Genetic Research and New Anxiety Medication

Anxiety disorders are among the most common mental health conditions in the United States and throughout the rest of the world. Unfortunately, millions of people with anxiety don’t respond well to anxiety medication typically prescribed to treat these disorders.

Most medications currently in use to treat anxiety disorders focus on neurotransmitters such as serotonin and norepinephrine. Continued research into the genetic component of anxiety offers hope for pharmacological advances that can help those who do not benefit from existing medications.

The Scope of the Problem

In informal conversations, people often use the word anxiety as a synonym for nervousness. In a clinical context, it’s different. It’s a category that includes several distinct mental health disorders.

In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the anxiety disorders category includes the following entries:

• Generalized anxiety disorder (GAD)
• Separation anxiety disorder
• Social anxiety disorder (or social phobia)
• Specific phobia
• Selective mutism
• Panic disorder
• Agoraphobia

Anxiety disorders are characterized by excessive fear and overwhelming worry. In some cases, people who have an anxiety disorder may have physical symptoms such as dizziness, racing heart, chest pains, elevated body temperature, and sensation of being choked.

The main differentiator among the various forms of anxiety disorders is the type of experience or circumstance that triggers the onset of symptoms. In the case of generalized anxiety disorder and panic disorder, symptoms may occur at any time with no apparent cause.

The National Institute of Mental Health (NIMH) reports the following prevalence of anxiety disorders in the United States.

Anxiety in the U.S.: Facts and Figures

• 31% of adults aged 18 and older experience the symptoms of an anxiety disorder at some point in their lives.
• About 19% of adults report an anxiety disorder in the previous 12 months.
• The past-year rate of anxiety disorders is higher among adult women (23.4%) than among adult men (14.3%).
• Among adults who develop anxiety disorders:
  • 22.8% experience severe impairment
  • 33.7% experience moderate impairment

The 2020 census determined that the U.S. is currently home to 258.3 million adults. According to the statistics above, this means that more than 80 million adults may be affected by an anxiety disorder during their lifetime. These prevalence rates foreground the need for new and more effective anxiety medication.

With so many people at risk for anxiety disorders, it’s not hard to understand why so many researchers have attempted to determine possible causes and find more effective treatments. In the next section, we’ll look at a recent effort that may bring us much closer to both of these goals.

Exploring the Genetics of Anxiety

In April 2023, the open access journal Nature Communications published a study on how the brains of mice respond to prolonged stress. An international team led by a trio of experts from the University of Exeter in the UK conducted the study.

“Stress can trigger the onset of a number of neuropsychiatric conditions that have their roots in an adverse combination of genetic and environmental factors,” the researchers wrote.

“While low levels of stress are counterbalanced by the natural capacity of the brain to adjust,” they added, “severe or prolonged traumatic experience can overcome the protective mechanisms of stress resilience, leading to the development of pathological conditions such as psychotic states, depression and/or anxiety.”

How The Study Worked

• The research team created a stress response in a group of mice by restraining them for several hours.
• The team then analyzed the mice’s brains, along with the brains of a group of control mice not subjected to restraint.
• The researchers focused on the amygdala, a brain area associated with emotions such as fear and anxiety.

As described in an April 2023 Neuroscience News article, this led to the following findings.

Results: Genes and Anxiety

• The brains of the restrained/stressed mice showed elevated levels of a molecule called miR483-5p.
• The presence of additional miR483-5p led to suppression of the Pgap2 gene, linked to behaviors symptomatic of anxiety.
• The research team concluded that miR483-5p acts as a “molecular brake” to prevent changes in the amygdalae associated with anxiety.

One of the study’s lead authors, Dr. Valentina Mosienko, said in the Neuroscience News article that this finding may lead to improved treatment methods for people who have anxiety disorders.

“The miR483-5p/Pgap2 pathway we identified in this study, activation of which exerts anxiety-reducing effects, offers a huge potential for the development of anti-anxiety therapies for complex psychiatric conditions in humans,” Mosienko said.

Genomic Load & Personal History

The April 2023 study that we discussed in the previous section wasn’t the only recent exploration of the genetic component of anxiety disorders.

One prior effort was published by the Journal Dialogues in Clinical Neuroscience in June 2017. That article, which was a review of earlier research on this topic, was written by German researchers Michael G. Gottschalk, PhD, and Katharina Domschke, MD, PhD.

This review focused on generalized anxiety disorder (GAD) and related traits. GAD, the researchers wrote, presents an “epidemiological challenge” due in part to the relatively late age at which it is typically diagnosed, as well as the fact that people with GAD also often have co-occurring depression, trauma-related concerns, and other anxiety disorders.

The German review included a multitude of findings from a wide range of studies, including the following.

Review Article: Trends in the Genetics of Anxiety Disorder

• GAD has a “moderate genetic risk” with a heritability factor of about 30%.
• Twin studies document “high genetic correlations” between generalized anxiety disorder and related traits, including neuroticism.
• Nine studies and one meta-analysis link a specific genetic component with a lifetime risk of anxiedty disorders.
• Patients with generalized anxiety disorder show higher levels of a specific serotonin transporter (SLC6A4) than peoplw without GAD.
• An Estonian study found that female subjects revealed found a clear genetic impact on tests for neuroticism, anxiety, and depression.
• Several studies have found that the combination of childhood trauma, recent life stressors, and certain molecular plasticity markers can increase a person’s risk for generalized anxiety disorder and several anxiety-related traits.

“Broader predictive investigations of the GAD disease course development and trait anxiety therapy response might benefit from the growing impact of epigenetics in neuropsychiatry, defining a compelling cross-link between genomic load and personal history,” Gottschalk and Domschke wrote.

Implications for Treatment: Anxiety Medication

Mental health professionals have long theorized that a combination of genetic and environmental factors can influence whether or not a person will develop anxiety disorders. The many studies that we have referred to in this post support this theory.

When combined with psychotherapy, certain prescription medications are beneficial for people with anxiety. However, not all of these medications work for all patients.

Experts estimate that about 60%-85% of people who have anxiety disorders respond positively when treated with medication. However, only about half achieve recovery.

These statistics, the experts suggest, confirm the indaquecy of traditional anxiety medication. Here’s how they see the situation:

“Conventional treatments may not be effective for all patients and alternative pharmacotherapies should be developed.”

That’s why these new studies are important. They may lead to the development of more targeted medications for people who have GAD and other anxiety disorders.