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Hanipsych, biology of panic

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Hanipsych, biology of panic

  1. 1. Panic Disorder Biology and Management Prof. Hani Hamed DDeessssookkii,, MM..DD..PPssyycchhiiaattrryy PPrrooff.. PPssyycchhiiaattrryy CChhaaiirrmmaann ooff PPssyycchhiiaattrryy DDeeppaarrttmmeenntt BBeennii SSuueeff UUnniivveerrssiittyy SSuuppeerrvviissoorr ooff PPssyycchhiiaattrryy DDeeppaarrttmmeenntt EEll--FFaayyoouumm UUnniivveerrssiittyy AAPPAA mmeemmbbeerr
  2. 2. History • Panic has not always been recognized as an exclusively psychiatric condition. Research in this area continued along separate medical and psychological axes until 1980, when the development of Diagnostic and Statistical Manual (DSM)- III criteria established the overall concept of panic disorder.
  3. 3. History cont”d • The history of the word panic, of the concepts of Panic attack and of Panic Disorder is a complex one. • The adjective word panic, derived from the Greek, stressed initially the intensity of a feeling of unjustified, individual or collective, fear. • In their present meanings, the concepts belong to the group of anxiety states, the Panic attack being a symptom characterized by a paroxysmal anxiety which may appear in various psychopathological states, whereas the Panic Disorder is a nosological category whose diagnostic criterium is the appearance, with a definite frequency, of Panic attacks. • The disorder is frequently associated to agoraphobia considered, when it exists, as a complication.
  4. 4. Panic Attacks & Panic Disorder • It is common to confuse panic attacks with panic disorder. • To qualify for the diagnosis of panic disorder itself, patients must have some panic attacks that are entirely unexpected. • Panic attacks can also be reproducibly triggered by certain specific situations for various individuals & therefore can be expected. • Situations that frequently act as triggers for panic attacks e.g. driving or riding in a vehicle, esp over bridges, shopping in crowded stores. • The perception of lack of control or feeling "trapped" is a common theme in situational triggers.
  5. 5. • Panic disorder affects up to 2 % of the population, but < 1/3 receive treatment. • It typically begins in late adolescence or early adulthood but can present in childhood. • Onset is rare after age 45. • It is more prevalent in women (2:1). • Genetic studies demonstrate a 15 to 20% rate of panic disorder in relatives of patients with panic disorder, including a 40% concordance rate for panic disorder in monozygotic twins.
  6. 6. Panic Attack Facts • Panic attacks can occur at any time, even during sleep. • An attack usually peaks within 10 minutes, but some symptoms may last much longer. • Panic disorder affects about 6 million American adults • Panic disorder is twice as common in women as men. • Panic attacks often begin in late adolescence or early adulthood, • Not everyone who experiences panic attacks will develop panic disorder. Many people have just one attack and never have another. • The tendency to develop panic attacks appears to be inherited. • Panic disorder is often accompanied by other serious problems, such as depression, drug abuse, or alcoholism. http://www.nimh.nih.gov/publicat/anxiety.cfm
  7. 7. Comer, Fundamentals of Abnormal Psychology, 3e 9
  8. 8. DSM 5  This chapter no longer includes OCD and PTSD  DSM 5 creates new chapters for OCD and PTSD  Panic Attacks and Agoraphobia are “unlinked” in DSM- 5  DSM- IV terminology describing different types of panic attacks replaced in DSM-5 with the terms “expected” or “unexpected” panic attack
  9. 9. • Although not generally recognized, panic disorder patients have a suicide rate comparable with that of patients with MD. • 20 to 40% of panic disorder patients report having made suicide attempts & about 1/2 admit to having had suicidal ideation. • This high rate of suicide attempts does not appear to be caused by the presence of depression.
  10. 10. Biological Considerations
  11. 11. Panic Disorder: The Biological Perspective • It is also unclear why some people have such abnormalities in norepinephrine activity – Inherited biological predisposition is one possibility • Prevalence should be (and is) greater among close relatives – Among monozygotic (MZ, or identical) twins = 24% – Among dizygotic (DZ, or fraternal) twins = 11% • Issue is still open to debate
  12. 12. Panic Neurotransmitters Norepinephrine Serotonin GABA GABA 1. Brain stem: fires off systemically to create autonomic symptoms 2. Amygdala and Limbic System: generates anticipatory anxiety 3. Pre-frontal cortex: generates phobic avoidance
  13. 13. Biological Basis Neurotransmitter : dysregulation NE • NE
  14. 14. • The theory of initial excess of NE is supported by evidence that panic disorder patients are hypersensitive to alpha-2 antagonists & hyposensitive to alpha-2 agonists. • Thus, yohimbine, an alpha-2 antagonist, acts as a promoter of NE release by "cutting the brake cable" of the presynaptic NE autoreceptor → an exaggerated response in panic disorder patients, including the precipitation of overt panic attacks.
  15. 15. • Caffeine is also panicogenic (4-6 cups of coffee → panic attack). • It is an adenosine antagonist & can be synergistic with NE. • On the other hand, panic patients have a blunted physiological response to postsynaptic adrenergic agonists, perhaps as a consequence of an overactive noradrenergic system. • Thus, there may be a dysregulation in the noradrenergic system, with changes in the sensitivity of noradrenergic neurons & their receptors altering their physiological functioning.
  16. 16. • GABA & its allosteric modulation by bz have also been implicated in the biological basis of panic disorder i.e. the ability of bz to modulate GABA is out of balance. • This may be due to changes in the amounts of endogenous bz (i.e., "the brain's Xanax"), or to alterations in the sensitivity of the bz receptor itself. • Alternatively, it is possible that the brain is producing an excess in anxiogenic inverse agonists, causing the panic disorder patient to have more anxiety & panic attacks.
  17. 17. • Some data suggest an abnormality in the bz receptor in which the "set point" is shifted toward the inverse agonist conformation. • Thus, Cl channel conductance is already too diminished. • Evidence comes from the fact that such patients require administration of exogenous bz ligands (i.e. Xanax) to reset the receptor complex's set point back to normal. • Also, flumazenil, which is neutral & without behavioral effects in normal subjects because it acts as a relatively pure antagonist, can act differently in panic disorder patients. • It acts as an inverse agonist, perhaps via an abnormal shift of the set point to the right, toward an inverse agonist conformation → provokes panic attacks.
  18. 18. Intrinsic Activity at D2 Receptors Intrinsic Activity DDeessccrriibbeess tthhee AAbbiilliittyy ooff aa CCoommppoouunndd ttoo SSttiimmuullaattee RReecceeppttoorrss NNoo rreecceeppttoorr aaccttiivviittyy AAnnttaaggoonniisstt ((hhaallooppeerriiddooll,, eettcc)) PPaarrttiiaall rreecceeppttoorr aaccttiivviittyy PPaarrttiiaall aaggoonniisstt ((aarriippiipprraazzoollee)) FFuullll rreecceeppttoorr aaccttiivviittyy DD22 rreecceeppttoorr FFuullll aaggoonniisstt ((ddooppaammiinnee))
  19. 19. مقلدات كاملة هذه المقلدات تنشط الخلية وتعطي full agonist الثرر البيولوجي كاملاً

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