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A recent investigation provides new insight into generalized anxiety disorder. Natalie JEFFCOTT/Stocksy
  • Individuals with generalized anxiety disorder (GAD) experience excessive anxiety during everyday life.
  • GAD is one of the most difficult anxiety disorders to treat.
  • A new study investigates the role of the autonomic nervous system and interoception — a sense of the internal state of the body — in GAD.

GAD is the most common form of anxiety disorder, and it frequently occurs with other conditions, such as depression and substance use disorders.

Affecting nearly twice as many women as men, GAD causes excessive, uncontrollable anxiety and persistent worry lasting for at least 6 months.

Researchers at the Laureate Institute for Brain Research (LIBR) in Tulsa, OK, have identified an abnormal link in communication between the heart and the brain’s frontal cortex in women with GAD.

The study appears in JAMA Psychiatry.

People with GAD experience an excessive and pervasive worry about everyday life events. This makes it difficult for them to complete tasks at work, maintain healthy relationships, and take care of themselves.

“People with generalized anxiety disorder worry excessively and constantly about everything going on in their lives, and they find it very difficult to control this worry,” said Dr. Olivia Remes, a psychologist and researcher at the University of Cambridge in the United Kingdom, during a TED Talk on coping with anxiety.

As the neural basis for this anxious arousal in GAD is unclear, it is one of the most difficult anxiety disorders to treat. People with GAD often show resistance to drug treatment and talking therapies.

Hyperarousal symptoms, such as accelerated heart rate, shortness of breath, and sweating, are common among individuals with GAD.

However, these symptoms do not always correlate with physical responses. In other words, the person’s perception of their physiological state, which is called interoception, often does not match their physiological state. For instance, they might feel as though their heart is racing, but it is not. This inconsistency is a characteristic of GAD.

The authors of the new study hope that identifying why there is a disconnect between interoception and physiology might “provide novel targets for treatments.”

The authors of the recent study focused on whether people with GAD demonstrate abnormal physiological, perceptual, or neural responses.

They also asked how these responses might be associated with feelings of anxiety and interoception.

The participants included 58 females — 29 with a GAD diagnosis and 29 without. Each participant received an intravenous infusion of saline and isoproterenol — a substance that mimics the effects of epinephrine on the body without affecting brain activity.

The participants underwent MRI scans at the time of the infusions. These scans allowed the researchers to determine whether the brains of people with GAD processed information from the body differently.

The results showed that, during low dosage infusions of isoproterenol, the participants with GAD had higher heart rates.

They also perceived their heartbeats to be more intense compared with people without GAD. As the authors write, “the GAD group exhibited hypersensitivity to the lower dose of isoproterenol.”

The participants with GAD also exhibited lower neural activity in the ventromedial prefrontal cortex. This area of the brain is responsible for regulating the autonomic nervous system and generates feelings of fear or safety.

Lead author Adam Teed, a postdoctoral associate at LIBR, explains the results:

“[A]dministering isoproterenol allowed us to provide causal evidence that an abnormally sensitive cardiovascular system and an abnormally insensitive frontal cortex in GAD patients lower their ability to regulate bodily arousal. This could help to explain why they experience anxiety so frequently and in a wide variety of contexts.”

Medical News Today spoke with senior study author and psychiatrist Dr. Sahib Khalsa, MD, Ph.D., an associate professor at Oxley College of Health Sciences at the University of Tulsa. He explained that these results were not what the researchers expected to see.

“Our hypotheses were that we would see the anxious individuals having a heightened response to the adrenaline-like challenge in their insular cortex, but it was actually that they had more of a blunting in their ventromedial prefrontal cortex.”

As Khalsa explained, the study shows not only that the abnormal functioning of the autonomic nervous system is a factor in GAD but also that it occurs in combination with abnormal functioning in specific areas of the brain.

The researchers hope that this study will lead to further research on the ventromedial prefrontal cortex as a therapeutic target for innovative treatments for those with GAD.

“It is the interaction between our brain and body that may be essential for determining whether an innocuous situation creates a state of fear in individuals with GAD,” stressed Khalsa.

“We need to better understand how this abnormal physiological response relates to the functional impairments that commonly interfere with the daily lives of such individuals.”