Is There a New way to treat ADHD?

Attention disorders such as ADHD occur when the brain has difficulty distinguishing important signals from constant background stimuli. The brain continuously processes visual and auditory stimuli as well as internal thoughts, and the ability to concentrate depends on its ability to ignore distractions while responding to important stimuli. Most current treatments improve attention by increasing activity in the areas of the brain that control concentration, particularly in the prefrontal cortex. A new study suggests a different solution. Rather than increasing brain activity, the research indicates that reducing baseline activity is one way to reduce mental distractions and improve attention.

ADHD and Early Childhood

ADHD always has its origins in childhood. According to current medical and psychological understanding, it is a neurobiological developmental disorder that arises very early on—presumably even before birth due to genetic factors and brain development. The first signs of ADHD usually appear in early childhood, often as early as kindergarten age. Typical symptoms include pronounced motor restlessness, a strong need for movement, difficulty concentrating for long periods of time, and impulsive behavior. Some children seem to be constantly “wired,” frequently interrupting others or acting without thinking about the consequences. For others, hyperactivity is less prominent than inattention—they seem dreamy, forget things quickly, or are easily distracted.

The symptoms often become apparent by school age at the latest, because this is when demands on attention, self-organization, and rule-following increase. Children with ADHD then often have problems sitting still, completing tasks, or concentrating on lesson content for long periods of time. It is important to note that the symptoms persist over a long period of time, occur in several areas of life (e.g., school and family), and lead to noticeable impairments.

A Gene Associated with Calmer Concentration

In a study published in Nature Neuroscience, scientists report that a gene called Homer1 plays an important role in attention by influencing how quiet or loud the brain is at rest. Mice with reduced concentrations of two specific forms of this gene showed calmer brain activity and performed better on tasks that required concentration.

These findings could represent a first step toward new treatments that aim to calm the mind rather than stimulate it. The implications extend beyond ADHD, as Homer1 is also associated with disorders linked to early differences in sensory processing, including autism and schizophrenia. “The gene we discovered has a remarkable impact on attention and is relevant to humans,” said Priya Rajasethupathy, head of the Skoler Horbach Family Laboratory of Neural Dynamics and Cognition at Rockefeller.

Enormous Genetic Influence on Attention

When the research team began exploring the genetics of attention, Homer1 was not an obvious candidate. Scientists have long known about the gene because of its role in neurotransmission, and many proteins that interact with Homer1 have appeared in genetic studies of attention disorders, but Homer1 itself had not previously been identified as an important factor.

To conduct more comprehensive investigations, the researchers analyzed the genomes of nearly 200 mice bred from eight different parental strains, including some with wild ancestors. This approach was intended to reflect the genetic diversity of human populations and made it possible to uncover subtle genetic influences. “It was a Herculean task and truly novel for this field of research,” said Rajasethupathy, who praises doctoral student Zachary Gershon for leading the work.

This large-scale genetic analysis revealed a clear pattern. Mice that performed best on attention tasks had much lower levels of Homer1 in the prefrontal cortex, a region of the brain important for concentration. The gene was located in a DNA segment that accounted for nearly 20 percent of the differences in attention among the mice.

“That’s a huge effect,” Rajasethupathy said. “Even if you take into account a possible overestimation of the size of this effect, which can occur for many reasons, that’s a remarkable number. Most of the time, you’re lucky if you find a gene that influences even 1 percent of a trait.”

Timing is Crucial During Brain Development

Further analysis showed that not all forms of Homer1 contributed equally. Two specific versions, known as Homer1a and Ania3, were responsible for the differences in attention. Mice that excelled at attention tasks naturally had lower concentrations of these versions in their prefrontal cortex, while other forms of the gene remained unchanged.

When researchers experimentally reduced Homer1a and Ania3 during a brief developmental phase in adolescent mice, the effects were remarkable. The animals became faster, more accurate, and less distractible in several behavioral tests. The same changes in adult mice did not produce any benefits, showing that Homer1 influences attention during a limited window in early life.

How Calming the Brain Improves Concentration

The most surprising finding came from studying how Homer1 affects brain cells. Lowering Homer1 levels in the neurons of the prefrontal cortex caused these cells to produce more GABA receptors—the molecular brakes of the nervous system.

This change reduced unnecessary background activity while preserving strong, focused bursts of activity when important signals occurred. Instead of constantly responding, the neurons saved their activity for moments that required attention, resulting in more accurate responses. “We were sure that the more attentive mice would have more activity in the prefrontal cortex, not less,” Rajasethupathy said. “But it kind of made sense. Attention is partly about tuning out everything else.”

Rethinking Future Treatments

For Gershon, who lives with ADHD, the results were intuitively understandable. “That’s part of my story,” he says, “and one of the inspirations for me to apply genetic mapping to attention.” He was also the first in the lab to notice that lowering Homer1 improved concentration by reducing distractions. In his view, the results are consistent with general experience. Deep breathing, mindfulness, meditation, calming the nervous system—people consistently report better concentration after these activities.

Current treatments for attention disorders typically increase arousal signals in the prefrontal brain circuits through the use of stimulants. The new findings point to another possibility: therapies that improve attention by calming neural activity rather than amplifying it.

Since Homer1 and the proteins that interact with it are associated with ADHD, schizophrenia, and autism, further research could reshape scientists’ understanding of various neurodevelopmental disorders. Future studies from the Rajasethupathy lab will focus on refining the genetic understanding of attention with the goal of developing therapies that precisely modulate Homer1 levels. There is a splice site in Homer1 that can be pharmacologically targeted, which could be an ideal way to regulate signal-to-noise ratios in the brain. According to the researchers, this offers a concrete path to developing a drug that has a calming effect similar to meditation.