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Feb 11, 2014

Cortical Thickness, Braininess Linked at Genetic Level

  • The thickness of the cerebral cortex is both hereditable and linked to intellectual ability. So what, exactly, is passed from parents to children at the genetic level that could influence cortical thickness and, possibly, thick-headedness? Specific genetic variants of likely relevance remain obscure, but at least one has been identified. This variant, recently discovered by scientists at King’s College London, is by no means a gene for intelligence, which presumably depends on a host of genetic and environmental factors. Nonetheless, the newly found genetic link may help scientists better understand the biological mechanisms behind some forms of intellectual impairment.

    To find any genetic link, the scientists at King’s had to account for at least two factors complicating the hereditability of cortical thickness. First, the language-dominant left cerebral cortex appears to be under stronger genetic control than the right cortex. Second, age-related differences have been reported.

    Studies focused on regions of primary sensory and motor cortex, which develop earlier, showed relatively greater genetic effects in childhood than in adolescence. Yet other studies, focused on regions within the frontal cortex and the parietal and temporal lobes, showed relatively greater genetic effects in adolescence. These findings, the King’s scientists realized, suggested that it would be necessary to consider both region-specific effects and developmental stage (that is, age) of individuals while investigating links between genes, cortical thickness, and behavior.

    To help control for these complications, the King’s scientists chose to study a cohort that was very homogenous for age. They analyzed DNA samples and MRI scans from 1,583 health 14 year-old teenagers. The teenagers also underwent a series of tests to determine their verbal and nonverbal intelligence.

    These and other details were reported February 11 in Molecular Psychology, in an article entitled “Single nucleotide polymorphism in the neuroplastin locus associates with cortical thickness and intellectual ability in adolescents.” With respect to the focus on teenagers, the authors wrote, “This age homogeneity is a critical characteristic of our sample, given the reported changes in correlations between intelligence and cortical thickness from childhood to early adulthood.”

    The researchers reported looking at over 54,000 genetic variants possibly involved in brain development. They found that, on average, teenagers carrying a particular gene variant, rs7171755, had a thinner cortex in the left cerebral hemisphere, particularly in the frontal and temporal lobes, and performed less well on tests for intellectual ability. The genetic variation affects the expression of the NPTN gene, which encodes a protein acting at neuronal synapses and therefore affects how brain cells communicate.

    To confirm their findings, the researchers studied the NPTN gene in mouse and human brain cells. The researchers found that the NPTN gene had a different activity in the left and right hemispheres of the brain, which may cause the left hemisphere to be more sensitive to the effects of NPTN mutations. Their findings suggest that some differences in intellectual abilities can result from the decreased function of the NPTN gene in particular regions of the left brain hemisphere.

    Lead author of the study, Sylvane Desrivières, Ph.D., said: “We wanted to find out how structural differences in the brain relate to differences in intellectual ability. The genetic variation we identified is linked to synaptic plasticity—how neurons communicate. This may help us understand what happens at a neuronal level in certain forms of intellectual impairments, where the ability of the neurons to communicate effectively is somehow compromised.”

    Although the King’s scientists acknowledged that the genetic variation identified in their study accounted for only about 0.5% of the total variation in intelligence, they concluded that their findings still support a potential role for regional synaptic dysfunctions in forms of intellectual deficits.



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