The Plasticity Paradox: How Our Inherited Adaptability Shapes Neurodivergence

For decades, neurodivergence—particularly autism and ADHD—has been framed as a set of behavioural or cognitive differences, often examined through psychological or psychiatric lenses. However, emerging insights into genetic plasticity and the reactive HPA axis suggest a more complex, biological underpinning.

This isn’t just about an overactive or underactive HPA axis—it’s about a reactive stress system that responds differently due to an underlying genetic plasticity that is passed down through generations. This inherited trait sets the stage for differences not only in the brain but throughout the body, influencing everything from joint flexibility to hormone regulation.

How I Stumbled Upon the Connection

I first noticed a pattern when I was reading about how synaptic plasticity can lead to neurological differences. In that moment of clarity, it hit me—if the brain’s adaptability could shape cognition and behaviour, why wouldn’t the same principle apply to our joints? I began to see hypermobility as not merely a physical quirk, but as a visible expression of the same genetic plasticity that also influences neurodivergence. Once I saw that connection, I couldn’t unsee it, and it’s been a driving force behind my research ever since.

Genetic Plasticity: The Inherited Regulator

Plasticity is the body’s ability to change, adapt, and reshape itself—whether in the brain, the joints, or the nervous system. Importantly, this plasticity is not randomly acquired; it is genetically inherited. Key genes such as BDNF (Brain-Derived Neurotrophic Factor) and GRM5 (Glutamate Metabotropic Receptor 5) determine the brain’s capacity for growth, synapse formation, and adaptability. Similarly, variations in collagen genes like COL1A1 or COL5A1 can predispose individuals to hypermobility and other connective tissue traits.

This genetic plasticity forms the common denominator that underpins how our bodies and minds react to internal and external challenges. It’s not merely about how individual systems respond to stimuli—it’s a trait passed down from generation to generation that predisposes individuals to a spectrum of outcomes: from neurodivergence to connective tissue differences.

The Reactive HPA Axis: A Unique Stress Response and Hormonal Instability

Rather than being inherently dysfunctional, the HPA axis in neurodivergent individuals appears to be more reactive—responding with exaggerated or prolonged stress reactions. This heightened reactivity ties directly into the inherited plasticity:

• Instead of a steady hormonal baseline, individuals may experience extreme fluctuations in cortisol, adrenaline, and other key regulators.

• This can lead to sensory overload, emotional dysregulation, and a cycle of hyperactivity followed by burnout.

• The reactive nature of the HPA axis is a biological attempt to maintain homeostasis, though the inherited plasticity means that this system is more vulnerable to external stressors.

The Plasticity Paradox: More Isn’t Always Better

Too much inherited plasticity can be as problematic as too little.

• In the brain, excessive plasticity might contribute to conditions like ADHD and autism, with rapid cognitive shifts and sensory hypersensitivity.

• In the body, it can manifest as hypermobility—where joints are overly flexible yet lack stability.

• And when the HPA axis is overreactive, it can result in chronic hormonal imbalances that affect both mental and physical health.

This paradox challenges us to reconsider neurodivergence not as isolated disorders, but as different expressions of the same underlying genetic trait—a trait that governs our capacity for change, adaptation, and ultimately, our resilience.

What Comes Next?

If we’re right about this, it changes everything. Instead of treating neurodivergence, hypermobility, and stress dysfunction as separate issues, we might begin to identify a shared biological marker—one that helps us understand, diagnose, and support those whose inherited plasticity makes them uniquely adaptable, yet also vulnerable.

In future posts, we’ll dive deeper into:

1. The Genetics of Plasticity: Exploring key markers like BDNF, GRM5, and collagen genes.

2. How the Reactive HPA Axis Drives Hormonal Instability: Linking stress responses to behavioural and physical outcomes.

3. Implications for Diagnosis and Treatment: How understanding this inherited plasticity might pave the way for personalised support.

I invite you to join me in rethinking neurodivergence as not a set of isolated symptoms but as a window into our evolutionary design—a design where adaptability can be both our greatest strength and our greatest challenge.

If plasticity is the key to our greatest strengths and struggles, how do we learn to regulate it?

Further Reading & References

• Sale, A., Berardi, N., & Maffei, L. (2009). Enrich the environment to empower the brain. Trends in Neurosciences, 32(4), 233–239. https://doi.org/10.1016/j.tins.2008.12.004

• Ismail, F. Y., Fatemi, A., & Johnston, M. V. (2017). Cerebral plasticity: Windows of opportunity in the developing brain. European Journal of Paediatric Neurology, 21(1), 23–48. https://doi.org/10.1016/j.ejpn.2016.07.007

• Notaras, M., & van den Buuse, M. (2019). Neurobiology of BDNF in fear memory, sensitivity to stress, and stress-related disorders. Molecular Psychiatry, 24(10), 1225–1244. https://doi.org/10.1038/s41380-019-0639-2

• Csecs, J., Ludwig, N. N., Rauch, A. V., & Engelbert, R. H. H. (2022). Joint hypermobility links neurodivergence to dysautonomia and pain. Frontiers in Psychiatry, 13, 884715. https://doi.org/10.3389/fpsyt.2022.884715

• Zorn, J. V., Schür, R. R., Boks, M. P., et al. (2017). Cortisol stress reactivity across psychiatric disorders: A systematic review and meta-analysis. Psychoneuroendocrinology, 77, 25–36. https://doi.org/10.1016/j.psyneuen.2016.11.036

• Malfait, F., Wenstrup, R. J., & De Paepe, A. (2010). Clinical and genetic aspects of Ehlers-Danlos syndrome, classic type. Genetics in Medicine, 12(10), 597–605. https://doi.org/10.1097/GIM.0b013e3181eed412