ADHD Study Reveals a Collection of Discrete Disorders

Michael Stevens, PhD, of the Olin Neuropsychiatry Research Center, Hartford, Conn., and Yale University

Michael Stevens, PhD

Attention-deficit/hyperactivity disorder (ADHD) is a collection of discrete disorders in which the brain functions in completely different ways, a new study suggests.

The finding is a departure from views of ADHD as a single disorder with small variations —– and may lead clinicians to rethink a one-size-fits-all approach to assessment and care.

“The study raises the possibility that ADHD patients might require different treatments,’’ lead author Michael Stevens, PhD, of the Olin Neuropsychiatry Research Center, Hartford, Conn., and Yale University told MD Magazine.

The paper, published in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, found evidence to support the idea that ADHD-diagnosed adolescents are not all the same neurobiologically, Stevens said.

“The most important thing at this point is to increase the awareness that not every patient who meets diagnostic criteria for ADHD has symptoms that arise from the same neurobiological abnormality,’’ he said. “Once the field gets comfortable with the idea that this assumption is a roadblock to progress, we can get down to the business of conceptualizing new treatments based on different suspected etiologies.”

Stevens and his team set out to address the issue by better characterizing the nature of pathway-related neurocognitive deficits in ADHD.

Researchers often favor single-deficit explanations for a disorder and rely on case-control models to identify the neurobiological dysfunction that underpins it, the team wrote.

“But what if no single neurobiological abnormality is common to all patients who meet the criteria for a specific diagnosis?’’ the authors asked.

For instance, a single deficit approach typically does not try to explain the diverse and inconsistent evidence that can exist for brain-function abnormalities. In contrast, models that take into account multiple neurocognitive pathways suggest that symptoms arise from abnormalities in several distinct neural systems, the team said.

To explore ADHD in light of this divergent thinking, the researchers tested 117 adolescents with the disorder.

The team identified 3 distinct subgroups based on the participants' performance on tasks assessing impulsive behaviors associated with ADHD.

The first group was impaired only on executive function tests that assess the ability to get things done. This group demonstrated impulsive motor responses during fast-moving visual tasks.

A second group was impaired on both executive function and reward tests. These members showed a preference for immediate rewards.

The third group performed relatively normally on both tasks when compared to 134 non-ADHD adolescents.

The researchers then characterized brain dysfunction in the subgroups using functional magnetic resonance imaging (fMRI). The technique lets scientists make connections between behavior and brain function, in this case allowing them to investigate how the test profiles of the subgroups related to brain dysfunction.

It turned out that each group had dysfunction in different brain regions related to their specific type of behavioral impairment, supporting proposed ADHD multiple-pathway theories.

“Our study could not find a single brain function abnormality that was shared by all 3 neurocognitively defined ADHD subgroups, even when assessed across 4 theoretically relevant fMRI task conditions using the most liberal statistical thresholds,’’ the team wrote.

Do the findings mean that different treatments or therapies should be designed for the different ADHD subgroups?

“It certainly is possible to design studies that are tailored for different types of neurobiological impairments,’’ Stevens said. “Behavioral therapies designed for a particular type of motivational style might be more effective for some patients, while medications more effective for others.’’

He noted that several studies currently identify subgroups within children, adolescents and adults diagnosed with ADHD based on the types of tests his team used.

“Our study simply links these subgroup profiles to different brain function abnormalities,’’ he said. “It will take additional study to optimize exactly which tests best classify any given patient to a subgroup.’’

Stevens cited the potential promise of a clinical approach that considers whether ADHD patients show reward-related deficits, executive function-related impairments, no impairments, or other types of cognitive impairments.

“For the time being, if clinical trials researchers and clinicians begin to regularly assess these cognitive test characteristics and examine whether or not they moderate outcomes, it would accelerate our understanding of whether or not cognitive profiles can predict optimal treatment success,’’ he said.