Why Two People With ADHD Can Have Completely Different Root Causes
Picture two people sitting across from each other in a waiting room. Both have ADHD. Both have struggled with focus, emotional regulation, and daily functioning for years. Both have tried the same supplements, read the same books, and been given similar advice.
One of them started magnesium and omega-3s and noticed a meaningful shift within weeks. The other tried the same protocol and felt nothing. One parent cleaned up their child's diet, removed dairy and gluten, and watched their kid's behavior stabilize in a way that surprised even the pediatrician. Another parent did everything right, followed every recommendation, and the needle barely moved.
Same diagnosis. Completely different biology.
This is not a failure of effort or compliance. It is what happens when a behavioral diagnosis is treated as if it were a biological explanation — when the label is mistaken for the root cause.
It is not.
The Diagnosis Describes What. Not Why.
ADHD is diagnosed based on a pattern of symptoms, inattention, impulsivity, hyperactivity, or some combination — that cause meaningful impairment across settings. The criteria come from the DSM-5, and they are useful for identifying who is struggling and establishing that the struggle is real.
But the diagnostic criteria do not tell you why those symptoms exist in any particular person's body. They describe the what. The why (the underlying biology) is where everything diverges.
This distinction matters more than most people realize. ADHD is one of the most heritable conditions in psychiatry, with twin studies consistently estimating heritability around 80% (Demontis et al., 2023). And yet the largest genome-wide association study to date has identified over 80 associated genetic loci that still capture only a fraction of that heritable variance. Researchers who study ADHD at the biological level increasingly recognize that the DSM subtypes, inattentive, hyperactive-impulsive, and combined — do not map cleanly onto distinct neurobiological mechanisms (Nigg et al., 2020).
In other words, the same behavioral profile can emerge from meaningfully different underlying systems. And when the underlying systems are different, the same intervention will not work for everyone.
This is the central challenge, and the central opportunity of a root cause approach to ADHD.
Root Cause #1: The Gut
One of the most significant shifts in ADHD research over the past decade has been the growing recognition that what happens in the gut does not stay in the gut.
The gut-brain axis, the bidirectional communication network between the gastrointestinal system and the central nervous system, operates through neurological, hormonal, and immune pathways. The gut microbiome influences neurotransmitter production, inflammatory signaling, and brain development in ways that are directly relevant to ADHD (Ming et al., 2018).
Individuals with ADHD frequently experience gastrointestinal symptoms at higher rates than neurotypical peers, and research has found meaningful differences in gut microbiome composition between ADHD and control groups. Studies have identified alterations in the Actinobacteria phylum, changes in Bifidobacterium abundance, and a genetically encoded capacity in the ADHD gut microbiome for producing monoamine precursors (including a dopamine precursor) at levels that correlate with altered brain reward responses (Aarts et al., 2017).
Gut dysbiosis can disrupt neurotransmitter production, increase intestinal permeability, and trigger immune activation, all of which contribute to neuroinflammation and worsen ADHD symptoms (Boonchooduang et al., 2020). The relationship runs in both directions: a dysregulated nervous system can further destabilize gut function, creating a cycle that is difficult to break without addressing both systems.
Early microbial exposures also matter. A large Swedish population study found that maternal antibiotic use during pregnancy and early childhood antibiotic exposure were both associated with an elevated risk of ADHD and autism in children, with effects influenced by the quantity, type, and timing of exposure (Njotto et al., 2023). This connects directly to the maternal microbiome as a shaping force in neurodevelopment, an area of growing clinical and research importance.
Two people with ADHD can have entirely different gut profiles. One may have significant dysbiosis and intestinal permeability driving inflammation and neurotransmitter disruption. The other may have a relatively intact gut but significant nutrient insufficiencies. Both present with ADHD symptoms. Both need different interventions.
Root Cause #2: Nutrient Status
The brain is a metabolically demanding organ. It requires a continuous supply of specific nutrients to synthesize neurotransmitters, regulate gene expression, protect against oxidative stress, and maintain the structural integrity of neuronal membranes. When those nutrients are insufficient, brain function is directly affected.
A 2025 study published in Frontiers in Nutrition examined nutrient blood levels in 57 children and adults with ADHD and other neurodivergent conditions. The findings were striking (Hunter et al., 2025):
95% had suboptimal omega-3 index scores
88% had insufficient vitamin B2 (riboflavin)
71% had zinc levels below recommended ranges
65% had insufficient vitamin D
100% of those tested had at least one food intolerance, with over 80% reacting to dairy and casein
These were not incidental findings. The study found statistically significant relationships between nutrient levels and ADHD symptom severity. Lower red blood cell magnesium was associated with higher disruptive behavior scores. Lower omega-3 index was correlated with greater learning and language difficulties. Lower alpha-carotene was associated with higher overall ADHD symptom scores (Hunter et al., 2025).
Each of these nutrients plays a specific mechanistic role. Omega-3 fatty acids (particularly EPA and DHA) are essential for dopaminergic and serotonergic signaling, neuronal membrane fluidity, and anti-inflammatory activity. Zinc is a direct cofactor in dopamine synthesis and transport, and zinc insufficiency may contribute to ADHD symptoms through disrupted dopamine pathways. B vitamins are required for the production of dopamine, serotonin, norepinephrine, and GABA. Magnesium supports nervous system regulation, stress resilience, and neurotransmitter balance.
Vitamin D supports serotonin synthesis and immune regulation (Hunter et al., 2025).
But here is the critical point: not every person with ADHD is deficient in the same nutrients. Someone with low ferritin and adequate zinc has a fundamentally different nutritional picture than someone with low omega-3s and low B2. Treating without testing means supplementing based on population averages rather than individual biochemistry, which explains why the same protocol helps one person and does nothing for another.
Root Cause #3: Neurotransmitter Metabolism
Dopamine and norepinephrine are the primary neurotransmitters involved in ADHD. But how those neurotransmitters are produced, utilized, and broken down varies significantly between individuals and that variability is rarely assessed in conventional care.
Some people with ADHD have impaired dopamine synthesis, producing insufficient amounts from the start. Others have elevated dopamine metabolites on functional testing, suggesting the dopamine is being broken down too rapidly rather than utilized effectively. Still others have disruptions in receptor sensitivity, meaning the neurotransmitter is present but the downstream signaling is impaired. These are mechanistically distinct problems that call for different interventions.
The gut microbiome is directly involved in this process. Research has identified a predicted increase in bacterial gene function related to the synthesis of phenylalanine, tyrosine, and tryptophan, the amino acid precursors to dopamine, noradrenaline, and serotonin respectively, in the ADHD gut microbiome. This predicted capacity for dopamine precursor production correlated with altered neural responses during reward anticipation, suggesting that microbial composition shapes neurotransmitter availability in clinically meaningful ways (Aarts et al., 2017).
B vitamins are required cofactors at multiple points in neurotransmitter synthesis. Zinc influences dopamine metabolism directly. Magnesium affects GABA activity and nervous system excitability. When any of these are insufficient, downstream neurotransmitter production is compromised, but in ways that differ depending on which nutrients are low and how each individual's metabolic pathways are functioning.
The Organic Acids Test is currently one of the most useful tools for seeing neurotransmitter metabolism patterns directly. Urinary markers of dopamine and serotonin metabolism, B vitamin functional status, mitochondrial function, and oxidative stress can be assessed simultaneously, revealing the specific metabolic context in which ADHD is operating for that individual.
Root Cause #4: Inflammation
Research increasingly supports the idea that low-grade neuroinflammation plays a role in ADHD, but the picture is more nuanced than a simple "ADHD equals inflammation" narrative.
A PROSPERO-registered systematic review and meta-analysis by Misiak and colleagues (2022), pooling 10 studies comparing peripheral blood cytokine levels in ADHD versus healthy controls, found that IL-6 was significantly elevated in ADHD with a moderate-to-large effect size. However, the pooled results were fragile, removing individual studies from the analysis made the overall effect non-significant, suggesting that the inflammatory signal in ADHD is real but inconsistent across individuals (Misiak et al., 2022).
This inconsistency is itself clinically meaningful. It suggests that neuroinflammation is not a universal feature of ADHD but rather a root cause contributor in a subset of individuals. Some people with ADHD have measurably elevated inflammatory markers. Others do not. Treating everyone as if inflammation is driving their symptoms, or conversely, dismissing inflammation as irrelevant, misses the individual variation that defines this condition.
A meta-analysis of hematological inflammatory ratios found that neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios were elevated in ADHD, consistent with a mild systemic inflammatory state in at least some individuals (Gędek et al., 2023).
And the epidemiological data is notable — ADHD co-occurs with autoimmune and allergic disorders at rates that suggest shared inflammatory mechanisms, even when cytokine measurements themselves are inconsistent (Leffa et al., 2018).
The sources of inflammation vary too. Gut dysbiosis, food intolerances, environmental toxin exposure, oxidative stress, and chronic psychological stress can all contribute to an inflammatory state that worsens ADHD symptoms. Two people with the same ADHD diagnosis may have completely different inflammatory drivers — or none that are measurable at all.
Root Cause #5: Hormones and the Stress System
As explored in last week's post on the HPAT axis, the stress response system behaves differently in ADHD and that difference has direct consequences for symptoms, recovery, and treatment response.
The HPA axis interacts with dopamine, norepinephrine, and thyroid function in ways that shape how ADHD presents day to day. Hormonal context matters significantly. Estrogen influences dopamine receptor sensitivity, which is why many women with ADHD notice their symptoms shift across the menstrual cycle, worsen in the luteal phase, and change again in perimenopause. Cortisol patterns influence prefrontal cortex function and neurotransmitter availability. Thyroid hormone conversion, which can be disrupted by chronic stress, affects energy, cognition, and mood in ways that overlap significantly with ADHD symptoms.
This hormonal layer is part of the root cause picture for many people, particularly women and it is frequently missed when ADHD is assessed without considering the broader endocrine context.
Root Cause #6: Genetics — The Layer Underneath Everything
Here is where the picture becomes even more individual.
ADHD is approximately 80% heritable, but that heritability is distributed across hundreds of genetic variants, each contributing a small effect. The largest genome-wide association study to date has identified over 80 associated loci and still captures only a portion of the genetic architecture (Demontis et al., 2023).
What researchers are beginning to understand is that clinically distinct subgroups within ADHD have different genetic profiles. A study of approximately 14,000 individuals with ADHD found that subgroups defined by comorbidity, ADHD with autism, ADHD with substance use disorder, adult-onset ADHD, showed meaningfully different polygenic score profiles across psychiatric, cognitive, and behavioral traits. One comorbid subgroup even showed a genome-wide significant locus that was not shared with ADHD more broadly (LaBianca et al., 2024).
This matters clinically because it means that two people carrying the same diagnosis may have different genetic architectures underlying their symptoms and those differences likely influence how they respond to nutrients, medications, and interventions.
Genetic variants affect how nutrients are absorbed and metabolized. They influence enzyme activity in neurotransmitter pathways. They shape detoxification capacity, inflammatory responses, and stress physiology. This is not about genetics being destiny. It is about understanding the biological instructions each person is working from and using that understanding to make more targeted decisions about support.
This is an area I am beginning to integrate more intentionally into my clinical work, and it is something I will be sharing more about in the coming weeks.
Why This Matters for Treatment
When the root cause is not identified, treatment becomes educated guessing. And educated guessing has a predictable outcome, it helps some people and not others, with no clear way to know in advance which group any individual belongs to.
This explains why two children with the same ADHD diagnosis can have opposite responses to the same dietary change. Why a supplement that helps one adult focus better makes another feel worse. Why medication that works beautifully for one person feels flat or overstimulating for someone else with identical symptoms.
None of this is personal failure. It is the predictable result of treating a label rather than a person.
The root causes of ADHD are multiple, interacting, and individually variable. Gut health, nutrient status, neurotransmitter metabolism, inflammatory load, hormonal context, and genetic architecture can each contribute, in different combinations and different magnitudes, to the same behavioral presentation. Identifying which factors are active for a specific person requires actually looking.
What Functional Labs Reveal
The GI-MAP, Organic Acids Test, HTMA, and targeted blood work do not diagnose ADHD. What they do is show the biological context in which ADHD is operating, the nutrient gaps, the gut patterns, the neurotransmitter metabolism, the inflammatory markers, the stress physiology.
That context is where the root cause lives.
And it is different for everyone.
If you have tried protocols that worked for someone else and felt nothing (or watched your child not respond the way you expected) this is likely why.
The missing piece is not more effort. It is more information about your specific biology.
This is exactly the kind of picture I build with clients inside my 3-Month Functional Lab Package. Using the GI-MAP, Organic Acids Test, and targeted lab work, we look at what is actually driving your symptoms rather than guessing based on what worked for someone else.
Let’s talk through what is going on and whether functional lab testing makes sense for you.
References
Aarts, E., Ederveen, T. H. A., Naaijen, J., Zwiers, M. P., Boekhorst, J., Timmerman, H. M., Smeekens, S. P., Netea, M. G., Buitelaar, J. K., Franke, B., van Hijum, S. A. F. T., & Vasquez, A. A. (2017). Gut microbiome in ADHD and its relation to neural reward anticipation. PLOS ONE, 12(9), e0183509. https://doi.org/10.1371/journal.pone.0183509
Anand D, Colpo GD, Zeni G, Zeni CP and Teixeira AL (2017) Attention-Deficit/Hyperactivity Disorder And Inflammation: What Does Current Knowledge Tell Us? A Systematic Review. Front. Psychiatry 8:228. doi: 10.3389/fpsyt.2017.00228
Boonchooduang, N., Louthrenoo, O., Chattipakorn, N., & Chattipakorn, S. C. (2020). Possible links between gut–microbiota and attention-deficit/hyperactivity disorders in children and adolescents. European Journal of Nutrition, 59(8), 3391–3403. https://doi.org/10.1007/s00394-020-02383-1
Demontis, D., Walters, G. B., Athanasiadis, G., Walters, R., Therrien, K., Nielsen, T. T., Farajzadeh, L., Voloudakis, G., Bendl, J., Zeng, B., Zhang, W., Grove, J., Als, T. D., Duan, J., Satterstrom, F. K., Bybjerg-Grauholm, J., Bækved-Hansen, M., Gudmundsson, O. O., Magnusson, S. H., Baldursson, G., … Børglum, A. D. (2023). Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains. Nature genetics, 55(2), 198–208. https://doi.org/10.1038/s41588-022-01285-8
Gędek, A., Modrzejewski, S., Gędek, M., Antosik, A. Z., Mierzejewski, P., & Dominiak, M. (2023). Neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, and monocyte to lymphocyte ratio in ADHD: a systematic review and meta-analysis. Frontiers in psychiatry, 14, 1258868. https://doi.org/10.3389/fpsyt.2023.1258868
Hunter, C., Smith, C., Davies, E., Dyall, S. C., & Gow, R. V. (2025). A closer look at the role of nutrition in children and adults with ADHD and neurodivergence. Frontiers in Nutrition, 12, 1586925. https://doi.org/10.3389/fnut.2025.1586925
LaBianca, S., Brikell, I., Helenius, D., Loughnan, R., Mefford, J., Palmer, C. E., Walker, R., Gådin, J. R., Krebs, M., Appadurai, V., Vaez, M., Agerbo, E., Pedersen, M. G., Børglum, A. D., Hougaard, D. M., Mors, O., Nordentoft, M., Mortensen, P. B., Kendler, K. S., Jernigan, T. L., … Schork, A. J. (2024). Polygenic profiles define aspects of clinical heterogeneity in attention deficit hyperactivity disorder. Nature genetics, 56(2), 234–244. https://doi.org/10.1038/s41588-023-01593-7
