| Abstract: | There is a growing realization that early life influences have lasting impact on brain function and structure. Recent research has demonstrated that genetic relationships in adults can be used to parcellate the cortex into regions of maximal shared genetic influence, and a major hypothesis is that genetically programmed neurodevelopmental events cause a lasting impact on the organization of the cerebral cortex observable decades later. Here we tested how developmental and lifespan changes in cortical thickness fit the underlying genetic organizational principles of cortical thickness in a longitudinal sample of 974 participants between 4.1 and 88.5 y of age with a total of 1,633 scans, including 773 scans from children below 12 y. Genetic clustering of cortical thickness was based on an independent dataset of 406 adult twins. Developmental and adult age-related changes in cortical thickness followed closely the genetic organization of the cerebral cortex, with change rates varying as a function of genetic similarity between regions. Cortical regions with overlapping genetic architecture showed correlated developmental and adult age change trajectories and vice versa for regions with low genetic overlap. Thus, effects of genes on regional variations in cortical thickness in middle age can be traced to regional differences in neurodevelopmental change rates and extrapolated to further adult aging-related cortical thinning. This finding suggests that genetic factors contribute to cortical changes through life and calls for a lifespan perspective in research aimed at identifying the genetic and environmental determinants of cortical development and aging.There is a growing realization that events during development impact brain and cognition throughout the entire lifespan (1). For instance, the major portion of the relationship between cortical thickness and IQ in old age can be explained by childhood IQ (2), and genotype may explain a substantial part of the lifetime stability in intelligence (3). Effects of genes on the organization of the cortex have been shown in adults (4–6), but it is unknown whether and how regional differences in cortical development correspond to these regional genetic subdivisions.Although consensus has not been reached for the exact trajectories, cortical thickness as measured by MRI appears to decrease in childhood (7–12). The exact foundation for this thinning is not known, as MRI provides merely representations of the underlying neurobiology, and available histological data cannot with certainty be used to guide interpretations of MRI results. Although speculative, apparent thickness decrease may be grounded in factors such as synaptic pruning and intracortical myelination, although the link between established synaptic processes (13–15) and cortical thickness has not been empirically confirmed. After childhood, cortical thinning continues throughout the remainder of the lifespan, speculated to reflect neuronal shrinkage and reductions in number of spines and synapses (16), although similar to development, we lack data to support a direct connection between cortical thinning and specific neurobiological events.It has been demonstrated that genetic correlations between thickness in different surface locations can be used to parcellate the adult cortex into regions of maximal shared genetic influence (4). This result can be interpreted according to the hypothesis that genetically programmed neurodevelopmental events cause lasting impact on the organization of the cerebral cortex detectable decades later (4–6). Here we tested how developmental and lifespan changes fit the genetic organization of cortical thickness in a large longitudinal sample with 1,633 scans from 974 participants between 4.1 and 88.5 y of age, including 773 scans from children below 12 y Genetically based subdivisions of cortical thickness from an independent dataset of 406 twins (4) were applied to the data, yielding 12 separate regions under maximum control of shared genetic influences. We hypothesized that thickness in cortical regions with overlapping genetic architecture would show similar developmental and adult age change trajectories and dissimilar trajectories for regions with low genetic overlap. |
