Symptoms of Panic Disorder Linked to Benzodiazepine Binding Activity in the Insular Cortex
Editor, Primary Psychiatry and Psychiatry
Weekly, Professor of Psychiatry, New York University School of Medicine
First published in Psychiatry Weekly, Volume 2, Issue
30, on August 6, 2007
Panic disorder is a frequently disabling condition that typically erupts during
adolescence or young adulthood. In most cases, individuals who develop the
disorder were seemingly well-adjusted and highly functional prior to the onset
of their first panic attack. From that point forward, there are significant
changes in behavior that reflect their fear and avoidance of common places
and activities. While many patients benefit from cognitive-behavioral therapy,
the vast majority of people with panic disorder are successfully treated with
benzodiazepines or antidepressants, such as the TCAs or SSRIs.
Studies have focused on identifying the specific brain areas involved in panic
disorder. Areas of interest have included the locus ceruleus and the amygdala.
However, the results of a just-published study point to the insular region
of the brain as a critical area in this disorder.
In order to study the role of brain benzodiazepine receptor binding in the
manifestation of panic disorder, Cameron and colleagues1 used positron emission
tomography to study 11 individuals with DSM-IV defined panic disorder
and 21 unaffected control controls. Benzodiazepines, particularly alprazolam
and clonazepam, have been shown to be highly effective treatments for patients
with panic disorder. These drugs are presumed to produce their clinical effects
by acting on the chloride ion channel macromolecular complex. The neurotransmitter γ-aminobutyric
acid (GABA) is a major inhibitory neurotransmitter in the brain.
The researchers found that there was decreased bilateral binding specifically
in the insular cortex.1 No binding abnormality was observed in any other brain
region, and there was no evidence of abnormal cerebral blood flow anywhere
in the brain. In addition, they observed that individuals with both panic disorder
and depression, indicative of a more severe disorder, exhibited the lowest
binding. The investigators conclude that, “because the insula is strongly
involved in visceral-somatic afferent and efferent function, activation of
the insula is consistent with the occurrence of the physical symptoms prominently
associated with panic disorder.”1
Benzodiazepines may be abused and are sometimes associated with severe rebound
or withdrawal symptoms (when doses are missed or the drug is stopped). When
used properly, however, on a prophylactic basis, benzodiazepines can be very
effective. Sedation may be a common side effect, but these drugs are not associated
with sexual dysfunction and weight gain, as are the SSRIs.
This study, while clarifying the anatomic basis of panic disorder, also reinforces
the role of GABAergic mechanisms in the pathophysiology of the disorders. It
can also help patients understand that they are not psychologically maladjusted,
but that they have symptoms associated with decreased benzodiazepine binding
in their insular cortex. While the real story may be more complicated, and
it is well known that the insula communicates with the amygdala and other parts
of the limbic system, there is something reassuring to both the doctor and
the patient that there is a basis for understanding why something has gone
wrong and why a treatment provides its clinical benefits.
1. Cameron OG, Huang GC, Nichols T. Reduced gamma-aminobutyric acid(A)-benzodiazepine
binding sites in insular cortex of individuals with panic disorder. Arch
Gen Psychiatry. 2007;64:793-800.
Disclosure: Dr. Sussman has received honoraria from AstraZeneca, Bristol-Myers
Squibb, and GlaxoSmithKline.