UC Davis researchers find potential biomarker for ADHD

SACRAMENTO—A study out of UC Davis has honed in on a potential biomarker for certain types of attention-deficit/hyperactivity disorder (ADHD), a finding that may help distinguish between different ADHD subtypes and aid in the diagnosis and treatment of a condition that affects more than 5 million children in the United States.

 

According to the U.S. Centers for Disease Control and Prevention, an estimated 5.5 million children 4 to 17 years of age were diagnosed with ADHD in 2007. The percentage of children with parent-reported ADHD increased by 22 percent between 2003 and 2007. ADHD is approximately twice as common among boys as girls, and is one of the most commonly diagnosed psychiatric illnesses among children.

 

“ADHD is a real brain disorder, not a ‘pull-up-your-socks’ or a ‘better parenting’ issue,” says Dr. Catherine Fassbender, a research scientist at the UC Davis MIND Institute and a lead author on the study. “Kids struggle with this every day, and ADHD is also a huge economic drain on the country—involving more ER visits, higher divorce rates, people not doing as well in their jobs as they could be. One of our passions is to make people realize that ADHD is a real disorder, and here is one more study showing that these children have different challenges to deal with than regular kids do.”

 

ADHD subtypes appear subjectively very different in the clinical setting, but there are few objective physiological markers that have been able to detect those differences. The goal of the study was to use oscillatory changes in the electroencephalogram (EEG) related to informative cue processing, motor preparation and top-down control to investigate neurophysiological differences between typically developing (TD) adolescents, and those diagnosed with predominantly inattentive (IA) or combined (CB) (associated with symptoms of inattention as well as impulsivity/hyperactivity) subtypes of ADHD.

 

“In the old days, we didn’t have technology like we do now, so we could only look at observable behaviors, like how many items a child gets right on certain tests, or how they perform certain tasks. But there may be very different upstream reasons for what is happening. Electrophysiology gives us a window into the brain and what is going on, and a better handle on the different sorts of impairments that might be producing these behaviors,” explains Fassbender.

 

The EEG was recorded from 57 rigorously screened adolescents (12 to 17 years old; 23 TD, 17 IA, and 17 CB), while they performed a cued flanker task. The UC Davis researchers examined the oscillatory changes in theta (3–5 Hz), alpha (8–12 Hz) and beta (22–25 Hz) EEG bands after cues that informed participants with which hand they would subsequently be required to respond.

 

Some cues were more helpful than others, so the task required the participants to sometimes override an initial impulse in order to respond correctly—situations that are particularly challenging for people with ADHD. For example, brain waves were recorded during evaluations of the subjects’ performance on a computer task during which they were asked to look at a series of arrows pointing in different directions on a computer screen, and then indicate the direction in which the center arrow pointed by pressing a button for either left or right.

 

The researchers examined the teens’ alpha and beta brain waves after they viewed the visual cues, and found differences between the teens with the subtypes of ADHD and typically developing teens. The alpha wave patterns of teens with the inattentive type did not process the important information in the visual cues, limiting their ability to succeed.

 

The researchers also examined the subjects’ beta waves, which are associated with the performance of motor tasks. These also differed among those with and without ADHD and were most deficient in teens with the combined type, suggesting that these teens had greatest difficulty accomplishing the motor task—pressing a button.

 

“We found both distinct and common task-related neurophysiological impairments in ADHD subtypes. Our results suggest that task-induced changes in EEG oscillations provide an objective measure, which in conjunction with other sources of information might help distinguish between ADHD subtypes and therefore aid in diagnoses and evaluation of treatment,” the researchers concluded.

 

According to Fassbender, researchers in the field of ADHD have questioned whether the ADHD combined subtype simply represents a more severe form of ADHD.

 

“Our study suggests differential impairment profiles in the ADHD subtypes, and not simply an additive effect of impairments in the ADHD combined subtype,” Fassbender says. “The inattentive group had problems processing the cues, whereas the combined type had problems using the cues to prepare a motor response.”

 

The UC Davis finding could also inform the development of treatments to address the underlying processing differences between ADHD subtypes, Fassbender adds.

 

“Most treatments for ADHD do not take subtype differences into account,” she notes. “Our findings suggest targets for treatment should differ for the ADHD inattentive versus combined subtypes, and that advanced analysis of brain waves may provide a biomarker for testing treatment responses.”

 

There may be non-medical implications as well, she adds.

 

“Studies like ours can pinpoint exactly what the different impairment is for different children, so you can even develop teaching strategies for specific impairments,” she gives as an example.

 

However, Fassbender notes, “It’s still early in the game, and this would require more extensive testing of our methods, but I feel that the more you understand the underlying biology, the better chance we have of developing an obvious commercial application down the road.

 

The study, “Differential Oscillatory Electroencephalogram Between Attention-Deficit/Hyperactivity Disorder Subtypes and Typically Developing Adolescents,” was published online on Oct. 11 in Biological Psychiatry, a journal of the Society of Biological Psychiatry. Fassbender’s co-authors included Ali Mazaheri, assistant professor at the University of Amsterdam’s Academic Medical Center and a guest researcher at the UC Davis Center for Mind and Brain, as well as Sharon Coffey-Corina, Tadeus A. Hartanto, Julie B. Schweitzer and George. R. Mangun. The study was funded by grants from the National Institute of Mental Health of the U.S. National Institutes of Health, the UC Davis MIND Institute and the Netherlands Organisation for Scientific Research, as well as a Klingenstein Third Generation Foundation ADHD Fellowship.