An investigation of cortical thickness and antidepressant response in major depressive disorder: A CAN-BIND study report

Jee Su Suh; Luciano Minuzzi; Pradeep Reddy Raamana; Andrew Davis; Geoffrey B Hall; Jacqueline Harris; Stefanie Hassel; Mojdeh Zamyadi; Stephen R Arnott; Gésine L Alders; Roberto B Sassi; Roumen Milev; Raymond W Lam; Glenda M MacQueen; Stephen C Strother; Sidney H Kennedy; Benicio N Frey

doi:10.1016/j.nicl.2020.102178

An investigation of cortical thickness and antidepressant response in major depressive disorder: A CAN-BIND study report

Neuroimage Clin. 2020:25:102178. doi: 10.1016/j.nicl.2020.102178. Epub 2020 Jan 13.

Authors

Jee Su Suh¹, Luciano Minuzzi², Pradeep Reddy Raamana³, Andrew Davis⁴, Geoffrey B Hall⁴, Jacqueline Harris⁵, Stefanie Hassel⁶, Mojdeh Zamyadi³, Stephen R Arnott³, Gésine L Alders¹, Roberto B Sassi⁷, Roumen Milev⁸, Raymond W Lam⁹, Glenda M MacQueen⁶, Stephen C Strother³, Sidney H Kennedy¹⁰, Benicio N Frey¹¹

Affiliations

¹ Neuroscience Graduate Program, McMaster University, Hamilton, ON, Canada; Mood Disorders Program and Women's Health Concerns Clinic, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada.
² Neuroscience Graduate Program, McMaster University, Hamilton, ON, Canada; Mood Disorders Program and Women's Health Concerns Clinic, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada; Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.
³ Rotman Research Institute, Baycrest Health Sciences; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
⁴ Department of Psychology, Neuroscience and Behaviour, McMaster University, Hamilton, ON, Canada.
⁵ Department of Computing Science, University of Alberta, Edmonton, AB, Canada.
⁶ Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Mathison Centre for Mental Health Research and Education, University of Calgary, Calgary, AB, Canada.
⁷ Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.
⁸ Departments of Psychiatry and Psychology, Queen's University and Providence Care Hospital, Kingston, ON, Canada.
⁹ Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
¹⁰ Canadian Biomarker Integration Network for Depression, St. Michael's Hospital, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
¹¹ Neuroscience Graduate Program, McMaster University, Hamilton, ON, Canada; Mood Disorders Program and Women's Health Concerns Clinic, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada; Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada. Electronic address: freybn@mcmaster.ca.

Abstract

Major depressive disorder (MDD) is considered a highly heterogeneous clinical and neurobiological mental disorder. We employed a novel layered treatment design to investigate whether cortical thickness features at baseline differentiated treatment responders from non-responders after 8 and 16 weeks of a standardized sequential antidepressant treatment. Secondary analyses examined baseline differences between MDD and controls as a replication analysis and longitudinal changes in thickness after 8 weeks of escitalopram treatment. 181 MDD and 95 healthy comparison (HC) participants were studied. After 8 weeks of escitalopram treatment (10-20 mg/d, flexible dosage), responders (>50% decrease in Montgomery-Åsberg Depression Scale score) were continued on escitalopram; non-responders received adjunctive aripiprazole (2-10 mg/d, flexible dosage). MDD participants were classified into subgroups according to their response profiles at weeks 8 and 16. Baseline group differences in cortical thickness were analyzed with FreeSurfer between HC and MDD groups as well as between response groups. Two-stage longitudinal processing was used to investigate 8-week escitalopram treatment-related changes in cortical thickness. Compared to HC, the MDD group exhibited thinner cortex in the left rostral middle frontal cortex [MNI(X,Y,Z=-29,9,54.5,-7.7); CWP=0.0002]. No baseline differences in cortical thickness were observed between responders and non-responders based on week-8 or week-16 response profile. No changes in cortical thickness was observed after 8 weeks of escitalopram monotherapy. In a two-step 16-week sequential clinical trial we found that baseline cortical thickness does not appear to be associated to clinical response to pharmacotherapy at 8 or 16 weeks.

Keywords: Antidepressant response; Clinical trial; Cortical thickness; Major depressive disorder; Structural neuroimaging.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antidepressive Agents / administration & dosage
Antidepressive Agents / pharmacology*
Aripiprazole / administration & dosage
Aripiprazole / pharmacology*
Cerebral Cortex / diagnostic imaging
Cerebral Cortex / drug effects*
Cerebral Cortex / pathology*
Citalopram / administration & dosage
Citalopram / pharmacology*
Depressive Disorder, Major / diagnostic imaging
Depressive Disorder, Major / drug therapy*
Depressive Disorder, Major / pathology*
Drug Therapy, Combination
Female
Humans
Longitudinal Studies
Magnetic Resonance Imaging
Male
Middle Aged
Neuroimaging / methods*
Outcome Assessment, Health Care

Substances

Antidepressive Agents
Citalopram
Aripiprazole

Grants and funding

MOP 125880/CIHR/Canada