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Sleep architecture of social phobics
Anxiety and Panic Disorders
BIOL PSYCHIATRY 199| :29:43A- | 8SA
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221 CORTISOL RESPONSE TO LOW DOSES OF DEXAMETHASONE IN PTSD Rachel Yehuda, Ph.D., Earl L. Giller Jr., M.D., Ph.D., David Boisoneau, Martin T. Lowy, Ph.D., Steven M. Southwick, M.D., John W. Mason, M.D. University of Cor,necticut Health Center, Farmington, CT 06030. Previous neurodocrine work in our laboratory has provided support for |ower pituitary-a~enocortic~ activity in FFSD compared with normal controls as evidenced by lovcer mean 24-hr urinary cortiso| excretion and increased lymphocyte glucocorticoid receptor number. To further characterize HPA alteraaons in ~ S D we administered low' doses of dexamethasone {0.5 and 0.25 rag) to 8 male combat veterans with PTSD 12 nonpsychiau'ic healthy males. Low doses were used to test the hypothesis that a "'supersuppression" of coRisol to dexamethasone might occur under conditions of low ambient cortisol levels and increased glucocorticoid receptor number. PTSD patients were medication-free at the time of biological assessment and none met diagnostic criteria for a concurrent major depression. Subjects were tested with both doses of dexamethasone at least 1 week apar~ but within a 5-week period. The results showed that PTSD patients suppressed cortisol to a significantly greate~ extent than normal controls in response to both do~es of dexamethasone. The mean ( +_ SD) 4 i'M postdexamethasone cortisol levels after 0.5 mg was 1.67 _ I. l and 3.94 _+ 2.6 Ixg/dl in PTSD and normals, respectively. Cortiso, levels following the 0.25-rag dose were 3.30 -+ 1.3 Izg/dl for PTSD and 6.08 +_ 3.2 p.m/di for normals. The data support the hypothesis of an enhanced negative feedback sensitivity of the HPA axis in PTSD.
222 H.UOXETINE FOR TREATMENT OF SOCIAL PHOEIA Bruce Black, M.D. (by invitation), Manuel E. Tancer, M.D. (by in',itation), Thomas W. Uhde, M.D. National Institute of Mental Health Bethesda, MD 20892. We openly treated 12 patients with social phobia with fiuoxetine. All patients were treated as outpatients in an anxiety disorders research clinic. All were assessed prior to treatment using a modified version of the SADS-LA and the social phobia section of the ADIS-R, md were given a primary DSM-m-R diagnosis of social phobia, generalized subtype. One patient also had an atypical major depression, two had mild obsessions or compulsions not meeting DSM-III-R criteria for obsessive-compulsive disorder, and four met DSM-m-R criteria for panic disorder. Ten were treated with fluoxetine alone, while two were treated with fluoxetine in combination with another medication. Overall, 8 of 12 patients were moderately to markedly improved with treatment with fluoxetine. Six of the ten patients treated with fluoxetine alone were moderately to markedly improved. One patient had shown a partial response to atenolol and another had shown a partial response to clonazepam; both improved markedly when fluoxetine was added to their current medications. One patient was unable to tolerate fluoxetine treatment because of worsening of anxiety symptoms ("jitters"), one discontinued fluoxetine after developing alopecia, and two showed no change. Of six patients who suffered from social phobia alone without comorbid diagnosis, four were treated with fluoxetine alone, and two of these were moderately to markedly improved. We conclude that fluoxetine may be of benefit to some patients with social phobia, and that further treatment studies are warranted.
223 SLEEP ARCHITECTURE OF SOCIAL PHOBICS Terry M. Brown, D.O. (by invitation), Bruce Black, M.D. (by invitation), Thomas W. Uhde, M.D. National Institute of Mental Health fiethesda, MD 20892. Previous studies of patients with mood disorders have found sign/ficant differences in polysomnographic variables compared with control subjects. Polysomnographic studies of patients with panic disorder have revealed abrupt arousals (sleep panic attacks) from non-REM sleep, increased movement, and increased
146A
alOL PSYCHIATRY 1991:29:43A- 185A
Anxiety and Panic Disorders
difficulties in initiating and maintaining sleep. A single study of obsessive--compulsive disorder patients found reduced REM latencies, although many of these patients also met criteria for major depression. We are not aware of any previous polysomnographic studies of patients with social phobia. We investigated the sleep architecture of 13 patients meeting DSM-III-R criteria for social phobia, compared with 9 normal volunteers. All subjects were studied two or three consecutive nights in oar sleep laboratory. All had been medication free for a period of at least 2 weeks prior to study. Standard polysomnographic variables were measured and Rechtshaffen and Kales criteria were used for scoring the records. All records were s c o l d by the same individual, who was blind to diagnostic category. Study night number 2 was selected for preliminary comparisons using two-tailed unpaired t-tests. Twenty standard polysomnographic variables were examined, as well as an additional variable of number of sleep stage changes (a measure of sleep continuity). No significant differences were found to distinguish social phobics from normal controls.
224 BEHAVIORAL AND GROWTH H O ~ O N E
RESPONSES TO ORAL CAFFEINE IN PANIC DISORDER PATIENTS VERSUS CONTROLS Bruce Black, M.D. (by invitation), Manuel E. Tancer, M.D., Thomas W. Uhde, M.D.
National Institute of Mental Health, Bethesda, MD 20892. Panic disorder patients have blunted growth hormone (GH) responses to clonidine and to GRH relative to normal controls, indicating possible abnormalities in the noradrenergic control of GH release. Caffeine increases noradrenergic function, has dose-related anxiogenic effects, and can mimic clinical anxiety syndromes. We investigated behavioral and neuroendocrine responses to 480 nag oral caffeine-base or placebo administered blindly to 14 nondepressed panic disorder patients and 1 i matched normal controls. Anxiety ratings were obtained at baseline and at + 90 rain. Serum GH levels were determine0 at baseline at at + 60 and + 90 min after drug administration. Caffeine significantly increased GH levels compared to placebo. There was a trend (p < 0.06) toward a significant Diagnosis x Drug x Time interaction, with patients having a reduced GH response to caffeine compared with controls. None of the controls experienced panic attacks, whereas 4 of 14 patients had one or more panic attacks after caffeine. No subjects had panic attacks after placebo. Caffeine produced significantly greater increases in peak anxiety ratings than placebo. Anxiogenic effects were more pronounced ha pat, ents than controls. Baseline measures of an~ iety ~ignificantly correlated with peak GH levels after caffeine in the patients. Patients with the highest baseline ratings of anxiety had the greatest absolute change in GH levels. There was no relationship between ratings of anxiety and peak levels of change in GH levels in the normal control subjects. Blunted GH responses to caffeine may represent further evidence of a hyporesponsive hypothalamic-GH system in panic disorder.
225 GROWTH HORMONE RESPONSES TO CLONIDINE AND
GROWTH HORMONE RELEASING FACTOR IN PATIENTS WITH PANIC DISORDER (PD) Manny E. Tancer, M.D., Murray B. Stein, M.D., Thomas W. Uhde, M.D. National !nstitute of Mental Health, Bethesda, MD 20892. We have previously reported blunted growth hormone (GH) response to c!onidine in PD. More recently, Rapaport et al. reported a blunted GH response to GRF in PD. This study was designed to replicate these studies and to examine the GH response pattern to both probes within an individual. Thus, 13 PD patients and 20 normals (NV) received 2 lxg/kg clonidine and l p.g/kg GRF. Peak GH response to clonidine in PD was blunted compared with NV [PD, 2.6 ± 3.9 ng/ml; NV, 6.5 __ 6.0 ng/ml (Mann-Whitney U = 177; p = 0 026)] as was the area under the GH-secretory curve (GH^tJc) [PD, 83 ± 137 ng-min/ml; N'V, 195
BIOL PSYCHIATRY 199| :29:43A- | 8SA
[45A
221 CORTISOL RESPONSE TO LOW DOSES OF DEXAMETHASONE IN PTSD Rachel Yehuda, Ph.D., Earl L. Giller Jr., M.D., Ph.D., David Boisoneau, Martin T. Lowy, Ph.D., Steven M. Southwick, M.D., John W. Mason, M.D. University of Cor,necticut Health Center, Farmington, CT 06030. Previous neurodocrine work in our laboratory has provided support for |ower pituitary-a~enocortic~ activity in FFSD compared with normal controls as evidenced by lovcer mean 24-hr urinary cortiso| excretion and increased lymphocyte glucocorticoid receptor number. To further characterize HPA alteraaons in ~ S D we administered low' doses of dexamethasone {0.5 and 0.25 rag) to 8 male combat veterans with PTSD 12 nonpsychiau'ic healthy males. Low doses were used to test the hypothesis that a "'supersuppression" of coRisol to dexamethasone might occur under conditions of low ambient cortisol levels and increased glucocorticoid receptor number. PTSD patients were medication-free at the time of biological assessment and none met diagnostic criteria for a concurrent major depression. Subjects were tested with both doses of dexamethasone at least 1 week apar~ but within a 5-week period. The results showed that PTSD patients suppressed cortisol to a significantly greate~ extent than normal controls in response to both do~es of dexamethasone. The mean ( +_ SD) 4 i'M postdexamethasone cortisol levels after 0.5 mg was 1.67 _ I. l and 3.94 _+ 2.6 Ixg/dl in PTSD and normals, respectively. Cortiso, levels following the 0.25-rag dose were 3.30 -+ 1.3 Izg/dl for PTSD and 6.08 +_ 3.2 p.m/di for normals. The data support the hypothesis of an enhanced negative feedback sensitivity of the HPA axis in PTSD.
222 H.UOXETINE FOR TREATMENT OF SOCIAL PHOEIA Bruce Black, M.D. (by invitation), Manuel E. Tancer, M.D. (by in',itation), Thomas W. Uhde, M.D. National Institute of Mental Health Bethesda, MD 20892. We openly treated 12 patients with social phobia with fiuoxetine. All patients were treated as outpatients in an anxiety disorders research clinic. All were assessed prior to treatment using a modified version of the SADS-LA and the social phobia section of the ADIS-R, md were given a primary DSM-m-R diagnosis of social phobia, generalized subtype. One patient also had an atypical major depression, two had mild obsessions or compulsions not meeting DSM-III-R criteria for obsessive-compulsive disorder, and four met DSM-m-R criteria for panic disorder. Ten were treated with fluoxetine alone, while two were treated with fluoxetine in combination with another medication. Overall, 8 of 12 patients were moderately to markedly improved with treatment with fluoxetine. Six of the ten patients treated with fluoxetine alone were moderately to markedly improved. One patient had shown a partial response to atenolol and another had shown a partial response to clonazepam; both improved markedly when fluoxetine was added to their current medications. One patient was unable to tolerate fluoxetine treatment because of worsening of anxiety symptoms ("jitters"), one discontinued fluoxetine after developing alopecia, and two showed no change. Of six patients who suffered from social phobia alone without comorbid diagnosis, four were treated with fluoxetine alone, and two of these were moderately to markedly improved. We conclude that fluoxetine may be of benefit to some patients with social phobia, and that further treatment studies are warranted.
223 SLEEP ARCHITECTURE OF SOCIAL PHOBICS Terry M. Brown, D.O. (by invitation), Bruce Black, M.D. (by invitation), Thomas W. Uhde, M.D. National Institute of Mental Health fiethesda, MD 20892. Previous studies of patients with mood disorders have found sign/ficant differences in polysomnographic variables compared with control subjects. Polysomnographic studies of patients with panic disorder have revealed abrupt arousals (sleep panic attacks) from non-REM sleep, increased movement, and increased
146A
alOL PSYCHIATRY 1991:29:43A- 185A
Anxiety and Panic Disorders
difficulties in initiating and maintaining sleep. A single study of obsessive--compulsive disorder patients found reduced REM latencies, although many of these patients also met criteria for major depression. We are not aware of any previous polysomnographic studies of patients with social phobia. We investigated the sleep architecture of 13 patients meeting DSM-III-R criteria for social phobia, compared with 9 normal volunteers. All subjects were studied two or three consecutive nights in oar sleep laboratory. All had been medication free for a period of at least 2 weeks prior to study. Standard polysomnographic variables were measured and Rechtshaffen and Kales criteria were used for scoring the records. All records were s c o l d by the same individual, who was blind to diagnostic category. Study night number 2 was selected for preliminary comparisons using two-tailed unpaired t-tests. Twenty standard polysomnographic variables were examined, as well as an additional variable of number of sleep stage changes (a measure of sleep continuity). No significant differences were found to distinguish social phobics from normal controls.
224 BEHAVIORAL AND GROWTH H O ~ O N E
RESPONSES TO ORAL CAFFEINE IN PANIC DISORDER PATIENTS VERSUS CONTROLS Bruce Black, M.D. (by invitation), Manuel E. Tancer, M.D., Thomas W. Uhde, M.D.
National Institute of Mental Health, Bethesda, MD 20892. Panic disorder patients have blunted growth hormone (GH) responses to clonidine and to GRH relative to normal controls, indicating possible abnormalities in the noradrenergic control of GH release. Caffeine increases noradrenergic function, has dose-related anxiogenic effects, and can mimic clinical anxiety syndromes. We investigated behavioral and neuroendocrine responses to 480 nag oral caffeine-base or placebo administered blindly to 14 nondepressed panic disorder patients and 1 i matched normal controls. Anxiety ratings were obtained at baseline and at + 90 rain. Serum GH levels were determine0 at baseline at at + 60 and + 90 min after drug administration. Caffeine significantly increased GH levels compared to placebo. There was a trend (p < 0.06) toward a significant Diagnosis x Drug x Time interaction, with patients having a reduced GH response to caffeine compared with controls. None of the controls experienced panic attacks, whereas 4 of 14 patients had one or more panic attacks after caffeine. No subjects had panic attacks after placebo. Caffeine produced significantly greater increases in peak anxiety ratings than placebo. Anxiogenic effects were more pronounced ha pat, ents than controls. Baseline measures of an~ iety ~ignificantly correlated with peak GH levels after caffeine in the patients. Patients with the highest baseline ratings of anxiety had the greatest absolute change in GH levels. There was no relationship between ratings of anxiety and peak levels of change in GH levels in the normal control subjects. Blunted GH responses to caffeine may represent further evidence of a hyporesponsive hypothalamic-GH system in panic disorder.
225 GROWTH HORMONE RESPONSES TO CLONIDINE AND
GROWTH HORMONE RELEASING FACTOR IN PATIENTS WITH PANIC DISORDER (PD) Manny E. Tancer, M.D., Murray B. Stein, M.D., Thomas W. Uhde, M.D. National !nstitute of Mental Health, Bethesda, MD 20892. We have previously reported blunted growth hormone (GH) response to c!onidine in PD. More recently, Rapaport et al. reported a blunted GH response to GRF in PD. This study was designed to replicate these studies and to examine the GH response pattern to both probes within an individual. Thus, 13 PD patients and 20 normals (NV) received 2 lxg/kg clonidine and l p.g/kg GRF. Peak GH response to clonidine in PD was blunted compared with NV [PD, 2.6 ± 3.9 ng/ml; NV, 6.5 __ 6.0 ng/ml (Mann-Whitney U = 177; p = 0 026)] as was the area under the GH-secretory curve (GH^tJc) [PD, 83 ± 137 ng-min/ml; N'V, 195