ADHD Explained: Symptoms, Neurobiology and Emerging Treatments

For millions, attention-deficit/hyperactivity disorder (ADHD) is more than an occasional distraction – it’s a persistent neurodevelopmental condition that can profoundly affect school, work and relationships.

The condition affects an estimated 5–7% of children worldwide  and ~2–4% of adults. Once considered primarily a childhood disorder, ADHD is now recognized as a lifelong condition with a broad spectrum of presentations, ranging from overt hyperactivity in youth to more subtle challenges in attention and executive functioning in adulthood.

Advances in genetics, neuroimaging and clinical research have transformed our understanding of ADHD, highlighting its complex neurobiological underpinnings and the interplay of environmental, hormonal and societal factors. This evolving perspective has opened new avenues for diagnosis, treatment and personalized interventions, which we explore in this article.

ADHD symptoms and diagnosis

While ADHD presentation may change over time – appearing more obvious in children and subtler in adults – its impact on daily life remains significant.

ADHD is classically defined by three hallmark symptoms: inattention, hyperactivity and impulsivity. These remain central to diagnosis; however, recent research shows the picture is more nuanced. “When we think of ADHD symptomatology, we think of the ADHD trademarks: inattention, hyperactivity and impulsivity. However, recent studies have revealed emotion dysregulation as a main symptom of the disorder,” explained Dr. Ryan S. Sultan, a board-certified psychiatrist and an assistant professor of clinical psychiatry, who has extensively studied the neurobiology and clinical management of ADHD. “For a while, we thought that emotional dysregulation was a comorbidity, but it’s actually core to ADHD itself.”

Sleep disturbances have also come into sharper focus in understanding the complexity of ADHD characteristics. “Until recently, sleep has not been studied extensively in the context of ADHD. A 2025 study published in BMJ Mental Health found that insomnia was a mediator of ADHD symptom severity. In other words, adults with stronger ADHD traits tend to suffer from more severe insomnia, which is linked to increased depressive symptoms and lower quality of life,” said Sultan.

Another important shift in recent studies concerns gender differences in diagnosis. Historically, ADHD was viewed as a “boys’ disorder” because hyperactivity is more visible in this sex. “We are now more aware of inattentive symptoms, which are more commonly present in females, and more females are getting diagnosed,” said Sultan.

Diagnosis typically involves a comprehensive clinical assessment, including structured interviews, standardized questionnaires and reports from family or teachers. For adults, retrospective evaluation of childhood symptoms is essential.

“ADHD is by definition a condition that begins in childhood. Its symptoms are clear and obvious. Children are often in situations that elicit the presentation of symptoms, such as classrooms where demands to pay attention and remain still reveal difficulty focusing, distractibility and restlessness,” said Sultan.

“Symptom presentation in adults is complicated by how untreated ADHD has interacted with their life, often leading to increases in anxiety, depression, self-esteem issues and substance abuse,” said Sultan. 

The biological basis of ADHD

Although ADHD has long been described in terms of behavior, recent research underscores that it is fundamentally a neurodevelopmental disorder rooted in brain biology and genetics.

For decades, scientists relied on the dopamine hypothesis, which suggested that ADHD symptoms stemmed from abnormally low dopamine levels in the brain. This framework helped explain why stimulant medications, which increase dopamine availability, often improve attention and reduce hyperactivity, and why ADHD patients are vulnerable to drug dependence, which could be explained by an overlap of ADHD with the dopamine deficiency syndrome.

“However, current research reveals that dopamine levels might actually appear higher in certain brain regions or under specific conditions,” said Sultan.

The idea that ADHD is fundamentally a state of low dopamine everywhere has been convincingly questioned. One influential critique comes from François Gonon’s 2009 paper, where he argues that much of the evidence supporting a global dopamine deficit is inconsistent: dopamine transporters or receptor densities sometimes differ only slightly, or not at all, between ADHD and non-ADHD populations.

More recently, a study from Cambridge also found evidence against a basic hypodopaminergic model. Administration of methylphenidate to both adults with ADHD and healthy controls resulted in similar increases in dopamine and similar improvements in attention and concentration, suggesting that the drug's effect may not correct a pre-existing dopamine dysfunction unique to ADHD.

“This leads us to a refined hypothesis: it is harder for ADHD brains to maintain the consistent, low-level dopamine activity normally present in the brain. We are also seeing that the normal dopamine spikes in response to rewards are greater in ADHD brains,” said Sultan.

“We can’t really rely on the simple ‘dopamine-hypothesis’ for ADHD anymore,” Sultan explained.

Genetics also plays a central role. “ADHD is more heritable than the majority of psychiatric disorders. It has a polygenic architecture, meaning that we cannot attribute its cause to a specific genetic source,” Sultan said.

Large-scale genome-wide association studies, such as a meta-analysis of over 38,000 individuals with ADHD, have identified 27 risk loci across the genome.

Dozens of genes are now implicated in the condition and several of these are involved in brain signaling systems. These include dopamine-related genes (DRD4, DRD5, DAT1/SLC6A3), serotonin-related genes (SERT, HTR1B) and synaptic communication genes such as SNAP-25.

“SNAP-25 is a gene that helps cells ‘talk' to each other. In people with ADHD, this gene does not function properly,” said Sultan.

Neuroimaging advances in ADHD research

Techniques such as functional magnetic resonance imaging (fMRI), diffusion tensor imaging and high-density electroencephalography (EEG) are helping researchers trace ADHD to specific circuits and patterns of activity.

“fMRI has revealed that when anticipating a reward, ADHD brains struggle to correctly time dopamine release in the striatum,” said Sultan.

ADHD may not be about the amount of dopamine, but the regulation and timing of its release.

“High-density sleep EEG analyses have found that children and adolescents with ADHD had ~20% lower slow-wave activity compared to non-ADHD individuals, which becomes normalized with stimulant treatment,” said Sultan.

The study indicates that disrupted sleep-related brain activity may also be part of the disorder’s neurodevelopmental signature.

“Meta-analysis reveals that slow-wave activity is higher in early childhood compared to late childhood, reflecting developmental shifts in ADHD,” said Sultan.

Large-scale imaging efforts are also yielding new insights. “The NIH recently analyzed around 10,000 functional brain images from adolescents with and without ADHD. The study found that individuals with ADHD had higher functional connectivity between the frontal cortex and deep subcortical regions, providing insight into the role of functional circuitry abnormalities in the presentation of the disorder,” said Sultan.

By identifying individual patterns of connectivity or neural activity, clinicians may one day tailor interventions – whether medication, behavioral therapy or neuromodulation – to the unique brain profile of each person with ADHD. These advances highlight the promise of imaging not only for refining diagnosis but also for personalized treatment approaches.

Emerging ADHD treatments and experimental approaches

ADHD is most often managed with stimulant medications such as methylphenidate or amphetamines, which remain the gold standard of care. Non-stimulant drugs, including atomoxetine and viloxazine, are alternatives for those who cannot tolerate stimulants.

However, reports have suggested that up to 40% of patients do not achieve adequate symptom control or experience side effects that limit treatment, highlighting the need for new options.

“Living with untreated ADHD has the potential to be detrimental. Individuals with ADHD have double the mortality rate than others, with accidents the leading cause,” said Sultan.

“People with ADHD are twice as likely to be injured and have significantly higher rates of arrests and convictions. ADHD is associated with an increased number of motor vehicle crashes, with crash rates lower during periods when these individuals are on ADHD medication. The risk of depression, substance abuse and suicidality is also greater in populations with ADHD,” he added.

Novel medications are emerging to fill these gaps. For instance, solriamfetol, a non-stimulant dopamine and norepinephrine reuptake inhibitor, recently showed a 45% reduction in symptoms in a Phase 3 clinical trial.

Other experimental approaches include psychedelic microdosing, although evidence remains weak. A recent double-blind clinical trial of low-dose LSD in adults with ADHD found no significant benefit over placebo, with improvements likely driven by expectation bias rather than pharmacological effects.

Beyond medication, researchers are testing neuromodulation techniques. “Neurofeedback is being used to ‘listen’ to the activity of the ADHD brain. It provides real-time feedback, and over multiple sessions, your brain learns to associate certain mental states or efforts with the positive feedback. It’s a fancier way of classical conditioning,” explained Sultan. “By training the brain to shift activity patterns, neurofeedback works to improve attention, impulse control and hyperactivity.”

Neuromodulation approaches for ADHD include a variety of techniques. Transcranial direct current stimulation and transcranial random noise stimulation (tRNS) deliver weak electrical currents through the scalp to modulate cortical excitability, while repetitive transcranial magnetic stimulation uses magnetic pulses to target specific brain regions.

A recent randomized controlled trial of tRNS combined with cognitive training in children with ADHD reported clinically meaningful improvements in inattentive and hyperactive-impulsive symptoms, along with EEG changes consistent with enhanced brain plasticity. These benefits also persisted at follow-up.

Another promising neuromodulation device is the FDA-approved external trigeminal nerve stimulation (eTNS) system, which delivers mild pulses through the forehead, “triggering the release of therapeutic signals to brain regions involved in attention and behavior regulation,” said Sultan.

eTNS is currently being tested in a large, multi-site clinical trial with over 180 children with ADHD. The trial aims to confirm earlier findings that eTNS can reduce ADHD symptoms.

Digital therapeutics are also entering the ADHD space. Prescription video games, such as EndeavorRx – the first FDA-cleared digital treatment for pediatric ADHD – use game-like tasks to train attention and working memory. Early studies suggest modest but measurable improvements in cognitive performance, and similar app-based platforms are now being tested in adults.

While still early in development, these tools highlight a shift toward personalized, non-pharmacological interventions that can complement traditional care.

Research gaps in ADHD and future directions

Despite decades of study, several key questions remain in ADHD research. Sultan emphasized the need to understand the long-term effects of stimulant treatment, and there is a concern about how chronic use of stimulant or non-stimulant medications shapes brain development and functional outcomes across the lifespan.

Gender differences also require more attention, as women are often underdiagnosed and may experience ADHD differently across hormonal cycles, pregnancy and menopause.

Another pressing area is the identification of biological markers that could improve diagnosis and predict treatment response. While genetics and neuroimaging provide clues, the interplay between genes and the environment remains poorly understood.

“How do the genes we know contribute to ADHD interact with the environment? How much of the manifested ADHD symptoms are being driven by societal changes? For example, the Industrial Revolution prompted an increase in the number of repetitive, mundane jobs not conducive to someone with ADHD,” said Sultan.  

“Humans aren’t designed to do the same task over and over again. We aren’t designed to sit all day at a computer or sit for hours on end in a lecture hall,” he added.

Looking ahead, the field is moving toward a multimodal, lifespan-focused understanding of ADHD; one that considers biological, cognitive and societal influences, hopefully leading to more precise diagnostics, individualized therapies and improved outcomes for patients across all ages.