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Cortical thickness or grey matter volume? The importance of selecting the phenotype for imaging genetics studies.

ABSTRACT: Choosing the appropriate neuroimaging phenotype is critical to successfully identify genes that influence brain structure or function. While neuroimaging methods provide numerous potential phenotypes, their role for imaging genetics studies is unclear. Here we examine the relationship between brain volume, grey matter volume, cortical thickness and surface area, from a genetic standpoint. Four hundred and eighty-six individuals from randomly ascertained extended pedigrees with high-quality T1-weighted neuroanatomic MRI images participated in the study. Surface-based and voxel-based representations of brain structure were derived, using automated methods, and these measurements were analysed using a variance-components method to identify the heritability of these traits and their genetic correlations. All neuroanatomic traits were significantly influenced by genetic factors. Cortical thickness and surface area measurements were found to be genetically and phenotypically independent. While both thickness and area influenced volume measurements of cortical grey matter, volume was more closely related to surface area than cortical thickness. This trend was observed for both the volume-based and surface-based techniques. The results suggest that surface area and cortical thickness measurements should be considered separately and preferred over gray matter volumes for imaging genetic studies.

SUBMITTER: Winkler AM

PROVIDER: S-EPMC2891595 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Cortical thickness or grey matter volume? The importance of selecting the phenotype for imaging genetics studies.

Winkler Anderson M AM Kochunov Peter P Blangero John J Almasy Laura L Zilles Karl K Zilles Karl K Fox Peter T PT Duggirala Ravindranath R Glahn David C DC

NeuroImage 20091216 3

Choosing the appropriate neuroimaging phenotype is critical to successfully identify genes that influence brain structure or function. While neuroimaging methods provide numerous potential phenotypes, their role for imaging genetics studies is unclear. Here we examine the relationship between brain volume, grey matter volume, cortical thickness and surface area, from a genetic standpoint. Four hundred and eighty-six individuals from randomly ascertained extended pedigrees with high-quality T1-we ...[more]

PMID: 20006715

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Project description:Structural neuroimaging studies of posttraumatic stress disorder (PTSD) have typically reported reduced cortical thickness (CT) and gray matter volume (GMV) in subcortical structures and networks involved in memory retrieval, emotional processing and regulation, and fear acquisition and extinction. Although PTSD is more common in women, and interpersonal violence (IPV) exposure is a more potent risk factor for developing PTSD relative to other forms of trauma, most of the existing literature examined combat-exposed men with PTSD. Vertex-wise CT and subcortical GMV analyses were conducted to examine potential differences in a large, well-characterized sample of women with PTSD stemming from IPV-exposure (n = 99) compared to healthy trauma-free women without a diagnosis of PTSD (n = 22). Subgroup analyses were also conducted to determine whether symptom severity within specific PTSD symptom clusters (e.g., re-experiencing, active avoidance, hyperarousal) predict CT and GMV after controlling for comorbid depression and anxiety. Results indicated that a diagnosis of PTSD in women with IPV-exposure did not significantly predict differences in CT across the cortex or GMV in the amygdala or hippocampus compared to healthy controls. However, within the PTSD group, greater re-experiencing symptom severity was associated with decreased CT in the left inferior and middle temporal gyrus, and decreased CT in the right parahippocampal and medial temporal gyrus. In contrast, greater active avoidance symptom severity was associated with greater CT in the left lateral fissure, postcentral gyrus, and middle/lateral occipital cortex, and greater CT in the right paracentral, posterior cingulate, and superior occipital gyrus. In terms of GMV, greater hyperarousal symptom severity was associated with reduced left amygdala GMV, while greater active avoidance symptom severity was associated with greater right amygdala GMV. These findings suggest that structural brain alterations among women with IPV-related PTSD may be driven by symptom severity within specific symptom clusters and that PTSD symptom clusters may have a differential (increased or decreased) association with brain structures.

Dataset Information

Cortical thickness or grey matter volume? The importance of selecting the phenotype for imaging genetics studies.

Publications

Cortical thickness or grey matter volume? The importance of selecting the phenotype for imaging genetics studies.

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