The Seven Pillars of Metabolic Dysregulation
How they shape the neurodivergent woman's lived experience
Neurodivergent women inhabit a unique biological landscape, where inherent vulnerabilities in seven interconnected systems exist even before the complexities of life have fully begun to unfold. This pre-existing biological reality is further compounded by the lifelong performance of neurotypicality, or what you and I know as the act of masking.
Decades of suppressing natural responses, maintaining constant hypervigilance, and navigating social interactions with meticulous monitoring, accumulate over time as significant “biological debt”.
This chronic masking stress acts as a powerful amplifier, escalating every existing metabolic dysregulation and creating profound, systemic biological disruption that fundamentally shapes the neurodivergent woman's lived experience.
In the following paragraphs, I break down what I call The seven major pillars of metabolic dysregulation and the effects each one of them has on the embodied reality of the neurodivergent woman.
Pillar 1: The Gut Microbiome - Your Gut-Brain Highway
The gut microbiome in neurodivergent women is already severely disrupted. Beneficial bacteria like Bifidobacterium and Lactobacillus are depleted, while pathogenic microbes like Clostridium and Candida flourish. This dysbiosis creates what researchers call "leaky gut” - increased intestinal permeability that allows bacterial toxins to escape into the bloodstream.
These toxins trigger immune alarm bells, flooding your system with inflammatory cytokines. Since 90% of serotonin is produced in the gut, this disruption directly affects mood, sleep, and emotional regulation.
Chronic masking stress accelerates this destruction. The constant hypervigilance, dietary restrictions from sensory aversions, and biological stress of suppressing natural responses create the perfect storm for gut dysfunction. Every performed smile, every suppressed stim, every social interaction where you monitor and adjust your behavior adds another layer of stress to an already compromised system.
Pillar 2: Neurotransmitters - Your Chemical Messengers
Neurotransmitter metabolism in neurodivergent women is fundamentally different. Dopamine systems are already dysregulated - the very neurotransmitter that governs attention, motivation, and reward processing. Serotonin patterns show peripheral excess but central deficiency, creating a biochemical paradox where your body produces plenty but your brain can't access it.
These imbalances affect every aspect of cognitive and emotional function. Low dopamine makes focus and motivation feel impossible. Disrupted serotonin creates mood instability and sleep disorders.
Masking depletes these already limited reserves. Every moment spent performing neurotypical behavior requires conscious cognitive control - a process that burns through dopamine at an unsustainable rate. The mental effort of translating social cues, suppressing natural responses, and maintaining a neurotypical facade creates a constant drain on neurotransmitter systems that are already running on empty.
Pillar 3: Neuroinflammation - Your Internal Fire Department
Chronic low-grade inflammation is a hallmark of neurodivergent biology. Elevated levels of inflammatory cytokines - TNF-α, IL-6, and IL-1β - circulate through your system, creating a state of constant immune activation. Microglia in the brain, normally protective immune cells, become overactive and begin attacking healthy neural tissue.
This inflammatory state affects brain development, synaptic function, and neuroplasticity. It's not just background noise, but active destruction of neural architecture.
Masking intensifies this inflammatory cascade. The chronic stress of performing neurotypicality activates mast cells, which release multiple inflammatory compounds directly into brain tissue. Every social situation becomes an inflammatory event. The psychological stress of hiding your authentic self triggers the same immune response as physical injury, creating a cycle where social interaction literally inflames your brain.
Pillar 4: Mitochondria - Your Cellular Power Plants
Mitochondrial dysfunction is widespread in neurodivergent women. These cellular powerhouses that convert food and oxygen into energy are already compromised, leading to impaired ATP production and increased oxidative stress. This manifests as the crushing fatigue that defines so many neurodivergent experiences.
The NO/ONOO(-) cycle - a vicious biochemical loop involving free radicals and inflammatory cytokines - creates ongoing mitochondrial damage. Environmental toxins, dietary factors, and psychological stress all contribute to this energy crisis at the cellular level.
Masking places enormous additional demands on already struggling mitochondria. The cognitive load of constant social monitoring, emotional regulation, and behavioral suppression requires massive amounts of cellular energy. Every performed interaction, every suppressed authentic response, every moment of hypervigilant social scanning draws from energy reserves that are already critically depleted.
Pillar 5: Epigenetic Factors - Your Genetic Switches
Epigenetic patterns in neurodivergent women show widespread dysregulation. DNA methylation patterns, histone modifications, and microRNA expression are altered in ways that affect gene expression throughout life. These changes, established early in development through factors like maternal immune activation and environmental exposures, create an enduring molecular "footprint."
These epigenetic modifications affect stress response systems, immune function, and neurotransmitter production. In addition to being genetic predispositions, they're active, ongoing influences on how your body responds to stress and environmental challenges.
Chronic masking creates additional epigenetic changes. The sustained activation of stress response systems alters gene expression patterns, potentially creating heritable changes that affect future generations. The psychological and physiological stress of performing neurotypicality literally rewrites your genetic expression, embedding the cost of masking into your cellular memory.
Pillar 6: Environmental Toxicity - Your Toxic Load
Environmental toxicity disproportionately affects neurodivergent women. Heavy metals like arsenic, cadmium, and manganese are associated with increased neurodevelopmental disorder risk. Mycotoxins from indoor mold exposure - affecting up to 57% of households according to a Harvard University study - create what researchers call a "dangerous soup" of biological toxins that damage gut integrity, compromise immune function, and impair mitochondrial energy production.
These toxins not only trigger immediate symptoms - they create lasting changes in cellular function. Mycotoxins directly damage tight junction proteins in the gut, while heavy metals disrupt neurotransmitter synthesis and increase intracellular calcium levels that trigger neuronal death.
Masking stress overwhelms your body's detoxification capacity. The liver and other detox organs are already working overtime to process environmental toxins. The additional metabolic burden of chronic stress hormones, inflammatory cytokines, and oxidative stress from masking creates a bottleneck in detoxification pathways. Toxins that might normally be cleared efficiently begin to accumulate, creating a compound effect where environmental and psychological stressors amplify each other.
Pillar 7: Hormonal Dysregulation - Your Hormonal Orchestra
Hormonal dysregulation in neurodivergent women creates cascading effects throughout all other systems. The HPA (hypothalamic-pituitary-adrenal) axis shows chronic activation, leading to disrupted cortisol patterns and downstream effects on sex hormones, thyroid function, and metabolic regulation.
Beyond direct hormonal shifts, a critical, interconnected factor is insulin resistance (IR) and the broader metabolic syndrome, which significantly impacts neurodivergent individuals and their offspring. Metabolic dysfunctions, including insulin resistance, are frequently associated with Autism Spectrum Disorder (ASD). Maternal obesity and diabetes, conditions closely linked to IR, significantly increase the risk of having an autistic child, with some studies showing a quadrupled risk.
Insulin resistance is associated with an exaggerated immune response, leading to increased production of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α, and activating Toll-like receptors.
This chronic inflammation, along with gut dysbiosis and increased intestinal permeability, contributes to systemic insulin resistance, which in turn promotes neuroinflammation and neurodevelopmental changes associated with ASD.
Disruptions to metabolism and mitochondrial function, often underlying insulin resistance, are consistently linked to an increased risk for autism and other brain conditions.
Estrogen fluctuations during menstrual cycles, pregnancy, and menopause dramatically affect neurotransmitter function. When estrogen levels drop, dopamine and serotonin become even more dysregulated, creating the phenomenon where ADHD symptoms worsen during certain cycle phases or life transitions. Two-thirds of women with ADHD report severe PMS/PMDD - far exceeding national rates.
Masking stress disrupts this delicate hormonal balance. Chronic cortisol elevation from performed neurotypicality interferes with sex hormone production and sensitivity. The stress of constant social performance affects gut permeability through hormonal pathways, creating another link between masking and the gut-brain axis dysfunction. Perimenopause becomes particularly devastating because declining estrogen removes the last buffer against already dysregulated neurotransmitter systems.
Putting it all Together: The Cascade Effect
These seven systems don't operate independently - they form an interconnected web where dysfunction in one area triggers problems in all others.
Gut dysbiosis increases inflammation, which damages mitochondria, which affects neurotransmitter production, which disrupts hormonal balance, which increases toxic load, which creates epigenetic changes that perpetuate the cycle.
Masking stress acts as an accelerant in this cascade. Every performed social interaction, every suppressed authentic response, every moment of hypervigilant behavioral monitoring adds stress to systems that are already compromised. The metabolic cost compounds over decades, creating the profound exhaustion and mysterious health issues that define so many late-diagnosed women's experiences.
The Lived Biological Reality
The profound exhaustion you feel isn’t complacency, laziness, or poor stress management; it’s the biological cost of forcing a complex, sensitive system to operate outside its natural parameters for decades. Your body has performed a metabolically expensive routine while battling environmental toxins, navigating hormonal fluctuations, enduring chronic inflammation, and carrying genetic vulnerabilities that research has largely ignored until now.
Acknowledging this complex biological architecture won’t instantly undo the damage, but it equips you with a framework to work with your neurodivergent biology instead of against it. The first step toward authentic healing is recognizing your struggles have measurable, biological roots - and honoring your neurodivergent biology instead of forcing it into rigid, neurotypical molds.
Key References:
Sorboni, S. G., Moghaddam, H. S., Jafarzadeh-Esfehani, R., & Soleimanpour, S. (2022). A Comprehensive Review on the Role of the Gut Microbiome in Human Neurological Disorders. Clin Microbiol Rev, 35(1), e00338-20.
Autism: oxidative stress, inflammation, and immune abnormalities. (2010). Boca Raton: Taylor & Francis.
Ruiz-Pozo, V. A., Tamayo-Trujillo, R., Cadena-Ullauri, S., Frias-Toral, E., Guevara-Ramírez, P., Paz-Cruz, E., Chapela, S., Montalván, M., Morales-López, T., Simancas-Racines, D., & Alzamora-Rodríguez, A. K. (2025). Mechanistic Links Between Gut Dysbiosis, Insulin Resistance, and Autism Spectrum Disorder. Int. J. Mol. Sci., 26(14), 650313.
Puricelli, C., Rolla, R., Gigliotti, L., Boggio, E., Beltrami, E., Dianzani, U., & Keller, R. (2022). The Gut-Brain-Immune Axis in Autism Spectrum Disorders: A State-of-Art Report. Front Psychiatry, 12, 755171.
Pall, M. L. (2024). Central Causation of Autism/ASDs via Excessive [Ca2+]i Impacting Six Mechanisms Controlling Synaptogenesis during the Perinatal Period: The Role of Electromagnetic Fields and Chemicals and the NO/ONOO(−) Cycle, as Well as Specific Mutations. Brain Sciences, 14(4), 454.
Wong, G. C., Montgomery, J. M., & Taylor, M. W. (2021). The Gut-Microbiota-Brain Axis in Autism Spectrum Disorder. In Grabrucker, A. M. (Ed.), Autism Spectrum Disorders. Exon Publications.
"Hormonal Fluctuations Exert Outsized Influence on ADHD Symptoms: New ADDitude Survey". (2024). ADDitude Magazine.
Adams, J. B., Sorenson, J. C., Kirby, J. K., & Audhya, T. (2021). Evidence-Based Recommendations for an Optimal Prenatal Supplement for Women in the U.S., Part Two: Minerals. Nutrients, 13(6), 1849.
McWilliams, S., Singh, I., Leung, W., Stockler, S., & Ipsiroglu, O. S. (2022). Iron deficiency and common neurodevelopmental disorders—A scoping review. PLoS One, 17(9), e0273819.
Woeller, K. N. (2025). Autism and Toxic Microbial Organic Acids - The Compounds Every Practitioner Should Know About and Why. Dr. Woeller Substack.
Katiraei, P. (2025). The Role of Dampness and Mold in The Onset of Autism. Pejman’s Substack.
Woeller, K. N. (2024). Autism, Food Sensitivity, and Gastrointestinal Candidiasis. Dr. Woeller Substack.
Krakowiak, P., Walker, C. K., & Hertz-Picciotto, I. (2021). Prenatal and Perinatal Metabolic Risk Factors for Autism: A Review and Integration of Findings from Population Based Studies. Curr Opin Psychiatry, 34(2), 94–104.
Skogheim, T. S., et al. (2021). Prenatal exposure to toxic metals and essential elements and association with ADHD and ASD: a population-based prospective study. Environment International, 152, 106468.
Abdallah, M. W., et al. (2012a). Neonatal levels of cytokines and risk of autism spectrum disorders: an exploratory register-based historic birth cohort study utilizing the Danish Newborn Screening Biobank. J Neuroimmunol, 252(1-2), 75-82.
Adams, J. M., et al. (2015). Maternal dietary methanol during pregnancy was a factor in the etiology of autism spectrum disorders. Medical Hypotheses, 85(6), 849-854.
Frye, R. E., Cakir, J., Rose, S., Delhey, L., Bennuri, S. C., Tippett, M., et al. (2021a). Prenatal air pollution influences neurodevelopment and behavior in autism spectrum disorder by modulating mitochondrial physiology. Mol. Psychiatry, 26, 1561-1577.
Brady, M. J., Jenkins, C. A., Gamble-Turner, J. M., Moseley, R. L., Janse van Rensburg, M., & Matthews, R. J. (2024). “A perfect storm”: Autistic experiences of menopause and midlife. Autism.
McMahon, K., et al. (2025). Maternal pre- and perinatal depression and the risk of autism spectrum disorders in offspring. Cambridge University Press.
Skalny, A.V., Mazaletskaya, A.L., Ajsuvakova, O.P., Bjørklund, G., Skalnaya, M.G., Chao, J.C.J., Tinkov, A.A. (2020). Serum zinc, copper, zinc-to-copper ratio, and other essential elements and minerals in children with attention deficit/hyperactivity disorder (ADHD). J. Trace Elem. Med. Biol., 58, 126445.