John W Rutland1, Stephanie Brown2, Gaurav Verma2, Rebecca E Feldman2, Himanshu Sharma2, Matthew Markowitz2, Molly Schneider3, Bradley N Delman4, James Murrough5, Priti Balchandani2. 1. Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States. Electronic address: jack.rutland@icahn.mssm.edu. 2. Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States. 3. Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States. 4. Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States. 5. Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Abstract
OBJECTIVE: Diffusion magnetic resonance imaging (dMRI) enables non-invasive characterization of white matter (WM) structures in vivo. Prior studies suggest that certain WM tracts may be affected in major depressive disorder (MDD), however, hippocampal subfield-specific dMRI measures have not yet been explored in MDD. We use 7 Tesla dMRI to investigate differences in hippocampal subfield connectivity of MDD patients. METHODS: Eighteen MDD patients and eighteen matched healthy volunteers underwent 7 Tesla MRI. The hippocampal formations were segmented by subfields and tractography was performed to determine streamline count (SC), fractional anisotropy (FA), and mean diffusivity (MD) in patients and controls. Significant subfield connectivity measures were also correlated with age at depression onset. RESULTS: Compared with controls, MDD patients exhibited reduced SC in the molecular layer of the left dentate gyrus (p < 0.001). SC count in the left dentate gyrus was shown to positively correlate with age at disease onset (p < 0.05). Increased MD was observed in streamlines emanating from both the left (p = 0.0001) and right (p < 0.001) fimbriae in MDD patients. CONCLUSIONS: Increased MD of tracts in the fimbriae suggests compromised neuronal membranes in the major hippocampal output gate. Reduced SC of the dentate gyri indexes a disruption of normal cellular processes such as neurogenesis. These findings may have significant implications for identifying biomarkers of MDD and elucidating the neurobiological underpinnings of depression.
OBJECTIVE: Diffusion magnetic resonance imaging (dMRI) enables non-invasive characterization of white matter (WM) structures in vivo. Prior studies suggest that certain WM tracts may be affected in major depressive disorder (MDD), however, hippocampal subfield-specific dMRI measures have not yet been explored in MDD. We use 7 Tesla dMRI to investigate differences in hippocampal subfield connectivity of MDDpatients. METHODS: Eighteen MDDpatients and eighteen matched healthy volunteers underwent 7 Tesla MRI. The hippocampal formations were segmented by subfields and tractography was performed to determine streamline count (SC), fractional anisotropy (FA), and mean diffusivity (MD) in patients and controls. Significant subfield connectivity measures were also correlated with age at depression onset. RESULTS: Compared with controls, MDDpatients exhibited reduced SC in the molecular layer of the left dentate gyrus (p < 0.001). SC count in the left dentate gyrus was shown to positively correlate with age at disease onset (p < 0.05). Increased MD was observed in streamlines emanating from both the left (p = 0.0001) and right (p < 0.001) fimbriae in MDDpatients. CONCLUSIONS: Increased MD of tracts in the fimbriae suggests compromised neuronal membranes in the major hippocampal output gate. Reduced SC of the dentate gyri indexes a disruption of normal cellular processes such as neurogenesis. These findings may have significant implications for identifying biomarkers of MDD and elucidating the neurobiological underpinnings of depression.
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