Brain & Mental Health Genes

Emerging evidence suggests a strong correlation between several single nucleotide polymorphisms (SNPs) and altered brain biology. SNPs change gene codes slightly, which results in a protein that either has improved or reduced functions, or becomes completely inactive. Therefore, SNPs may play key roles in the development of various pathologies, specifically within the brain tissue, and can greatly affect brain biology and therefore mental health outcomes.

Neurotransmitters in the brain

Under normal conditions, neurotransmitter release is perfectly timed and ensures that the neurotransmitters access and bind correctly to the neurons in the brain. This is a finely tuned process and therefore if an imbalance in the release or uptake of the neurotransmitters exist, conditions such as depression, anxiety, bipolar disorder, and ADHD may develop1. The major neurotransmitters in the brain include:

• Glutamate – the main excitatory neurotransmitter 
• GABA – the inhibitory neurotransmitter.  

The neuromodulators which play an equally important role in maintaining neuronal function include: 

• Dopamine
• Serotonin
• Norepinephrine
• Acetylcholine. 

The concentration of the neurotransmitters, the availability of their associated receptors, as well as the enzymes that degrade these neurotransmitters, work together in an orchestrated fashion to closely regulate mood and behaviour which ultimately govern brain and mental health.

Neurotransmitter Receptors

Research has shown that SNPs in the receptors of these neurotransmitters induce alterations in neuronal signaling and have pathophysiological consequences in most cases. Studies have also highlighted the complexity of the various SNPs in the same protein or receptor, leading to largely different mental outcomes. 

The Dopamine Receptor

Several SNPs of the dopamine receptor gene in the striatum of the brain, for example, produce various risk alleles that are associated with increased dopamine signaling and are associated with the development of schizophrenia 2. A different, unrelated SNP in the gene of the dopamine receptor was found to be associated with the pathogenesis of childhood ADHD in male subjects 3. There is also evidence of SNPs in the dopamine gene promoting obesity, metabolic dysfunction, and cognitive change and show that these SNPs are sensitive to obesogenic eating behavior 4,5. 

The SNPs mentioned above all cause slight changes in the dopamine receptor which dictate the affinity of the receptor to bind efficiently to dopamine. This binding then, in combination with external environmental factors, ultimately determines mental health outcomes/pathologies that are experienced by the individual.

Neurotransmitter Degrading Enzymes

As mentioned previously, the uptake and secretion of neurotransmitters are tightly regulated, and if the specific neurotransmitter in question is not readily degraded, or is degraded too slowly after release, neuronal signaling is disrupted. Studies have found that SNPs in genes that code for enzymes that catabolize (break down) neurotransmitters such as dopamine underlie the pathogenesis of a significant number of mental disorders 6,7, but also induce positive changes in pain perception and memory, depending on the SNP 8. 

Those enzymes responsible for the degradation of serotonin and norepinephrine from neurons are also prone to functional abnormalities due to SNPs, and several studies have demonstrated that SNPs in the gene may confer susceptibility to panic disorder, schizophrenia, depression, and ADHD. Further, low functioning SNPs of the enzyme that degrades serotonin are associated with increased levels of aggression and uniquely correlates with violence.

Neuronal Signaling Molecules 

Biological processes within the brain, such as cell growth, survival, metabolism, memory formation, and synaptic plasticity may also be disrupted by the dysfunction of key signaling molecules associated with these functions. SNPs in the genes encoding these proteins lead to alterations in their intracellular levels, activation and/or inhibition, and their interactions with other molecules. As a result, the SNPs in these susceptible genes have been associated with severe schizophrenia, bipolar disorder, and sporadic Parkinson’s disease.

Apolipoproteins

In the normal brain, apolipoproteins play an important role in the clearance of aged proteins to maintain neuronal functioning. They also inhibit inflammation, and ensure neuronal network signaling occurs properly 9. Research has found that SNPs in these genes cause poorly functioning apolipoproteins that aggregate in the brain tissue and are associated with the development of Alzheimer’s disease 10. The effect of these SNPs on apolipoproteins are so pronounced, that they have been shown to have an impact on other diseases 10 such as:

• Cerebral amyloid angiopathy
• Dementia with Lewy bodies
• Tauopathy
• Cerebrovascular disease
• Multiple sclerosis
• Vascular dementia

Behavioral phenotypes are generally complex and multi-faceted and reflect the action of multiple genes and their association with one another and their environment. There is supportive evidence that certain genes and their SNPs can alter signaling activity within specific neuronal circuits and as a result, influence particular cognitive-affective phenomena. Knowledge of the presence of these SNPs may therefore inform the individual and practitioner to seek personalized options for treatment.