Biochemical and Hemispheric Imbalances in Autism: Bridging Brain, Body, and Behaviour.

Autism Spectrum Disorder (ASD) is not one condition but a constellation of neurodevelopmental differences arising from multiple interacting systems — genetic, biochemical, immunological, and neurological. It represents not a single “defect,” but a unique pattern of functional disconnection between the brain’s hemispheres and body systems.

The work of Dr Robert Melillo and Professor Gerry Leisman has profoundly expanded our understanding of autism beyond behaviour, introducing the concept of Functional Disconnection Syndrome — a state in which one hemisphere of the brain develops or activates out of sync with the other. This imbalance affects timing, coordination, sensory processing, language, emotion, and social engagement. When the two hemispheres fail to communicate effectively, the brain’s internal “conversation” becomes fragmented — much like two musicians playing the same song, but one slightly out of rhythm.

From a functional medicine perspective, this hemispheric desynchronisation doesn’t occur in isolation. The brain’s structure and connectivity are built upon a biochemical foundation — neurotransmitters, mitochondrial energy, immune regulation, and nutritional status all influence how neurons grow, connect, and communicate.

Inflammation, oxidative stress, impaired methylation, and altered neurotransmitter activity can shift the developmental tempo of one hemisphere relative to the other, amplifying the gap between them.

In early childhood, the right hemisphere typically dominates, guiding attachment, sensory processing, and emotional regulation, while the left hemisphere gradually assumes leadership from around three to six years, refining language, logic, and social cognition. When this transition is disrupted — by retained primitive reflexes, mitochondrial inefficiency, immune activation, or nutritional insufficiency — hemispheric growth becomes uneven. The result is a brain that’s working hard, but not always in harmony: a functional imbalance underpinned by biochemical disharmony.

Understanding autism through both these lenses — biochemical and hemispheric — allows practitioners to approach assessment and treatment with greater precision. Correcting biochemical imbalances supports the physical integrity of neurons and synapses, while hemispheric-based therapies restore synchrony between the right and left brain. In combination, they move us closer to the ultimate goal: helping each child’s brain and body reconnect, communicate, and thrive.

Hemispheric Development and Child Neurobiology

The human brain develops in a carefully choreographed sequence, guided by both genetic programming and environmental experience. During the first three years of life, the right hemisphere leads development — specialising in sensory integration, nonverbal communication, emotional bonding, and spatial awareness. It forms the foundation for attachment and regulation, allowing a child to feel safe in the world. Between roughly three and six years of age, the left hemisphere assumes dominance, refining language, sequencing, logic, and analytical thinking.

Dr Robert Melillo and Prof Gerry Leisman describe this process as a hemispheric relay, where dominance shifts from right to left much like a baton passed in a relay race. Each hemisphere must mature at the correct time and intensity for optimal synchrony. When one hemisphere develops more slowly—or is biochemically hindered by inflammation, oxidative stress, or mitochondrial inefficiency—the relay becomes mistimed. One side of the brain “runs ahead,” while the other struggles to keep pace. The result is a Functional Disconnection Syndrome, where communication between hemispheres becomes inefficient or incomplete.

Movement, Sensory Input, and Primitive Reflexes

Melillo and Leisman emphasise that movement drives brain development. Each wriggle, roll, and reach provides sensory feedback that sculpts neural circuits and strengthens interhemispheric communication through the corpus callosum. Primitive reflexes—automatic movements present at birth—are meant to integrate as higher cortical control emerges. When these reflexes persist, they continually send immature signals into the nervous system, preventing higher brain regions from coordinating smoothly.

In this sense, retained primitive reflexes are neurological echoes of incomplete development. For example, an unintegrated Moro reflex can keep a child in a constant state of physiological alarm, reinforcing right-hemisphere overactivity and sympathetic dominance. Likewise, a retained asymmetrical tonic neck reflex (ATNR) can interfere with midline crossing, handwriting, and reading—skills dependent on left-hemisphere activation and interhemispheric integration.

How Biochemistry Shapes Brain Timing

Biochemical balance provides the fuel, structure, and messaging system for this hemispheric growth. When mitochondrial energy production falters, neurons in high-demand regions may “brown out” during critical developmental windows. When inflammation or histamine overactivation persist, microglia—the brain’s immune cells—remain in an activated state, pruning connections too aggressively or failing to prune enough.

Similarly, neurotransmitter imbalances (such as excessive glutamate or reduced GABA signalling) disturb the brain’s internal rhythm. The right hemisphere, typically more sensitive to emotional and sensory input, can become overexcited and reactive. Meanwhile, inadequate left-hemisphere maturation can manifest as language delays, poor sequencing, and reduced social reciprocity. The result is not global brain damage, but asymmetrical development — a brain that is bright and active, yet unevenly wired.

(Analogy: The developing brain is like a duet between two instruments. When tuned and timed correctly, they create harmony; but if one is slightly out of tune or off-tempo due to biochemical interference, the melody of development becomes disjointed.)

Neuroplasticity and the Window for Correction

Fortunately, the brain’s capacity for neuroplasticity means this imbalance is modifiable. Melillo and Leisman’s research demonstrates that targeted sensory–motor stimulation can strengthen the underactive hemisphere and restore timing between neural networks. When paired with nutritional and biochemical interventions that enhance mitochondrial function, reduce neuroinflammation, and balance neurotransmitters, the effects are synergistic.

Correcting hemispheric imbalance is therefore not solely a matter of therapy or supplements—it is a process of re-synchronising biology and experience so the brain can resume its natural developmental rhythm.

Biochemical Imbalances in Autism

The biochemical landscape of autism is complex, influencing and being influenced by the developing brain. Every neurotransmitter, antioxidant, immune molecule, and nutrient contributes to how neurons fire, connect, and communicate between hemispheres. When these biochemical systems are imbalanced, the synchrony of neural timing — the “metronome” of the brain — can drift off-beat.

The sections below outline key biochemical pathways involved in autism, and how each can alter hemispheric balance and developmental timing.

1. Neurotransmitter Imbalances

Neurotransmitters act as the language of the brain. They determine how efficiently one neuron speaks to the next — and whether the conversation is excitatory, inhibitory, or harmonious. When neurotransmitters are out of balance, one hemisphere can become overactive, while the other remains underdeveloped or poorly connected.

Serotonin Dysregulation

Research has consistently shown elevated whole-blood serotonin levels in many individuals with autism. Serotonin modulates mood, social behaviour, and sensory perception. Excess serotonin in peripheral tissues, or altered serotonin receptor sensitivity in the brain, can affect emotional regulation and adaptive social engagement — skills largely mediated by right-hemisphere processing during early childhood.

Abnormal serotonin signalling may also interfere with hemispheric handover: the gradual transition from right- to left-brain dominance between ages three and six. A “stuck” right hemisphere can perpetuate emotional reactivity, anxiety, and rigidity — mirroring the child’s difficulty moving from sensory–emotional to logical–linguistic processing.

(Analogy: Serotonin functions like a dimmer switch for mood and social sensitivity. When the circuitry is uneven, one side of the brain receives too much light while the other stays in shadow.)

Glutamate and GABA Imbalance

Glutamate is the primary excitatory neurotransmitter; GABA is its inhibitory counterpart. A healthy brain requires a delicate balance between the two, providing both stimulation and restraint. In autism, this balance often tilts toward excitation, producing neural “noise” that disrupts sensory filtering and interhemispheric communication.

The right hemisphere, more attuned to emotion and global processing, is particularly vulnerable to hyperexcitation. Meanwhile, GABA deficits can weaken the brain’s inhibitory control — a function strongly associated with left-hemisphere maturation. The resulting pattern is one of sensory hypersensitivity, anxiety, and poor modulation between hemispheres. Functional MRI and magnetoencephalography studies show that GABAergic dysfunction correlates with abnormal gamma oscillations — the very neural rhythms required for synchronous communication between cortical regions. In short, glutamate–GABA imbalance distorts the timing signals that keep the hemispheres in sync.

Dopamine and Reward Processing

Dopamine shapes motivation, reward learning, and motor control. Alterations in dopamine pathways — particularly within the basal ganglia and prefrontal cortex — are frequently observed in autism. The left hemisphere relies heavily on dopamine-mediated reward feedback for learning language and cause–effect relationships, whereas the right hemisphere governs movement, emotion, and global awareness.

An underactive left-hemisphere dopamine network may manifest as reduced motivation for social interaction or verbal expression, while right-hemisphere underactivation can drive repetitive motor behaviours and rigid routines. This dual imbalance contributes to the characteristic asymmetry in reward perception seen in autism: intense focus on preferred activities, yet limited reward from social reciprocity.

(Analogy: The dopamine system is like the brain’s “yes” button. When one side of the brain keeps pressing it while the other can’t reach it, motivation and balance falter.)

2. Oxidative Stress and Mitochondrial Dysfunction

Mitochondria are the energy factories of neurons — and brain cells are the body’s most energy-hungry. When oxidative stress overwhelms mitochondrial function, neurons fatigue and signal less efficiently. Multiple studies show elevated oxidative markers and reduced antioxidant capacity in autism, especially in regions associated with sensory integration and motor coordination.

The brain’s hemispheres have slightly different metabolic demands: the right hemisphere matures earlier and is highly energy-dependent during infancy, while the left hemisphere’s growth surges in the preschool years. If mitochondrial inefficiency or oxidative stress occurs during these windows, the hemisphere undergoing rapid growth may fall behind, setting the stage for developmental asynchrony.

Low glutathione, impaired methylation, or chronic inflammation further deplete mitochondrial reserves, leaving neurons vulnerable to excitotoxicity and impaired synaptic timing. Functional disconnection may therefore be partly energetic: the hemispheres are trying to communicate, but the cellular “power supply” can’t keep up.

3. Immune System, Inflammation, and Th2 Dominance

Immune dysregulation is one of the most replicated findings in autism research. Elevated pro-inflammatory cytokines, microglial activation, and Th2 dominance create a state of chronic neuroinflammation.

The developing brain is exquisitely sensitive to immune signalling. Cytokines influence synaptic pruning and plasticity — the very processes that sculpt hemispheric balance. When the immune system remains in a pro-inflammatory state, microglia may prune connections excessively in one region while leaving others intact, resulting in uneven cortical maturation.

Maternal immune activation during pregnancy is another key factor. Studies have shown that prenatal inflammation can bias hemispheric development, leading to right–left structural asymmetries detectable even in infancy.

(Analogy: Inflammation is like static on a radio — the music of neural development still plays, but with distortion that makes it harder for the hemispheres to stay in tune.)

4. Histamine, Mast Cells, and Neuroinflammation

Histamine is more than an allergy mediator — it also acts as a neuromodulator influencing wakefulness, attention, and learning. Elevated histamine and mast cell activation have been identified in many children with autism.

When mast cells release histamine, dopamine, and other inflammatory mediators, they signal to nearby microglia, sustaining a feedback loop of neuroinflammation. This chronic activation disproportionately affects subcortical and limbic regions associated with right-hemisphere emotional processing. The result is an over-reactive brainstem and limbic system — the same regions that must quieten for higher cortical control to emerge.

In this way, mast cell activation may lock the brain into a persistent right-hemisphere survival bias, limiting the left hemisphere’s ability to regulate and socialise effectively. Therapeutic approaches that stabilise mast cells and support methylation of histamine can therefore have far-reaching effects on behaviour and attention.

5. Nutrigenomics and Genetic Susceptibilities

Nutrigenomics examines how nutrients interact with genes to influence metabolism and cellular function. In autism, polymorphisms affecting methylation (such as MTHFR, MTRR, COMT, and CBS) can alter neurotransmitter synthesis, detoxification, and redox balance.

• Methylation and Detoxification: Impaired methylation disrupts DNA expression, neurotransmitter metabolism, and myelination — all vital for hemispheric growth and connectivity. Proper supplementation with methylated B vitamins (methylfolate, methylcobalamin, riboflavin) might be helpful to support these pathways, though single-gene testing (e.g., MTHFR alone) is insufficient to capture the full picture and is clinically inadvisable. It is still unknown what the epigenetic effects are from supplementing methyl groups.

• Glutathione and Antioxidant Defence: Glutathione depletion impairs mitochondrial efficiency and leaves neurons vulnerable to oxidative stress. Supporting glutathione directly with liposomal forms should be used as a priority. Attempting to increase glutathione availability through N-acetylcysteine (NAC) may be counterproductive, as NAC can donate the cysteine molecules to produce TGF-B, a cytokine that can promote autoimmune processes. Glycine can also be helpful to help restore redox balance and cellular resilience, as exposure to glyphosate (a particularly prevalent pesticide) can disrupt this portion of glutathione synthesis. Glycine is a common added ingredient in supplements.

• Fatty Acid Metabolism: Omega-3 fatty acids (EPA, DHA) support membrane fluidity, neurotransmission, and anti-inflammatory balance. The brain’s hemispheres, with their differing synaptic densities, rely on adequate lipid composition for signal fidelity. Poor omega-3 status can therefore distort neural signalling and impede hemispheric synchronisation.

• Microbiome and Gut–Brain Axis:The gut microbiota modulates neurotransmitter availability, immune tone, and vagal signalling. Dysbiosis can heighten systemic inflammation and skew neurochemical balance toward excitatory dominance — another factor tipping the scales of hemispheric regulation.

  
  

(Analogy: Genes are the blueprint, but nutrition provides the construction materials. Without the right materials, even the best design can’t become a stable structure — and the hemispheres are built from the same scaffolding.)

Integrating Biochemistry and Connectivity

When viewed through both biochemical and hemispheric lenses, autism appears less like a fixed disorder and more like a dynamic imbalance between systems trying to communicate. Correcting biochemistry restores the foundation; stimulating hemispheric integration builds the bridge. The two processes are inseparable.

Integrating Biochemistry with Functional Connectivity

Functional medicine and developmental neuroscience share a core truth: the brain cannot be treated in isolation from the body, nor the body from the brain. Every neurotransmitter molecule, immune signal, and nutritional substrate influences how neural networks fire and connect. Likewise, every motor movement and sensory experience feeds back to shape biochemical demand and genetic expression.

Dr Robert Melillo and Professor Gerry Leisman’s hemispheric model of neurodevelopment highlights how early sensory–motor experiences drive cortical growth through continuous feedback loops. The functional medicine model complements this by explaining why those loops may fail — due to underlying biochemical obstacles that limit energy, increase inflammation, or distort neurotransmission. When these frameworks are combined, a holistic picture emerges: autism as an integrative systems imbalance, where biochemistry and hemispheric communication continuously influence one another.

(Analogy: You can’t fine-tune an orchestra if half the instruments are out of power. Biochemistry supplies the voltage; neural connectivity performs the symphony.)

Neural Synchrony through Movement and Sensory Stimulation

Hemispheric exercises work by activating the underperforming side of the brain through targeted sensory and motor tasks — balancing timing, proprioception, and vestibular integration. These exercises might include eye-tracking, rhythmic movement, postural control, and primitive reflex integration.

Functional medicine enhances this process by ensuring the biochemical terrain supports plasticity. Nutritional interventions that improve mitochondrial function and reduce oxidative stress make neurons more adaptable; anti-inflammatory nutrients enhance signal fidelity across hemispheres. Together, these approaches transform fragmented signals into coordinated activity.

Both hemispheres — and every biochemical pathway supporting them — are parts of one adaptive system. When we stabilise the biochemical terrain, we create the internal environment for neuroplasticity. When we stimulate the brain through patterned, rhythmic movement, we reinforce those biochemical gains with functional rewiring.

Healing, therefore, is not a linear process but a rhythmic one: each intervention sets the pace for the next, gradually bringing the brain and body back into synchrony.

Functional Medicine Implications and Conclusion

The convergence of biochemical and hemispheric science offers practitioners a more complete understanding of autism — not as a fixed genetic fate, but as a condition of dynamic imbalance between body and brain systems. Each child’s neurodevelopmental trajectory is sculpted by a continuous dialogue between their biochemical environment and neural activity. When that dialogue falters — through inflammation, oxidative stress, mitochondrial dysfunction, or hemispheric desynchrony — symptoms of disconnection appear.

Functional Medicine and developmental neuroscience both recognise that no single intervention restores harmony; rather, healing occurs through synchrony. By addressing the biochemical foundations while supporting hemispheric integration, we engage both the physical and functional layers of neurodevelopment.

1. Restoring the Biochemical Terrain

Optimising the biochemical environment lays the foundation for neural connectivity. Practitioners should consider:

• Reducing oxidative stress

• Supporting mitochondrial function

• Calming immune activation

• Enhancing methylation and detoxification

• Nourishing the microbiome

  
  

When biochemical stability improves, the nervous system gains the resources it needs to reorganise — neurons fire more efficiently, glial cells regulate inflammation more precisely, and the hemispheres can resume their natural developmental dialogue.

2. Reinforcing Neural Connectivity

Biochemistry sets the stage, but experience rewires the brain. Hemispheric-based therapies — sensory–motor programs, vestibular and oculomotor training, primitive reflex integration, rhythm and timing exercises — directly stimulate underactive networks and strengthen interhemispheric communication.

Each sensory input, movement, or reflex integration exercise acts as a pulse of synchrony, driving the maturation of the weaker hemisphere and recalibrating the “neural metronome.” When performed alongside nutritional and metabolic support, these interventions not only enhance function but promote true neuroplastic repair.

(Analogy: It is the difference between watering a seedling and turning toward the sun — both nourishment and stimulation are needed for full growth.)

3. Integrating Body, Brain, and Environment

Environmental medicine also plays a vital role. Reducing toxin exposure, optimising sleep, managing electromagnetic load, and ensuring adequate sunlight and grounding all contribute to calmer neural oscillations and improved parasympathetic tone. Practitioners can empower parents to see these as extensions of the same healing process — creating a physiological environment that communicates safety and coherence to the child’s nervous system.

This systems-based approach reflects the essence of both functional and developmental medicine: that biology, movement, emotion, and environment are inseparable.

4. A Unified Model of Hope

Autism is not simply a behavioural or biochemical condition — it is an expression of how a child’s body and brain adapt to stress, genetics, and environment. When hemispheric balance is restored through targeted stimulation, and when biochemistry is simultaneously supported through functional medicine, children often show profound improvements in attention, emotional regulation, language, and social connection.

This dual approach reminds us that the brain is never static — it is responsive, trainable, and capable of healing when the right conditions are created.The goal is not to change who the child is, but to unlock their full potential by restoring the balance and synchrony their nervous system was designed to have.

(Analogy: The child’s brain already holds the music — our task is simply to retune the instruments and quiet the static so the melody can be heard.)

Conclusion

Autism represents a spectrum not only of behaviour but of biological individuality. Each child’s pattern of biochemical imbalance and hemispheric disconnection is unique — but the underlying principle remains constant: balance begets function.

By integrating the insights of Melillo and Leisman’s hemispheric model with the biochemical precision of Functional Medicine, practitioners can approach autism with deeper understanding and greater effectiveness. When we nourish the cells, calm inflammation, stabilise energy, and synchronise hemispheric activity through movement and sensory integration, we begin to see the extraordinary capacity for growth that lies within every developing brain.

In this model, healing is not about correction — it is about connection.

Amanda Downsborough, BSc, PGDip, GCert, MSc, ACAAM,

Functional & Nutrigenomic Medicine Practitioner

Brain Kids – www.brainkids.com.au

About the Author

Amanda Downsborough, BSc, PGDip, GCert, MSc, ACAAM, is a Functional and Nutrigenomic Medicine Practitioner specialising in autism and child neurodevelopment. Through her practice, Brain Kids, Amanda combines functional medicine, genetics, and neuroscience to uncover the biochemical and environmental factors affecting children’s health. Her work empowers families with science-based strategies to support brain balance, behaviour, and lifelong wellbeing.

Disclaimer

This information is provided for educational purposes only and is not intended as a

substitute for medical advice, diagnosis, or treatment. Always seek the advice of a

qualified healthcare provider with any questions regarding a medical condition or before

making changes to your or your child’s care plan.