Alexis E Whitton1, Christian A Webb1, Daniel G Dillon1, Jürgen Kayser2, Ashleigh Rutherford3, Franziska Goer3, Maurizio Fava4, Patrick McGrath2, Myrna Weissman2, Ramin Parsey5, Phil Adams2, Joseph M Trombello6, Crystal Cooper6, Patricia Deldin7, Maria A Oquendo8, Melvin G McInnis7, Thomas Carmody6, Gerard Bruder2, Madhukar H Trivedi6, Diego A Pizzagalli9. 1. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts; Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Massachusetts. 2. New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, New York. 3. Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Massachusetts. 4. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts; Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts. 5. Department of Psychiatry, Stony Brook University, Stony Brook, New York. 6. Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas. 7. Department of Psychiatry, University of Michigan, Ann Arbor, Michigan. 8. Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. 9. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts; Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Massachusetts. Electronic address: dap@mclean.harvard.edu.
Abstract
BACKGROUND:Baseline rostral anterior cingulate cortex (rACC) activity is a well-replicated nonspecific predictor of depression improvement. The rACC is a key hub of the default mode network, which prior studies indicate is hyperactive in major depressive disorder. Because default mode network downregulation is reliant on input from the salience network and frontoparietal network, an important question is whether rACC connectivity with these systems contributes to depression improvement. METHODS: Our study evaluated this hypothesis in outpatients (N = 238; 151 female) enrolled in the Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) 8-week randomized clinical trial ofsertraline versus placebofor major depressive disorder. Depression severity was measured using the Hamilton Rating Scale for Depression, and electroencephalography was recorded at baseline and week 1. Exact low-resolution electromagnetic tomography was used to compute activity from the rACC, and key regions within the default mode network (posterior cingulate cortex), frontoparietal network (left dorsolateral prefrontal cortex), and salience network (right anterior insula [rAI]). Connectivity in the theta band (4.5-7 Hz) and beta band (12.5-21 Hz) was computed using lagged phase synchronization. RESULTS: Stronger baseline theta-band rACC-rAI (salience network hub) connectivity predicted greater depression improvement across 8 weeks of treatment for both treatment arms (B = -0.57, 95% confidence interval = -1.07, -0.08, p = .03). Early increases in theta-band rACC-rAI connectivity predicted greater likelihood of achieving remission at week 8 (odds ratio = 2.90, p = .03). CONCLUSIONS: Among patients undergoing treatment, theta-band rACC-rAI connectivity is a prognostic, albeit treatment-nonspecific, indicator of depression improvement, and early connectivity changes may predict clinically meaningful outcomes.
RCT Entities:
BACKGROUND: Baseline rostral anterior cingulate cortex (rACC) activity is a well-replicated nonspecific predictor of depression improvement. The rACC is a key hub of the default mode network, which prior studies indicate is hyperactive in major depressive disorder. Because default mode network downregulation is reliant on input from the salience network and frontoparietal network, an important question is whether rACC connectivity with these systems contributes to depression improvement. METHODS: Our study evaluated this hypothesis in outpatients (N = 238; 151 female) enrolled in the Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) 8-week randomized clinical trial of sertraline versus placebo for major depressive disorder. Depression severity was measured using the Hamilton Rating Scale for Depression, and electroencephalography was recorded at baseline and week 1. Exact low-resolution electromagnetic tomography was used to compute activity from the rACC, and key regions within the default mode network (posterior cingulate cortex), frontoparietal network (left dorsolateral prefrontal cortex), and salience network (right anterior insula [rAI]). Connectivity in the theta band (4.5-7 Hz) and beta band (12.5-21 Hz) was computed using lagged phase synchronization. RESULTS: Stronger baseline theta-band rACC-rAI (salience network hub) connectivity predicted greater depression improvement across 8 weeks of treatment for both treatment arms (B = -0.57, 95% confidence interval = -1.07, -0.08, p = .03). Early increases in theta-band rACC-rAI connectivity predicted greater likelihood of achieving remission at week 8 (odds ratio = 2.90, p = .03). CONCLUSIONS: Among patients undergoing treatment, theta-band rACC-rAI connectivity is a prognostic, albeit treatment-nonspecific, indicator of depression improvement, and early connectivity changes may predict clinically meaningful outcomes.
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