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The Neuroconnective Phenotype

What Is the Neuroconnective Phenotype?

The concept of the Neuroconnective phenotype comes mainly from research by Eccles and colleagues as well as Casanova and colleagues studying hypermobility, interoception, and neurodevelopment.

Their work suggests that connective tissue variants may influence brain development and body-brain signaling, producing a combined pattern of neurological and physical traits.

Evidence includes:

  • higher rates of joint hypermobility in autism and ADHD

  • shared features such as sensory sensitivity, motor differences, and autonomic dysfunction

This led researchers to hypothesize a neuroconnective phenotype.

What Are the Core Components of the Neuroconnective Phenotype?

Studies commonly describe four clusters of traits:

1. Neurodevelopmental Differences

Examples:

  • autism

  • ADHD

  • dyspraxia / motor coordination disorder

  • sensory processing differences

These conditions frequently appear in people with hypermobility.

3. Autonomic Nervous System Dysfunction

Common findings:

  • POTS (postural orthostatic tachycardia syndrome)

  • orthostatic intolerance

  • dizziness

  • heart-rate variability abnormalities

  • fatigue

These symptoms are also overrepresented in people with hypermobility and neurodevelopmental conditions.

2. Connective Tissue Variation

Typical signs:

  • generalized joint hypermobility

  • hypermobile Ehlers-Danlos syndrome (hEDS)

  • fragile connective tissue

  • joint instability and chronic pain

Joint hypermobility is significantly more common in neurodivergent populations than in the general population.

4. Sensory & Proprioceptive Differences

Shared features include:

  • sensory hypersensitivity

  • impaired proprioception (body awareness)

  • motor coordination differences

  • altered interoception (awareness of internal body signals)

Autism and hypermobility share these neurological characteristics.

What Are the Clinical Patterns Seen in Neuroconnective Individuals?

Physical

  • hypermobile joints

  • chronic musculoskeletal pain

  • frequent injuries

  • fatigue

Autonomic

  • POTS

  • temperature regulation issues

  • dizziness or fainting

Neurological

  • autism or ADHD traits

  • sensory sensitivities

  • motor coordination differences

Other Common Comorbidities

  • migraines

  • gastrointestinal dysmotility

  • mast-cell activation

How Might These Traits & Conditions Be Linked?

1. Connective tissue isn't only in your joints, it's also in the nervous system.

It affects:

  • blood vessels

  • the meninges (brain coverings)

  • extracellular matrix in the brain

Differences in connective tissue could influence neural development and signaling.

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2. Hypermobility is associated with heightened interoceptive signals (body sensations like heartbeat). Researchers propose that altered body-brain feedback could contribute to:

  • anxiety

  • sensory overload

  • emotional processing differences

 

3. Shared genetic and immune factors:

  • immune regulation

  • collagen or extracellular matrix genes

  • epigenetic regulation

Although, no single gene explains the overlap, research from Petrucci-Nelson and colleagues points to possible genetic links.

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What is Neurodivergence?

Neurodivergence refers to natural variations in how a person’s brain develops and functions, leading to differences in cognition, perception, behavior, and sensory processing compared to what is considered “typical.”

It is an umbrella term that includes conditions such as autism, ADHD, dyslexia, dyspraxia, and others. Rather than framing these differences as deficits, neurodivergence emphasizes that they are part of normal human diversity, with distinct strengths as well as challenges.

Neurodivergence can affect areas such as:

  • Attention and executive functioning

  • Sensory processing and perception

  • Communication and social interaction

  • Learning styles and information processing

Importantly, neurodivergence often interacts with the body as well as the brain, influencing factors like sensory sensitivity, motor coordination, and—in some individuals—conditions such as hypermobility, chronic pain, or autonomic regulation differences.

In this framework, the focus shifts from “fixing” individuals to understanding and supporting different neurotypes in ways that improve functioning, well-being, and quality of life.

 

Is there a link between autism/ADHD and hypermobility?

Yes—multiple studies show higher rates of joint hypermobility in autistic and ADHD populations compared to the general population.

The relationship isn’t fully explained yet, but likely involves:

  • Shared genetic pathways (collagen / connective tissue)

  • Nervous system regulation differences

  • Developmental factors (ECM + brain development)

 

Why do so many neurodivergent people have chronic pain?

Several overlapping reasons:

  • Joint instability → micro-injuries

  • Poor proprioception → inefficient movement

  • Central sensitization → amplified pain signals

  • Autonomic dysfunction → fatigue + inflammation

It’s usually not “just one cause”, but a layered system variations leading to chronic pain for neurodivergent individuals.

 

What is the “neuroconnective phenotype”?

A proposed model describing people who have:

  • Neurodivergence (autism/ADHD)

  • Hypermobility or connective tissue differences

  • Dysautonomia (e.g., POTS)

  • Chronic pain and fatigue

Currently, it’s a research framework and not a formal diagnosis.

 

Why does my body feel unstable or “loose”?

In hypermobility:

  • Ligaments don’t stabilize joints well → muscles must compensate → leads to fatigue, guarding, and pain

Many people describe:

  • “Floating joints”

  • “Falling into positions”

Constant need to brace

 

Why am I both flexible AND stiff?

This is extremely common.

  • Hypermobility = too much passive range

  • Muscles tighten to protect joints → feels like stiffness

So you can be:

  • Very flexible in some directions

  • Extremely tight or restricted in others

 

Why does strength training help more than stretching?

Because the core issue is stability, not flexibility.

Strength training:

  • Improves joint control

  • Reduces micro-injury

  • Enhances proprioception

Stretching alone can sometimes worsen instability, but so can strength training if done incorrectly - it is very important to use adaptive capacity and gradual load tolerance.

 

What is proprioception, and why does it matter here?

Proprioception = your brain’s sense of where your body is.

In hypermobility:

  • Signals from joints are less reliable → brain has to “guess” more

This leads to:

  • Clumsiness

  • Overcorrection

  • Muscle overuse → pain

 

Why do I get exhausted so easily?

Common reasons include:

  • Muscles working overtime to stabilize joints

  • Autonomic dysfunction (POTS, etc.)

  • Poor movement efficiency

  • Chronic pain draining energy

Your body is often doing more work than it should for basic tasks.

 

Is chronic pain in neurodivergence all psychological or anxiety-related?

No—but there is interaction.

  • Hypermobility is a physical connective tissue trait

  • Pain and dysautonomia are physiological

  • Anxiety can co-occur due to:

    • Autonomic differences

    • Interoceptive sensitivity

It’s biological + neurological + experiential, not “just in your head.”

 

Why is hypermobility or chronic pain with neurodivergence often missed or misdiagnosed?

Neurodivergent individuals suffering from hypermobility and chronic pain often get bounced around to various specialties (rheumatology, neurology, psychiatry) treating symptoms but not the underlying issue itself.

  • Hypermobility is often dismissed as benign

  • Chronic pain without clear injury gets minimized

  • Neurodivergence may mask or complicate presentation

So people get labeled with anxiety, Fibromyalgia, or “Unexplained pain” without the full picture being recognized.

2026

Lisa Quadt, Georgia Savage, Rod Bond, Kevin A Davies, Hugo D Critchley, Jessica A Eccles

2022

Jenny L L Csecs, Valeria Iodice, Charlotte L Rae, Alice Brooke, Rebecca Simmons, Lisa Quadt, Georgia K Savage, Nicholas G Dowell, Fenella Prowse, Kristy Themelis, Christopher J Mathias, Hugo D Critchley, Jessica A Eccles 

2020

Emily L Casanova, Carolina Baeza-Velasco, Caroline B Buchanan, Manuel F Casanova

2017

Raoul H H Engelbert, Birgit Juul-Kristensen, Verity Pacey, Inge de Wandele, Sandy Smeenk, Nicoleta Woinarosky, Stephanie Sabo, Mark C Scheper, Leslie Russek, Jane V Simmonds

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