The Importance of Genetic Profiling in the Pharmacological Treatment of Anxiety Disorders

Anxiety is one of the most common psychiatric disorders affecting the population. According to the World Health Organization (WHO), one in 13 people worldwide suffers from anxiety. Although effective treatments for anxiety exist, only a portion of people receive them, and finding the most appropriate option can be a challenging process.

Pharmacogenetics evaluates individual responses based on the analysis of genetic variants most frequently associated with the metabolism of medications used in anxiety treatment, enabling the selection of a more assertive, effective, and safe treatment for the patient. 

What is Anxiety?

Anxiety is characterized by excessive and uncontrollable worry about certain situations, even in the absence of the respective stimuli or in a way that is disproportionate to the presented risk (1). 

Anxiety can also occur alongside depression. According to the Anxiety and Depression Association of America, nearly half of people diagnosed with depression also suffer from anxiety (2). There are several types of anxiety disorders, with the main ones being generalized anxiety disorder, panic disorder, and various phobia-related disorders (3). 

Is Anxiety Genetic?

Anxiety has a strong genetic component, but it cannot be attributed exclusively to heredity. Studies show that certain genetic variants, such as those described in the BDNF gene, can increase the predisposition to anxiety disorders. These variants influence the expression of genes that regulate stress response and anxious behavior, indicating that genetics plays an important role in susceptibility to anxiety (4). 

Heredity, which involves the genetic transmission from parents to children, is not the only determining factor in anxiety. The expression of these genes can be modulated by environmental factors, such as trauma, prolonged stress, and living conditions, which interact with the genetic predisposition to develop or worsen anxiety disorders. This means that although genetics provides a foundation for vulnerability to anxiety, the environment and individual experiences also play a crucial role. 

Therefore, anxiety can be considered both a result of genetic factors and hereditary influences, but its final manifestation arises from a complex interaction between genes and the environment. Recent studies explore this interaction, demonstrating how genetic variations can modulate anxious behavior in different contexts (4). 

What Are the Types of Anxiety and Their Symptoms?

Anxiety disorders comprise a group of psychiatric conditions where anxiety is the predominant and persistent symptom, going beyond the normal and temporary reactions that everyone faces in challenging situations. Differentiating between normal anxiety and an anxiety disorder can be difficult, but it is essential to observe whether the anxious response is prolonged, disproportionate to the stimulus, and interferes with daily life. 

It is important to remember that anxious symptoms can also be present in other psychiatric disorders. For example, anxiety can appear at the onset of a schizophrenic episode or as separation anxiety in a child with major depression. In these cases, anxiety is secondary to another primary disorder. 

Additionally, it is common for a person to present more than one anxiety disorder simultaneously. It is estimated that about half of children with anxiety disorders have more than one coexisting diagnosis. 

There are different types of anxiety disorders, each with its specific characteristics: 

Generalized Anxiety Disorder (GAD)

Individuals with this disorder experience excessive worry on most days for at least six months concerning everyday situations such as health, work, and social interactions. This is the most common anxiety disorder among older adults, although these cases are often linked to traumatic events. 

The most common symptoms of generalized anxiety disorder include: 

• Restlessness, tension, or nervousness
• Fatigue
• Difficulty concentrating
• Irritability
• Muscle tension
• Insomnia

Panic Disorder

Individuals with panic disorder experience recurrent panic attacks. Panic attacks are sudden periods of fear that peak within minutes and can occur unexpectedly or due to a trigger. 

Symptoms during a panic attack include: 

• Tachycardia
• Sweating
• Trembling
• Feelings of shortness of breath, choking, or suffocation
• Feelings of impending danger
• Feelings of being out of control 

People with panic disorder often worry about the possibility of a new attack and actively try to prevent it by avoiding places, situations, or behaviors they associate with the attacks. This constant concern about future panic attacks can lead to the development of agoraphobia. 

Phobia-Related Disorders

A phobia is an intense fear or aversion to specific objects or situations, such as flying, heights, or certain animals. Although it is normal to feel anxious in some situations, people with phobia experience anxiety that is disproportionate to the actual danger that the situation or object presents.

People with phobia present: 

• Excessive worry/anxiety about encountering the feared object or situation
• An attitude of avoiding the feared object or situation
• Resisting unavoidable objects and situations with intense anxiety 

Social Anxiety Disorder

People with social anxiety disorder experience intense fear or anxiety in social or performance situations. They fear that their actions or behaviors, influenced by anxiety, will be judged negatively by others, leading them to avoid social situations. 

Agoraphobia

An anxiety disorder characterized by intense and persistent fear of being in situations or places where the person feels they cannot easily escape or receive help if they have a panic attack or other debilitating symptoms. 

Individuals with this condition present intense fear of two or more of the following situations: 

• Using public transportation
• Being in open spaces
• Being in enclosed spaces
• Being in a crowd
• Being outside the home alone 

In the most severe form of agoraphobia, an individual may become confined to their home. 

Separation Anxiety Disorder

People with this disorder have an intense fear of being separated from people to whom they are very attached. This fear leads them to avoid separation from their attachment figures and to stay alone. 

Although generally associated with children, separation anxiety disorder can also be diagnosed in adults. 

How Does an Anxiety Crisis Occur, and How Is It Treated? 

An anxiety crisis is characterized by an exacerbation of symptoms, leading the individual to lose control of the situation and feel incapable of acting appropriately in response to the presented signs. 

Today, most patients with anxiety disorders can be effectively treated through appropriate professional intervention, which usually involves a combination of pharmacological treatment and psychotherapy (5). 

Among the available therapeutic approaches, Cognitive Behavioral Therapy (CBT) is widely recommended. CBT is based on the principle that how individuals perceive and interpret reality directly influences their feelings and behaviors (6). 

Therapeutic Approaches for Anxiety Disorders

Anxiety disorders have a high treatment potential, often being treated with psychotherapy, medication, or a combination of these approaches, as directed by a specialist. However, despite the effectiveness of available treatments, only 36.9% of patients receive the necessary treatment (3). 

However, despite the effectiveness of available treatments, only 36.9% of patients receive the necessary treatment (3). 

Pharmacological Treatment 

Pharmacological treatment for anxiety is generally safe and effective, often used in conjunction with psychotherapy (7). Four main classes of medications are used in treating anxiety disorders: 

• Selective Serotonin Reuptake Inhibitors (SSRIs): SSRIs improve symptoms by blocking the reabsorption or reuptake of serotonin by nerve cells in the brain, increasing the level of available serotonin.
• Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): SNRIs increase serotonin and norepinephrine levels by inhibiting their reabsorption by brain cells.
• Benzodiazepines: These are generally used for short-term anxiety control and as an adjunct in treatment-resistant cases. Benzodiazepines are highly effective in promoting relaxation and reducing muscle tension and other physical symptoms of anxiety. Long-term use may require higher doses to achieve the same effect, which can lead to issues related to tolerance and dependence.
• Tricyclic Antidepressants: Concerns about the prolonged use of benzodiazepines have led many doctors to prefer tricyclic antidepressants (which block the reuptake of monoamines, primarily norepinephrine, serotonin, and dopamine). 

However, finding an effective treatment for anxiety can be a long process, as different medications and dosages are often tested until the treatment that truly helps the patient is identified. 

Pharmacogenetics for Anxiety 

Various genes influence the expression of cytochrome P450 enzymes, the primary metabolizers of drugs. Variants in these genes can result in diverse responses to medications (8). Pharmacogenetics aims to assess the influence of genes on individual responses to medications (9). 

About SYNLAB’s FG Neuro Anxiety Test

To assist in the precision and individualization of pharmacological treatment for anxiety, SYNLAB offers the FG Neuro Anxiety test, which studies genetic variants in the key genes (CYP3A4, CYP3A5, and CYP2C19) involved in the expression of metabolizing enzymes related to the efficacy and toxicity of the 13 most commonly used medications for anxiety treatment: 

• Alprazolam
• Bromazepam
• Clobazam
• Clorazepate
• Chlordiazepoxide
• Diazepam
• Doxepin
• Flunitrazepam
• Ketazolam
• Lormetazepam
• Triazolam
• Zolpidem
• Zopiclone

What Methodology Is Used for the Test?

SYNLAB’s FG Neuro Anxiety test is conducted using Next-Generation Sequencing (NGS), providing greater process agility, high throughput, and higher sensitivity of analysis (99%). 

What Benefits Does the FG Neuro Anxiety Test Offer?

By analyzing variants in the main genes involved in the expression of drug-metabolizing enzymes, it is possible to classify the metabolism for each analyzed medication, aiming to assist the prescribing physician in more effective treatment with a lower risk of side effects, enabling a more assertive treatment in less time. 

Who Is It Recommended For?

SYNLAB’s FG Neuro Anxiety test is recommended for: 

• Patients undergoing pharmacological treatment who wish to personalize their medication based on their genetic profile.
• Patients experiencing side effects from medications.
• Patients whose pharmacological treatments do not produce the expected results.
• Patients who are about to start pharmacological treatment. 

Get to Know SYNLAB, a Leader in Medical Diagnostic Services!

Conducting precise and up-to-date tests is essential for more accurate diagnoses and better treatment direction. SYNLAB is here to help you. 

We offer diagnostic solutions with strict quality control to the companies, patients, and doctors we serve. We have been in Brazil for over 10 years, operate in 36 countries and three continents, and are leaders in service delivery in Europe. 

Contact the SYNLAB team and learn about the available tests. 

References

1) Gottschalk MG, Domschke K. Genetics of generalized anxiety disorder and related traits. Dialogues in Clinical Neuroscience – Vol 19 . No. 2 . 2017

2) Anxiety Disorders – Facts & Statistics. Anxiety and Depression Association of America (ADAA). Disponível em: https://adaa.org/understanding-anxiety/facts-statistics

3) Anxiety Disorders. Disponível em: https://www.nimh.nih.gov/health/topics/anxiety-disorders?rf=32471

4) McEwan AR, Hing B, Erickson JC, Hutchings G, Urama C, et al. An ancient polymorphic regulatory region within the BDNF gene associated with obesity modulates anxiety-like behaviour in mice and humans. Molecular Psychiatry. 2024;29:660–670.

5) Gabriela Lenhardtk G, Calvetti PÜ. When turn illness anxiety? How to treat disorders eager under the perspective cogntive-behavioral. Aletheia. 2017;50(1-2).

6) Beck, A. & Knapp, P. (2008). Fundamentos, modelos conceituais, aplicações e pesquisa da terapia cognitiva. Revista Brasileira de Psiquiatria, 30(2), 54-64.

7) Manage life with anxiety, OCD, PTSD, depression, and co-occurring disorders.

8) Da-Yong Lu. Pharmacogenetics. Personalized Cancer Chemotherapy. 2015:21-28.

9) Meyer UA. Pharmacogenetics – five decades of therapeutic lessons from genetic diversity. Nat Rev Genet. 2004 Sep;5(9):669-76. doi: 10.1038/nrg1428.