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ADHD is usually framed as a dopamine-and-norepinephrine condition, but recent studies have revealed that serotonin may also play a significant role. To delve deeper into this, we conducted a systematic literature review of studies looking at serotonin, its receptors, and the serotonin transporter (SERT) in relation to ADHD. The result: serotonin appears to be an important piece of the puzzle, but the overall picture is quite complex.
An ADHD & Serotonin Literature Review:
The authors searched the literature without time limits and screened thousands of records to end up with 95 relevant publications. Those included animal/basic-science work, neuroimaging, pharmacodynamics, a couple of large genetic/transcriptomic studies (GWAS and a cortico-striatal TWAS), and a few clinical reports. Each paper was graded for quality: 17 high, 59 medium, and 19 low.
As the study points out, the idea that serotonin may play a role in the neurobiology of ADHD is not new, but this literature review “identified multiple individual strands of evidence gathered over several decades and brought them into a more coherent focus”. It concludes that serotonergic neurotransmission is implicated in ADHD. This doesn’t mean variations in serotonin levels cause ADHD, but that serotonin may be a plausible target for future treatments and research.
ADHD is polygenic and multi-systemic. For now, clinicians and patients should view serotonin as part of a complex network that may contribute to ADHD symptoms. More research is needed before making treatment decisions based on these findings.
Faraone, S. V., Ward, C. L., Boucher, M., Elbekai, R., & Brunner, E. (2025). Role of serotonin in the neurobiology of attention-deficit/hyperactivity disorder: a systematic literature review. Expert Opinion on Therapeutic Targets, 1–18. https://doi.org/10.1080/14728222.2025.2552324
Although there has been much research documenting that ADHD adults are at risk for other psychiatric and substance use disorders, relatively little is known about whether ADHD puts adults at risk specifically for somatic medical disorders.
Given that people with ADHD tend toward being disorganized and inattentive, and that they tend to favor short-term over long-term rewards, it seems logical that they should be at higher risk for adverse medical outcomes. But what does the data say?
In a systematic review of the literature, Instances and colleagues have provided a thorough overview of this issue. Although they found 126 studies, most were small and were of "modest quality". Thus, their results must be considered to be suggestive, not definitive for most of the somatic conditions they studied.
Also, they excluded articles about traumatic injuries because the association between ADHD and such injuries is well established. Using qualitative review methods, they classified associations as being a) well-established; b) tentative, or c) lacking sufficient data.
Only three conditions met their criteria for being a well-established association: asthma, sleep disorders, and obesity.
They found tentative evidence implicating ADHD as a risk factor for three conditions: migraine headaches, celiac disease, and diseases of the circulatory system.
These data are intriguing, but cannot tell us why ADHD people are at increased risk for somatic conditions. One possibility is that suffering from ADHD symptoms can lead to an unhealthy lifestyle, which leads to increased medical risk. Another possibility is that the biological systems that are dysregulated in ADHD are also dysregulated in some medical disorders. For example, we know that there is some overlap between the genes that increase the risk for ADHD and those that increase the risk for obesity. We also know that the dopamine system has been implicated in both disorders.
Instances and colleagues also point out that some medical conditions might lead to symptoms that mimic ADHD. They give sleep-disordered breathing as an example of a condition that can lead to the symptom of inattention.
But this seems to be the exception, not the rule. Other medical conditions co-occurring with ADHD seem to be true comorbidities, rather than the case of one disorder causing the other. Thus, primary care clinicians should be alert to the fact that many of their patients with obesity, asthma, or sleep disorders might also have ADHD.
By screening such patients for ADHD and treating that disorder, you may improve their medical outcomes indirectly via increased compliance with your treatment regime and an improvement in health behaviors. We don't yet have data to confirm these latter ideas, as the relevant studies have not yet been done.
Serotonin is a key chemical in the body that helps regulate mood, behavior, and also many physical functions such as sleep and digestion. It has also been linked to how ADHD (attention-deficit/hyperactivity disorder) develops in the brain. This study looks at how serotonin may be involved in both the mental health and physical health conditions that often occur alongside ADHD.
It is well-established that ADHD is more than just trouble focusing or staying still. For many, it brings along a host of other physical and mental health challenges. It is very common for those with ADHD to also have other diagnosed disorders. For example, those with ADHD are often also diagnosed with depression, anxiety, or sleep disorders. When these issues overlap, they are called comorbidities.
A new comprehensive review, led by Dr. Stephen V. Faraone and colleagues, delves into how serotonin (5-HT), a major brain chemical, may be at the heart of many of these common comorbidities.
Serotonin is a neurotransmitter most often linked to mood, but its role in regulating the body has much broader implications. It regulates sleep, digestion, metabolism, hormonal balance, and even immune responses. Although ADHD has long been associated with dopamine and norepinephrine dysregulation, this review suggests that serotonin also plays a central role, especially when it comes to comorbid conditions.
This research suggests that serotonin dysregulation could explain the diverse and sometimes puzzling range of symptoms seen in ADHD patients. It supports a more integrative model of ADHD—one that goes beyond the brain’s attention, reward and executive control circuits and considers broader physiological and psychological health.
future research into the role of serotonin could help develop more tailored interventions, especially for patients who don't respond well to stimulant medications. Future studies may focus on serotonin’s role in early ADHD development and how it interacts with environmental and genetic factors.
This study is a strong reminder that ADHD is a complex, multifaceted condition. Differential diagnosis is crucial to properly diagnosing and treating ADHD. Clinicians' understanding of the underlying link between ADHD and its common comorbidities may help future ADHD patients receive the individualized care they need. By shedding light on serotonin’s wide-reaching influence, this study may provide a valuable roadmap for improving how we diagnose and treat those with complex comorbidities in the future.
Taiwan's National Health Insurance program is a single-payer system that covers 99.6% of the island's 23 million residents. It includes family relationships.
This enabled a Taiwanese study team to examine the comorbidity of psychiatric disorders among close relatives in the entire population over eleven years, beginning at the start of 2001 and concluding at the end of2011.
For greater certainty of diagnosis, only persons twice diagnosed with the same psychiatric disorder were included as index individuals. There were 431,887 index patients, 152,443 of whom were ADHD index patients.
These index patients were then compared with all of their first-degree relatives (FDRs): parents, children, siblings, and twins. This produced 1,017,430 patient-FDR pairs, of which 401,301 were ADHD patient-FDR pairs.
Next, four controls were matched by age, gender, and type relative to each case, resulting in 4,069,720 control pairs.
After adjusting for age, gender, urbanization, and income level, ADHD patients were seven times more likely than controls to have first-degree relatives with ADHD. They were also seven times more likely to have FDRs with major depressive disorder, four times more likely to have FDRs with autism spectrum disorder, twice as likely to have FDRs with bipolar disorder, and 80%more likely to have FDRs with schizophrenia.
The Background:
Motor vehicle crashes remain one of the most significant public health challenges in the United States. In 2022 alone, nearly 44,000 people died on American roads, and more than 2.6 million crash-related injuries required emergency care. Most people are familiar with the usual suspects: drunk driving, speeding, and distracted driving from phones. These risks are well-documented and the focus of ongoing public safety campaigns.
But a serious risk factor has been flying under the radar: untreated ADHD. Despite receiving little attention from the public, policymakers, or transportation safety agencies, it may belong in the same conversation as these better-known dangers.
ADHD is not currently recognized by the National Highway Traffic Safety Administration as a driving risk factor; yet inattention and impulsivity, two of its defining features, are consistently cited as common contributors to crashes. Beyond these core symptoms, adults with ADHD may also experience emotional dysregulation, which can further impair driving behavior.
The Research:
Prior studies on ADHD and crash risk have produced estimates ranging from a 5% to a 70% increase. This massive heterogeneity has made it difficult to draw firm conclusions. This new meta-analysis set out to offer some clarity on these numbers.
Researchers focused specifically on adults aged 18 to 65 with a formal ADHD diagnosis who were not receiving treatment, comparing them to controls without ADHD. Four studies met these criteria, collectively covering more than 2.75 million people.
The Results:
The findings were striking: untreated ADHD was associated with a 93% increase in crash risk (95% confidence interval: 88%–99%). There was no evidence of publication bias. Although there was meaningful variation across studies, most of it stemmed from the smallest study (just 36 participants) which reported an outlier estimate of a 16-fold increase.
To put the 93% figure in context: a separate meta-analysis found that alcohol use is associated with a 150% increase in crash risk. Another way to understand just how significant this risk really is, untreated ADHD raises crash risk by more than half as much as alcohol does.
The analysis also found a dose-response relationship between ADHD symptom severity and crash risk: each incremental increase in symptom severity corresponded to a 5–6% higher crash risk. At the highest severity levels, crash risk approached that associated with alcohol use. This gradient reinforces that we're not looking at a binary distinction between “has ADHD” and “doesn’t” — the worse the symptoms, the greater the danger on the road.
The Takeaway:
These findings have practical implications for patients, families, clinicians, and policymakers alike. Untreated ADHD is not a minor footnote in the driving safety literature; rather, it is a substantial, measurable, and potentially modifiable risk factor. The question of whether and how it should be factored into licensing policy, clinical practice, and public health messaging deserves serious attention.
As populations grow, more children are growing up surrounded by traffic noise and polluted air. In most cities, these two factors tend to go hand-in-hand; yet, most previous research has examined these exposures separately. Many reviews focused on a single pollutant (such as fine particulate matter, PM2.5), or on a single developmental window, such as pregnancy or early childhood. Few have asked how noise and air pollution compare as risk factors, or how prenatal and postnatal exposures differ in their effects.
A new meta-analysis set out to address those gaps. It examined evidence on both environmental noise and several major air pollutants in relation to ADHD, compared exposures before versus after birth, and pooled data across countries and regions. Eligible studies involved children and adolescents under 18, used objective measures of environmental exposure, and assessed ADHD using either clinical diagnosis or standardized rating scales.
Noise
Nine studies, combining data from over 100,000 children and adolescents (all in European countries and Canada) found that high noise exposure was associated with 3% greater odds of ADHD. Prenatal noise exposure showed no effect; childhood exposure alone drove the association, at 4% greater odds. This is a negligible effect size that could easily reflect unmeasured confounding factors rather than a true causal relationship.
Nitrogen dioxide
Thirteen studies covering nearly one million children and adolescents in Europe, Canada, China, and South Korea found that nitrogen dioxide (NO₂) exposure was associated with 11% greater odds of ADHD. As with noise, prenatal exposure showed no independent effect. When the analysis was restricted to the five studies that used clinical diagnoses alone — generally considered the most reliable measure — the estimated odds rose to between 20% and 80% higher. The wide range reflects substantial variation across studies.
Pollutants with no significant effect
Four studies (97,500 participants) examining nitric oxide (NO), three studies (over 63,000 participants) on ozone, and three studies (over 28,000 participants) on sulfur dioxide found no significant associations with ADHD.
Particulate matter
The strongest associations emerged for particulate matter. Twelve studies involving nearly 160,000 participants in China, the US, Canada, and Europe found that exposure to fine particles (PM2.5, 2.5 microns in diameter) was associated with 30% greater odds of ADHD. Ten studies covering more than a quarter of a million participants in India, China, South Korea, and Europe found that coarser particles (PM10, 10 microns) were associated with 50% greater odds. In both cases, prenatal exposure showed no association, which is consistent with the fact that fetuses do not breathe air through developed lungs. When restricted to clinically diagnosed ADHD, PM2.5 was associated with roughly 50% greater odds, and PM10 with more than double the odds.
The Results
Across all exposures examined, particulate matter showed the clearest and strongest associations with ADHD, followed by nitrogen dioxide. Noise reached statistical significance but at a trivially small effect size. Nitric oxide, ozone, and sulfur dioxide showed no significant associations.
The authors found no evidence of publication bias which strengthens confidence in the overall pattern. However, there was marked heterogeneity across individual studies: results varied considerably, which urges caution in treating any single estimate as definitive. These are associations, not proven causal relationships, and the possibility that unmeasured factors explain part of the signal cannot be ruled out.
The Background:
Over the past two decades, diagnostic rates for adult ADHD have roughly doubled, and stimulant prescriptions in the United States skyrocketed by more than 50% between 2012 and 2023, particularly among girls and women. While these medications help many individuals manage their symptoms, a landmark 2026 article published in European Neuropsychopharmacology tackles an important question that is rarely discussed: When should doctors and patients consider stopping them?
The Discussion:
To answer this, the American Society of Clinical Psychopharmacology (ASCP) gathered a task force of 45 international experts spanning 12 countries. Through a rigorous evaluation process, they reached an overwhelming agreement on a framework for "deprescribing", the planned, supervised reduction or cessation of a medication. Here are the core insights from these ground-breaking guidelines and what they mean for adults navigating long-term ADHD treatment.
When the Treatment Isn’t Yielding Benefits
One of the most straightforward reasons to consider stopping a stimulant is if it simply isn’t doing its job. The task force agreed that if a patient does not experience an optimal response, measured by actual symptom reduction, improved daily functioning, and a better quality of life, even after trying a high, optimized dose, it may be time to step back and look at alternative options.
Sometimes, the issue goes back to the initial evaluation. The criteria for diagnosing ADHD have expanded over the years, and brief psychiatric evaluations can occasionally lead to diagnostic inaccuracies. If a thorough reevaluation reveals that the original ADHD diagnosis was incorrect, the expert consensus is clear: stimulant deprescribing is appropriate unless another stimulant-responsive condition is evident. Furthermore, if a patient develops a persistent tolerance to the drug that cannot be resolved by safe dose adjustments, a temporary taper or drug holiday may be recommended.
When the Risks to Health Outweigh the Rewards
Our bodies and health needs naturally shift over time, meaning a medication that worked safely years ago might pose a threat to your health today. The experts concluded that deprescribing should be heavily considered if stimulants exacerbate a concurrent medical or psychiatric illness. For example, although rare, stimulants can unintentionally trigger mania or psychosis in adults with unstable or unrecognized comorbid bipolar disorder.
Physical health developments are equally critical. If an adult develops a newly arising or unstable cardiovascular condition, such as a cardiac arrhythmia, ischemia, or cardiomyopathy, the risk-benefit balance changes dramatically. Additionally, if severe side effects occur that cannot be managed by reducing the dosage, or if dangerous new drug-drug interactions emerge, stopping the medication under medical supervision protects the patient's long-term well-being.
Addressing Misuse and the Complex Role of Cannabis
Because stimulant medications target brain reward and wakefulness circuitry, they can foster a propensity for misuse. Studies indicate that more than 1 in 5 adults prescribed stimulants have misused them, and 1 in 6 have diverted their medication to others. The task force emphasizes that deprescribing is warranted if a patient persistently takes doses higher than prescribed against medical advice, uses the medication purely for unauthorized performance enhancement, or has an untreated, coexisting substance use disorder.
And what about cannabis? This topic sparked the most debate among the experts, falling just short of an official consensus with 71% agreement that regular cannabis use alone shouldn't automatically trigger a stimulant stoppage. Recognizing the complexity, such as how chronic cannabis use can overlap with ADHD executive function deficits, the task force proposed a structured monitoring approach instead of an immediate cutoff. Clinicians are encouraged to track the patient every 1 to 3 months using standardized symptom tools and random urine drug screens to verify whether cannabis use is actively neutralizing the stimulant's therapeutic benefits.
The Path Forward: Safe Tapering and Lifestyle Support
If you and your doctor decide that stopping a stimulant is the right path, it shouldn’t happen overnight. The task force strongly recommends that medications be gradually tapered off at a rate tailored to the individual to minimize potential disruptions and distinguish between transient withdrawal and a true return of ADHD symptoms.
Crucially, stopping a medication doesn't mean stopping treatment. The experts highlight that the success of any deprescribing plan is significantly enhanced when patients focus on optimizing modifiable lifestyle factors. Prioritizing sleep hygiene, staying physically active, and implementing structured behavioral strategies can support executive functioning and help sustain your cognitive gains even as the medication is reduced or eliminated.
The Takeaway:
The decision to continue or stop an ADHD medication is a deeply personal one that requires balancing real-world efficacy, safety, and individual health changes. These new consensus recommendations provide an essential roadmap to help adults navigate their long-term mental health journeys safely and effectively.
Are you or a loved one currently evaluating your long-term relationship with ADHD medication? Consider scheduling a check-in with your healthcare provider to discuss whether your current treatment plan still perfectly matches your health needs today.
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