Rajapillai L I Pillai1, Chuan Huang2, Andrew LaBella3, Mengru Zhang4, Jie Yang5, Madhukar Trivedi6, Myrna Weissman7, Patrick McGrath7, Maurizio Fava8, Benji Kurian6, Crystal Cooper6, Melvin McInnis9, Maria A Oquendo10, Diego A Pizzagalli8, Ramin V Parsey1, Christine DeLorenzo11. 1. Department of Psychiatry, Stony Brook University, Stony Brook, NY, United States. 2. Department of Psychiatry, Stony Brook University, Stony Brook, NY, United States; Department of Radiology, Stony Brook University, Stony Brook, NY, United States. Electronic address: chuan.huang@stonybrookmedicine.edu. 3. Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, United States. 4. Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, United States. 5. Department of Family, Population, & Preventive Medicine, Stony Brook University, Stony Brook, NY, United States. 6. Department of Psychiatry, University of Texas Southwestern Medical Center, United States. 7. Department of Psychiatry, College of Physicians and Surgeons, Columbia University and the New York Psychiatric Institute, United States. 8. Department of Psychiatry, Harvard Medical School, United States. 9. Department of Psychiatry, University of Michigan, United States. 10. Department of Psychiatry, University of Pennsylvania, United States. 11. Department of Psychiatry, Stony Brook University, Stony Brook, NY, United States; Department of Psychiatry, Molecular Imaging and Neuropathology Division, Columbia University, New York, NY, United States.
Abstract
BACKGROUND: Our lab has previously found that structural integrity in tracts from the raphe nucleus (RN) to the amygdala, measured by fractional anisotropy (FA), predicts remission to selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder (MDD). This could potentially serve as a biomarker for remission that can guide clinical decision-making. To enhance repeatability and reproducibility, we replicated our study in a larger, more representative multi-site sample. METHODS: 64 direction DTI was collected in 144 medication-free patients with MDD from the Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) study. We performed probabilistic tractography between the RN and bilateral amygdala and hippocampus and calculated weighted FA in these tracts. Patients were treated with either sertraline or placebo, and their change in Hamilton Depression Rating Scale (HDRS) score reported. Pretreatment weighted FA was compared between remitters and nonremitters, and correlation between FA and percent change in HDRS score was assessed. Exploratory moderator and voxel analyses were also performed. RESULTS: Contrary to our hypotheses, FA was greater in nonremitters than in remitters in RN-left and right amygdala tracts (p = 0.02 and 0.01, respectively). Pretreatment FA between the raphe and left amygdala correlated with greater, not reduced, HDRS (r = 0.18, p = 0.04). This finding was found to be greater in the placebo group. Moderator and voxel analyses yielded no significant findings. CONCLUSIONS: We found greater FA in nonremitters between the RN and amygdala than in remitters, and a correlation between FA and symptom worsening, particularly with placebo. These findings may help reveal more about the nature of MDD, as well as guide research methods involving placebo response.
BACKGROUND: Our lab has previously found that structural integrity in tracts from the raphe nucleus (RN) to the amygdala, measured by fractional anisotropy (FA), predicts remission to selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder (MDD). This could potentially serve as a biomarker for remission that can guide clinical decision-making. To enhance repeatability and reproducibility, we replicated our study in a larger, more representative multi-site sample. METHODS: 64 direction DTI was collected in 144 medication-free patients with MDD from the Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) study. We performed probabilistic tractography between the RN and bilateral amygdala and hippocampus and calculated weighted FA in these tracts. Patients were treated with either sertraline or placebo, and their change in Hamilton Depression Rating Scale (HDRS) score reported. Pretreatment weighted FA was compared between remitters and nonremitters, and correlation between FA and percent change in HDRS score was assessed. Exploratory moderator and voxel analyses were also performed. RESULTS: Contrary to our hypotheses, FA was greater in nonremitters than in remitters in RN-left and right amygdala tracts (p = 0.02 and 0.01, respectively). Pretreatment FA between the raphe and left amygdala correlated with greater, not reduced, HDRS (r = 0.18, p = 0.04). This finding was found to be greater in the placebo group. Moderator and voxel analyses yielded no significant findings. CONCLUSIONS: We found greater FA in nonremitters between the RN and amygdala than in remitters, and a correlation between FA and symptom worsening, particularly with placebo. These findings may help reveal more about the nature of MDD, as well as guide research methods involving placebo response.
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