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Diffusion tractography of the fornix in schizophrenia

Institution:	1Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 2Clinical Neuroscience Division, Laboratory of Neuroscience, Department of Psychiatry, VA Boston Healthcare System, Harvard Medical School, Boston, MA, USA. chandlee_dickey@hms.harvard.edu 3Laboratory of Mathematical Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 4Surgical Planning Laboratory, MRI Division, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Publisher:	Schizophr Res
Publication Date:	Jan-2009
Citation:	Schizophr Res 2009 Jan; 107:39–46.
PubMed ID:	19046624
PMCID:	PMC2646850
Keywords:	Diffusion Tensor Imaging, Schizophrenia, Fractional Anisotropy, Fornix
Appears in Collections:	PNL, LMI, NA-MIC, SPL
Sponsors:	NIH K05 MH070047 NIH R01 MH 50740 NIH R01 MH 40799 NIH R01 MH 074794 NIH P50 MH 080272 Department of Veterans Affairs Merit Awards VA Schizophrenia Center Grant NIH Roadmap for Medical Research, U54 EB005149
Generated Citation:	Fitzsimmons J, Kubicki M, Smith K, Bushell G, San José Estepar R, Westin C, Nestor P, Niznikiewicz M, Kikinis R, McCarley R, Shenton M. Diffusion tractography of the fornix in schizophrenia. Schizophr Res 2009 Jan; 107:39–46. PMID: 19046624. PMCID: PMC2646850.
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Background: White matter fiber tracts, especially those interconnecting the frontal and temporal lobes, are likely implicated in pathophysiology of schizophrenia. Very few studies, however, have focused on the fornix, a compact bundle of white matter fibers, projecting from the hippocampus to the septum, anterior nucleus of the thalamus and the mamillary bodies. Diffusion Tensor Imaging (DTI), and a new post-processing method, fiber tractography, provides a unique opportunity to visualize and to quantify entire trajectories of fiber bundles, such as the fornix, in vivo. We applied these techniques to quantify fornix diffusion anisotropy in schizophrenia. Methods: DTI images were used to evaluate the left and the right fornix in 36 male patients diagnosed with chronic schizophrenia and 35 male healthy individuals, group matched on age,parental socioeconomic status, and handedness. Regions of interest were drawn manually, blind to group membership, to guide tractography, and fractional anisotropy (FA), a measure of fiber integrity, was calculated and averaged over the entire tract for each subject. The Doors and People test (DPT) was used to evaluate visual and verbal memory, combined recall and combined recognition. Results: Analysis of variance was performed and findings demonstrated a difference between patients with schizophrenia and controls for fornix FA (p = 0.006). Protected post-hoc independent sample t-tests demonstrated a bilateral FA decrease in schizophrenia, compared with control subjects (left side: p = 0.048; right side p = 0.006). Higher fornix FA was statistically significantly correlated with DPT and measures of combined visual memory (r = 0.554,p = 0.026), combined verbal memory (r = 0.647, p = 0.007), combined recall (r = 0.516, p = 0.041), and combined recognition (r = 0.710, p = 0.002) for the control group. No such statistically significant correlations were found in the patient group. Conclusions: Our findings show the utility of applying DTI and tractography to study white matter fiber tracts in vivo in schizophrenia. Specifically, we observed a bilateral disruption in fornix integrity in schizophrenia, thus broadening our understanding of the pathophysiology of this disease.

Fitzsimmons-SchizophrRes2009-fig2.jpg (80.813kB)