Shared and Unique Changes in Brain Connectivity Among Depressed Patients After Remission With Pharmacotherapy Versus Psychotherapy
Publication: American Journal of Psychiatry
Abstract
Objective:
The authors sought to determine the shared and unique changes in brain resting-state functional connectivity (rsFC) between patients with major depressive disorder who achieved remission with cognitive-behavioral therapy (CBT) or with antidepressant medication.
Methods:
The Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) trial randomized adults with treatment-naive major depressive disorder to 12 weeks of treatment with CBT (16 1-hour sessions) or medication (duloxetine 30–60 mg/day or escitalopram 10–20 mg/day). Resting-state functional MRI scans were performed at baseline and at week 12. The primary outcome was change in the whole-brain rsFC of four seeded brain networks among participants who achieved remission.
Results:
Of the 131 completers with usable MRI data (74 female; mean age, 39.8 years), remission was achieved by 19 of 40 CBT-treated and 45 of 91 medication-treated patients. Three patterns of connectivity changes were observed. First, those who remitted with either treatment shared a pattern of reduction in rsFC between the subcallosal cingulate cortex and the motor cortex. Second, reciprocal rsFC changes were observed across multiple networks, primarily increases in CBT remitters and decreases in medication remitters. And third, in CBT remitters only, rsFC increased within the executive control network and between the executive control network and parietal attention regions.
Conclusions:
Remission from major depression via treatment with CBT or medication is associated with changes in rsFC that are mostly specific to the treatment modality, providing biological support for the clinical practice of switching between or combining these treatment approaches. Medication is associated with broadly inhibitory effects. In CBT remitters, the increase in rsFC strength between networks involved in cognitive control and attention provides biological support for the theorized mechanism of CBT. Reducing affective network connectivity with motor systems is a shared process important for remission with both CBT and medication.
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History
Received: 18 July 2021
Revision received: 19 April 2022
Revision received: 13 June 2022
Accepted: 21 June 2022
Published online: 18 January 2023
Published in print: March 01, 2023
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Author Contributions
Drs. Craighead and Mayberg contributed equally to this work.
Competing Interests
Dr. Dunlop has received research support from Acadia, Aptinyx, Compass, NIMH, Otsuka, Sage, and Takeda and has served as a consultant for Cerebral Therapeutics, Greenwich Biosciences, Myriad Neuroscience, Otsuka, Sage, and Sophren Therapeutics. Dr. Choi has served as a consultant for Abbott Laboratories. Dr. Nemeroff has served as a consultant for AbbVie, Acadia Pharmaceuticals, Alfasigma, ANeuroTech (a division of Anima BV), Axsome, BioXcel Therapeutics, Clexio, Corcept Therapeutics, EcoR1, EMA Wellness, Engrail Therapeutics, GoodCap Pharmaceuticals, Intra-Cellular Therapies, Janssen Research and Development, Magstim, Navitor Pharmaceuticals, Neuritek, Ninnion Therapeutics, Pasithea Therapeutics, Sage, Senseye, Signant Health, Silo Pharma, SK Life Science, Sunovion Pharmaceuticals, and XW Pharma; he has served on scientific advisory boards for ANeuroTech, the Anxiety and Depression Association of America (ADAA), the Brain and Behavior Research Foundation, Heading Health, the Laureate Institute for Brain Research, Magnolia CNS, Pasithea Therapeutics, Sage, Signant Health, Skyland Trail, and TRUUST Neuroimaging and on the boards of directors for ADAA, Gratitude America, Lucy Scientific Discovery, and Xhale Smart; he holds stock in Antares, BI Gen Holdings, Corcept Therapeutics, EMA Wellness, Naki Health, Seattle Genetics, TRUUST Neuroimaging, and Xhale; and he is named on U.S. patents 6,375,990B1 and 7,148,027B2. Dr. Craighead has served as a consultant for the George West Mental Health Foundation, as a board member of Hugarheill ehf (an Icelandic company dedicated to the prevention of depression), and as a scientific advisory board member for AIM for Mental Health and ADAA; he is supported by the Mary and John Brock Foundation, the Pitts Foundation, and the Fuqua family foundations; and he receives book royalties from John Wiley. Dr. Mayberg has received consulting and intellectual property licensing fees from Abbott Neuromodulation. The other authors report no financial relationships with commercial interests.
Funding Information
Supported by NIH grants P50 MH077083, RO1 MH080880, UL1 RR025008, M01 RR0039, and K23 MH086690. Forest Laboratories and Elli Lilly donated the study medications (escitalopram and duloxetine, respectively).
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