In women with generalised anxiety disorder (GAD), researchers using functional magnetic resonance imaging (fMRI) have identified an abnormal link between the heart and the prefrontal cortex.
The researchers were seeking to determine whether individuals suffering from GAD show dysfunction in the neural circuitry underlying cardiovascular arousal, and if it is associated with certain disorder-related symptoms such as anxiety and body sensation. To conduct the study, they completed a randomised clinical trial of 58 adult female participants (29 with GAD and 29 healthy controls).
During the study, they stimulated the cardiovascular system using isoproterenol, which mimics the effects of adrenaline but, unlike adrenaline, cannot cross the blood-brain-barrier to directly impact brain activity. Intravenous infusions of isoproterenol or saline were administered during fMRI, allowing them to assess whether the brains of patients with GAD differ in the processing of information received from the body, a function known as ‘interoception’. The main findings were that patients with GAD perceived their heartbeats to be more intense and had relatively higher heart rates and lower neural activity in the ventromedial prefrontal cortex. However, these were only observed during the lower of two dosages of isoproterenol: a key finding. Self-reported anxiety was higher only for those with GAD compared to healthy participants in response to either dose.
The findings were published in JAMA Psychiatry.
Lead author Adam Teed, a postdoctoral associate at Laureat Institute of Brain Research, said “administering isoproterenol allowed us to provide causal evidence that an abnormally sensitive cardiovascular system and an abnormally insensitive frontal cortex in GAD patients lowers their ability to regulate bodily arousal. This could help to explain why they experience anxiety so frequently and in a wide variety of contexts.” The authors hope that their study prompts further research into the ventromedial prefrontal cortex as a therapeutic target for novel treatments helping individuals with GAD to regulate physiological and emotional responses to stress.
In addition to this link, the observation of cardiovascular hypersensitivity in GAD patients was also noteworthy. This is because the DSM-5 describes autonomic symptoms such as sweating, rapid heart rate, or shortness of breath, as being less prominent in GAD than other anxiety disorders, such as panic disorder. As senior author Sahib Khalsa, MD, PhD, a psychiatrist and principal investigator at LIBR explains, “this study shows us that anxiety is not only something that happens within our brains but within our bodies as well.”
Thus abnormal autonomic nervous system functioning is not only a factor in GAD, but it occurs in combination with abnormal functioning of certain areas of the brain. Dr Khalsa believes that this finding is the most important research outcome: “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. 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.”
