Brain EEG and the Genetics of ADHD

Twin studies in ADHD demonstrate a significant genetic contribution to the disorder.

Linking this genetic influence to specific biomarkers may provide a better understanding of the pathophysiology of ADHD.

Grainne McLoughlin and colleagues at the University of California San Diego and King's College London recently published a twin study of brain EEG and the genetics of ADHD.

In their study 67 twin pairs (34 monozygotic and 33 dizygotic) between the ages of 12 and 15 years completed tasks measuring brain frontocentral EEG theta patterns and reaction time.

Brain EEG frontocentral theta EEG levels increase under tasks requiring cognitive control, reaction time and handling reaction under conflict.

The authors were able to identify a specific type of EEG response in twins with ADHD compared to twins without the disorder. 

• Twins without ADHD showed changes in reaction time variability (RTV) and EEG theta performance with an attention and reaction task. 
• Twins with ADHD showed no change in these measures with the same attention and reaction task.

Of note, the authors were able to link this specific RTV and theta response to genetic features contributing to ADHD.

The authors note in their conclusion:

"This is the first finding that confirms the genetic link between frontal midline EEG activity and ADHD, as previously suggested by family studies."

This is an important finding and has significant implications in:

• Furthering understanding an EEG evoked response that may assist in the diagnosis of the ADHD phenotype
• Provide a biomarker for future family, twin and genome-wide genetic studies of ADHD
• Be helpful in teasing out environmental from genetic factors in ADHD

Readers with more interest in this study can access the free full-text manuscript by clicking on the PMID link in the citation below.

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McLoughlin G, Palmer JA, Rijsdijk F, & Makeig S (2014). Genetic overlap between evoked frontocentral theta-band phase variability, reaction time variability, and attention-deficit/hyperactivity disorder symptoms in a twin study. Biological psychiatry, 75 (3), 238-47 PMID: 24001472

ADHD and Autism Overlap: Adult Twin Study

Clinical studies show high rates of ADHD in adults with autism or autism spectrum disorder (ASD). 

These studies have estimated the prevalence of ADHD in adults with ASD at between 28 and 44% of individuals. The prevalence of ADHD in the adult general population without ASD is estimated at 2.5%.

Given the overlap between these two developmental disorders, it makes sense to examine genetic factors that might contribute to co-occurrence.

TJC Polderman along with colleagues from the Netherlands, the UK and Sweden looked at this issue using a sample of adult twins. Twin studies provide a powerful tool for teasing out genetic from environmental influence by comparing identical (monozygotic) to fraternal (dizygotic) twin pairs.

All twins in the studies rated their ASD and ADHD symptoms from those used as criteria in the Fifth Revision of the Diagnostic and Statistical Manual (DSM-5). This produced scores in four key symptom domain scores:

• ASD social/communication deficits
• ASD repetitive and restrictive behavior interest
• ADHD inattention
• ADHD hyperactivity/impulsivity

Using the twin study design the authors were able to identify:

• A strong genetic contribution to the overlap of ASD repetitive scores with ASDH inattention in both men and women
• A strong genetic contribution to the overlap of ASD repetitive scores with ADHD hyperactivity/impulse control in both men and women
• ASD social/communication deficit showed only modest

The authors conclude their study is one of the first suggesting ASD repetitive/restriction symptoms contribute specifically to high ADHD symptom levels. One potential explanation would be a common genetic factor or factors that produce both repetitive/restrictive ASD symptoms along with inattention and hyperactivity.

The authors note their findings support giving attention to specific symptom domains in designing research in ADHD and ASD. Specific symptom domains may have specific genetic and environmental risk factors.

Readers with more interest in this topic can access the free full-text manuscript by clicking on the PMID link in the citation below.

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Polderman TJ, Hoekstra RA, Posthuma D, & Larsson H (2014). The co-occurrence of autistic and ADHD dimensions in adults: an etiological study in 17,770 twins. Translational psychiatry, 4 PMID: 25180574

Twin Studies in ADHD: Research Links

Twin studies provide a strong research study design in understanding the genetics of a variety of brain conditions.

This is true for understanding the genetics of ADHD.

Here are a few selected recent twin studies in ADHD that I think are important and noteworthy.

Readers can access the abstract and in some cases the free full-text manuscript by clicking on the title.

Shared Features of ADHD and Autism

This study featured results of an analysis of over 17000 adult twins from Sweden. The authors examined scores on two features of autism (social/communication and repetitive/restricted behavior) and scores on two features of ADHD (inattention and hyperactivity/impulsivity). The authors found support for a genetic overlap between the repetitive/restrictive autism dimension with both the attention and hyperactivity dimensions of ADHD.

Cognitive Impairments, Reading Difficulty and ADHD

Using a sample of twins between ages 7 and 10 the authors found a link between ADHD inattention scores and three measures of cognition (reaction time variability, verbal short-term memory and working memory. These associations accounted for a significant portion of the reading difficulties in children with ADHD.

ADHD, Autism Traits and Substance Use and Misuse

3080 adult Australian twins participated in a study of the overlap between ADHD, autism traits and substance use. Both ADHD symptoms and autism traits were linked to smoking and cannabis use. Autism traits were linked to lower frequency of drinking to intoxication but higher rates of alcohol dependence once drinking was initiated.

EEG Theta Activity, Reaction Time and ADHD

EEG abnormalities have been noted in ADHD. In this twin study, twins between 12 and 15 years of age completed EEG frontal theta phase assessments, reaction time variability and ADHD symptomatology. The authors found evidence to support a genetic link between frontal EEG theta, reaction time variability and ADHD status.

ADHD, Homework Behavior and Reading Comprehension

This study analyzed data from the Florida Twin Project on Behavior and Environment. Overlapping genetic contributions for found for ADHD symptoms, homework behavior and reading comprehension. Additionally, some shared environmental influences contributed to the association between homework behavior and reading comprehension. This study supports both genetic and environmental influences on the link between ADHD and reading performance.

The findings from these recent twin studies show the importance of genetic influences in ADHD and highlight the key overlap with autism, cognitive function and academic achievement.

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Autism Twin Studies Point to Key Next Steps

Angelica Ronald and Rosa Hoekstra have written a nice review of recent twin studies in autism spectrum and autism traits.  The review is online prior to print in the American Journal of Medical Genetics Neuropsychiatric Genetics.

They note in the review that twin studies have evolved from a perspective of looking at narrowly defined autism, to the broader category of autism spectrum to an even broader phenotype, the dimensional character of autistic traits in the general population.

I don't know much about autism traits in the general population but this twin studies review highlighted some current understanding.

• Relatives of individuals with autism spectrum disorder show elevated autistic traits
• Autistic traits in the general population show a smooth distribution through the normal range to the clinical extreme--this suggests a biological continuum rather than a normal or disease clinical status
• Understanding the cause of variation of autistic traits in the general population is likely to aid in the understanding of autism
• The heritability of autistic traits in the population is very heritable (genetic) ranging from 40 to 60% in young twins but increasing to 60 to 90% in adolescence.

Another insightful section of the manuscript dealt with the degree of genetic and environmental overlap between different autistic symptoms.  Autism spectrum is made up of a triad of symptoms: social impairment, communication impairment and restrictive behaviors and interests.  Twin studies suggest these different symptom clusters may be "fractionable", meaning they may have some independence from each of the other clusters.  The authors note more genetic and twin studies should focus on one symptom cluster of the triad, rather than only studying those who have all three components.

The authors note that twin studies have helped explain the relationship between autism and intellectual disability and low IQ.  There appears to be some common genetic contribution to autism and intellectual disability.  However, since some individuals with autism and ASD have relatively normal intelligence, the picture is complex.  Studying ASD in those with normal intelligence may provide further insight into specific autism genetic influences. 

What needs to be done in the future?

Need for twin studies to tease out genetic and environmental factors that explain the common co-occurence of autism, ASD and autism traits with conduct disorder, sleep disorders, antisocial behavior and depression.

More attention needs to focus on genetic and environmental effects on developmental change in ASD and autistic traits in children (only two current studies published) and in adults (zero studies published).

More research on age-appropriate measures of autism traits--measures appropriate for one developmental age may not be appropriate for other ages.

More studies are necessary to look at cognitive phenotypes in autism and autism traits .

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Ronald, A., & Hoekstra, R. (2011). Autism spectrum disorders and autistic traits: A decade of new twin studies American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 156 (3), 255-274 DOI: 10.1002/ajmg.b.31159