Working out the genetic risk for ADHD

December 7, 2016

Genetics play a strong part in the development of attention-deficit/hyperactivity disorder (ADHD), but the path from a gene to risk for the disorder has remained a black box to researchers.. A new study in Biological Psychiatry suggests how the risk gene ADGRL3 (LPHN3) might work. ADGRL3 encodes the protein latrophilin 3, which regulates communication between brain cells. According to the study, a common variation of the gene associated with ADHD disrupts its ability to regulate gene transcription - the formation of mRNA from DNA that leads to expression of the gene.

Evidence for ADGRL3 in ADHD risk had already been stacked against it - common variants of the gene predispose people to ADHD and predict severity of the disorder. The study, led by Dr. Maximilian Muenke of the National Human Genome Research Institute in Bethesda, Maryland, brings scientists closer to understanding how ADGRL3 contributes to risk by providing functional evidence that implicates a transcription factor in the pathology of the disorder.

According to first author Dr. Ariel Martinez, the study is an effort to address limitations of existing ADHD medications that don't work for all patients, and develop new medication targeting the protein encoded by the ADGRL3 gene.

"In this new era of genomics and precision medicine, the key to success lies in dissecting genetic contributions and involving some level of patient stratification," Martinez said.

The researchers analyzed the ADGRL3 genomic region in 838 people, 372 of whom were diagnosed with ADHD. Variants in one particular segment within the gene, the transcriptional enhancer ECR47, showed the highest association with ADHD and with other disorders that commonly occur alongside ADHD, such as disruptive behaviors and substance use disorder.

ECR47 functions as a transcriptional enhancer to boost in the brain. However, the researchers found that a variation of ECR47 associated with ADHD disrupted ECR47's ability to bind an important neurodevelopmental transcription factor, YY1 - an indication that the risk variant interferes with .

In an analysis of postmortem human brain tissue from 137 control subjects, they also found an association between the ECR47 risk variant and reduced ADGRL3 expression in the thalamus, a key brain region for coordinating sensory processing in the brain. The findings link the gene to a potential mechanism for ADHD pathophysiology.

"The is extraordinarily complex. Yet we are starting to pull on the threads of that complex biology that reveal mechanisms through which disorders like ADHD might develop," said Professor John Krystal, Editor of Biological Psychiatry. "In this case, Martinez and colleagues help us to understand how variation in the ADGRL3 gene might contribute to thalamic dysfunction in ADHD."

Explore further: Study looks at ADHD treatment in teens at risk for bipolar disorder

More information: Ariel F. Martinez et al. An Ultraconserved Brain-Specific Enhancer Within ADGRL3 (LPHN3) Underpins Attention-Deficit/Hyperactivity Disorder Susceptibility, Biological Psychiatry (2016). DOI: 10.1016/j.biopsych.2016.06.026

Related Stories

ADHD or just immature?

March 10, 2016

Attention-deficit hyperactivity disorder (ADHD) is typically diagnosed in childhood and manifests as an inability to sustain attention and control activity levels and impulse control. Some reports have indicated a prevalence ...

Mutant gene linked to ADHD

April 18, 2011

(PhysOrg.com) -- In a recent study published in Nature Medicine, Dr. Eunjin Kim from the Korea Advanced Institute of Science and Technology uncovers a genetic fault that triples the chances of a child having ADHD (Attention ...

Study highlights multiple factors of ADHD medication use

June 8, 2016

Youth who take Ritalin, Adderall or other stimulant medications for ADHD over an extended period of time early in life are no more at risk for substance abuse in later adolescence than teens without ADHD, according to a University ...

Scientists show how gene variant linked to ADHD could operate

August 16, 2011

A study using mice provides insight into how a specific receptor subtype in the brain could play a role in increasing a person's risk for attention-deficit hyperactivity disorder (ADHD). The research, conducted by the Intramural ...

Recommended for you

Children with ADHD often live in chaotic households

March 9, 2017

Researchers often observe inadequate parenting, a negative emotional climate and household chaos in families of children with ADHD. A research group at Goethe University Frankfurt and the universities of Bremen, Heidelberg, ...

Could the 'Mediterranean' diet help prevent ADHD?

January 30, 2017

(HealthDay)—Kids who follow a Mediterranean diet—high in fruits, vegetables and "good" fats—may be less likely to have attention deficit hyperactivity disorder (ADHD), a small study suggests.

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

BubbaNicholson
1 / 5 (1) Dec 09, 2016
Funny, ADHD is cured by oral administration of 250mg of healthy adult male facial skin surface lipid.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.