Genetic variations that affect the metabolism, receptor binding and neuronal activation associated with the neurotransmitters Dopamine, Adrenaline, Noradrenaline, and Serotonin. A functional variant affecting the production of Brain Derived Neurotrophic Factor (BDNF), a critical protein in the brain that impacts neuronal plasticity and health, is also evaluated.
1. Changes in neurotransmitter metabolism and binding
2. Tendency toward reward and pleasure seeking behavior
3. Propensity to develop addictive, depressive, binge and/or manic behaviors
4. Ability to deal with emotive memories as well as process real time emotive events Increased risk for poor post-concussion recovery
Genes and SNPs
1. COMT rs4680
2. Dopamine Receptor D2 (DRD2) rs1800497
3. Alpha-2 Adrenergic Receptor (ADRA2B) Indel rs28365031, rs29000568, rs4066772.
4. 5-Hydroxytryptamine Transporter (5-HTTLPR) Indel rs25531, rs25532; the minor allele (G) of rs25531
5. Brain-derived Neurotrophic Factor (BDNF) rs6265
Gene: COMT
SNP: rs4680
Catechol-O-methyltransferase (COMT) is an important Phase II metabolism enzyme. Specifically, it is responsible for metabolizing/inactivating catechol neurotransmtters (such as dopamine, adrenaline and noradrenaline) via methylation.
The COMT enzyme is encoded by the COMT gene. In the brain, COMT metabolizes/inactivates catecholamine neurotransmitters such as dopamine, adrenaline and noradrenaline via methylation. The enzyme uses methyl donor groups provided by S-adenosylmethionine (SAMe). COMT activity is particularly important in the prefrontal cortex, which is involved with personality, planning, inhibition of behaviors, abstract thinking, emotion, and working (short- term) memory. To function efficiently, the prefrontal cortex requires signalling by the neurotransmitters dopamine and norepinephrine, regulated by the COMT enzyme through inactivation.
Genetic Variation Tested
The COMT gene is located on chromosome 22 at 22q11.21. A G>A SNP (rs4680), corresponding to a Val158Met amino acid substitution, has been well studied and shown to affect the kinetics of the encoded COMT enzyme.
Implications of the Genetic Variation
The COMT gene is located on chromosome 22 at 22q11.21. A G>A SNP (rs4680), corresponding to a Val158Met amino acid substitution, has been well studied and shown to affect the kinetics of the encoded COMT enzyme.
G Genotypes
1. Have increased COMT activity and lower prefrontal extracellular (synaptic) dopamine compared to A
genotypes
2. Exhibit reduced dopamine half-life when compared to A/A genotypes. This e ect is greatest in the G/G genotype
3. Associated with shortened pleasure response due to increased rate of dopamine clearance. This e ect is greatest in the G/G genotype
4. Associated with an advantage in processing aversive s muli (warrior strategy). Under condi ons of increased dopamine and noradrenaline release (e.g., stress), G genotypes may have improved dopaminergic/adrenergic transmission and be er performance
5. Some studies suggest that the G/G genotype tends to be more prone to schizophrenic behaviour if cannabis in used early life
A Genotypes
1. Have decreased COMT activity and increased extracellular (synaptic) dopamine compared to G genotypes
2. Exhibit increased dopamine half-life when compared to G/G genotypes. This effect is greatest in the A/ A genotype
3. Associated with an advantage in memory and attention tasks (worrier strategy)
4. Associated with lengthened pleasure response due to decreased rate of dopamine clearance. This effect is greatest in the A/A genotype
5. Associated with anxiety and impaired fear inhibition response commonly found in PTSD
6. The A/A genotype tends to be more prone to obsessive/compulsive disorder (OCD) in males but less so in females
Gene: Dopamine Receptor D2 (DRD2)
SNP: rs1800497
Dopamine receptor D2 is one of the most important dopamine receptors and is responsible for dopamine binding to the post-synaptic neuron. Binding stimulates the dopaminergic pathway, establishes the experience of pleasure, and is important in reward-motivated behavior.
The DRD2 receptor is encoded by the DRD2 gene. Substantial evidence suggests that lower DRD2 expression in the striatum of the brain, with concomitant reduced post-synaptic dopamine binding and pleasure response (satisfaction), increases the risk for substance abuse and obesity.
Genetic Variation Tested
The DRD2 gene (and its neighboring ANKK1 gene) is located on chromosome 11 at 11q23. A G>A SNP (rs1800497) within exon 8 of the ANKK1 gene (also known as the Taq1A RFLP) has been well studied and shown to affect the expression of DRD2 on post-synaptic neurons.
Implications of the Genetic Variations
The A (DRD2*A1) allele is associated with significantly lower DRD2 gene expression and decreased dopamine receptor density on post-synaptic neurons, when compared to the G (DRD2*A2) allele.