ADHD’s Curious Connections to Chronic Inflammation and Dysautonomia
Emerging research is exploring how a range of physical health conditions affects people with ADHD in previously unknown ways.
Many of the conditions that co-occur with ADHD, such as anxiety, depression, sleep problems, and addiction, are well understood. Less clear is ADHD’s curious association with asthma, allergies, autoimmune disorders, gut issues, and hypermobility.
Can the overlap between these diverse physical health problems and ADHD teach us anything about the condition and its underpinnings? A growing body of research seems to highlight the role of chronic inflammation and dysautonomia, a disordered autonomic nervous system function that controls heart rate, blood pressure, digestion, and body temperature.
Central to understanding these connections may be ADHD’s strong overlap with joint hypermobility, caused by overly elastic connective tissue. Strikingly, about half of people with ADHD are hypermobile. While many experience no issues, some develop hypermobile Ehlers-Danlos syndrome (hEDS) or Hypermobility Spectrum Disorder (HSD), in which lax connective tissues in the skin and around the joints, blood vessels, and gut trigger symptoms across multiple systems. These syndromes are strongly linked to inflammation, in the form of mast cell activation syndrome, and dysautonomia.
Understanding the brain-body connections between these seemingly unrelated issues has the potential to reshape how we think about ADHD. In time, this understanding may provide new targets for treatment.
What Drives Inflammation?
Inflammation is the body’s natural healing response to injury or infection. It is protective in the short-term, but when it becomes chronic, it can lead to serious medical problems. Sources of chronic inflammation include allergies, asthma, eczema, autoimmunity, gut dysfunction and food intolerances, persistent infections, and exposure to toxicity in the environment. It is also linked to enduring stress or trauma, disordered sleep, and diets high in ultra-processed foods. Chronic inflammation increases the chances of developing cardiovascular disease, cancer, diabetes, metabolic disturbances, and other conditions.
[Self-Test: Am I Hypermobile?]
Research has linked inflammation to ADHD in the following ways:
- Several inflammatory markers have been found at higher levels in people with ADHD vs. non-ADHD peers; and a higher level of inflammation has been linked to more severe ADHD symptoms.
- Deficiencies in vitamin D and iron are common among people with ADHD – notable as vitamin D has anti-inflammatory properties, and iron deficiency can impair immune function.
- Certain genes linked to inflammation are more commonly found in people with ADHD.
There is also a clear association between ADHD and a range of inflammatory conditions, such as chronic gastrointestinal issues, allergies, and autoimmune conditions such as celiac disease, ulcerative colitis, autoimmune thyroid disease, psoriasis, and Type 1 Diabetes. Many health care providers are unaware of the connections between these co-occurring issues.
As cutting-edge research continues to explore these connections, some forward-thinking clinicians believe one common thread could be mast cell activation syndrome (MCAS), a disorder in which the immune system overreacts to a wide range of triggers, resulting in widespread, chronic inflammation and worsening dysautonomia. However more research into MCAS is needed to inform clinical practice.
Mast Cells Activation Syndrome
What are mast cells?
Part of the ‘innate’ (first responder) immune system, these white blood cells are concentrated in tissues of the body exposed to the outside world: the skin, and the linings of the respiratory, gastrointestinal, and genitourinary tracts. They are also present in the brain, and close to nerves and blood vessels. When mast cells start misbehaving, the areas of the body where they’re found are particularly affected.
What do they do?
As a key component of the body’s surveillance system, the surface of mast cells is full of receptors that can register potential threats. When activated, mast cells release chemicals like histamine, cytokines, and interleukins that help coordinate the immune response. When your lungs tighten in asthma, or your face flushes with embarrassment, it’s because of mast cells.
What is MCAS?
Mast cells are incredibly effective at addressing actual threats. In some people, however, they respond too aggressively or erroneously, releasing excessive amounts of chemicals that cause wide-ranging inflammatory and allergic symptoms. Triggers may include:
- Allergens, certain foods, drugs, alcohol
- Infections (e.g., Lyme disease, COVID-19) or fevers
- Hormonal shifts
- Physical stimuli (e.g., trauma, heat/cold)
- Emotional stress
- Toxins (e.g., mold, lead, pesticides, heavy metals, air pollution)
Mast cell activation is well known to cause problems like hay fever, asthma, hives, angioedema (rapid swelling under the skin, such as in the lips, tongue, and eyelids), and anaphylaxis (a severe allergic reaction). Less recognized are its neuropsychiatric symptoms, such as anxiety and depression, which are often overlooked compared to the allergic reactions.
MCAS Symptoms
Flushing, itching, abdominal pain with diarrhea or nausea, fast heart rate and low blood pressure, fatigue, and brain fog span various organ systems and are symptoms of MCAS.
For a diagnosis, a patient must demonstrate repeated episodes of typical symptoms in two or more body systems at once.
How Is MCAS Diagnosed?
It’s possible to formally diagnose MCAS through bloodwork or urine that shows increased levels of chemical mediators, including tryptase. However, it is difficult to capture evidence of mast cell dysfunction because:
- Many mast cell mediators act locally, making it hard to measure systemically
- Many have short half-lives, so testing must be done soon after onset of symptoms
- Specimens must be handled carefully and refrigerated immediately
Patients whose tests are normal may still need treatment if they consistently show characteristic symptoms, and other medical conditions have been ruled out. A convincing response to first-line pharmacological treatments is a good clue to the presence of MCAS.
MCAS Treatment Options
The first step is to try to uncover what is driving the mast cells. Are you reacting to certain foods or products, or to mold in your home?
Antihistamines, including H1 blockers (like Claritin or Zyrtec) and H2 blockers (like Pepcid), block the action of the histamine produced by mast cells. For a patient with MCAS, these medications can lead to dramatic improvement in anxiety, mood, and possibly ADHD symptoms. Patients often need to try different antihistamines, and may need a morning and evening dose of both an H1 and an H2 blocker.
Mast cell stabilizers, like cromolyn sodium, stop the initial release of chemicals by mast cells and may be added.
An experienced clinician should oversee MCAS treatment. If your allergist, primary care provider, or immunologist isn’t familiar with MCAS or open to learning more, you may consider seeing a functional medicine practitioner with relevant experience.
ADHD and Dysautonomia
Dysautonomia is an umbrella term for disorders of autonomic nervous system (ANS) function. Like ADHD, dysautonomia can start in childhood and continue throughout the lifespan. A common form of dysautonomia is postural orthostatic tachycardia syndrome (POTS).
Preliminary evidence suggests that ADHD and POTS may be closely connected.
POTS
POTS is a condition in which the body has difficulty regulating blood flow and heart rate when moving from a sitting or lying position to standing. Instead of adjusting smoothly, the nervous system responds with an increase in heart rate, often causing people to feel dizzy, lightheaded or fatigued, due to reduced blood flow to the brain.
More research is needed to explore the association between POTS and ADHD, though a 2008 study showed that patients with POTS demonstrate more symptoms of inattention and score higher on ADHD scales than do control subjects.
POTS Symptoms
How Is POTS Diagnosed?
POTS is formally diagnosed through a tilt table test, in which your heart rate and blood pressure are measured while your posture and position are adjusted.
A telltale sign of POTS is the sudden increase in heart rate (by > 30 beats/minute in adults) within 10 minutes of standing. When you stand up from a chair, for example, your autonomic nervous system must ensure that blood continues to reach the brain, despite the opposing gravitational force. With POTS, due to blood pooling in the abdomen and insufficient blood reaching the brain, the heart works harder to compensate, causing a spike in heart rate.
POTS Treatment
A specialist must oversee treatment, which may include:
- Salt and fluids: Many people with POTS have a low blood volume and can benefit from drinking more fluids and consuming more salt, through diet or supplements, assuming blood pressure allows.
- Exercise: Walking, yoga, and physical therapy can improve blood circulation. Patients should begin to exercise slowly, and ramp up gradually.
- Compression garments: Compression legging or shorts can help POTS symptoms by pushing blood from the lower to the upper half of the body.
If POTS cannot be sufficiently managed with salt, fluids, exercise, or compression, medication may be helpful.
Stomach Issues and ADHD
Problems with the digestive system frequently occur in people with ADHD, causing bowel disturbance, chronic pain, and discomfort. MCAS, dysautonomia, and hEDS/HSD can each contribute to gastrointestinal dysfunction in different ways. Digestive problems can, in turn, exacerbate MCAS. The gastrointestinal problems that have been associated with ADHD include:
MCAS, POTS and ADHD: Next Steps
- Read: The Gut-Brain Axis Could Accelerate Autism Understanding
- Watch: “Why Chronic Pain is So Common Among Neurodivergent Youth“
- Read: Hypermobility Often Misdiagnosed as Mental Illness
This article was derived from the ADDitude ADHD Experts webinar, “The Surprising Association Between ADHD & Inflammation” [Video Replay & Podcast #545] with James Kustow, BMedSci, BMBS, MRCPsych, which was broadcast on February 27, 2025.
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