National Human Genome Institute: Why Some people Grow Out Of Childhood Attention Deficit Hyperactivity Disorder (ADHD)

https://www.genome.gov?utm_source=NHGRI+Email+Updates&utm_campaign=5b96bdbf21-Skin+Pigmentation+publications&utm_medium=email&utm_term=0_3d227b0341-5b96bdbf21-118937769
Adult ADHD: An imbalance between the online and offline brain (https://www.genome.gov/27569602/2017-news-feature-adult-adhd-an-imbalance-between-the-online-and-offline-brain/?utm_source=NHGRI+Email+Updates&utm_campaign=5b96bdbf21-Skin+Pigmentation+publications&utm_medium=email&utm_term=0_3d227b0341-5b96bdbf21-118937769)
https://www.genome.gov/27569602/2017-news-feature-adult-adhd-an-imbalance-between-the-online-and-offline-brain/?utm_source=NHGRI+Email+Updates&utm_campaign=5b96bdbf21-Skin+Pigmentation+publications&utm_medium=email&utm_term=0_3d227b0341-5b96bdbf21-118937769
By Jeannine Mjoseth (mailto:Jeannine.Mjoseth@nih.gov)
November 7, 2017

A new study by researchers at the National Human Genome Institute (NHGRI) examined why some people grow out of childhood attention deficit hyperactivity disorder (ADHD), while others continue to have symptoms into adulthood. They discovered that adults with ADHD persisting from childhood partly lose the usual balance of connections between brain networks that control action and those that control daydreaming or introspecting. Researchers have argued that this imbalance – between the brain “online” and the brain “offline”- might account for the lapses of attention that are found in ADHD.  By contrast, adults who had “grown out” of their childhood ADHD, did not show such a loss of balanced brain activity, according to findings published October 31, 2017, in The Proceedings of the National Academy of Science (PNAS).

“We hope to understand the mechanisms that explain why some people outgrow ADHD and other do not,” said Philip Shaw, B.M.B.Ch., Ph.D., senior author and an investigator in NHGRI’s Social and Behavioral Research Branch (https://www.genome.gov/11508935/Social-and-Behavioral-Research-Branch/Social-and-Behavioral-Research-Branch/Social-and-Behavioral-Research-Branch?utm_source=NHGRI+Email+Updates&utm_campaign=5b96bdbf21-Skin+Pigmentation+publications&utm_medium=email&utm_term=0_3d227b0341-5b96bdbf21-118937769) .  “If we can understand why some people can recover from ADHD, we also might be able to apply this knowledge to other neuro-developmental conditions like learning disabilities or problems with social interaction.”

ADHD (https://www.nimh.nih.gov/health/topics/attention-deficit-hyperactivity-disorder-adhd/index.shtml?utm_source=NHGRI+Email+Updates&utm_campaign=5b96bdbf21-Skin+Pigmentation+publications&utm_medium=email&utm_term=0_3d227b0341-5b96bdbf21-118937769)  is a heritable and treatable brain disorder marked by inattention and/or hyperactivity-impulsivity that can cause great difficulties with impulse control, attention span in school, social situations and the workplace. Around 20 to 30 percent of people with ADHD retain the full syndrome as young adults and about 50 percent show partial, though not complete remission.

The researchers looked at brain function in 205 adult participants: 101 participants had been diagnosed with childhood ADHD and 104 subjects never had ADHD. They looked at changes in the brain’s oxygen levels to determine the location of brain networks using functional magnetic resonance imaging (fMRI) (mailto:http://fmri.ucsd.edu/Research/whatisfmri.html) , and they studied the different levels of neuronal activity that by looking at the brain’s magnetic fields using magnetoencephalography (mailto:http://ilabs.washington.edu/what-magnetoencephalography-meg) .

Regardless of the type of brain imaging used, the researchers found that adults who had inattentive symptoms persisting from childhood lost the usual balance of connections between the online and offline brain networks. Specifically, a network that is prominent when a person is introspective is usually switched off when a person engages in tasks. This balance was partly lost in the adults with persistent inattention. By contrast, this pattern of connections between brain networks in adults who outgrew ADHD looked very similar to the adults who never had ADHD. These findings support the theory that among individuals who recover from ADHD, there is a childhood disruption to brain function that corrects itself by adulthood.

“Most adults have a balance between the online, task-oriented brain and the offline, day-dreaming brain, but we found that’s not the case for adults whose ADHD persists,” said Gustavo Sudre, Ph.D., study co-author and postdoctoral research fellow in Dr. Shaw’s lab. “We found that adults who recovered from ADHD had a very similar balance of online and offline brains to those who never had ADHD.”

NHGRI’s investment in this type of high impact, longitudinal research and the participants’ long-term commitment to ADHD research make studies like this possible.

“We first met these individuals at the National Institutes of Health Clinical Center when they were eight years old,” Dr. Shaw said. “They are so committed to ADHD research that they have kept coming back for 14 years. It’s great to see so many of the children who had severe ADHD grow into adults who are managing very well.”

In the next step of their research, Drs. Shaw and Gustavo will collaborate with an international ADHD research consortium to find genes associated with the disrupted brain networks.
Read the study

Sudre G, Szekely E, Sharp W, Kasparek S, Shaw P. Multimodal mapping of the brain’s functional connectivity and the adult outcome of attention deficit hyperactivity disorder (http://www.pnas.org/content/114/44/11787.full?utm_source=NHGRI+Email+Updates&utm_campaign=5b96bdbf21-Skin+Pigmentation+publications&utm_medium=email&utm_term=0_3d227b0341-5b96bdbf21-118937769) . PNAS, October 31, 2017.
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The African American Sequencing Project 23andMe

The African American Sequencing Project 23andMe

The African American Sequencing Project

In a move to improve diversity in genetic research, this week 23andMe will start recruiting eligible customers to participate in the creation of an African American sequencing panel for research.

With the help of a grant from the National Human Genome Research Institute, 23andMe scientists will use contributions from customers who’ve consented to participate in this research to create a reference dataset and make the de-identified genetic data available to other qualified and vetted genetic researchers at educational and research institutions around the world.

“We are very excited about this project and its potential to make a difference in people’s lives,” said the project’s Principal Investigator, Adam Auton, a 23andMe senior scientist and statistical geneticist. “This work will help address the genetic  research disparities for African Americans in particular, something that has long needed attention.”

Only a fraction of the genetic research studies done to date include people with African ancestry. According to recent data focusing on this disparity,  only about 19 percent of all published genetic research includes data from non-Europeans, and only about two percent are conducted on those of African ancestry. While the bias towards European studies reflects many complicated logistic, systemic, and societal issues, it has a huge impact on what scientists can determine about the genetics underlying diseases and other conditions that impact not just non-European populations but everyone. A recent study by the University of Maryland School deftly explains the implications of these disparities:

“As long as ancestry-related biases are not addressed, and most studies continue to predominantly sample from European populations, the genetics community will face challenges with implementation, interpretation and cost-effectiveness when treating minority populations.”

To help address these disparities, 23andMe is recruiting African American customers who are are willing to have their genome sequenced. Those who are interested would then be asked to complete an additional level of consent, that would allow 23andMe to add their de-identified genetic data to a library of genetic and phenotypic data. This means the library would not receive any personally identifiable information  connected to the genetic and phenotypic information. This library of data is managed by the NIH and used by qualified scientific researchers.

As part of this work we will ask a subset of our African American customers, who have consented to participate in research, if they would be willing to participate and have their DNA sequenced to become part of this reference panel. Reference panels are important because they allow scientists to improve the accuracy of genome wide association studies, which drive much of genetic research conducted today.

When a customer of 23andMe sends in their saliva sample, they are genotyped at hundreds of thousands of sites that are known to vary between individuals. However, there are tens of millions of variable sites in the genome that are not genotyped. By having access to a large number of fully sequenced genomes — a sequence panel — researchers are able to use “genotype imputation” to infer or predict the genotypes at these unobserved positions. Much like a code breaker filling in missing letters in a message, scientists — using algorithms and data from whole genome sequences panels — can predict, or impute, the missing letters of genetic data. Having a sequence panel like this gives researchers a tool to study conditions that are specific to African Americans.

Ultimately, the sequence panel data will be shared with the NIH, who will make it available to other researchers. This in turn will expand scientists’ ability to make genetic discoveries for African Americans and help build a broader understanding of how genetics influence diseases and traits across multiple populations.

This is the latest in a number of efforts by 23andMe to help alleviate some of the existing disparities in genetic research. Last year, 23andMe was awarded another NIH grant to use “admixture mapping” as a means to improve the detection of disease-causing genetic variants among people of African, Latino and Asian ancestry. In 2011, 23andMe launched its Roots into the Future® project to study the genetics of disease specific to African Americans. The African Genetics Project is a part of this growing effort to improve our knowledge of African genetic diversity.

 

 

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