July 14, 2025

The Role of Serotonin in ADHD and Its Many Comorbidities

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.

Wait! I thought ADHD had to do with Dopamine–Why are we looking at Serotonin?

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.

The Study:

  • Objective: To systematically review which conditions commonly co-occur with ADHD and determine whether serotonin dysfunction might be a common thread linking them.

  • Method: The authors combed through existing literature up to March 2024, analyzing evidence for serotonin involvement in each comorbidity associated with ADHD.

  • Scope: 182 psychiatric and somatic conditions were found to frequently occur in people with ADHD.

Key Findings

  • 74% of Comorbidities Linked to Serotonin: Of the 182 comorbidities identified, 135 showed evidence of serotonergic involvement—91 psychiatric and 44 somatic (physical) conditions.

  • Psychiatric Comorbidities: These include anxiety disorders, depression, bipolar disorder, and obsessive-compulsive disorder—all of which have long-standing associations with serotoninergic dysfunction.

  • Somatic Comorbidities: Conditions like irritable bowel syndrome (IBS), migraines, and certain sleep disorders also showed a significant serotonergic link.

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.

The Take-Away: 

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. 

Faraone SV, Ward CL, Boucher M, Elbekai R, Brunner E. Role of serotonin in psychiatric and somatic comorbidities of attention-deficit/hyperactivity disorder: A systematic literature review. Neurosci Biobehav Rev. 2025 Jul 5:106275. doi: 10.1016/j.neubiorev.2025.106275. Epub ahead of print. PMID: 40623558.

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Swedish nationwide population study finds mothers with ADHD have elevated risk of depression and anxiety disorders after childbirth

Swedish nationwide population study finds mothers with ADHD have elevated risk of depression and anxiety disorders after childbirth

In the general population, most mothers experience mood disturbances right after childbirth, commonly known as postpartum blues, baby blues, or maternity blues. Yet only about one in six develop symptoms with a duration and magnitude that require treatment for depressive disorder, and one in ten for anxiety disorder.

To what extent does ADHD contribute to the risk of such disorders following childbirth? A Swedish study team used the country’s single-payer health insurance database and other national registers to conduct the first nationwide population study to explore this question.

They used the medical birth register to identify all 420,513 women above 15 years of age who gave birth to their first child, and all 352,534 who gave birth to their second child, between 2005 and 2013. They excluded miscarriages. They then looked for diagnoses of depression and/or anxiety disorders up to a year following childbirth.

In the study population, 3,515 mothers had been diagnosed with ADHD, and the other 769,532 had no such diagnosis. 

Following childbirth, depression disorders were five times more prevalent among mothers with ADHD than among their non-ADHD peers. Excluding individuals with a prior history of depression made little difference, lowering the prevalence ratio to just under 5. Among women under 25, the prevalence ratio was still above 3, while for those 25 and older it was above 6.

Similarly, anxiety disorders were over five times more prevalent among mothers with ADHD than among their non-ADHD peers. Once again, excluding individuals with a prior history of depression made little difference, lowering the prevalence ratio to just under 5. Among women under 25, the prevalence ratio was still above 3, while for those 25 and older it was above 6.

The team cautioned, “There is a potential risk of surveillance bias as women diagnosed with ADHD are more likely to have repeated visits to psychiatric care and might have an enhanced likelihood of also being diagnosed with depression and anxiety disorders postpartum, compared to women without ADHD.”

Nevertheless, they concluded, “ADHD is an important risk factor for both depression and anxiety disorders in the postpartum period and should be considered in the post- pregnancy maternal care, regardless of sociodemographic factors and the presence of other psychiatric disorders. Parental education prior to conception, psychological surveillance during, and social support after childbirth should be provided to women diagnosed with ADHD.”

December 22, 2023

Siblings of Those With ADHD at Higher Risk for ADHD & Other Disorders

Israel-wide population study:siblings of individuals with ADHD have highly elevated risk of ADHD, slightly elevated risk of anxiety and personality disorders, no greater risk for other disorders or low IQ

Israel has a military draft that applies to males and females alike, except orthodox women and orthodox male seminary(yeshiva) students, who are exempt. Upon turning 17 every Israeli undergoes a medical review, including both a physical and psychiatric assessment, in preparation for the draft. The Draft Board Registry maintains comprehensive health information on all unselected Israelis until they turn 21. The registry also tracks all family members of draft registrants, including full siblings.

An Israeli study team used registry records from 1998 through2014 to obtain data for a total of over a million individuals (1,085,388). Because of the exemption for orthodox women, 59% were male.

The team identified 903,690 full siblings in the study population (58% males), including 166,359 male-male sibling pairs, 104,494 female-female sibling pairs, and 197,571 opposite-sex sibling pairs.

Next, the team identified all cases in the study population with a diagnosis of a psychiatric disorder, low IQ (≥2 standard deviations below the population mean), Type-1 diabetes, hernia, or hematological malignancies. It matched each case with ten age- and sex-matched controls selected at random from the study population. Then, for each case and case-matched controls, it identified all siblings.

There were 3,272 cases receiving treatment for ADHD, 2,128 with autistic spectrum disorder, 9,572 with severe/profound intellectual disability, 7,902 with psychotic disorders, 9,704 with mood disorders, 10,606with anxiety disorders, 24,815 with personality disorders, 791 with substance abuse disorders, 31,186 with low IQ, 2,770 with Type-1 diabetes, 30,199 with a hernia, and 931 with hematological malignancies.

Draftees with ADHD were five and a half times more likely to have a sibling with ADHD than controls.

There were no significant associations between ADHD and any of the somatic disorders - Type-1 diabetes, hernia, or hematological malignancies - nor between ADHD and low IQ.

There were also no significant associations between ADHD and autism spectrum disorder, severe/profound intellectual disability, mood disorders, and substance use disorders.

On the other hand, draftees with ADHD were more than 40% more likely to have siblings with anxiety or personality disorders than controls.

Surprisingly, draftees with ADHD were less than half as likely to have siblings with psychotic disorders than controls.

There were some limitations. The psychiatric classification system used by the Israeli military did not permit assessing the risk of bipolar disorder and depression separately. That meant having to use a broader category of mood disorders, including both disorders. In addition, the military diagnostic system does not allow diagnosis of comorbid psychiatric disorders in the same individual, instead of assigning only the most severe diagnosis.

March 27, 2022

Adult ADHD and Comorbid Somatic Disease

Adult ADHD and Comorbid Somatic Disease

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.

April 5, 2021

Beyond Dopamine: How Serotonin Influences ADHD Symptoms

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.

The Results:
  • Most studies support a serotonergic role. About 81% (77/95) of the papers reported altered serotonin production, binding, transport, or degradation linked to ADHD or ADHD-like behaviors.

  • Multiple lines of evidence: animal models frequently show that changing serotonin levels or receptor activity alters hyperactivity and impulsivity; human imaging and clinical studies provide supportive but smaller and sometimes mixed signals; genetic/transcriptomic work points to serotonin-related pathways among many implicated systems.

  • Receptors and SERT matter: Multiple serotonin receptor subtypes (5-HT1A, 1B, 2A, 2C, 7) and SERT show associations with impulsivity, hyperactivity, attention, or brain activity patterns in ADHD models and some human studies.

  • Mixed and conflicting data: Central measures (brain, CSF) more often show serotonin deficits, while peripheral measures (platelets, plasma) sometimes show higher serotonin — methodological differences likely explain some contradictions.

  • Drugs used for ADHD can affect serotonin: Stimulants and non-stimulant drugs approved by FDA for treating ADHD (e.g., methylphenidate, atomoxetine, extended release viloxazine) or under investigation (centafafadine) have direct or indirect effects on serotonin systems, supporting the idea that monoamines interact rather than acting separately.  Because drugs that mainly affect serotonin are not useful for ADHD it seems likely that a pathway forward for ADHD drug development would be drugs that target multiple neurotransmitter systems.  A complex treatment for an etiologically complex disorder.

The Role of Serotonin in ADHD: What's The Take-Away?

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. 

Registry-based Cohort Study Finds No Association Between Maternal Diabetes and Offspring ADHD

Background:

A previous meta-analysis found that children born to mothers with diabetes had a 34% higher risk of developing ADHD compared to those born to non-diabetic mothers.  

However, previous studies suffered methodological limitations, such as small sample sizes, case-control or cross-sectional designs, and insufficient adjustment for key confounders such as maternal socio-economic status, mental health conditions, obesity, and substance use disorders.  

Moreover, many studies relied on self-reported maternal diabetes, and on non-clinical ADHD assessments, such as parental reports or screening tools, which are prone to bias and inaccuracies.  

Furthermore, the role of maternal antidiabetic medication use in relation to ADHD risk has rarely been examined. Antidiabetic medications are effective in controlling high blood sugar during pregnancy, but many can cross the placenta and the blood-brain barrier, raising concerns about potential effects on fetal brain development.  

Study:

To address these gaps, an Australian study team used a large cohort of linked health administrative data from New South Wales to investigate both the association between maternal diabetes and the risk of ADHD and the independent effect of prenatal exposure to antidiabetic medications. 

The study encompassed all mother-child pairs born from 2003 through 2005, with follow-up conducted through 2018 to monitor hospital admissions related to ADHD. That yielded a final cohort of almost 230,000 mother-child pairs. 

The team adjusted for potential confounders including maternal age, socioeconomic status, previous children, pregnancy-related hypertension, caesarean delivery, birth order and plurality, maternal anxiety, depression, schizophrenia, bipolar disorder, substance use (alcohol, tobacco, stimulants, opioids, cannabis), and child factors such as Apgar score, sex, prematurity, and low birth weight. 

Results:

For maternal diabetes overall, there was no significant association with offspring ADHD. That was also true when broken down into pre-existing maternal diabetes and gestational (pregnancy-induced) diabetes.  

In a subset of 11,668 mother-child pairs, including 3,210 involving exposure to antidiabetic medications, there was likewise no significant association with offspring ADHD

Conclusion:

The team concluded, “Our findings did not support the hypothesis that maternal diabetes increases the risk of ADHD in children. Additionally, maternal use of antidiabetic medication was not associated with ADHD.” 

This study highlights the importance of high-quality research. A previous meta-analysis linking ADHD and maternal diabetes did not appropriately adjust for confounders and cited many small studies that may have included biased self-report scales. This large, registry-based cohort study of nearly 230,000 mother–child pairs found no evidence that maternal diabetes—whether pre-existing or gestational—or prenatal exposure to antidiabetic medications was associated with subsequent offspring ADHD as measured by hospital-recorded ADHD outcomes. The study’s strengths include its population scale, prolonged follow-up, and extensive adjustment for maternal and perinatal confounders (including maternal mental health and substance-use disorders), which address many limitations of earlier, smaller studies that reported elevated risks.  

September 8, 2025

Population Study Finds Association Between COVID-19 Infection and ADHD

Background: 

The COVID-19 pandemic brought environmental changes that may have influenced ADHD symptoms and contributed to higher diagnosis rates. School closures, the transition to remote learning, and restrictions on outdoor activities led to increased screen time and isolation, both of which can affect attention and behavioral regulation. Children and adolescents, who usually depend on social interactions and structured routines, experienced significant disruptions during this period.  

Method:

South Korea has a nationwide single-payer health insurance system that keeps detailed health records on virtually its entire population. To explore the impact of COVID-19 on ADHD, a Korean research team used a database established by the Korean government that tracked all patients with COVID-19 between 2020 and 2023, nationwide COVID vaccination records, and insurance claims. They included all participants aged 6 through 29 years old. 

The onset of ADHD was determined by diagnosis combined with the prescription of ADHD medication. 

Altogether, the study encompassed almost 1.2 million Koreans, including over 150,000 children (6-12), more than 220,000 adolescents (13-19), and almost 800,000 young adults (20-29). 

The team adjusted for age, sex, income, Charlson Comorbidity Index, and medical visits. The Charlson Comorbidity Index predicts the mortality for a patient who may have a range of 17 concurrent conditions, such as heart disease, AIDS, or cancer. 

Results:

With these adjustments, young adults known to be infected with COVID-19 were about 40% more likely to be subsequently diagnosed with ADHD than their counterparts with no record of such infection

Adolescents known to be infected with COVID-19 were about twice as likely to be subsequently diagnosed with ADHD than their counterparts with no record of such infection. 

Children known to be infected with COVID-19 were 2.4 times as likely to be subsequently diagnosed with ADHD than their counterparts with no record of such infection

All these results were highly significant, and point to much greater impact on the youngest persons infected. 

Interpretation: 

The team concluded, “our nationwide study revealed that the COVID-19 pandemic significantly influenced ADHD incidence (raising incidence between 2020 and 2023), with SARS-CoV-2 infection identified as a critical risk factor,” and “In particular, early intervention and neurological evaluations are needed for children, adolescents, and young adults with a history of SARS-CoV-2 infection.”