Full access
Regular Articles
Published Online: 13 May 2020

Effect of Functional BDNF and COMT Polymorphisms on Symptoms and Regional Brain Volume in Frontotemporal Dementia and Corticobasal Syndrome

Edward D. Huey, M.D. [email protected], Rachel Fremont, M.D., Ph.D., Masood Manoochehri, B.A., Yunglin Gazes, Ph.D., Seonjoo Lee, Ph.D., Stephanie Cosentino, Ph.D., Michael Tierney, M.S, Eric M. Wassermann, M.D., Parastoo Momeni, Ph.D., and Jordan Grafman, Ph.D.Authors Info & Affiliations
Publication: The Journal of Neuropsychiatry and Clinical Neurosciences
Volume 32, Number 4
https://doi.org/10.1176/appi.neuropsych.19100211
PDF/EPUBformats

Abstract

Objective:

The authors examined the effects of two common functional polymorphisms—brain-derived neurotrophic factor (BDNF) Val66Met and catechol-O-methyltransferase (COMT) Val158Met—on cognitive, neuropsychiatric, and motor symptoms and MRI findings in persons with frontotemporal lobar degeneration (FTLD) syndromes.

Methods:

The BDNF Val66Met and COMT Val158Met polymorphisms were genotyped in 174 participants with FTLD syndromes, including behavioral variant frontotemporal dementia, primary progressive aphasia, and corticobasal syndrome. Gray matter volumes and scores on the Delis-Kaplan Executive Function System, Mattis Dementia Rating Scale, Wechsler Memory Scale, and Neuropsychiatric Inventory were compared between allele groups.

Results:

The BDNF Met allele at position 66 was associated with a decrease in depressive symptoms (F=9.50, df=1, 136, p=0.002). The COMT Val allele at position 158 was associated with impairment of executive function (F=6.14, df=1, 76, p=0.015) and decreased bilateral volume of the head of the caudate in patients with FTLD (uncorrected voxel-level threshold of p<0.001). Neither polymorphism had a significant effect on motor function.

Conclusions:

These findings suggest that common functional polymorphisms likely contribute to the phenotypic variability seen in patients with FTLD syndromes. This is the first study to implicate BDNF polymorphisms in depressive symptoms in FTLD. These results also support an association between COMT polymorphisms and degeneration patterns and cognition in FTLD.

Formats available

You can view the full content in the following formats:

View PDF/ePubView Full Text

Information & Authors

Information

Published In

Go to The Journal of Neuropsychiatry and Clinical Neurosciences
Go to The Journal of Neuropsychiatry and Clinical Neurosciences
The Journal of Neuropsychiatry and Clinical Neurosciences
Volume 32 • Number 4 • Fall 2020
Pages: 362 - 369
PubMed: 32397876

History

Received: 1 October 2019
Revision received: 14 February 2020
Accepted: 19 February 2020
Published online: 13 May 2020
Published in print: Fall 2020

Keywords

  1. Frontotemporal Dementia
  2. Corticobasal Syndrome
  3. BDNF
  4. COMT
  5. Dementia
  6. Genetics

Authors

Affiliations

Edward D. Huey, M.D. [email protected]
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, New York (Huey, Manoochehri, Gazes, Cosentino); Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York (Huey, Fremont); Department of Neurology, College of Physicians and Surgeons, Columbia University, New York (Huey, Manoochehri, Gazes, Cosentino); Department of Biostatistics, Mailman School of Public Health, Columbia University, New York (Lee); Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Md. (Huey, Tierney, Wassermann, Grafman); RONA Holdings, Silicon Valley, Calif. (Momeni); and Cognitive Neuroscience Laboratory, Think and Speak Lab, Shirley Ryan AbilityLab, Chicago (Grafman).
View all articles by this author
Rachel Fremont, M.D., Ph.D.
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, New York (Huey, Manoochehri, Gazes, Cosentino); Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York (Huey, Fremont); Department of Neurology, College of Physicians and Surgeons, Columbia University, New York (Huey, Manoochehri, Gazes, Cosentino); Department of Biostatistics, Mailman School of Public Health, Columbia University, New York (Lee); Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Md. (Huey, Tierney, Wassermann, Grafman); RONA Holdings, Silicon Valley, Calif. (Momeni); and Cognitive Neuroscience Laboratory, Think and Speak Lab, Shirley Ryan AbilityLab, Chicago (Grafman).
View all articles by this author
Masood Manoochehri, B.A.
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, New York (Huey, Manoochehri, Gazes, Cosentino); Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York (Huey, Fremont); Department of Neurology, College of Physicians and Surgeons, Columbia University, New York (Huey, Manoochehri, Gazes, Cosentino); Department of Biostatistics, Mailman School of Public Health, Columbia University, New York (Lee); Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Md. (Huey, Tierney, Wassermann, Grafman); RONA Holdings, Silicon Valley, Calif. (Momeni); and Cognitive Neuroscience Laboratory, Think and Speak Lab, Shirley Ryan AbilityLab, Chicago (Grafman).
View all articles by this author
Yunglin Gazes, Ph.D.
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, New York (Huey, Manoochehri, Gazes, Cosentino); Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York (Huey, Fremont); Department of Neurology, College of Physicians and Surgeons, Columbia University, New York (Huey, Manoochehri, Gazes, Cosentino); Department of Biostatistics, Mailman School of Public Health, Columbia University, New York (Lee); Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Md. (Huey, Tierney, Wassermann, Grafman); RONA Holdings, Silicon Valley, Calif. (Momeni); and Cognitive Neuroscience Laboratory, Think and Speak Lab, Shirley Ryan AbilityLab, Chicago (Grafman).
View all articles by this author
Seonjoo Lee, Ph.D.
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, New York (Huey, Manoochehri, Gazes, Cosentino); Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York (Huey, Fremont); Department of Neurology, College of Physicians and Surgeons, Columbia University, New York (Huey, Manoochehri, Gazes, Cosentino); Department of Biostatistics, Mailman School of Public Health, Columbia University, New York (Lee); Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Md. (Huey, Tierney, Wassermann, Grafman); RONA Holdings, Silicon Valley, Calif. (Momeni); and Cognitive Neuroscience Laboratory, Think and Speak Lab, Shirley Ryan AbilityLab, Chicago (Grafman).
View all articles by this author
Stephanie Cosentino, Ph.D.
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, New York (Huey, Manoochehri, Gazes, Cosentino); Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York (Huey, Fremont); Department of Neurology, College of Physicians and Surgeons, Columbia University, New York (Huey, Manoochehri, Gazes, Cosentino); Department of Biostatistics, Mailman School of Public Health, Columbia University, New York (Lee); Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Md. (Huey, Tierney, Wassermann, Grafman); RONA Holdings, Silicon Valley, Calif. (Momeni); and Cognitive Neuroscience Laboratory, Think and Speak Lab, Shirley Ryan AbilityLab, Chicago (Grafman).
View all articles by this author
Michael Tierney, M.S
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, New York (Huey, Manoochehri, Gazes, Cosentino); Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York (Huey, Fremont); Department of Neurology, College of Physicians and Surgeons, Columbia University, New York (Huey, Manoochehri, Gazes, Cosentino); Department of Biostatistics, Mailman School of Public Health, Columbia University, New York (Lee); Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Md. (Huey, Tierney, Wassermann, Grafman); RONA Holdings, Silicon Valley, Calif. (Momeni); and Cognitive Neuroscience Laboratory, Think and Speak Lab, Shirley Ryan AbilityLab, Chicago (Grafman).
View all articles by this author
Eric M. Wassermann, M.D.
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, New York (Huey, Manoochehri, Gazes, Cosentino); Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York (Huey, Fremont); Department of Neurology, College of Physicians and Surgeons, Columbia University, New York (Huey, Manoochehri, Gazes, Cosentino); Department of Biostatistics, Mailman School of Public Health, Columbia University, New York (Lee); Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Md. (Huey, Tierney, Wassermann, Grafman); RONA Holdings, Silicon Valley, Calif. (Momeni); and Cognitive Neuroscience Laboratory, Think and Speak Lab, Shirley Ryan AbilityLab, Chicago (Grafman).
View all articles by this author
Parastoo Momeni, Ph.D.
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, New York (Huey, Manoochehri, Gazes, Cosentino); Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York (Huey, Fremont); Department of Neurology, College of Physicians and Surgeons, Columbia University, New York (Huey, Manoochehri, Gazes, Cosentino); Department of Biostatistics, Mailman School of Public Health, Columbia University, New York (Lee); Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Md. (Huey, Tierney, Wassermann, Grafman); RONA Holdings, Silicon Valley, Calif. (Momeni); and Cognitive Neuroscience Laboratory, Think and Speak Lab, Shirley Ryan AbilityLab, Chicago (Grafman).
View all articles by this author
Jordan Grafman, Ph.D.
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, New York (Huey, Manoochehri, Gazes, Cosentino); Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York (Huey, Fremont); Department of Neurology, College of Physicians and Surgeons, Columbia University, New York (Huey, Manoochehri, Gazes, Cosentino); Department of Biostatistics, Mailman School of Public Health, Columbia University, New York (Lee); Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Md. (Huey, Tierney, Wassermann, Grafman); RONA Holdings, Silicon Valley, Calif. (Momeni); and Cognitive Neuroscience Laboratory, Think and Speak Lab, Shirley Ryan AbilityLab, Chicago (Grafman).
View all articles by this author

Notes

Send correspondence to Dr. Huey ([email protected]).

Funding Information

Supported by the Intramural Program of NIH/National Institute of Neurological Disorders and Stroke and by the Division of Extramural Research of NIH/National Institute of Neurological Disorders and Stroke (grant R00 NS060766 to Dr. Huey).The authors report no financial relationships with commercial interests.

Metrics & Citations

Metrics

Citations

Export Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download.

For more information or tips please see 'Downloading to a citation manager' in the Help menu.

Format
Citation style
Style
Copy to clipboard
Tips for downloading citations

There are no citations for this item

View Options

View options

PDF/ePub

View PDF/ePub

Full Text

View Full Text

Get Access

Login options

Already a subscriber? Access your subscription through your login credentials or your institution for full access to this article.

Personal login Institutional Login Open Athens login
Item saved, go to cart
Purchase Options

Purchase this article to access the full text.

PPV Articles - Journal of Neuropsychiatry and Clinical Neurosciences

PPV Articles - Journal of Neuropsychiatry and Clinical Neurosciences

Not a subscriber?

Subscribe Now / Learn More

PsychiatryOnline subscription options offer access to the DSM-5-TR® library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development.

Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.).

Media

Figures

Other

Tables

Share

Share

Share article link

Share