title: Genetic and environmental influences on cortical mean diffusivity.
abstract: Magnetic resonance imaging (MRI) has become an important tool in the early detection of age-related and neuropathological brain changes. Recent studies suggest that changes in mean diffusivity (MD) of cortical gray matter derived from diffusion MRI scans may be useful in detecting early effects of Alzheimer's disease (AD), and that these changes may be detected earlier than alterations associated with standard structural MRI measures such as cortical thickness. Thus, due to its potential clinical relevance, we examined the genetic and environmental influences on cortical MD in middle-aged men to provide support for the biological relevance of this measure and to guide future gene association studies. It is not clear whether individual differences in cortical MD reflect neuroanatomical variability similarly detected by other MRI measures, or whether unique features are captured. For instance, variability in cortical MD may reflect morphological variability more commonly measured by cortical thickness. Differences among individuals in cortical MD may also arise from breakdowns in myelinated fibers running through the cortical mantle. Thus, we investigated whether genetic influences on variation in cortical MD are the same or different from those influencing cortical thickness and MD of white matter (WM) subjacent to the cortical ribbon. Univariate twin analyses indicated that cortical MD is heritable in the majority of brain regions; the average of regional heritability estimates ranged from 0.38 in the cingulate cortex to 0.66 in the occipital cortex, consistent with the heritability of other MRI measures of the brain. Trivariate analyses found that, while there was some shared genetic variance between cortical MD and each of the other two measures, this overlap was not complete (i.e., the correlation was statistically different from 1). A significant amount of distinct genetic variance influences inter-individual variability in cortical MD; therefore, this measure could be useful for further investigation in studies of neurodegenerative diseases and gene association studies.
authors.affiliation: Department of Psychiatry, University of California San Diego, CA, USA; Center for Behavior Genetics of Aging, University of California San Diego, CA, USA. Electronic address: jaelman@ucsd.edu.
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Elman
authors.affiliation: Department of Psychiatry, University of California San Diego, CA, USA; Center for Behavior Genetics of Aging, University of California San Diego, CA, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Panizzon
authors.affiliation: Department of Radiology, University of California San Diego, CA, USA.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Hagler
authors.affiliation: Department of Psychiatry, University of California San Diego, CA, USA; Department of Radiology, University of California San Diego, CA, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Fennema-Notestine
authors.affiliation: Department of Psychiatry, University of California San Diego, CA, USA; San Diego VA Health Care System, San Diego, CA 92161, USA.
authors.forename: Lisa T
authors.initials: LT
authors.lastname: Eyler
authors.affiliation: Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, VA, USA.
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Gillespie
authors.affiliation: Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, VA, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Neale
authors.affiliation: Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lyons
authors.affiliation: Department of Psychiatry, University of California San Diego, CA, USA; Center for Behavior Genetics of Aging, University of California San Diego, CA, USA.
authors.forename: Carol E
authors.initials: CE
authors.lastname: Franz
authors.affiliation: Department of Radiology, University of California San Diego, CA, USA.
authors.forename: Linda K
authors.initials: LK
authors.lastname: McEvoy
authors.affiliation: Department of Radiology, University of California San Diego, CA, USA; Department of Neurosciences, University of California San Diego, CA, USA.
authors.forename: Anders M
authors.initials: AM
authors.lastname: Dale
authors.affiliation: Department of Psychiatry, University of California San Diego, CA, USA; Center for Behavior Genetics of Aging, University of California San Diego, CA, USA; San Diego VA Health Care System, San Diego, CA 92161, USA.
authors.forename: William S
authors.initials: WS
authors.lastname: Kremen
mesh_terms: D000368:Aged; D002540:Cerebral Cortex / Q000033:anatomy & histology* / Q000378:metabolism*; D038524:Diffusion Magnetic Resonance Imaging; D056324:Diffusion Tensor Imaging; D059647:Gene-Environment Interaction; D066128:Gray Matter / Q000033:anatomy & histology / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D066127:White Matter / Q000033:anatomy & histology* / Q000378:metabolism*
keywords: Cortex; Heritability; Magnetic resonance imaging; Mean diffusivity; Twins