TY - JOUR
T1 - Effect of functional bdnf and comt polymorphisms on symptoms and regional brain volume in frontotemporal dementia and corticobasal syndrome
AU - Huey, Edward D.
AU - Fremont, Rachel
AU - Manoochehri, Masood
AU - Gazes, Yunglin
AU - Lee, Seonjoo
AU - Cosentino, Stephanie
AU - Tierney, Michael
AU - Wassermann, Eric M.
AU - Momeni, Parastoo
AU - Grafman, Jordan
N1 - 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 thank Karen Detucci, Alyson Cavanagh, Leila Glass, Anne Leopold, and Carolee Noury for patient testing and data management; the National Institute of Neurological Disorders and Stroke/Clinical Center nurses for patient care; and Kristine Knutson for imaging assistance.
Funding Information:
Send correspondence to Dr. Huey (edh2126@cumc.columbia.edu). 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 thank Karen Detucci, Alyson Cavanagh, Leila Glass, Anne Leopold, and Carolee Noury for patient testing and data management; the National Institute of Neurological Disorders and Stroke/Clinical Center nurses for patient care; and Kristine Knutson for imaging assistance.
Publisher Copyright:
© 2020, American Psychiatric Association. All rights reserved.
PY - 2020
Y1 - 2020
N2 - 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 poly-morphisms 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 In-ventory 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 signif-icant 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.
AB - 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 poly-morphisms 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 In-ventory 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 signif-icant 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.
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U2 - 10.1176/appi.neuropsych.19100211
DO - 10.1176/appi.neuropsych.19100211
M3 - Article
C2 - 32397876
AN - SCOPUS:85094894470
SN - 0895-0172
VL - 32
SP - 362
EP - 369
JO - Journal of Neuropsychiatry and Clinical Neurosciences
JF - Journal of Neuropsychiatry and Clinical Neurosciences
IS - 4
ER -
