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Open AccessArticle

High and Low Levels of an NTRK2-Driven Genetic Profile Affect Motor- and Cognition-Associated Frontal Gray Matter in Prodromal Huntington’s Disease

1
Neuroscience Institute, Georgia State University, Atlanta, GA 30302, USA
2
The Mind Research Network, Albuquerque, NM 87106, USA
3
Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM 87131, USA
4
Iowa Mental Health Clinical Research Center, Department of Psychiatry, University of Iowa, Iowa City, IA 52242, USA
5
Department of Psychology, Georgia State University, Atlanta, GA 30302, USA
6
Department of Neurology, University of Iowa, Iowa City, IA 52242, USA
7
Department of Psychology, University of Iowa, Iowa City, IA 52242, USA
*
Author to whom correspondence should be addressed.
Detailed information in Author Contribution part.
Brain Sci. 2018, 8(7), 116; https://doi.org/10.3390/brainsci8070116
Received: 16 May 2018 / Revised: 12 June 2018 / Accepted: 20 June 2018 / Published: 22 June 2018
(This article belongs to the Special Issue New Insights in Huntington's Disease)
This study assessed how BDNF (brain-derived neurotrophic factor) and other genes involved in its signaling influence brain structure and clinical functioning in pre-diagnosis Huntington’s disease (HD). Parallel independent component analysis (pICA), a multivariate method for identifying correlated patterns in multimodal datasets, was applied to gray matter concentration (GMC) and genomic data from a sizeable PREDICT-HD prodromal cohort (N = 715). pICA identified a genetic component highlighting NTRK2, which encodes BDNF’s TrkB receptor, that correlated with a GMC component including supplementary motor, precentral/premotor cortex, and other frontal areas (p < 0.001); this association appeared to be driven by participants with high or low levels of the genetic profile. The frontal GMC profile correlated with cognitive and motor variables (Trail Making Test A (p = 0.03); Stroop Color (p = 0.017); Stroop Interference (p = 0.04); Symbol Digit Modalities Test (p = 0.031); Total Motor Score (p = 0.01)). A top-weighted NTRK2 variant (rs2277193) was protectively associated with Trail Making Test B (p = 0.007); greater minor allele numbers were linked to a better performance. These results support the idea of a protective role of NTRK2 in prodromal HD, particularly in individuals with certain genotypes, and suggest that this gene may influence the preservation of frontal gray matter that is important for clinical functioning. View Full-Text
Keywords: Huntington’s disease; brain-derived neurotrophic factor; tropomyosin receptor kinase B; supplementary motor; independent component analysis Huntington’s disease; brain-derived neurotrophic factor; tropomyosin receptor kinase B; supplementary motor; independent component analysis
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Ciarochi, J.A.; Liu, J.; Calhoun, V.; Johnson, H.; Misiura, M.; Bockholt, H.J.; Espinoza, F.A.; Caprihan, A.; Plis, S.; Turner, J.A.; Paulsen, J.S.; The PREDICT-HD Investigators and Coordinators of the Huntington Study Group. High and Low Levels of an NTRK2-Driven Genetic Profile Affect Motor- and Cognition-Associated Frontal Gray Matter in Prodromal Huntington’s Disease. Brain Sci. 2018, 8, 116.

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