Genetic Testing in Psychiatry.

Psychiatric genetic testing provides a wealth of information that can be used to inform treatment options. This reduces the “trial and error" approach to mental health treatment and may reveal some of the root causes of psychiatric illness.

Psychiatric genetic testing provides information about several genes and how they function. Genes are the blueprints for proteins and enzymes that serve several bodily functions. Psychogenomics is the study of specific genes related to mental health. A landmark study revealed that those with genetic testing experienced 40% fewer emergency room visits and 58% fewer inpatient hospitalizations than those in the control group who did not receive genetic testing to help guide their treatment (Perlis et al., 2018).

Genes and Corresponding Impact

Below I will share some of the key findings in psychiatric genetic testing that inform the plan of care. As an emerging field of study, several areas of psychogenomics require further studies to examine the exact nature, effect, and clinical implications of genetic abnormalities. Here I have synthesized the most current evidence basis and related interpretation of clinical application.

Cytochrome P450 (CYP450).

These enzymes are “drug information processing genes” and are used to inform how you metabolize psychiatric medications. These genes encode liver enzymes that are responsible for the breakdown of all drugs. What a psychiatric genetic panel will provide is how your specific cytochrome P450 genes and enzymes interact with many psychiatric medicines. This reveals how fast or slow medications may be metabolized and takes some of the “guesswork” out of which medication may or may not be a good fit for you.

Methylenetetrahydrofolate Reductase (MTHFR).

This gene and the associated enzyme are responsible for the conversion of dietary folic acid into a usable form (L-methylfolate), which is an ingredient required in the manufacturing of major brain chemicals (serotonin, dopamine, norepinephrine). This enzyme has been extensively studied in depression (up to 10-20% of the population with this deficiency). Still, it has also been studied in the context of ADHD, anxiety, bipolar disorder, and schizophrenia (Halaris et al., 2021). Individuals who do not have the genetic abnormality may have reduced enzyme activity if they are on mood stabilizers, antiepileptic drugs, oral contraceptives, antacids, or metformin. If this enzyme has sluggish activity, individuals may benefit from an L-methylfolate supplement. Hypothetically, this enzyme is more effective in combination with other micronutrients and vitamins such as B-complex, magnesium, iron, vitamin D, and zinc, among others.

Catechol-O-Methyltransferase (COMT).

This is sometimes referred to as the stress response gene. COMT is responsible for breaking down dopamine and norepinephrine. Those with high activity of this enzyme will experience reduced dopamine and norepinephrine. With high activity, individuals may benefit from treatments that reduce this activity to manage the stress response, such as acetyl-l-carnitine, phosphatidyl serine, green tea, or L-theanine. Those with low activity will experience an increase in dopamine and norepinephrine and associated effects and may benefit from options to help boost the activity of this enzyme, such as SAMe, magnesium, folic acid, N-acetyl-cysteine, ashwagandha, and vitamin D.

Brain-Derived Neurotrophic Factor (BDNF).

This enzyme is commonly referred to as “brain fertilizer.” It is upregulated by several treatment modalities, including lifestyle modification (e.g., exercise, sleep), psychotherapeutic techniques (e.g., cognitive restructuring, behavioral activation, et al.), and biologic options (e.g., several psychotropic medications, L-theanine, phosphatidyl serine, and omega-3 fatty acids, among others).

Serotonin Transporter Gene (SLC6A4).

This is the serotonin pump gene. This gene informs the likelihood of serotonergic drug response (i.e., antidepressants). Abnormalities of this gene correspond with a likelihood of side effects and the effectiveness of these options.

Dopamine-2 Receptor (D2R).

This is the primary dopamine receptor gene. This gene corresponds with the risk of addiction as well as psychosis (hallucinations and delusions) among other psychiatric illnesses. It also helps to predict the responsiveness and tolerance of antipsychotic treatments. Because antipsychotics are used to treat depression and bipolar disorder, abnormalities in this gene may suggest the need for alternative mood stabilizers and antidepressants to treat symptoms or at least antipsychotics with lower dopamine-2 receptor activity.

Serotonin 2C (5HT2C) and Melanocortin 4 (MC4R).

These are metabolic genes that inform the risk of weight gain with certain psychiatric medications. Genetic abnormalities also inform the risk of binge eating, excessive hunger, and greater food-seeking behavior.

Ankyrin-3 (ANK3) and Calcium Channel alpha 1 C (CACNA1C).

These are the mood swing genes and inform treatment. ANK3 codes for sodium ion channels, and CACNA1C codes for calcium ion channels. These channels are typically targets of several mood stabilizers. An understanding of these genes and their activity can inform mood stabilizer options.

Adrenoreceptor Alpha 2A (ADRA2A).

This is the ADHD gene. This gene codes receptors that non-stimulant ADHD medications are designed for. Variants of this gene equate to a reduced responsiveness to non-stimulant medications. One gene variant predicts the responsiveness of methylphenidate-derivative stimulants (e.g., Ritalin, Concerta, Daytrana, etc.).

Opioid Mu Receptor 1 (OPRM1).

This is commonly referred to as the addiction gene. This gene encodes the Mu opioid receptor, which responds to opioid medications as well as endogenous (bodily derived) opioids. This gene influences an individual’s reaction to pleasure and coping with pain. Certain abnormalities here correspond with a greater risk of addiction and the need for higher doses of opioids to achieve the same pain relief.

Glutamate Ionotropic Receptor Kainate subunit 1 (GRIK1).

This is referred to as the alcoholism gene. It encodes an excitatory brain chemical called glutamate, which becomes toxic in high concentrations. Extensive study of this gene is underway, but some studies have revealed that those with a variant of this gene who struggle with alcohol addiction may respond well to topiramate for cravings.

How is the Test Performed?

Typically this testing is performed by cheek swab. A swab is sent to you in the mail (or used in the office) to swab each side of the cheeks inside your mouth for a saliva sample. No pain, no blood work! This sample is then sent in to conduct the testing. Typically results are in within 1-2 weeks.

What is the Cost of Genetic Testing?

Most major insurance companies cover the cost of genetic testing! This is especially true if you have historically tried at least a few treatment options for the symptoms you are experiencing. Coverage may vary depending on your condition. With most psychogenic companies, you will often be notified before running the test if insurance does not cover the cost to ensure you want to move forward with testing.

References.

Halaris, A., Sohl, E., & Whitham, E. A. (2021). Treatment-Resistant Depression Revisited: A Glimmer of Hope. Journal of personalized medicine, 11(2), 155. https://doi.org/10.3390/jpm11020155

Perlis, R. H., Mehta, R., Edwards, A. M., Tiwari, A., Imbens, G. W. (2018). Pharmacogenetic testing among patients with mood and anxiety disorders is associated with decreased utilization and cost: A propensity-score matched study. Depression and Anxiety, 35(10), 946-952.