Abstract
Anatomical differences in the corpus callosum have been found in various psychiatric disorders, but data on the genetic contributions to these differences have been limited. The current study used morphometric MRI data to assess the heritability of corpus callosum size and the genetic correlations among anatomical sub-regions of the corpus callosum among individuals with and without mood disorders. The corpus callosum (CC) was manually segmented at the mid-sagittal plane in 42 women (healthy, n = 14; major depressive disorder, n = 15; bipolar disorder, n = 13) and their 86 child or adolescent offspring. Four anatomical sub-regions (CC-genu, CC2, CC3 and CC-splenium) and total CC were measured and analyzed. Heritability and genetic correlations were estimated using a variance components method, with adjustment for age, sex, diagnosis, and diagnosis x age, where appropriate. Significant heritability was found for several CC sub-regions (P<0.01), with estimated values ranging from 48% (splenium) to 67% (total CC). There were strong and significant genetic correlations among most sub regions. Correlations between the genu and mid-body, between the genu and total corpus callosum, and between anterior and mid body were all >90%, but no significant genetic correlations were detected between ventral and rostral regions in this sample. Genetic factors play an important role in corpus callosum size among individuals. Distinct genetic factors seem to be involved in caudal and rostral regions, consistent with the divergent functional specialization of these brain areas.
Highlights
The corpus callosum (CC) plays a major role in connecting the cerebral hemispheres, enabling inter-hemispheric communication [1]
The results demonstrate that genetic factors play an important role in CC volume, and suggest that distinct genetic factors are involved in the development of caudal and rostral regions, consistent with the divergent functional specialization of these CC sub regions
Covariates that significantly influenced one or more CC subregions were included in the final model estimating heritability and genetic correlations
Summary
The corpus callosum (CC) plays a major role in connecting the cerebral hemispheres, enabling inter-hemispheric communication [1]. The CC is the brain’s largest white matter structure [2,3], and five anatomical sub-regions are commonly recognized: rostrum, genu, body, isthmus, and splenium [4]. Further work is needed to characterize the functional roles of the inter-hemispheric projections contained within the CC, but the entire structure appears to play an integrative role [2] by facilitating the coordinated and rapid transfer of information involved in sensorimotor, attention, language, and other cognitive processes between contralateral, homologous cortical regions [7,8,9,10]. CC abnormalities have been implicated in some of the cognitive and other symptoms that occur in bipolar disorder [7,17]; possibly reflecting compromised efficiency of information transfer between cerebral hemispheres [18]. The relationship between CC structure and function under normal conditions, together with the evidence of structural alterations in mood disorders, underscores the importance of understanding the role of genes in influencing the size of the various substructures of the CC, and inter-relationships that reflect shared genetic factors
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