Brain Chemical Receptor Effects in Patients With Panic Disorder and Post-Traumatic Stress Disorder
Condition: Panic Disorder; Posttraumatic Stress Disorder; Major Depressive Disorder
MeSH terms: Depressive Disorder; Depressive Disorder, Major; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Panic Disorder
Study type: Observational

Summary: 
      The purpose of this study is to examine how certain brain chemicals work in patients with
      Panic Disorder (PD) and Post-Traumatic Stress Disorder (PTSD) with and without major
      depressive disorder (MDD).

      Brain chemicals that regulate emotion, anxiety, sleep, stress hormones, and other body
      functions bind to serotonin (5-HT1A) and benzodiazepine (BZD) receptors. Evidence suggests
      that 5-HT1A and BZD receptor function is abnormal in patients with PD, PTSD, and depression.
      This study will use positron emission tomography (PET) scans to examine BZD and 5-HT1A
      receptor binding potential in patients with PD and patients with PTSD with and without
      co-morbid MDD, as well as in healthy volunteers. This study will also determine the effects
      of the stress hormone cortisol on 5-HT1A and BZD receptors.

      The current emotional state and psychiatric, medical, and family history of potential
      participants will be evaluated during an initial telephone interview. After entering the
      study, participants will be asked questions about general mood, degree of nervousness, and
      behavior. A physical examination, an electrocardiogram (EKG), and tests of intelligence and
      cognition will be given. Urine, blood, and saliva samples will be taken. Women will be given
      pregnancy tests and tests to determine menstrual phase and time of ovulation. All volunteers
      will undergo magnetic resonance imaging (MRI) and PET scans of the brain.

      ...
    

Detailed description: 
      Evidence suggests that serotonin1A (5-HT1A) receptor, serotonin transporter (5-HTT) and
      benzodiazepine (BZD) receptor function is abnormal in panic disorder (PD), postraumatic
      stress disorder (PTSD) and depression (MDD). The hypotheses for the role of 5-HT1A receptors
      have been obtained by assessing behavioral, neuroendocrine and temperature responses to the
      selective partial 5-HT1A agonist ipsapirone in anxiety disorders subjects and healthy
      controls, and examining effects on 5-HT1A receptor function in rats following antidepressant
      drug (AD) administration. 5-HT1A receptors knockout mice show behaviors that have been used
      as a model for anxiety disorders in humans. Moreover, 5-HT1A receptor agonists have been
      shown to be effective in the treatment of patients with anxiety disorders. The serotonin
      transporter is implicated in these disorders by virtue of the efficacy of selective serotonin
      reuptake inhibitors in relieving symptoms in these subjects. Evidence arguing for a role of
      BZD/GABA receptor dysfunction in anxiety disorders comes from studies showing anxiolytic and
      anxiogenic properties of BZD agonists and antagonists, respectively. BZD receptor sensitivity
      has been shown to be reduced in patients with anxiety disorders. Brain imaging studies using
      positron emission tomography (PET) and single photon emission computed tomography (SPECT)
      suggest decreased BZD receptor binding in PD and PTSD.

      Animal studies link together serotonin and GABA suggesting a pathological pathway originating
      from 5-HT1A receptor deficit leading towards dysfunctions within GABAergic systems, resulting
      in increased levels of anxiety. Yet, association between disturbed interactions between
      5-HT1A receptor binding and alterations in BZD receptor binding has not been explored in
      humans. The proposed study will advance knowledge regarding the neurobiology of PD and PTSD
      by employing PET and [11C]flumazenil, [18F]FC-WAY100635([18F]FCWAY) and [11C]DASB to compare
      BZD receptor, 5-HT1A receptors and the serotonin transporter binding potential, respectively,
      between PD, PTSD and MDD patients and healthy controls. Because central 5-HT1A receptor
      density is down-regulated in rodents by corticosterone administration and by stress-mediated
      corticosterone secretion, assessments of HPA-axis activity will be assessed to determine
      whether down-regulation of 5-HT1A receptors correlates with cortisol hypersecretion in PD,
      PTSD and MDD.

      The following hypotheses will be tested: 1) PD/PTSD/MDD patients have reduced GABA(A)-BZD
      receptor binding relative to healthy controls. 2) PD/PTSD/MDD patients have reduced 5-HT1A
      receptor binding potential relative to healthy controls. 3) 5-HT1A receptor binding will be
      more prominently reduced in PD and PTSD patients with comorbid MDD relative to anxiety
      disorders patients without comorbid MDD and healthy controls. 4) There will be a positive
      correlation between the reduction in 5-HT1A receptor binding and BZD binding in PD/PTSD/MDD
      patients. 5) There will be an inverse correlation between reduction in 5-HT1A receptor
      binding and BZD binding in PD/PTSD/MDD patients and cortisol secretion. 6) Serotonin
      transporter binding, measured using [11C]DASB, will be reduced in PD subjects relative to
      healthy controls.
    

Keywords: PET; 5-HT1A Receptors; Benzodiazepine Receptors; Panic Disorder; PTSD; Serotonin Type 1A Receptors; Post-Traumatic Stress Disorder; Major Depression; Anxiety; Depression; Healthy Volunteer; HV; Normal Control