TY - JOUR
T1 - Cortical inhibition, facilitation and plasticity in late-life depression
T2 - Effects of venlafaxine pharmacotherapy
AU - Lissemore, Jennifer I.
AU - Mulsant, Benoit H.
AU - Rajji, Tarek K.
AU - Karp, Jordan F.
AU - Reynolds, Charles F.
AU - Lenze, Eric J.
AU - Downar, Jonathan
AU - Chen, Robert
AU - Daskalakis, Zafiris J.
AU - Blumberger, Daniel M.
N1 - Funding Information:
Funding: This work was directly supported by NIMH grant NIH
Funding Information:
Capital Solution Design LLC, HAPPYneuron, Bristol-Myers Squibb and Eli Lilly; grants from Brain Canada, the Patient-Centered Outcomes Research Institute (PCORI), the Canadian Institutes of Health Research (CIHR), the National Institutes of Health (NIH) and the Centre for Addiction and Mental Health (CAMH) Foundation; and other support from General Electric. T. Rajji has received research support from Brain Canada, the Brain and Behavior Research Foundation, the BrightFocus Foundation, the Canada Foundation for Innovation, a Canada Research Chair, CIHR, the Centre for Aging and Brain Health Innovation, NIH, the Ontario Ministry of Health and Long-Term Care, the Ontario Ministry of Research and Innovation and the Weston Brain Institute; in-kind equipment support for an investigator-initiated study from Magstim; and in-kind research accounts from Scientific Brain Training Pro. J. Karp is a scientific advisor to NightWare and received medication supplies for investigator-initiated trials from Pfizer and In-divior and honoraria for development and presentation of a webinar (disease-state, not product-focused) from Otsuka. C. Reynolds III reports grants from the NIH during the conduct of the study; grants from the NIH, the PCORI, the Center for Medicare and Medicaid Services, the American Foundation for Suicide Prevention, the Brain and Behavior Research Foundation and the Commonwealth of Pennsylvania outside the submitted work; and non-financial support from Bristol Meyers Squib and Pfizer, outside the submitted work. E. Lenze received research support from the National Institute on Aging, the National Center for Complementary and Integrative Health, the National Institute of Mental Health (NIMH), the Office of Behavioral and Social Sciences Research, the United States Food and Drug Administration, PCORI, the McKnight Brain Research Foundation, the Taylor Family Institute for Innovative Psychiatric Research, the Barnes Jewish Foundation, Takeda, Acadia Alkermes, Aptinyx and Lundbeck; and consulting fees from Janssen and Jazz Pharmaceuticals. J. Downar reports grants from the Arrell Family Foundation, the Buchan Family Foundation, Brain Canada, the Canadian Biomarker Integration Network in Depression, CIHR, the Klarman Family Foundation, NIMH, the Ontario Brain Institute and the Weston Family Foundation; and other support from ANT Neuro, BrainCheck, Restorative Brain Clinics and TMS Neuro Solutions, all outside the submitted work. R. Chen received honoraria from Allergan, Merz and Ipsen. Z. Daskalakis reports non-financial support from Brainsway Inc; non-financial support from Magventure Inc; grants from the Ontario Mental Health Foundation, CIHR, NIMH, the Temerty Family, the Grant Family, the CAMH Foundation and the Campbell Institute, all outside the submitted work. D. Blumberger has received research support from CIHR, NIMH, Brain Canada and the Temerty Family through the CAMH Foundation and the Campbell Family Research Institute; received research support and in-kind equipment support for an investigator-initiated study from Brainsway Ltd; is the site principal investigator for one sponsor-initiated study for Brainsway Ltd.; receives in-kind equipment support from Magventure for investigator-initiated research; and received medication supplies for an investigator-initiated trial from Indivior. No other competing interests were declared.
Funding Information:
This work was directly supported by NIMH grant NIH R34MH101365.
Publisher Copyright:
© 2021 Joule Inc. or its licensors.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - Background: Late-life depression is often associated with non-response or relapse following conventional antidepressant treatment. The pathophysiology of late-life depression likely involves a complex interplay between aging and depression, and may include abnormalities in cortical inhibition and plasticity. However, the extent to which these cortical processes are modifiable by antidepressant phar-macotherapy is unknown. Methods: Sixty-eight patients with late-life depression received 12 weeks of treatment with open-label venla-faxine, a serotonin-norepinephrine reuptake inhibitor (≤ 300 mg/d). We combined transcranial magnetic stimulation of the left motor cortex with electromyography recordings from the right hand to measure cortical inhibition using contralateral cortical silent period and paired-pulse short-interval intracortical inhibition paradigms; cortical facilitation using a paired-pulse intracortical facilitation paradigm; and short-term cortical plasticity using a paired associative stimulation paradigm. All measures were collected at baseline, 1 week into treatment (n = 23) and after approximately 12 weeks of treatment. Results: Venlafaxine did not significantly alter cortical inhibition, facilitation or plasticity after 1 or 12 weeks of treatment. Improvements in depressive symptoms during treatment were not associated with changes in cortical physiology. Limitations: The results presented here are specific to the motor cortex. Future work should investigate whether these findings extend to cortical areas more closely associated with depression, such as the dorsolateral prefrontal cortex. Conclusion: These findings suggest that antidepressant treatment with venlafaxine does not exert meaningful changes in motor cortical inhibition or plasticity in late-life depression. The absence of changes in motor cortical physiology, alongside improvements in depressive symptoms, suggests that age-related changes may play a role in previously identified abnormalities in motor cortical processes in late-life depression, and that venlafaxine treatment does not target these abnormalities.
AB - Background: Late-life depression is often associated with non-response or relapse following conventional antidepressant treatment. The pathophysiology of late-life depression likely involves a complex interplay between aging and depression, and may include abnormalities in cortical inhibition and plasticity. However, the extent to which these cortical processes are modifiable by antidepressant phar-macotherapy is unknown. Methods: Sixty-eight patients with late-life depression received 12 weeks of treatment with open-label venla-faxine, a serotonin-norepinephrine reuptake inhibitor (≤ 300 mg/d). We combined transcranial magnetic stimulation of the left motor cortex with electromyography recordings from the right hand to measure cortical inhibition using contralateral cortical silent period and paired-pulse short-interval intracortical inhibition paradigms; cortical facilitation using a paired-pulse intracortical facilitation paradigm; and short-term cortical plasticity using a paired associative stimulation paradigm. All measures were collected at baseline, 1 week into treatment (n = 23) and after approximately 12 weeks of treatment. Results: Venlafaxine did not significantly alter cortical inhibition, facilitation or plasticity after 1 or 12 weeks of treatment. Improvements in depressive symptoms during treatment were not associated with changes in cortical physiology. Limitations: The results presented here are specific to the motor cortex. Future work should investigate whether these findings extend to cortical areas more closely associated with depression, such as the dorsolateral prefrontal cortex. Conclusion: These findings suggest that antidepressant treatment with venlafaxine does not exert meaningful changes in motor cortical inhibition or plasticity in late-life depression. The absence of changes in motor cortical physiology, alongside improvements in depressive symptoms, suggests that age-related changes may play a role in previously identified abnormalities in motor cortical processes in late-life depression, and that venlafaxine treatment does not target these abnormalities.
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U2 - 10.1503/jpn.200001
DO - 10.1503/jpn.200001
M3 - Article
C2 - 33119493
AN - SCOPUS:85099072894
VL - 46
SP - E88-E96
JO - Psychiatric Journal of the University of Ottawa
JF - Psychiatric Journal of the University of Ottawa
SN - 1180-4882
IS - 1
ER -