Institute of Medical Science, University of Toronto, Canada; Centre for Depression and Suicide Studies, Unity Health Toronto, Canada; and Cumming School of Medicine, University of Calgary, Canada
Shijing Wang
Institute of Medical Science, University of Toronto, Canada; and Centre for Depression and Suicide Studies, Unity Health Toronto, Canada
Sakina J. Rizvi
Institute of Medical Science, University of Toronto, Canada; Centre for Depression and Suicide Studies, Unity Health Toronto, Canada; Department of Psychiatry, University of Toronto, Canada; Department of Psychiatry, Unity Health Toronto, Canada; and Li Ka Shing Knowledge Institute, Unity Health Toronto, Canada
Wendy Lou
Dalla Lana School of Public Health, University of Toronto, Canada; and Department of Biostatistics, University of Toronto, Canada
Stefanie Hassel
Cumming School of Medicine, University of Calgary, Canada; and Department of Psychiatry, University of Calgary, Canada
Glenda M. MacQueen
Cumming School of Medicine, University of Calgary, Canada; and Department of Psychiatry, University of Calgary, Canada
Keith Ho
Centre for Depression and Suicide Studies, Unity Health Toronto, Canada; Department of Psychiatry, Unity Health Toronto, Canada; and Li Ka Shing Knowledge Institute, Unity Health Toronto, Canada
Benicio N. Frey
Department of Psychiatry and Behavioural Neurosciences, McMaster University, Canada
Raymond W. Lam
Department of Psychiatry, University of British Columbia, Canada
Roumen V. Milev
Department of Psychiatry, Providence Care, Queen's University, Canada
Susan Rotzinger
Centre for Depression and Suicide Studies, Unity Health Toronto, Canada
Arun V. Ravindran
Department of Psychiatry, University of Toronto, Canada
Stephen C. Strother
Institute of Medical Science, University of Toronto, Canada; Rotman Research Institute, Baycrest Centre, Canada; and Department of Medical Biophysics, University of Toronto, Canada
Sidney H. Kennedy
Institute of Medical Science, University of Toronto, Canada; Centre for Depression and Suicide Studies, Unity Health Toronto, Canada; Department of Psychiatry, University of Toronto, Canada; Department of Psychiatry, Unity Health Toronto, Canada; Li Ka Shing Knowledge Institute, Unity Health Toronto, Canada; and Krembil Research Institute, University Health Network, Toronto, Canada
Background Identifying neuroimaging biomarkers of antidepressant response may help guide treatment decisions and advance precision medicine. Aims To examine the relationship between anhedonia and functional neurocircuitry in key reward processing brain regions in people with major depressive disorder receiving aripiprazole adjunct therapy with escitalopram. Method Data were collected as part of the CAN-BIND-1 study. Participants experiencing a current major depressive episode received escitalopram for 8 weeks; escitalopram non-responders received adjunct aripiprazole for an additional 8 weeks. Functional magnetic resonance imaging (on weeks 0 and 8) and clinical assessment of anhedonia (on weeks 0, 8 and 16) were completed. Seed-based correlational analysis was employed to examine the relationship between baseline resting-state functional connectivity (rsFC), using the nucleus accumbens (NAc) and anterior cingulate cortex (ACC) as key regions of interest, and change in anhedonia severity after adjunct aripiprazole. Results Anhedonia severity significantly improved after treatment with adjunct aripiprazole. There was a positive correlation between anhedonia improvement and rsFC between the ACC and posterior cingulate cortex, ACC and posterior praecuneus, and NAc and posterior praecuneus. There was a negative correlation between anhedonia improvement and rsFC between the ACC and anterior praecuneus and NAc and anterior praecuneus. Conclusions Eight weeks of aripiprazole, adjunct to escitalopram, was associated with improved anhedonia symptoms. Changes in functional connectivity between key reward regions were associated with anhedonia improvement, suggesting aripiprazole may be an effective treatment for individuals experiencing reward-related deficits. Future studies are required to replicate our findings and explore their generalisability, using other agents with partial dopamine (D2) agonism and/or serotonin (5-HT2A) antagonism.
