Neurodiversity: The Role of Genetics

Neurodiversity is a concept that recognises and embraces the variety of ways the brain can function and process information. It celebrates neurological differences, such as autism, ADHD, dyslexia and other cognitive variations, as part of human diversity rather than viewing them as disorders. Genetic factors play a critical role in shaping the brain's development and function, and understanding the genetic basis of neurodiversity can offer valuable insights into individual strengths, challenges and potential interventions. This article explores key genes that influence neurological development and cognitive functions. Understanding these genes can empower individuals and their loved ones to make informed choices about their health, optimise brain function and explore personalised strategies for support in terms of nutrition, lifestyle and supplementation, which can quite literally be life changing for some individuals.

The Genetic Foundation of Neurodiversity

Genetics significantly influence brain structure, cognitive abilities, behavior and neurological development, conditions and decline. While genetics is not the sole determinant, it provides a foundational framework for how the brain develops and functions over time, as well as predispositions to states (such as oxidative stress and inflammation), decline and chronic disease that can impact the brain. Genes related to neurotransmitter regulation, neural plasticity and cognitive processing can impact how individuals think, learn and interact with the world. Key neurotransmitter systems, such as serotonin, dopamine and GABA, are regulated by specific genes. These systems influence mood, focus, sleep and stress responses, and genetic variants within these pathways can contribute to neurodiverse traits. Below is a breakdown of critical genes associated with each system:

1. Serotonin: Emotional Regulation and Sensory Processing

Serotonin plays a crucial role in mood stability, emotional resilience and sensory processing, often affected in neurodiverse individuals. Variants in the following genes can contribute to serotonin imbalances:

● ALDH2: Impacts serotonin metabolism, potentially influencing mood and sensitivity to environmental stressors.

● HTR1A & HTR2A: Affect serotonin receptor function, influencing emotional processing and sensory sensitivity. These genes are often studied in autism and anxiety. In particular, variants in HTR2A are linked to reduced receptor expression and function, implicated in ASD-related core symptoms like social interaction and repetitive behaviors.

● MAOA: Known as the "warrior gene", variants influence serotonin breakdown, linked to impulsivity, aggression and mood swings, which are traits often seen in ADHD. They can also impact mood regulation and susceptibility to environmental stress.

● MTHFR: Impacts folate metabolism and levels of circulating folate, which is essential for producing serotonin. Variants can exacerbate mood disorders common in neurodiverse populations.

● SLC18A1: Regulates serotonin storage and release, affecting signalling efficiency.

● VDR: Modulates serotonin synthesis via vitamin D, with implications for mood regulation and cognitive development.

● TPH1 & TPH2: Critical for serotonin production, disruptions may contribute to heightened anxiety or depression, often seen in neurodiverse conditions.

2. Kynurenic Acid: Immune Function and Cognitive Flexibility

The kynurenine pathway, which connects immune activity to neurotransmitter function, plays a key role in neurodiversity by influencing neuroinflammation (inflammation of the brain) and cognitive processing. Central to tryptophan metabolism, this pathway produces metabolites like kynurenic acid (KYNA) and quinolinic acid (QUIN) that regulate brain activity. Disruptions, often linked to mitochondrial dysfunction, can lead to oxidative stress and excitotoxicity, which can exacerbate neurodiverse traits and behaviours. Genes involved:

● FKBP5: Modulates stress responses, variants may exacerbate anxiety or PTSD, conditions often comorbid with neurodiverse traits.

● IFNG (Interferon-Gamma): Influences immune-driven neuroinflammation which can impact focus and cognition in ADHD and autism.

● TNF (Tumor Necrosis Factor-alpha): Influences inflammation which can impact neuroinflammation and sensory sensitivities.

3. Melatonin: Sleep and Circadian Rhythms

Sleep challenges are common in neurodiverse individuals, from difficulty falling asleep to maintaining regular circadian rhythm (inner body clock). Sleep is essential for brain health, supporting emotional regulation, cognitive function and neural repair, meaning circadian disruption can exacerbate symptoms of neurodiversity. Genes involved:

● ASMT: Mutations reduce melatonin synthesis, leading to disrupted sleep-wake transitions and circadian rhythm disturbances.

● MTNR1B: Variants affect melatonin receptor function, impairing the brain’s ability to regulate circadian rhythms and respond to melatonin. 4. Dopamine: Focus, Motivation and Reward Sensitivity Dopamine is central to executive function, reward processing and emotional regulation, areas often impacted in ADHD, autism and related conditions. Genes involved:

● ALDH2: Impacts dopamine metabolism which can affect energy levels and motivation.

● COMT: Plays a key role in regulating dopamine clearance in the prefrontal cortex, influencing traits such as focus, emotional flexibility and stress resilience. Genetic variants can worsen ADHD-like symptoms and increase stress sensitivity. Additionally, COMT's interaction with other dopamine-related genes, like TH and SLC6A3, highlights the importance of dopamine metabolism in attention and executive function, both of which are crucial in understanding ADHD and ASD profiles.

● DRD2: The dopamine receptor gene DRD2 influences reward sensitivity, impulse control and motivation. Variations in DRD2 are linked to repetitive behaviors (such as hand-flapping or rigid routines) and contribute to motor and reward system dysregulation, common in ADHD and autism.

● MAOB & MAOA: Influence dopamine breakdown; variants can lead to mood instability or hyperactivity.

● MTHFR: Supports dopamine synthesis, deficiencies can exacerbate focus and motivation challenges.

● OPRM1: Linked to reward processing, impacting motivation and emotional sensitivity.

● SLC6A3: Dopamine transporter gene affecting reuptake, critical in ADHD-related focus and reward challenges.

● TH: Essential for dopamine production, variants can disrupt reward-seeking behavior or focus.

● VDR: Modulates dopamine synthesis via vitamin D, supporting cognitive and emotional stability.

5. Adrenergic: Stress Response and Attention

The adrenergic system drives the fight-or-flight response, closely linked to stress reactivity and attention regulation, both significant in neurodiverse individuals. The following genes are involved:

● ADRB2: Affects receptor sensitivity to adrenaline, influencing stress responses and energy regulation.

● COMT: Impacts adrenaline breakdown, shaping focus and anxiety levels.

● DBH: Converts dopamine to norepinephrine, variants may heighten stress responses and impact concentration.

● MAOA: Regulates norepinephrine breakdown, influencing hyperactivity or aggression.

● PNMT: Involved in adrenaline synthesis, linked to heightened stress reactivity.

● SLC6A2: A norepinephrine transporter critical for reuptake and maintaining focus.

● SLC18A1: Regulates storage and release of adrenaline and norepinephrine, impacting stress resilience.

6. GABA: Relaxation and Sensory Overload

GABA calms the brain and reduces overstimulation, a key challenge in neurodiversity, particularly autism and anxiety:

● ALPL: Impacts vitamin B6 metabolism, essential for GABA synthesis.

● GAD1 & GAD2: These genes encode enzymes critical for converting glutamate to GABA, the brain's primary inhibitory neurotransmitter. Disruptions can heighten sensory overload, anxiety and hyperexcitability in neural circuits, commonly seen in ASD. Age-related declines in GAD expression exacerbate this imbalance, increasing susceptibility to neuroinflammation and cognitive decline over time.

● GABRA2: Encodes GABA receptor subunits, shaping neuronal responses to GABA.

7. Cannabinoid: Sensory Integration and Emotional Balance

The endocannabinoid system regulates sensory perception, mood and neuroprotection, areas often dysregulated in neurodiverse individuals:

● CNR1: Encodes cannabinoid receptors, influencing stress tolerance and sensory integration. Additionally, CNR1 variants have been associated with more serious psychiatric conditions such as schizophrenia and bipolar disorder, as well as with an increased risk of addiction.

● TRPV1: Linked to sensory perception and pain modulation, often heightened in neurodiverse populations. TRPV1 plays a role in regulating oxidative stress and neuroinflammation in the brain, suggesting its involvement in both sensory processing and broader neurophysiological processes relevant to neurodiversity.

● FAAH: Breaks down endocannabinoids; variants can impact emotional regulation and sensory sensitivity. FAAH activity is linked to neuroinflammatory regulation, with alterations influencing stress resilience and depressive-like behaviors, highlighting its role in modulating the emotional and neuroinflammatory responses relevant to neurodiversity.

Our Nervous System Report analyses these key genes associated with neurodiverse traits and other mental health imbalances, providing personalised insights to tailor dietary, lifestyle and supplement protocols. These strategies can improve behaviour, learning capacity, social experiences and overall quality of life.

Key Takeaways

Genetic testing offers actionable insights to better support neurodivergent individuals by identifying challenges like focus or sensory sensitivities and highlighting strengths. For children, it can improve behaviour, learning and social experiences. By understanding the genetic underpinnings of conditions like ADHD or autism, families can reduce trial-and-error in treatments, optimise brain health and enhance daily routines. For individuals of all ages, this information can be life-changing, empowering informed choices and self-compassion and unlocking opportunities for a more fulfilling and balanced life. Order our Nervous System Report here.

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