Genetic variant helps explain why anxiety disorders strike most often in the teen years
(Medical Xpress)—A team of researchers with members from Cornell University and the University of California has zeroed in on a genetic variant to help explain why it is that anxiety disorders tend to strike most often during the teen years. In their paper published in Proceedings of the National Academy of Sciences, the team describes how they obtained brain scans of over a thousand children and young adult volunteers to get a better look at the neural tract that connects the brain's limbic structures to frontal areas of the brain and what they found by doing so.
Scientists have known for some time that changes in gene expression during adolescence causes an increase in brain cannabinoid receptors –enzyme levels and signaling molecules also fluctuate more dramatically than in adults as well. Such changes are believed to be part of the reason why teenagers experience so many more anxiety disorders than adults. To better understand what actually happens during this stage of development, the researches obtained brains scans of 1,050, young adults and children, from age 21 down to 3, and looked at how the wiring was impacted for those 20 percent of people that carry a FAAH gene variant –FAAH encodes for a regulatory enzyme, and those who have the variant are known to have either more or less incidence of anxiety disorders, depending on which variant they have.
In studying the brain scans, the researchers were able to see that there was a stronger connection between the limbic and frontal areas in those with the variant, which coincided with reduced reported levels of anxiety. But, the team notes, the differences were only noted in brains of people who were 12 years of age or older, which suggested that the gene is normally involved at least partly in increased incidence of anxiety disorders in teens. To further confirm their findings, the researchers took brain scans of mice genetically altered to express similar variants, and found similar results.
The findings by the researchers suggest that it may be possible to create new therapies for teens suffering from anxiety disorders, tailor-made to address their unique needs due to their genetic differences from adults.
More information: Dylan G. Gee et al. Individual differences in frontolimbic circuitry and anxiety emerge with adolescent changes in endocannabinoid signaling across species, Proceedings of the National Academy of Sciences (2016). DOI: 10.1073/pnas.1600013113
Anxiety disorders peak in incidence during adolescence, a developmental window that is marked by dynamic changes in gene expression, endocannabinoid signaling, and frontolimbic circuitry. We tested whether genetic alterations in endocannabinoid signaling related to a common polymorphism in fatty acid amide hydrolase (FAAH), which alters endocannabinoid anandamide (AEA) levels, would impact the development of frontolimbic circuitry implicated in anxiety disorders. In a pediatric imaging sample of over 1,000 3- to 21-y-olds, we show effects of the FAAH genotype specific to frontolimbic connectivity that emerge by ∼12 y of age and are paralleled by changes in anxiety-related behavior. Using a knock-in mouse model of the FAAH polymorphism that controls for genetic and environmental backgrounds, we confirm phenotypic differences in frontoamygdala circuitry and anxiety-related behavior by postnatal day 45 (P45), when AEA levels begin to decrease, and also, at P75 but not before. These results, which converge across species and level of analysis, highlight the importance of underlying developmental neurobiology in the emergence of genetic effects on brain circuitry and function. Moreover, the results have important implications for the identification of risk for disease and precise targeting of treatments to the biological state of the developing brain as a function of developmental changes in gene expression and neural circuit maturation.
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