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A neural network model of panic disorder
616
THURSDAE, MAY 18
BIOL PSYCHIATRY 1995;37:593-683
subjective awareness of heart and respiratory changes, and subjective anxiety and discomfort, lsoproterenol significantly increased heart rate, systolic blood pressure, and all symptom ratings while significantly decreasing pC02 (all p < 0.01); diastolic blood pressure was nonsignificantly decreased. Isoproterenol decreased whole brain CBF (p < 0.05); no significant differences among regions were observed. Hypothesized relationships of changes in CBF in specific brain regions with changes in subjective symptom ratings were not observed.
gous to reducing patients' anxiety levels. Simulated therapy with either serotonergic agents and behavior therapy significantly improved panic disorder symptoms. The combination of these therapies also improved anxiety symptoms. This study thus shows that a computational model may be useful in exploring therapeutic strategies in panic disorder.
88. AUTONOMIC ACTIVITY IN PANIC DISORDER AND PTSD
86. ANXIETY IN UNIPOLAR AND BIPOLAR DEPRESSION
G.N.M. Gurguis t,2, D. Antai-Otong l, R. Andrews 1, F. Petty 1,2, & A.J. Rush 1,2
R.S. Salah & O.G. Cameron
nDepartment o f Veterans Affairs Medical Center, Dallas, T X 75216; 2The U n i v e r s i t y o f Texas S o u t h w e s t e r n Medical School, Dallas, T X 75235
University o f M i c h i g a n , D e p a r t m e n t of P s y c h i a t r y , A n n Arbor, MI It has often been repeated that depressed patients with unipolar depression seem to have greater anxiety than depressed bipolar patients; however, there is little objective evidence to back up this premise. The purpose of the present study was to test this hypothesis. A series of 59 consecutively hospitalized patients suffering a major depressive episode were used. Patients were placed into one of three groups based on the probability of a bipolar vs. unipolar diagnosis. A total of 49 patients could be reliably placed into one of those groups based on clinical evaluation, family history, and a SCID interview. The remaining 10 subjects were not utilized. Severity of anxiety and depression were measured with the Hamilton Anxiety and Hamilton Depression Scales, respectively, by a rater who was blind to the diagnosis. Self-reported anxiety and depression were quantitated with the Symptom Checklist-90. We found no difference in the level of anxiety in the three groups, or in the amount of agitation (as assessed by the Cohen-Mansfield Agitation Inventory). Severity of anxiety was strongly correlated with severity of depression. Results of this study do not support the hypothesis that unipolar patients have a higher level of anxiety than depressed patients with bipolar disorder.
Although autonomic hyperarousal is common to both panic disorder (PD) and post-traumatic stress disorder (PTSD), it is unclear if underlying pathophysiologic mechanisms are also common or if some are specific to either disorder. We investigated basal cardiovascular, respiratory and parasympathetic activity and responses to orthostatic challenge in 19 normal controls (NC), 18 PD, and 16 PTSD patients. Statistically significant higher respiratory rate and trends toward significance for lower withinnormal plasma potassium levels and higher anion gap were observed in PD but not PTSD patients. There were nonsignificant trends for higher basal cardiovascular measures in PD and PTSD patients. In PD, there was a statistically significant lower systolic, diastolic, and mean blood pressure, but normal heart rate in response to standing. In PTSD patients, cardiovascular responses fell on a continuum between NC and PD patients, with systolic blood pressure showing significant group by time interaction. In PD, basal vagal tone measures were not different from NC; however, heart period variance and heart range showed significant ~ o u p by time interactions where a rebound increase was observed after 8 minutes of standing. In PTSD, vagal tone measures, both basal and in response to standing, were normal. We will report on plasma norepinephrine levels. Collectively these results suggest that 1) abnormal respiratory function is specific to PD; 2) abnormal cardiovascular and vagal responses are more pronounced in PD than in PTSD; 3) basal cardiovascular and vagal parasympathetic activity and responses to neutral or physiologic (orthostatic) stimuli in PTSD are within normal.
87. A NEURAL NETWORK MODEL OF PANIC DISORDER
R.L. Ownby & C.N. Carmin
89. MONOAMINERGIC CORRELATES OF TEMPERAMENT IN PTSD PATIENTS
University of M i a m i School o f Medicine; St. Louis University School o f Medicine
J.W. Crayton & H.C. Bonbrest
Panic disorder is characterized by recurrent and severe episodes of anxiety, often without apparent cause. It may be significantly disabling and associated with comorbid conditions including agoraphobia and depression. Panic disorder is thus a significant problem because of the number of persons afflicted and the severity of their symptoms. Gorman et al (1989) developed a neuroanatomical model for panic disorder based on research suggesting that specific cites in the brain may be related to panic symptoms. Klein suggested that there are three basic elements to panic disorder: panic attacks, anticipatory anxiety, and phobic avoidance. Gorman et al relate these to three anatomic loci: the locus coeruleus, the limbic system, and the prefrontal cortex, respectively. We had previously constructed a neural network based on this anatomic theory and shown that it could model both normal and paroxysmal severe anxiety. This paper describes further development of a neural network model of panic disorder. The addition of serotonergic inputs to the model allowed investigation of pharmacologic therapeutic strategies. Cognitive-behavioral therapy was simulated by reducing simulated limbic system inputs, analo-
Biological P s y c h i a t r y L a b s (116A7), Hines VA Hospital, Hines, IL 60141 Schnurr's (1993) study of pre-Viet Nam psychological profiles of veterans who later developed post-traumatic stress disorder (PTSD) suggested the possibility that certain dimensions of personality might be considered risk factors for PTSD. Our previous work suggested that measures of serotonin receptor function and binding to the serotonin transporter were altered in PTSD. To determine whether personality and monoamine measures were related, we administered the Cloninger Tridimensional Personality Questionnaire (TPQ) and studied receptor binding to adrenergic and serotonergic binding sites on platelets from 26 patients with PTSD and 16 controls. Personality scores were generated for the three main TPQ dimensions: Harm Avoidance (HA); Novelty Seeking (NS); and Reward Dependence (RD). PTSD patients had significantly higher scores than controls on HA (21.0 + 8.4 vs. 9.44 + 6.4; p < 0.001 ; mean _+SD) and NS (19.6 + 5.1 vs. 14.2 + 3.4; p < 0.001 ) and lower on RD (7.7 + 3.7 vs. 13.1
THURSDAE, MAY 18
BIOL PSYCHIATRY 1995;37:593-683
subjective awareness of heart and respiratory changes, and subjective anxiety and discomfort, lsoproterenol significantly increased heart rate, systolic blood pressure, and all symptom ratings while significantly decreasing pC02 (all p < 0.01); diastolic blood pressure was nonsignificantly decreased. Isoproterenol decreased whole brain CBF (p < 0.05); no significant differences among regions were observed. Hypothesized relationships of changes in CBF in specific brain regions with changes in subjective symptom ratings were not observed.
gous to reducing patients' anxiety levels. Simulated therapy with either serotonergic agents and behavior therapy significantly improved panic disorder symptoms. The combination of these therapies also improved anxiety symptoms. This study thus shows that a computational model may be useful in exploring therapeutic strategies in panic disorder.
88. AUTONOMIC ACTIVITY IN PANIC DISORDER AND PTSD
86. ANXIETY IN UNIPOLAR AND BIPOLAR DEPRESSION
G.N.M. Gurguis t,2, D. Antai-Otong l, R. Andrews 1, F. Petty 1,2, & A.J. Rush 1,2
R.S. Salah & O.G. Cameron
nDepartment o f Veterans Affairs Medical Center, Dallas, T X 75216; 2The U n i v e r s i t y o f Texas S o u t h w e s t e r n Medical School, Dallas, T X 75235
University o f M i c h i g a n , D e p a r t m e n t of P s y c h i a t r y , A n n Arbor, MI It has often been repeated that depressed patients with unipolar depression seem to have greater anxiety than depressed bipolar patients; however, there is little objective evidence to back up this premise. The purpose of the present study was to test this hypothesis. A series of 59 consecutively hospitalized patients suffering a major depressive episode were used. Patients were placed into one of three groups based on the probability of a bipolar vs. unipolar diagnosis. A total of 49 patients could be reliably placed into one of those groups based on clinical evaluation, family history, and a SCID interview. The remaining 10 subjects were not utilized. Severity of anxiety and depression were measured with the Hamilton Anxiety and Hamilton Depression Scales, respectively, by a rater who was blind to the diagnosis. Self-reported anxiety and depression were quantitated with the Symptom Checklist-90. We found no difference in the level of anxiety in the three groups, or in the amount of agitation (as assessed by the Cohen-Mansfield Agitation Inventory). Severity of anxiety was strongly correlated with severity of depression. Results of this study do not support the hypothesis that unipolar patients have a higher level of anxiety than depressed patients with bipolar disorder.
Although autonomic hyperarousal is common to both panic disorder (PD) and post-traumatic stress disorder (PTSD), it is unclear if underlying pathophysiologic mechanisms are also common or if some are specific to either disorder. We investigated basal cardiovascular, respiratory and parasympathetic activity and responses to orthostatic challenge in 19 normal controls (NC), 18 PD, and 16 PTSD patients. Statistically significant higher respiratory rate and trends toward significance for lower withinnormal plasma potassium levels and higher anion gap were observed in PD but not PTSD patients. There were nonsignificant trends for higher basal cardiovascular measures in PD and PTSD patients. In PD, there was a statistically significant lower systolic, diastolic, and mean blood pressure, but normal heart rate in response to standing. In PTSD patients, cardiovascular responses fell on a continuum between NC and PD patients, with systolic blood pressure showing significant group by time interaction. In PD, basal vagal tone measures were not different from NC; however, heart period variance and heart range showed significant ~ o u p by time interactions where a rebound increase was observed after 8 minutes of standing. In PTSD, vagal tone measures, both basal and in response to standing, were normal. We will report on plasma norepinephrine levels. Collectively these results suggest that 1) abnormal respiratory function is specific to PD; 2) abnormal cardiovascular and vagal responses are more pronounced in PD than in PTSD; 3) basal cardiovascular and vagal parasympathetic activity and responses to neutral or physiologic (orthostatic) stimuli in PTSD are within normal.
87. A NEURAL NETWORK MODEL OF PANIC DISORDER
R.L. Ownby & C.N. Carmin
89. MONOAMINERGIC CORRELATES OF TEMPERAMENT IN PTSD PATIENTS
University of M i a m i School o f Medicine; St. Louis University School o f Medicine
J.W. Crayton & H.C. Bonbrest
Panic disorder is characterized by recurrent and severe episodes of anxiety, often without apparent cause. It may be significantly disabling and associated with comorbid conditions including agoraphobia and depression. Panic disorder is thus a significant problem because of the number of persons afflicted and the severity of their symptoms. Gorman et al (1989) developed a neuroanatomical model for panic disorder based on research suggesting that specific cites in the brain may be related to panic symptoms. Klein suggested that there are three basic elements to panic disorder: panic attacks, anticipatory anxiety, and phobic avoidance. Gorman et al relate these to three anatomic loci: the locus coeruleus, the limbic system, and the prefrontal cortex, respectively. We had previously constructed a neural network based on this anatomic theory and shown that it could model both normal and paroxysmal severe anxiety. This paper describes further development of a neural network model of panic disorder. The addition of serotonergic inputs to the model allowed investigation of pharmacologic therapeutic strategies. Cognitive-behavioral therapy was simulated by reducing simulated limbic system inputs, analo-
Biological P s y c h i a t r y L a b s (116A7), Hines VA Hospital, Hines, IL 60141 Schnurr's (1993) study of pre-Viet Nam psychological profiles of veterans who later developed post-traumatic stress disorder (PTSD) suggested the possibility that certain dimensions of personality might be considered risk factors for PTSD. Our previous work suggested that measures of serotonin receptor function and binding to the serotonin transporter were altered in PTSD. To determine whether personality and monoamine measures were related, we administered the Cloninger Tridimensional Personality Questionnaire (TPQ) and studied receptor binding to adrenergic and serotonergic binding sites on platelets from 26 patients with PTSD and 16 controls. Personality scores were generated for the three main TPQ dimensions: Harm Avoidance (HA); Novelty Seeking (NS); and Reward Dependence (RD). PTSD patients had significantly higher scores than controls on HA (21.0 + 8.4 vs. 9.44 + 6.4; p < 0.001 ; mean _+SD) and NS (19.6 + 5.1 vs. 14.2 + 3.4; p < 0.001 ) and lower on RD (7.7 + 3.7 vs. 13.1