Resting state functional connectivity in patients with remitted psychotic depression: A multi-centre STOP-PD studyResearch in context
Nicholas H. Neufeld,
Benoit H. Mulsant,
Erin W. Dickie,
Barnett S. Meyers,
George S. Alexopoulos,
Anthony J. Rothschild,
Ellen M. Whyte,
Matthew J. Hoptman,
Arash Nazeri,
Jonathan Downar,
Alastair J. Flint,
Aristotle N. Voineskos
Affiliations
Nicholas H. Neufeld
Kimel Family Translational Imaging-Genetics Laboratory, Research Imaging Centre, 250 College Street, Toronto, ON M5T 1R8, Canada; Campbell Family Mental Health Research Institute, 250 College Street, Toronto, ON M5T 1R8, Canada; Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada; Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON M5T 1R8, Canada
Benoit H. Mulsant
Campbell Family Mental Health Research Institute, 250 College Street, Toronto, ON M5T 1R8, Canada; Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada; Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON M5T 1R8, Canada
Erin W. Dickie
Kimel Family Translational Imaging-Genetics Laboratory, Research Imaging Centre, 250 College Street, Toronto, ON M5T 1R8, Canada; Campbell Family Mental Health Research Institute, 250 College Street, Toronto, ON M5T 1R8, Canada; Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada
Barnett S. Meyers
Weill Cornell Medical College, 21 Bloomingdale Road, White Plains, NY 10605, USA
George S. Alexopoulos
Weill Cornell Medical College, 21 Bloomingdale Road, White Plains, NY 10605, USA
Anthony J. Rothschild
University of Massachusetts Medical School and UMass Memorial Medical Centre, 55 Lake Avenue North, Worcester, MA 01655, USA
Ellen M. Whyte
University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA 15213, USA
Matthew J. Hoptman
Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA; Department of Psychiatry, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA; Department of Psychology, CUNY Graduate Centre, 365 Fifth Avenue, New York, NY 10016, USA
Arash Nazeri
Kimel Family Translational Imaging-Genetics Laboratory, Research Imaging Centre, 250 College Street, Toronto, ON M5T 1R8, Canada; Campbell Family Mental Health Research Institute, 250 College Street, Toronto, ON M5T 1R8, Canada; Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada; Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 South Kingshighway Boulevard, Saint Louis, MO 63110, USA
Jonathan Downar
Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON M5T 1R8, Canada; University Health Network, 200 Elizabeth Street, Toronto, ON M5G 2C4, Canada
Alastair J. Flint
Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON M5T 1R8, Canada; University Health Network, 200 Elizabeth Street, Toronto, ON M5G 2C4, Canada
Aristotle N. Voineskos
Kimel Family Translational Imaging-Genetics Laboratory, Research Imaging Centre, 250 College Street, Toronto, ON M5T 1R8, Canada; Campbell Family Mental Health Research Institute, 250 College Street, Toronto, ON M5T 1R8, Canada; Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada; Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON M5T 1R8, Canada; Corresponding author at: Kimel Family Translational Imaging-Genetics Laboratory, Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada.
Background: There is paucity of neurobiological knowledge about major depressive disorder with psychotic features (“psychotic depression”). This study addresses this knowledge gap by using resting state functional magnetic resonance imaging (R-fMRI) to compare functional connectivity in patients with psychotic depression and healthy controls. Methods: We scanned patients who participated in a randomized controlled trial as well as healthy controls. All patients achieved remission from depressive and psychotic symptoms with sertraline and olanzapine. We employed Independent Component Analysis in independent samples to isolate the default mode network (DMN) and compared patients and controls. Findings: The Toronto sample included 28 patients (mean [SD], age 56·2 [13·7]) and 39 controls (age 55·1 [13·5]). The Replication sample included 29 patients (age 56·1 [17·7]) and 36 controls (age 48·3 [17·9]). Patients in the Toronto sample demonstrated decreased between-network functional connectivity between the DMN and bilateral insular, somatosensory/motor, and auditory cortices with peak activity in the right planum polare (t = 4·831; p = 0·001, Family Wise Error (FWE) corrected). A similar pattern of between-network functional connectivity was present in our Replication sample with peak activity in the right precentral gyrus (t = 4·144; p = 0·003, FWE corrected). Interpretation: Remission from psychotic depression is consistently associated with an absence of increased DMN-related functional connectivity and presence of decreased between-network functional connectivity. Future research will evaluate this abnormal DMN-related functional connectivity as a potential biomarker for treatment trajectories. Funding: National Institute of Mental Health. Keywords: Default mode network, Functional connectivity, Biomarkers, Remission, Psychosis, Major depressive disorder
