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  1. #1

    Symptoms of Panic Disorder Linked to Benzodiazepine Binding Activity

    Symptoms of Panic Disorder Linked to Benzodiazepine Binding Activity in the Insular Cortex
    August 6, 2007
    by Norman Sussman, MD, DFAPA
    Editor, Primary Psychiatry and Psychiatry Weekly, Professor of Psychiatry, New York University School of Medicine
    Psychiatry Weekly, Volume 2, Issue 30

    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.

    Reference
    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.

  2. #2
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    Question Re: Symptoms of Panic Disorder Linked to Benzodiazepine Binding Activity

    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
    This is a very complex technical statement. Could someone interpret its significance for me? Is the study concluding there is a benefit or an impairment associated with decreased bilateral binding?
    Steve

    Dum spiro spero....While I breathe, I hope

  3. #3

    Re: Symptoms of Panic Disorder Linked to Benzodiazepine Binding Activity

    I don't pretend to fully understand this stuff either but what I get from it is that they are seeing a rather spcific impairment in the insular cortex.

    I think the major implication in the near ro intermediate future is that this kind of research, like the genetic markers research, may help to target better phramacological treatment of anxiety and disorders for individuals, reducing the need for trial and error with medications.

  4. #4
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    Re: Symptoms of Panic Disorder Linked to Benzodiazepine Binding Activity

    Well, that would be cool. When I tried Zoloft in the mid 90's I was one of the one's that experienced that rare side effect of suicidal thoughts and feelings. I crossed my fingers that the one I was presently on wouldn't cause anything like the above. I would rather skip the trial and error myself

  5. #5
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    Post Re: Symptoms of Panic Disorder Linked to Benzodiazepine Binding Activity

    When I tried Zoloft(sertraline) in the mid 90's I was one of the one's that experienced that rare side effect of suicidal thoughts and feelings
    Ladylore,

    Have you been treated since that experience with a different SSRI or other anti depressant with fewer unwanted side effects?
    Steve

    Dum spiro spero....While I breathe, I hope

  6. #6
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    British Columbia
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    Re: Symptoms of Panic Disorder Linked to Benzodiazepine Binding Activity

    25 ml amitriptyline (spelling is wrong). Very few side effects that I don't even notice anymore. However, PTSD symptoms seem worse then they were a couple months ago so I will need to talk to my psych when he gets back. The generalized anxiety is back and so are a few depression symptoms.

    Ladylore
    Last edited by David Baxter; August 7th, 2007 at 08:34 PM. Reason: spelling is now right :)

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