- Email: [email protected]
kg) in patients with panic disorder and controls
P.3 Anxiety disorders and anxiolytics
$308
complex, and CGP 37849, a competitive NMDA receptor antagonist, exhibit an anxiolytic-like activity in different animal models. In our previous experiment we found that both those compounds administered intraperitoneally (i.p.) showed an anticonftict effect in the conflict drinking test in rats, having increased the number of punished licks. Furthermore, the anticonflict effect of ACPC was not affected by parenteral administration of glycine. To analyze the mechanism of the anxiolytic-like activity of ACPC and CGP 37849 in the conflict drinking test and a possible interaction between glutamatergic and GABA-ergic neurotransmitter systems, the effect of flumazenil (Ro 15-1788), a benzodiazepine receptor antagonist, on the anticonflict effect of ACPC and CGP 37849 was examined. It is noteworthy that neither ACPC nor CGP 37849 shows affinity for benzodiazepine receptors. Diazepam was used as a reference drug in that test. ACPC or CGP 37849 were administered 30 min, diazepam 2 min prior to flumazenil or vehicle. Behavioral observation began 30 min after flumazenil or vehicle injection. ACPC administered in doses of 50, 100 and 200 mg/kg, i.p. significantly increased the number of punished licks by 169, 193 and 383%, respectively. Flumazenil (10 mg/kg, i.p.) effectively antagonized the anticonflict effect of ACPC at all the doses studied. The number of punished responses observed in rats treated with ACPC and flumazenil was similar to that in the vehicle group. CGP 37849 administered in doses of 2.5 and 5 mg/kg i.p. increased the number of punished licks by 145 and 259%, respectively. Flumazenil (10 mg/kg, i.p.) partly but significantly reduced (by ca. 40%) the anticonflict effect of CGP 37849 at either dose tested. Diazepam administered in doses of 2.5 and 5 mg/kg, i.p. increased the number of punished licks by 219 and 455%, respectively, that effect being completely abolished by flumazenil (10 mg/kg, i.p.). Flumazenil given alone had no effect in a conflict drinking test. The above findings seem to indicate an interaction between the glutamatergic and the GABA-benzodiazepine systems in the anticonflict activity of the investigated functional antagonists - especially in that of ACPC - at the NMDA receptor complex.
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Mini-SPIN: a brief screening assessment for social phobia
K.M. Connor 1, K. Kobak 2, L.E. Churchill 1, N.L.S. Potts3, D. Katzelnick2, J. Davidson 1. 1Department of Psychiatry and Behavioral
Sciences, Box 3812, Duke Uniuersity Medical Center, Durham, North Carolina 27710; 2Dean Foundation, Madison, Wisconsin, USA 3University of Adelaide, Adelaide, South Australia Background: Social phobia is rarely identified as a target of treatment in non-psychiatric clinical settings. A valid and reliable screening tool could facilitate identification of individuals likely to have the disorder; however, to date, no valid and reliable screening instrument has been developed. Methods: Using the Social Phobia Inventory (SPIN), a 17-item selfrated assessment of social phobia, a subset of three items yielding high sensitivity and specificity was identified. This abbreviated version of the SPIN, the Mini-SPIN, resulted in a sensitivity of 94.6% and specificity of 90.4% at a cutoff score of 6. To test the efficiency of these items, the Mini-SPIN was administered to two samples. The first group was comprised of US managed care patients in an epidemiological study of the cost of social phobia. Subjects (n = 7165) were sent a battery of assessments including the Mini-SPIN and the MOS depression screen. The social phobia module of the SCID and the MINI were subsequently administered to the following groups: subjects who screened positive for social phob: a using the Mini-SPIN and agreed to be contacted (n = 344); a random sample of subjects who screened positive for depression on the MOS but negative on the Mini-SPIN (n = 397); and a random sample of subjects who screened negative on both the Mini-SPIN and the MOS (n = 276). The second group was comprised of individuals who had participated in a random telephone survey of mental health issues in Southern Australia (SA). A random sample of participants (n = 2500) yielded 141 individuals with social phobia, 100 of whom were
then resampled by mail, along with 100 age and sex-matched controls, using the SPIN, Liebowitz Social Anxiety Scale, Brief Social Phobia Scale, and the Sheehan Disability Scale. In both the US and SA samples, sensitivity, specificity, and positive and negative predictive value for the Mini-SPIN were determined. Results: Using a cut-off score of 6 or greater, the Mini-SPIN administered to the US sample had a sensitivity of 88.7%, a specificity of 90.0% (extrapolated data), a positive predictive value of 52.5%, and negative predictive value of 98.5%. Similar results were observed in the SA sample. These data reveal prevalence rates of 8.2% and 5.6% for social phobia in the US and SA samples, respectively, and are similar to the 7.9% prevalence rate reported in the National Comorbidity Survey. Conclusions: The Mini-SPIN demonstrates solid psychometric properties supporting its utility as a screening tool for social phobia.
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Behavioural effects of rapid i.v. challenge with meta-chlorophenylpiperazine (0.1 mglkg) in patients with panic disorder and controls
N. van der Wee, J. Fiselier, H. van Megen, I. Van Vliet, H. Westenberg.
Utrecht Medical Center, Anxiety Research Unit, Department of Psychiatry, Utrecht, The Netherlands Introduction: Meta-chlorophenylpipemzine (m-CPP) is predominantly a (partial) 5 HT-2c agonist and a frequently used probe for the human serotonergic system. Administration of mCPP results in neuroendocrine and physiological effects. Depending on the method and time of administration there are also panicogenie and anxiogenic effects in both healthy volunteers and in patients with anxiety disorders (for a review see (1)). The effects of rapid i.v. administration of m-CPP (0.1 mg/kg) have been studied in healthy volunteers, but not in patients with panic disorder (PD). In healthy volunteers this approach elicited significant neuroendoerine and moderated behavioural responses (2). Healthy volunteers did not report panic attacks according to DSM-IIIR criteria. The aim of this study was to examine the anxiogenic and panicogenic effects of rapid i.v. administration of m-CPP (0.1 mg/kg) in patients with PD and in control subjects. Methods: Ten patients with PD with or without agoraphobia according to DSM-IV criteria and 10 for age and sex matched healthy volunteers participated. Subjects were told that they would receive m-CPP or a normale saline solution. Behavioural, physiological and neuroendocrine responses as well as m-CPP plasma levels were measured at baseline and at regular intervals until 150 minutes after IV m-CPP administration. MCPP 0.1 mg/kg was administered in 90 seconds by means of an automatic pump. Results: In 9 of the 10 patients (90%) with PD a panic attack according to DSM-IV criteria was provoked, starting within 30 minutes after the administration of m-CPP. In contrast; none of the 10 healthy (0%) volunteers experienced a panic attack. This was a significant difference (p < 0.001). Plasma m-CPP levels and physiological and neuroendocrine effects were not different between patients and healthy volunteers. Conclusion: Rapid i.v. administration of m-CPP (0.1 mg/kg) is a selective and reliable method for the provocation of panic attacks in patients with PD. Discussion: Other i.v. m-CPP challenges, probably resulting in lower peak m-CPP levels, induced panic attacks in maximal 50% of patients with PD. Our data indicate a relationship between the peak levels of m-CPP and the occurrence of panic attacks in patients with PD after i.v. m-CPP challenge, probably mediated via several 5-HT receptor systems.
References [1] Kahn, R.S., Wetzler, S., 1991, m-Chlorophenylpiperazineas a probe of serotonin function. Biological Psychiatry, 30, 1139-1166. [2] Murphy, D.L., Mueller, A.E., Hill L.J., Tolliver, TJ., Jacobson, EM., 1989, Comparative anxioganic, neuroendocrine, and other physiologic effects of mehlompbenylpiperazine given intravenously or orally to healthy volunteers, Psychopharmacology,98, 275-282.
$308
complex, and CGP 37849, a competitive NMDA receptor antagonist, exhibit an anxiolytic-like activity in different animal models. In our previous experiment we found that both those compounds administered intraperitoneally (i.p.) showed an anticonftict effect in the conflict drinking test in rats, having increased the number of punished licks. Furthermore, the anticonflict effect of ACPC was not affected by parenteral administration of glycine. To analyze the mechanism of the anxiolytic-like activity of ACPC and CGP 37849 in the conflict drinking test and a possible interaction between glutamatergic and GABA-ergic neurotransmitter systems, the effect of flumazenil (Ro 15-1788), a benzodiazepine receptor antagonist, on the anticonflict effect of ACPC and CGP 37849 was examined. It is noteworthy that neither ACPC nor CGP 37849 shows affinity for benzodiazepine receptors. Diazepam was used as a reference drug in that test. ACPC or CGP 37849 were administered 30 min, diazepam 2 min prior to flumazenil or vehicle. Behavioral observation began 30 min after flumazenil or vehicle injection. ACPC administered in doses of 50, 100 and 200 mg/kg, i.p. significantly increased the number of punished licks by 169, 193 and 383%, respectively. Flumazenil (10 mg/kg, i.p.) effectively antagonized the anticonflict effect of ACPC at all the doses studied. The number of punished responses observed in rats treated with ACPC and flumazenil was similar to that in the vehicle group. CGP 37849 administered in doses of 2.5 and 5 mg/kg i.p. increased the number of punished licks by 145 and 259%, respectively. Flumazenil (10 mg/kg, i.p.) partly but significantly reduced (by ca. 40%) the anticonflict effect of CGP 37849 at either dose tested. Diazepam administered in doses of 2.5 and 5 mg/kg, i.p. increased the number of punished licks by 219 and 455%, respectively, that effect being completely abolished by flumazenil (10 mg/kg, i.p.). Flumazenil given alone had no effect in a conflict drinking test. The above findings seem to indicate an interaction between the glutamatergic and the GABA-benzodiazepine systems in the anticonflict activity of the investigated functional antagonists - especially in that of ACPC - at the NMDA receptor complex.
•
T
h
e
Mini-SPIN: a brief screening assessment for social phobia
K.M. Connor 1, K. Kobak 2, L.E. Churchill 1, N.L.S. Potts3, D. Katzelnick2, J. Davidson 1. 1Department of Psychiatry and Behavioral
Sciences, Box 3812, Duke Uniuersity Medical Center, Durham, North Carolina 27710; 2Dean Foundation, Madison, Wisconsin, USA 3University of Adelaide, Adelaide, South Australia Background: Social phobia is rarely identified as a target of treatment in non-psychiatric clinical settings. A valid and reliable screening tool could facilitate identification of individuals likely to have the disorder; however, to date, no valid and reliable screening instrument has been developed. Methods: Using the Social Phobia Inventory (SPIN), a 17-item selfrated assessment of social phobia, a subset of three items yielding high sensitivity and specificity was identified. This abbreviated version of the SPIN, the Mini-SPIN, resulted in a sensitivity of 94.6% and specificity of 90.4% at a cutoff score of 6. To test the efficiency of these items, the Mini-SPIN was administered to two samples. The first group was comprised of US managed care patients in an epidemiological study of the cost of social phobia. Subjects (n = 7165) were sent a battery of assessments including the Mini-SPIN and the MOS depression screen. The social phobia module of the SCID and the MINI were subsequently administered to the following groups: subjects who screened positive for social phob: a using the Mini-SPIN and agreed to be contacted (n = 344); a random sample of subjects who screened positive for depression on the MOS but negative on the Mini-SPIN (n = 397); and a random sample of subjects who screened negative on both the Mini-SPIN and the MOS (n = 276). The second group was comprised of individuals who had participated in a random telephone survey of mental health issues in Southern Australia (SA). A random sample of participants (n = 2500) yielded 141 individuals with social phobia, 100 of whom were
then resampled by mail, along with 100 age and sex-matched controls, using the SPIN, Liebowitz Social Anxiety Scale, Brief Social Phobia Scale, and the Sheehan Disability Scale. In both the US and SA samples, sensitivity, specificity, and positive and negative predictive value for the Mini-SPIN were determined. Results: Using a cut-off score of 6 or greater, the Mini-SPIN administered to the US sample had a sensitivity of 88.7%, a specificity of 90.0% (extrapolated data), a positive predictive value of 52.5%, and negative predictive value of 98.5%. Similar results were observed in the SA sample. These data reveal prevalence rates of 8.2% and 5.6% for social phobia in the US and SA samples, respectively, and are similar to the 7.9% prevalence rate reported in the National Comorbidity Survey. Conclusions: The Mini-SPIN demonstrates solid psychometric properties supporting its utility as a screening tool for social phobia.
•
Behavioural effects of rapid i.v. challenge with meta-chlorophenylpiperazine (0.1 mglkg) in patients with panic disorder and controls
N. van der Wee, J. Fiselier, H. van Megen, I. Van Vliet, H. Westenberg.
Utrecht Medical Center, Anxiety Research Unit, Department of Psychiatry, Utrecht, The Netherlands Introduction: Meta-chlorophenylpipemzine (m-CPP) is predominantly a (partial) 5 HT-2c agonist and a frequently used probe for the human serotonergic system. Administration of mCPP results in neuroendocrine and physiological effects. Depending on the method and time of administration there are also panicogenie and anxiogenic effects in both healthy volunteers and in patients with anxiety disorders (for a review see (1)). The effects of rapid i.v. administration of m-CPP (0.1 mg/kg) have been studied in healthy volunteers, but not in patients with panic disorder (PD). In healthy volunteers this approach elicited significant neuroendoerine and moderated behavioural responses (2). Healthy volunteers did not report panic attacks according to DSM-IIIR criteria. The aim of this study was to examine the anxiogenic and panicogenic effects of rapid i.v. administration of m-CPP (0.1 mg/kg) in patients with PD and in control subjects. Methods: Ten patients with PD with or without agoraphobia according to DSM-IV criteria and 10 for age and sex matched healthy volunteers participated. Subjects were told that they would receive m-CPP or a normale saline solution. Behavioural, physiological and neuroendocrine responses as well as m-CPP plasma levels were measured at baseline and at regular intervals until 150 minutes after IV m-CPP administration. MCPP 0.1 mg/kg was administered in 90 seconds by means of an automatic pump. Results: In 9 of the 10 patients (90%) with PD a panic attack according to DSM-IV criteria was provoked, starting within 30 minutes after the administration of m-CPP. In contrast; none of the 10 healthy (0%) volunteers experienced a panic attack. This was a significant difference (p < 0.001). Plasma m-CPP levels and physiological and neuroendocrine effects were not different between patients and healthy volunteers. Conclusion: Rapid i.v. administration of m-CPP (0.1 mg/kg) is a selective and reliable method for the provocation of panic attacks in patients with PD. Discussion: Other i.v. m-CPP challenges, probably resulting in lower peak m-CPP levels, induced panic attacks in maximal 50% of patients with PD. Our data indicate a relationship between the peak levels of m-CPP and the occurrence of panic attacks in patients with PD after i.v. m-CPP challenge, probably mediated via several 5-HT receptor systems.
References [1] Kahn, R.S., Wetzler, S., 1991, m-Chlorophenylpiperazineas a probe of serotonin function. Biological Psychiatry, 30, 1139-1166. [2] Murphy, D.L., Mueller, A.E., Hill L.J., Tolliver, TJ., Jacobson, EM., 1989, Comparative anxioganic, neuroendocrine, and other physiologic effects of mehlompbenylpiperazine given intravenously or orally to healthy volunteers, Psychopharmacology,98, 275-282.