Relationship of a common OXTR gene variant to brain structure and default mode network function in healthy humans

Wang, Junping, Braskie, Meredith N., Hafzalla, George W., Faskowitz, Joshua, McMahon, Katie L., de Zubicaray, Greig I., Wright, Margaret J., Yu, Chunshui and Thompson, Paul M. (2017) Relationship of a common OXTR gene variant to brain structure and default mode network function in healthy humans. NeuroImage, 147 500-506. doi:10.1016/j.neuroimage.2016.12.062


Author Wang, Junping
Braskie, Meredith N.
Hafzalla, George W.
Faskowitz, Joshua
McMahon, Katie L.
de Zubicaray, Greig I.
Wright, Margaret J.
Yu, Chunshui
Thompson, Paul M.
Title Relationship of a common OXTR gene variant to brain structure and default mode network function in healthy humans
Formatted title
Relationship of a common OXTR gene variant to brain structure and default mode network function in healthy humans
Journal name NeuroImage   Check publisher's open access policy
ISSN 1053-8119
1095-9572
Publication date 2017-02-15
Year available 2017
Sub-type Article (original research)
DOI 10.1016/j.neuroimage.2016.12.062
Open Access Status PMC
Volume 147
Start page 500
End page 506
Total pages 7
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Language eng
Subject 2808 Neurology
2805 Cognitive Neuroscience
Abstract A large body of research suggests that oxytocin receptor (OXTR) gene polymorphisms may influence both social behaviors and psychiatric conditions related to social deficits, such as autism spectrum disorders (ASDs), schizophrenia, and mood and anxiety disorders. However, the neural mechanism underlying these associations is still unclear. Relative to controls, patients with these psychiatric conditions show differences in brain structure, and in resting state fMRI (rs-fMRI) signal synchronicity among default mode network (DMN) regions (also known as functional connectivity). We used a stepwise imaging genetics approach in 328 healthy young adults to test the hypothesis that 10 SNPs in OXTR are associated with differences in DMN synchronicity and structure of some of the associated brain regions. As OXTR effects may be sex-dependent, we also tested whether our findings were modulated by sex. OXTR rs2254298 A allele carriers had significantly lower rsFC with PCC in a cluster extending from the right fronto-insular cortex to the putamen and globus pallidus, and in bilateral dorsal anterior cingulate cortex (dACC) compared to individuals with the GG genotype; all observed effects were found only in males. Moreover, compared to the male individuals with GG genotype ofrs2254298, the male A allele carriers demonstrated significantly thinner cortical gray matter in the bilateral dACC. Our findings suggest that there may be sexually dimorphic mechanisms by which a naturally occurring variation of the OXTR gene may influence brain structure and function in DMN-related regions implicated in neuropsychiatric disorders.
Formatted abstract
A large body of research suggests that oxytocin receptor (OXTR) gene polymorphisms may influence both social behaviors and psychiatric conditions related to social deficits, such as autism spectrum disorders (ASDs), schizophrenia, and mood and anxiety disorders. However, the neural mechanism underlying these associations is still unclear. Relative to controls, patients with these psychiatric conditions show differences in brain structure, and in resting state fMRI (rs-fMRI) signal synchronicity among default mode network (DMN) regions (also known as functional connectivity). We used a stepwise imaging genetics approach in 328 healthy young adults to test the hypothesis that 10 SNPs in OXTR are associated with differences in DMN synchronicity and structure of some of the associated brain regions. As OXTR effects may be sex-dependent, we also tested whether our findings were modulated by sex. OXTR rs2254298 A allele carriers had significantly lower rsFC with PCC in a cluster extending from the right fronto-insular cortex to the putamen and globus pallidus, and in bilateral dorsal anterior cingulate cortex (dACC) compared to individuals with the GG genotype; all observed effects were found only in males. Moreover, compared to the male individuals with GG genotype ofrs2254298, the male A allele carriers demonstrated significantly thinner cortical gray matter in the bilateral dACC. Our findings suggest that there may be sexually dimorphic mechanisms by which a naturally occurring variation of the OXTR gene may influence brain structure and function in DMN-related regions implicated in neuropsychiatric disorders.
Keyword OXTR
Single nucleotide polymorphism
Functional magnetic resonance imaging
Resting-state functional connectivity
Default mode network
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID RF1 AG041915
U54 EB020403
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
Centre for Advanced Imaging Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 3 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 3 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Thu, 12 Jan 2017, 01:51:50 EST by Lorine Wilkinson on behalf of Centre for Advanced Imaging