Harvard Department Of PsychiatryHarvard Medical School


MR Diffusion Tensor Imaging of the Corpus Callosum and Other White Matter

Tracts in Chronic and First Episode Patients with Schizophrenia

Clinical Neuroscience Division, Laboratory of Neuroscience, Department of Psychiatry,

VA Boston Healthcare System, Brockton Division

Melissa Frumin, M.D., Martha E. Shenton, Ph.D., Robert W. McCarley, M.D, Ron Kikinis, M.D.,Ferenc Jolesz, M.D., Hatsuho Mamata, M.D., Marek Kubicki, M.D., Ph.D., Carl-Fredrick Westin Ph.D., Stephan Maier, M.D., Ph.D.


Disruption in the connectivity and organization of white matter fibers has been hypothesized as a possible etiology to explain hallucinations, delusions and cognitive impairment, hallmark symptoms of schizophrenia. MR diffusion imaging, a new technology, measures orientation, density and asymmetry of these fiber tracts, which cannot be visualized or quantified using conventional MR. This project will use MR diffusion tensor imaging to quantify the fiber tracts in schizophrenic patients and normal controls. Preliminary data from our lab with 16 patients with schizophrenia showed decreased diffusion in the corpus callosum as compared to controls, suggesting that schizophrenics may have less dense, or perhaps less white matter fiber connections in this brain region compared to normals.

Using the technique of MR diffusion tensor mapping, we will quantify the white matter fiber tracts in general, and the corpus callosum specifically, in chronic and first episode schizophrenic patients and normal controls. We predict that connections between the hemispheres will be disrupted in schizophrenia and that these connections will be more disrupted in the left hemisphere in patients with more positive symptoms, but bilaterally in patients with more negative symptoms. We further predict that these abnormalities will be most evident in links between the frontal and temporal lobes, in the corpus callosum and in medial temporal regions. Studying these white matter tracts can potentially help us to understand the brain pathology in patients who suffer from this devastating disorder.

Key Words. Schizophrenia, white matter, MR diffusion tensor imaging, corpus callosum

Grant Support. Support for this work comes from an Ethel Dupont-Warren Fellowship (MF), a VA Psychiatry/Neuroscience Research Fellowship Award (MF) a NARSAD Young Investigator Award (MF), and a Veteran Merit Review Award to use MR Brain Diffusion Tensor Imaging to Study Schizophrenia (MES).

Project Sites. Department of Psychiatry, Brain Imaging Laboratory, VA Boston Healthcare System, Brockton Division; Surgical Planning Laboratory and Department of Radiology, Brigham and Women's Hospital, Boston, MA;

Project Director. Melissa Frumin, M.D. Instructor in Psychiatry, Department of Psychiatry, Harvard Medical School, Boston VA Healthcare System, Brockton Division. Mail Address: Psychiatry 116A, 940 Belmont Street, Brockton, MA 02301. Email: melissa_frumin@http://hms.harvard.edu

Contact Person. Marie Fairbanks, Departmental Administrator. Tel. No.(508) 583-4500, X2479. FAX. (508) 586-0894. E-Mail Address: marie_fairbanks@http://hms.harvard.edu

Training Opportunities. Currently we have one Research Assistant assigned specifically to this project but there are fellows, two senior honors thesis students, a large number of junior faculty, and several full-time Research Assistants working in our laboratory. There are many opportunities for research training at all levels and we encourage interested undergraduates, graduate students, and fellows to join us in our research endeavors. Please visit us at our website: http://splweb.bwh.harvard.edu:8000/pages/projects/schiz/index.html

Representative Publications.

Shenton ME, Dickey CC, Frumin M, McCarley RW. A review of MRI findings in schizophrenia. Schizophr Res 2001;49:1-52.

Frumin M, Golland P, Kikinis R, Hirayasu Y, Salisbury DF, Hennen J, Dickey CC, Anderson M, Fischer IA, Yurgelun-Todd

D, Jolesz FA, Grimson WE, McCarley RW, Shenton ME. Shape differences in the corpus callosum in first psychotic

episode schizophrenia and first psychotic episode affective disorder. In Press. American Journal of Psychiatry.

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