsychological deficits similar to, but less severe than, those in schizophrenia.
Keywords: Schizophrenia, schizophrenia spectrum, schizotypal personality disorder, neurophysiology, MRI, fMRI, cognitive neuroscience.
Grant Support: NIMH: Neurophysiological Studies of Schizophrenia (RWM); NIMH: Biological Basis of Schizotypal Personality Disorder (RWM); NIMH: Computerized Image Analyses of MR Scans in Schizophrenia (MES), Veterans Administration Merit Review: MRI Anatomy of Schizophrenia (RWM), NIMH Career Awards: Research Scientist Development Award (MES). Veterans Administration Merit Review: MR Brain Diffusion Tensor Imaging in Schizophrenia (MES); Veterans Administration Merit Review: Cognitive Neuroscience Studies of Schizophrenia (PN & MN).
Project Director: R.W. McCarley, Neuroscience Laboratory, Psychiatry 116A, Brockton VA Medical Center, 940 Belmont St. Brockton, MA 02401. Contact Person: Marie Fairbanks, Administrative Assistant, Phone: (508) 583-4500 x3367, X3934. FAX: (508) 586-0894, e-mail marie_Fairbanks@http://hms.harvard.edu. NARSAD: MR brain diffusion tensor imaging of the corpus callosum in schizophrenia (MF); NARSAD: A magnetic diffusion tensor study of the cingulate fasciculus in schizophrenia (MK)
Project Sites: Brain Imaging Laboratory, Brockton VAMC; Brain Potential Imaging Laboratory, MMHC; Cognitive Neuroscience Lab., McLean Hospital; Surgical Planning Lab, Brigham & Women's Hospital, Department of Radiology.
Training Opportunities: Currently there are 5 post-doctoral fellows. This is a program site for the NIMH Clinical Research Training Program (HMS Psychiatry, ST Hauser, RW McCarley, ME Shenton, PI) and has openings for other departmental trainees.
Representative Publications:
McCarley RW, Salisbury DF, Hirayasu Y, Yurgelun-Todd, DA, Tohen M, Zarate C, Kikinis R, Jolesz FA, Shenton ME. Association between smaller left posterior superior temporal gyrus MRI volume and smaller left temporal P300 amplitude in first episode schizophrenia. Archives of General Psychiatry, 2001; In Press
Salisbury DF, Shenton ME, Griggs CB, Bonner-Jackson A, McCarley RW. Mismatch Negativity in chronic schizophrenia and first-episode schizophrenia. Archives of General Psychiatry, 2001; In Press.
Lee C-U, Shenton ME, Salisbury DF, Kasai K, Onitsuka T, Dickey CC, Yurgelun-Todd D, Kikinis R, Jolesz FA, McCarley RW. Fusiform gyrus volume reduction in first-episode schizophrenia: An MRI study. Archives of General Psychiatry, 2001; In Press.
McCarley RW, Structural magnetic resonance imaging studies in schizophrenia. In: Davis KL, Charney D, Coyle J, Nemeroff C (Eds.) Neuropsychopharmacology: The Fifth Generation of Progress. Baltimore: Lippincott,Williams & Wilkins, 2001; In Press.
Salisbury D, McCarley RW, Electrophysiology of schizophrenia. In: Hirsch J, Weinberger D (Eds.)Schizophrenia (2nd edition). Oxford: Blackwell Science Ltd, 2001; In Press.