Genes Impact Suspect Cortex Areas More as Youth Mature

Jules Asher
NIMH Press Office
301-443-4536
NIMHPress@nih.gov

Heritability Maps May Hold Clues to Delayed Onset of Mental Disorders

May 20, 2014 • Science Update

The thickness of later evolving and maturing areas of the brain’s outer mantle, or cortex, shows increasing genetic influence as the brain develops in childhood and adolescence, NIMH researchers have discovered.

“The heritability of cortex thickness increases gradually throughout late childhood and adolescence, with three more uniquely human areas, including circuitry supporting language and thinking, emerging as the most genetically influenced,” explained Jay Giedd, M.D., of the National Institute of Mental Health. “These same increasingly heritable brain areas are also most implicated in mental illnesses, which typically emerge in late adolescence. So the findings may provide insights into the workings of gene-by-environment-by age interactions that underlie the perplexing delayed onset of these disorders.”

Magnetic resonance imaging (MRI) scans revealed the ebb and flow of heritability and genetic variability of cortex thickness in children and teens as they grew up in the largest study of its kind.

Giedd, J. Eric Schmitt, Ph.D., and colleagues reported on their findings during the week of April 21, 2014 in the journal Proceedings of the National Academy of Sciences.

Prior to the NIMH study, knowledge about genetic influence on cortex development was limited to comparisons of cross-sections of youth at different ages. Hints that evolutionarily newer cortex areas are more influenced by genetics first emerged in an earlier phase of the NIMH study, which tracked a smaller number of youth, who were each scanned at just two developmental time points. To gain a finer-grained picture, Giedd’s team scanned 792 twins and their siblings, each at up to 8 time points as they grew up, yielding nearly 82,000 measures of cortex thickness, culled from 1,748 MRI scans.

Thickness of evolutionarily newer areas of the frontal, temporal and parietal lobes – which also are among the latest cortex areas to mature developmentally – emerged as the most genetically influenced. Most genetically influenced changes in thickness happen before puberty, with genetic variability stabilizing after puberty. Impact of environment on cortical thickness waned through childhood, and sex differences were relatively minor.

While regionally specific, the patterns of genetic change occurred in a back-to-front wave, similar to the pattern of gray matter density maturationreported by the NIMH researchers nearly a decade ago.

“The ever changing effects of genetics on brain structure echo those of recently reported findings from the Brainspan Atlas of the Developing Human Brain, underscoring the importance of genes expressed at particular developmental stages,” said Giedd.

Brain scans show cortex heritability and variability

Upper: Later evolving and maturing brain areas, which also are those most implicated in mental illness, showed gradually increasing heritability (red), peaking by late adolescence – the age-of-onset for most mental disorders. Lower: By contrast, genetic variance (red) gradually decreased over the same age range, in a back-to-front wave. Source: Jay Giedd, M.D., Eric Schmitt, Ph.D., NIMH Child Psychiatry Branch

Reference

The dynamic role of genetics on cortical patterning during childhood and adolescence . Schmitt JE, Neale MC, Fassassi B, Perez J, Lenroot RK, Wells EM, Giedd JN. Proc Natl Acad Sci U S A. 2014 May 6;111(18):6774-9. doi: 10.1073/pnas.1311630111. Epub 2014 Apr 21. PMID:24753564. Free Article .