Balon R, Pohl R, Yeragani VK, Ramesh C, Glitz DA: THE CHANGES OF THYROID HORMONE DURING PHARMACOLOGICAL TREATMENT OF PANIC DISORDER PATIENTS. Progress in Neuro-Psychopharmacology & Biological Psychiatry 1991; 15(5):595-600. Summary: 1. Because imipramine has lowered T4 in uncontrolled studies we examined the effect of imipramine on serum thyroid levels in panic disorder patients in a double-blind placebo and diazepam treatment controlled study. 2. Treatment with imipramine (10 subjects) was associated with a significant decrease of T4 and FTI and treatment with diazepam (8 subject) was associated with a significant decrease of T4. However, there was no significant difference across treatment groups. 3. This finding suggests that previously reported decreases in thyroid hormones during antidepressant therapy may be due to nonspecific effects of treatment rather than to the drug itself.
Vazquez Rodriguez AM, Arranz Pena MI, Lopez Ibor JJ, Garcia Aguilera M, Vinas R, Moreno I, Vecino Morales AM: CLOMIPRAMINE TEST: SERUM LEVEL DETERMINATION IN THREE GROUPS OF PSYCHIATRIC PATIENTS. Journal of Pharmaceutical & Biomedical Analysis 1991; 9(10-12):949-52. Summary: Concentrations of clomipramine, a specific and potent serotonin uptake inhibitor, are measured in 67 psychiatric patients and 12 normal volunteers. The psychiatric patients are grouped according to the DSM III R criteria namely; pathological gamblers, obsessive compulsives and sufferers of panic disorders. Before and 30, 60, 90 and 120 min after an intravenous infusion of the drug (12.5 mg in 10 min), serum samples are collected to evaluate the concentrations of cortisol, prolactine and growth hormone. Simultaneously the clomipramine concentration of these samples is determined and these results only are reported in this communication. Very different drug concentrations are observed in individual patients receiving the same amount of drug, indicating a substantial inter-individual variability of drug metabolism. No statistical differences (Newman-Keules test) between the clomipramine concentrations from the patients of the three psychiatric groups and the normal group are observed. Neither are statistical correlations observed when clomipramine concentrations from all individuals (n = 79) are related with the age, sex or consumer behaviour (cigarette smoking, alcohol and coffee intakes) of the patients.
Fontaine S, Ontiveros A, Fontaine R, Elie R: PANIC DISORDER: VASCULAR EVALUATION WITH TRANSCRANIAL DOPPLER ULTRASONOGRAPHY. Canadian Association of Radiologists Journal 1991; 42(6):412-6. Summary: Several recent studies have shown neurophysiologic and neuroanatomic abnormalities in panic disorder. This study aimed to assess by transcranial Doppler (TCD) ultrasonography the magnitude of the changes in blood flow during panic attacks induced by intravenous sodium lactate infusion. The subjects consisted of 30 patients with panic disorder (DSM-III-R) and 25 controls; all were between the ages of 18 and 40 years and were right-handed. The flow in the middle cerebral artery was recorded bilaterally before the infusion began (to provide baseline readings) and at 3-minute intervals during the infusion. The patients showed a more rapid acceleration of flow (p less than 0.05) than the controls. Higher maximal velocity and higher variations in velocity (p less than 0.05) were observed in the patients sensitive to lactate but only in the right middle cerebral artery. These results suggest that abnormalities of local cerebrovascular autoregulation occurred in the patients with panic disorder during attacks induced by sodium lactate.
Bradwejn J, Koszycki D, Bourin M: DOSE RANGING STUDY OF THE EFFECTS OF CHOLECYSTOKININ IN HEALTHY VOLUNTEERS. Journal of Psychiatry & Neuroscience 1991; 16(2):91-5. Summary: The authors determined whether response to cholecystokinin-tetrapeptide (CCK-4) was dose-dependent. Healthy volunteers (n = 36) received double-blind injections of either 9 micrograms, 25 micrograms, or 50 micrograms of CCK-4 and placebo in a randomized sequence of injection. Significant dose-related differences were found for the number of symptoms, sum intensity of symptoms and the time until onset of symptoms, but not for the duration of symptoms. The incidence of panic attacks with CCK-4 was 11%, 17% and 47% for the 9 micrograms, 25 micrograms and 50 micrograms dose, respectively. None of the controls panicked with placebo injections. These results support the notion of a dose-dependent effect of CCK-4-induced panic symptoms. Implications of these findings in the neurobiology of panic attacks are discussed.
Gokce O, Gokce C, Gunel S, Arisoy S, Arisoy E, Huseyinoglu K, Kismet K, Ucar O: PHEOCHROMOCYTOMA PRESENTING WITH HEADACHE, PANIC ATTACKS AND JAUNDICE IN A CHILD. Headache 1991; 31(7):473-5. Summary: Pheochromocytomas can mimic many unrelated diseases due to their various presenting signs; they are encountered very rarely in childhood. Recently, their neuropsychiatric aspects have become a subject of interest for many workers, but most of the findings reported previously have been observed in adults. We present a case report which is unique in that it concerns a child with pheochromocytoma and psychiatric findings consisting of depression and panic disorder, which were interpreted as being directly related to, since they disappeared after the removal of, the tumor. Depression was persistent and accompanied by a constricting-type headache, while panic disorder was acute and accompanied by a migraine-type headache. Another intriguing complication encountered in our case was jaundice; we considered that it could possibly have been due to an adverse effect of catecholamines on hepatocyte function. We conclude that a pheochromocytoma can be confused with neuropsychiatric disorders in children as well as in adults and that it should be considered in the differential diagnosis of such disorders.
Hikiami J, Kim YD, Kurata K, Kurachi M: A CASE OF LOCALIZATION-RELATED EPILEPSIES SUSPECTED OF PANIC DISORDER. Japanese Journal of Psychiatry & Neurology 1991; 45(2):378-9. Summary: Some localization-related epilepsies have autonomic symptoms as well as psychic symptoms. As these symptoms are similar to those of panic disorder, it is important to discriminate between the two disorders. In such cases, VTR-polygraphic examination is necessary for the correct diagnosis.
Knott V, Lapierre YD, Fraser G, Johnson N: AUDITORY EVOKED POTENTIALS IN PANIC DISORDER. Journal of Psychiatry & Neuroscience 1991; 16(4):215-20. Summary: Neuroimaging studies of behavioral-induced anxiety in non-patients and of lactate-induced anxiety in panic disorder patients have indicated that normal and pathological anxiety may share a common pathway involving the temporal poles. As panic-related anxiety may reflect faulty temporopolar evaluative processing of input, the objective of this study was to examine sensory reactivity in panic disorder patients via scalp recordings of the late auditory evoked 'vertex' potential (LAEP) which appears to have a predominantly temporal lobe origin. Twelve patients diagnosed according to DSM-III criteria as panic disorder and ten normal controls served as subjects in this study. EEG was recorded from 16 scalp sites using a monopolar fronto-occipital derivation and LAEPs were separately averaged in response to four acoustic intensities. Analysis focused on group and electrode-site differences in the negative (N1) and positive (P2) component amplitudes of the LAEPs. Panic disorder patients were found to exhibit significantly larger N1 amplitudes across all stimulus intensities and across all recording sites. No significant group differences were observed with P2. Although the results provide indirect support for a temporal focus, other modulating influences must be considered in data interpretation.
Rosenbaum JF, Biederman J, Hirshfeld DR, Bolduc EA, Chaloff J: BEHAVIORAL INHIBITION IN CHILDREN: A POSSIBLE PRECURSOR TO PANIC DISORDER OR SOCIAL PHOBIA. [REVIEW]. Journal of Clinical Psychiatry 1991; 52 Suppl:5-9. Summary: A biological-environmental interaction currently provides the best explanation of an anxiety disorder's evolution. In this sense, anxiety disorders are like other medical disorders for which a person may have a predisposition. Our knowledge of the evolution of anxiety disorders would be enhanced by the ability to identify those persons predisposed to anxiety and to identify such "proneness" before an anxiety disorder emerges in adulthood. We discuss the developmental aspects of panic disorder and social phobia, in particular findings suggesting that behavioral inhibition in children may be a precursor to phobic disorders in adults. Only longitudinal studies will resolve whether childhood response patterns are specifically linked to the risk of developing anxiety disorders or other psychopathology across the life cycle. In the interim, we suggest some guidelines for parents and clinicians to meet the unique needs of the inhibited child. [References: 23]
Klein E, Zohar J, Geraci MF, Murphy DL, Uhde TW: ANXIOGENIC EFFECTS OF M-CPP IN PATIENTS WITH PANIC DISORDER: COMPARISON TO CAFFEINE'S ANXIOGENIC EFFECTS. Biological Psychiatry 1991; 30(10):973-84. Summary: The behavioral and neuroendocrine effects of meta-chlorophenylpiperazine (m-CPP), a serotonergic agonist, were compared with the effects of caffeine, an adenosine antagonist, in panic disorder patients. Patients with panic disorder were given single oral doses of 0.5 mg/kg m-CPP, 480 mg caffeine, and placebo on separate days under double-blind conditions. Both m-CPP and caffeine had significantly greater anxiogenic and panic-inducing effects than placebo, although caffeine produced nonsignificantly greater increases on all anxiety rating scales than m-CPP. Both m-CPP and caffeine produced significant equivalent increases in plasma cortisol concentrations, but only m-CPP produced plasma prolactin increases. These findings provide further evidence implicating both the serotonergic and adenosinergic receptor systems in the neurobiology of panic disorder.
Sparks PJ, Ayars GH, Simon GE, Katon WJ, Altman LC, Johnson RL: DEPRESSION AND PANIC ATTACKS RELATED TO PHENOL-FORMALDEHYDE COMPOSITE MATERIAL EXPOSURE IN AN AEROSPACE MANUFACTURING PLANT. Allergy Proceedings 1991; 12(6):389-93. Summary: In a case series study we evaluated 53 composite-materials workers in an aerospace plant who filed workers' compensation claims for illness allegedly related to phenol-formaldehyde resin exposure. Symptoms ranged from mucosal and skin irritation to depression and cognitive impairment. Certain health practitioners implying they had immunologic dysfunction and organic brain injury, led workers to believe they were chemically poisoned. Industrial hygiene evaluation failed to show levels of chemicals above permissible levels. Thorough evaluation by our multidisciplinary panel failed to find significant objective abnormalities by physical exam and laboratory testing. Thirty-nine percent of the workers had sensory irritation and/or skin complaints that generally resolved rapidly with removal from exposure. Psychiatric diagnoses (including major depression and/or panic attacks) were made in 74% of the workers, but only 26% of these had antecedent disease. Fourteen (26%) had multiple somatic complaints that generally persisted despite removal from exposure, but they also had long histories of significant pre-existing psychological illness. Detailed neuropsychologic testing failed to show any definite evidence or organic brain dysfunction in any of the workers tested. We speculate that sensory irritation from low-level volatile organic compounds with autonomic arousal, reinforced by the belief they were "chemically poisoned," led to psychogenic illness.
Ramesh C, Yeragani VK, Balon R, Pohl R: A COMPARATIVE STUDY OF IMMUNE STATUS IN PANIC DISORDER PATIENTS AND CONTROLS. Acta Psychiatrica Scandinavica 1991; 84(4):396-7. Summary: Alterations of immunocompetence in various mental disorders have been reported. We studied white blood cell counts and immunoglobulin levels in 59 panic disorder patients and 30 controls. The significantly increased IgA levels and tendency toward increase in other immunoglobulins in panic disorder patients suggest an immune dysfunction.
Reich J: AVOIDANT AND DEPENDENT PERSONALITY TRAITS IN RELATIVES OF PATIENTS WITH PANIC DISORDER, PATIENTS WITH DEPENDENT PERSONALITY DISORDER, AND NORMAL CONTROLS. Psychiatry Research 1991; 39(1):89-98. Summary: Psychiatric researchers have long wondered whether personality traits might predispose toward or be integral to Axis I illnesses. The question is difficult to address because acute illness can either create personality traits or distort their measurement. The present study bypassed that problem by examining personality traits in relatives of patients. Panic disorder, dependent personality disorder, and control subjects were the proband groups. A cluster of traits that appeared to reflect low social self-confidence combined with a desire for social interaction occurred significantly more often in relatives of patients in both groups.
Zandbergen J, Pols H, de Loof C, Griez EJ: VENTILATORY RESPONSE TO CO2 IN PANIC DISORDER. Psychiatry Research 1991; 39(1):13-9. Summary: The Read rebreathing technique was used to measure the ventilatory response to inhalation of carbon dioxide in 15 panic disorder patients, 15 obsessive-compulsive disorder patients, and 15 healthy control subjects. No significant differences in ventilatory response were found among the three groups. The tidal volume and frequency components of the ventilatory response also did not differ among the groups. The hypothetical pCO2 value corresponding with zero ventilation was significantly lower in the panic disorder patients than in normal control subjects.
Argyle N: SKIN CONDUCTANCE LEVELS IN PANIC DISORDER AND DEPRESSION. Journal of Nervous & Mental Disease 1991; 179(9):563-6. Summary: Skin conductance level (SCL) was measured in 63 subjects with panic disorder, 21 of whom had major depression. Some evidence was found for low SCL being associated with depression, as has been recorded in depression without panic. The standard deviation of SCL was high and it is suggested that the etiology of depression in panic is different from primary depression, at least for some patients. High SCL was not associated with severity of illness. Recordings made in the usual small, isolated, sound-attenuated environment were compared with those made in a larger room with an investigator present for 10 patients and 10 normal controls. Lower SCLs were found in the larger room.
Ley R: VENTILATORY CONTROL OF HEART RATE DURING INHALATION OF 5% CO2 AND TYPES OF PANIC ATTACKS. Journal of Behavior Therapy & Experimental Psychiatry 1991; 22(3):193-201. Summary: Differences in the magnitude of increases in heart rate during prolonged inhalation of 5% CO2 range from a mean of 25 b/min for a group of eight panic-disorder patients who panicked (Woods, Charney, Goodman, & Heninger, 1988. Archives of General Psychiatry, 45, 43-52) to zero b/min for 16 patients, eight of whom panicked (Craske & Barlow, 1990. Journal of Abnormal Psychology, 99, 302-307). What accounts for this disparity? The present paper describes how heart rate can be increased by means of voluntary overbreathing during prolonged inhalation of 5% CO2 in air. This suggests that differences in the degree of overbreathing may explain differences in the magnitude of increases in heart rate during inhalation of 5% CO2. An explanation is also offered for the curious finding that some patients experience "panic attacks" with zero increase in heart rate. Evidence suggests that this is likely to happen in cognitively based panic attacks, in contrast to hyperventilatory attacks or anticipatory attacks.
Maddock RJ, Carter CS, Gietzen DW: ELEVATED SERUM LACTATE ASSOCIATED WITH PANIC ATTACKS INDUCED BY HYPERVENTILATION. Psychiatry Research 1991; 38(3):301-11. Summary: Several lines of evidence suggest that lactate metabolism may be altered in panic disorder. We recently reported exaggerated increases in serum lactate in panic patients following hyperventilation during glucose infusion. In the current study, lactate metabolism was stimulated by hyperventilation following glucose ingestion in 12 panic patients and 12 controls. The seven patients who panicked during hyperventilation exhibited larger increases in serum lactate levels than nonpanicking patients or controls. The lactate response was significantly correlated with peak ratings of anxiety and panic symptoms, but not correlated with insulin or cortisol levels, heart rate, pCO2, adiposity, exercise habits, or diet. Hyperventilation-induced panic appears to be associated with metabolic changes leading to elevated serum lactate.
Albus M, Zahn TP, Breier A: ANXIOGENIC PROPERTIES OF YOHIMBINE. II. INFLUENCE OF EXPERIMENTAL SET AND SETTING. European Archives of Psychiatry & Clinical Neuroscience 1992; 241(6):345-51. Summary: To study the pharmacological induction of stress along with psychological stress and their possible interaction, 20 mg yohimbine and placebo orally were administered to 8 panic patients on placebo treatment, 7 panic patients on alprazolam treatment and 12 controls in a double-blind crossover design. Two structured situations which can be considered as 'neutral' stressors were included: a mental arithmetic task and a continuous performance task. Mental arithmetic induced robust increases in ratings of panicky, anxiety, nervousness, heart rate and electrodermal activity, while the continuous performance task induced increases exclusively in skin conductance reaction. Patients responded to these tasks less than controls with regard to subjective ratings and electrodermal activity. Yohimbine did not potentiate the response to the tasks in the patients. In controls, heart rate during the mental arithmetic task, but not during rest, was increased after yohimbine. In contrast to other yohimbine challenge studies no panic attacks were observed. It is hypothesized that the experimental design together with an instructional set that reduces expectancy factors and the inclusion of structured and time-limited tasks in a challenge paradigm is able to reduce the anxiogenic effects of yohimbine.
Albus M, Zahn TP, Breier A: ANXIOGENIC PROPERTIES OF YOHIMBINE. I. BEHAVIORAL, PHYSIOLOGICAL AND BIOCHEMICAL MEASURES. European Archives of Psychiatry & Clinical Neuroscience 1992; 241(6):337-44. Summary: The anxiogenic effects of yohimbine, a specific alpha-2-receptor antagonist were examined by administering 20 mg yohimbine orally to 8 panic patients on placebo treatment, 7 panic patients on alprazolam treatment and 12 controls using a double-blind randomized design, instructions that minimized the expectancy of experiencing a panic attack and two additional structured situations. Yohimbine induced more pronounced increases in anxiety and panicky ratings, norepinephrine secretion, maximum heart rate and high heart rate variability and decreases in skin temperature in panic patients compared with controls. However, possibly owing to an instructional set and experimental design that distracted patients from unpleasant bodily sensations no panic attacks were observed.
Beitman BD, Logue MB, Thomas AM, Bartels K: RESPONSE TO 35% CO2 IN PATIENTS WITH CHEST PAIN AND ANGIOGRAPHICALLY NORMAL CORONARY ARTERIES. International Journal of Psychiatry in Medicine 1992; 22(3):197-203. Summary: OBJECTIVES: Several interview studies have suggested that panic disorder (PD) exists in patients with angiographically normal coronary arteries (NCA). Interview studies require corroboration by other studies in order to validate them. The purpose of this study is to test whether response to the inhalation of 35% CO2 reliably discriminates between PD and non-panic disorder patients in this population. METHOD: Three groups were studied: six with NCA and PD, five with NCA and no PD, and ten in the control group. All subjects breathed room air, then 35% CO2 in a single-blind fashion. Each completed the Acute Panic Inventory (API) before and during the procedure. RESULTS: The NCA-panic group scored significantly higher than the other two groups on the Acute Panic Inventory from baseline to post-inhalation. CONCLUSION: Despite several methodological limitations including a relatively small number people in each cells, 35% CO2 was shown to trigger more intense responses in panic patients, thus helping to validate the interview findings.
Brambilla F, Bellodi L, Perna G, Battaglia M, Sciuto G, Diaferia G, Petraglia F, Panerai A, Sacerdote P: PSYCHOIMMUNOENDOCRINE ASPECTS OF PANIC DISORDER. Neuropsychobiology 1992; 26(1-2):12-22. Summary: Immunological, neuroendocrine and psychological parameters were examined in 14 psychophysically healthy subjects and in 17 panic disorder patients before and after a 30-day course of alprazolam therapy. T lymphocyte proliferation in response to the mitogen phytohemagglutinin, lymphocyte beta-endorphin (beta-EP) concentrations, plasma ACTH, cortisol and beta-EP levels were examined in basal conditions and after corticotropin-releasing hormone (CRH) stimulation. Cortisol inhibition by dexamethasone (DST) and basal growth hormone (GH) and prolactin levels were also examined. Depression, state or trait anxiety, anticipatory anxiety, agoraphobia, simple and social phobias, severity and frequency of panic attacks were monitored by rating scales. The immune study did not reveal any significant difference between patients and controls, or any effect of alprazolam therapy. The hormonal data for the two groups were similar, except for higher than normal basal ACTH and GH plasma levels, lower than normal ratios between the ACTH and cortisol responses to CRH, and blunted DST in some patients. All the impairments improved after alprazolam therapy, in parallel with decreases in anxiety and in severity and frequency of panic attacks.
Lesch KP, Wiesmann M, Hoh A, Muller T, Disselkamp-Tietze J, Osterheider M, Schulte HM: 5-HT1A RECEPTOR-EFFECTOR SYSTEM RESPONSIVITY IN PANIC DISORDER. Psychopharmacology 1992; 106(1):111-7. Summary: To explore 5-HT1A receptor responsivity in panic disorder (PD), hypothermic, neuroendocrine and behavioral responses to the selective partial 5-HT1A receptor agonist ipsapirone (IPS) were investigated in patients with primary PD and healthy controls. Fourteen patients and matched controls received a single oral dose of 0.3 mg/kg IPS or placebo under double-blind, random-assignment conditions. IPS induced hypothermia and corticotropin (ACTH)/cortisol release but had only minimal effects on behavior. Compared with controls, the patients with PD exhibited significantly attenuated thermoregulatory and neuroendocrine responses to IPS. Although the healthy subjects reported increased drowsiness and the PD patients rated themselves more nervous and less calm following administration of IPS, no consistent changes in ratings of anxiety or panic symptoms were recorded. The impaired hypothermic and ACTH/cortisol responses following 5-HT1A receptor activation reflects subsensitivity of both the pre- and post-synaptic 5-HT1A receptor-effector system, thus supporting the hypothesis that a 5-HT1A receptor-related serotonergic dysfunction may be linked to the pathophysiology of PD. Future studies of 5-HT1A receptor-effector complex function in conjunction with assessment of the responsivity of other subtypes (e.g. 5-HT2, 5-HT3) should promote the evaluation of 5-HT system integrity in anxiety disorders and its involvement in anxiolytic drug effects.
Marazziti D, Ambrogi F, Vanacore R, Mignani V, Savino M, Palego L, Cassano GB, Akiskal HS: IMMUNE CELL IMBALANCE IN MAJOR DEPRESSIVE AND PANIC DISORDERS. Neuropsychobiology 1992; 26(1-2):23-6. Summary: We investigated subsets of peripheral immunologic cells in 12 drug-free patients affected by major depression according to DSM-III-R criteria, and who had recent evidence of somatic diseases. They were compared with 10 drug-free depressives, with 10 patients with panic disorder, and with 12 healthy volunteers, all without somatic disease. The immune subsets were measured by flow cytometry. The results showed that both groups of depressives had the same abnormalities in immune cells compared with the healthy volunteers or the panic disorder patients; in particular they presented a lower number of CD3+, CD8+ and HLA-DR+. The patients with panic attacks did not differ from healthy controls, except for CD4+ cells which were significantly lowered, even in comparison with the depressive groups. These data, although preliminary and in a small sample, suggest that some immune parameters may be influenced by the presence of a major psychiatric disorder.
Rosen MI, Kosten T: COCAINE-ASSOCIATED PANIC ATTACKS IN METHADONE-MAINTAINED PATIENTS. American Journal of Drug & Alcohol Abuse 1992; 18(1):57-62. Summary: The incidence of panic attacks methadone-maintained patients has increased over a 10-year period from 1 to 6-13%. Cocaine use appears to be associated with this increase, although other environmental and constitutional factors may be contributory. Patients with cocaine-associated panic differ from other panic patients in rates of psychiatric hospitalization and medical illness, but not in depression, other drug use, or agoraphobia.
Yeragani VK, Balon R, Pohl R, Weinberg P, Thomas S: LEFTWARD SHIFT OF R-AXIS ON ELECTROCARDIOGRAM IN PATIENTS WITH PANIC DISORDER AND DEPRESSION. Neuropsychobiology 1992; 25(2):91-3. Summary: In a prospective study, we have compared R-axis on routine electrocardiograms of panic disorder patients (n = 52) with that of depressed patients (n = 41) and normal controls (n = 65). All subjects were physically healthy and were normotensive. There was a significant leftward shift of R-axis in both depressed and panic disorder patients compared to normal controls. The implications of these findings are discussed.
Breslau N, Davis GC: MIGRAINE, MAJOR DEPRESSION AND PANIC DISORDER: A PROSPECTIVE EPIDEMIOLOGIC STUDY OF YOUNG ADULTS. Cephalalgia 1992; 12(2):85-90. Summary: We examined prospectively the risk for major depression (MDD) and panic disorder in persons with prior history of migraine. A random sample of 995 young adults was interviewed in 1989 and reinterviewed in 1990. A history of migraine at baseline increased fourfold the risk for MDD during the follow-up interval. A history of any anxiety disorder exacerbated the risk for MDD in persons with migraine. Persons with a history of migraine were twelve times more likely to become cases of panic disorder than those with no history of migraine. The risk for MDD and/or panic disorder was unrelated to whether or not migraine was active during the year preceding the baseline interview or in remission for more than one year. The findings suggest that migraine, major depression and anxiety disorders might share common predispositions.
Wang ZW, Crowe RR, Noyes R Jr: ADRENERGIC RECEPTOR GENES AS CANDIDATE GENES FOR PANIC DISORDER: A LINKAGE STUDY. American Journal of Psychiatry 1992; 149(4):470-4. Summary: OBJECTIVE: Several lines of investigation suggest that the noradrenergic neurotransmitter system may be involved in the pathogenesis of panic disorder. Since a mutation in a gene coding for one of the adrenergic receptors could account for both the familial nature and autonomic dysfunction of panic disorder, the authors performed analyses of the linkage between panic disorder and five adrenergic receptor loci. METHOD: The subjects were 14 multiplex pedigrees with DSM-III panic disorder or agoraphobia with panic attacks. The loci tested were the alpha 1/beta 2 pair on chromosome 5q32-q34, the alpha 2/beta 1 pair on chromosome 10q24-q26, and a second alpha 2 locus on chromosome 4. Flanking loci were included in the analysis on chromosomes 5 and 10 to increase the informativeness of the adrenergic receptor loci. RESULTS: Lod scores less than -2.0 were found at all five receptor loci. CONCLUSIONS: These findings provide strong evidence against the possibility that genetic mutation at any of these loci is responsible for panic disorder in these pedigrees.
Newman F, Stein MB, Trettau JR, Coppola R, Uhde TW: QUANTITATIVE ELECTROENCEPHALOGRAPHIC EFFECTS OF CAFFEINE IN PANIC DISORDER. Psychiatry Research 1992; 45(2):105-13. Summary: It has been demonstrated that patients with panic disorder are more sensitive than normal control subjects to the anxiogenic effects of caffeine. The underlying physiologic basis for this difference is unclear. We examined the electroencephalographic (EEG) activity of seven patients with panic disorder and seven normal control subjects during the randomized double-blind, placebo-controlled administration of oral caffeine (7 mg/kg). EEG data were collected on-line from 28 electrodes; artifact-free epochs were selected manually for off-line Fourier transformation. Caffeine was associated with a significant increase in peak occipital alpha frequency and significant decreases in occipital alpha amplitude, central beta amplitude, and central theta amplitude. Despite the observation that caffeine increased anxiety more in the patients with panic disorder than in the normal control subjects, the two groups did not differ in their EEG responses to caffeine.
Stein JM, Papp LA, Klein DF, Cohen S, Simon J, Ross D, Martinez J, Gorman JM: EXERCISE TOLERANCE IN PANIC DISORDER PATIENTS. Biological Psychiatry 1992; 32(3):281-7. Summary: Sixteen panic patients and fifteen normal controls performed submaximal exercise testing on a bicycle ergometer. Only one patient subject panicked. Biochemical, physiological, and psychological data showed similar exercise tolerance in both patients and controls. Exercise-induced distress and lactate increment do not appear to cause panic attacks.
Pitchot W, Ansseau M, Gonzalez Moreno A, Hansenne M, von Frenckell R: DOPAMINERGIC FUNCTION IN PANIC DISORDER: COMPARISON WITH MAJOR AND MINOR DEPRESSION. Biological Psychiatry 1992; 32(11):1004-11. Summary: Several lines of evidence suggest that dopamine might be involved in anxiety states. In this study, we assessed the growth hormone (GH) response to apomorphine (a dopaminergic agonist) 0.5 mg SC in nine drug-free inpatients meeting Research Diagnostic Criteria (RDC) for panic disorder who were age-matched and gender-matched with nine major depressive, and nine minor depressive inpatients. The three groups differed significantly in their mean GH peak response: 5.29 +/- 2.75 ng/ml in major depressives, 26.27 +/- 12.71 ng/ml in minor depressives, and 37.28 +/- 10.58 ng/ml in panics, with a significantly higher response in panic than in either minor or major depressive patients. These results support dopaminergic overactivity in panic disorder as compared with major and minor depression.
Nutt D, Lawson C: PANIC ATTACKS. A NEUROCHEMICAL OVERVIEW OF MODELS AND MECHANISMS. [REVIEW]. British Journal of Psychiatry 1992; 160:165-78. Summary: The delineation of panic disorder as a distinct diagnostic entity has provided renewed impetus for research into panic. This review describes and examines the range of neurobiological theories of panic attacks. It illustrates the diversity of mechanisms that have been invoked to explain the production of panic attacks, and which have influenced much of the current thinking about the neurochemistry of anxiety. [References: 171]
Uhde TW, Tancer ME, Rubinow DR, Roscow DB, Boulenger JP, Vittone B, Gurguis G, Geraci M, Black B, Post RM: EVIDENCE FOR HYPOTHALAMO-GROWTH HORMONE DYSFUNCTION IN PANIC DISORDER: PROFILE OF GROWTH HORMONE (GH) RESPONSES TO CLONIDINE, YOHIMBINE, CAFFEINE, GLUCOSE, GRF AND TRH IN PANIC DISORDER PATIENTS VERSUS HEALTHY VOLUNTEERS. [REVIEW]. Neuropsychopharmacology 1992; 6(2):101-18. Summary: Given the abrupt and time-limited nature of daytime-awake and nocturnal-sleep panic attacks, several chemical and neuroendocrine challenge tests have been employed to investigate the neurobiology of "spontaneous" panic attacks. Previously we demonstrated that panic disorder patients have blunted growth hormone (GH) responses to clonidine, an alpha 2-adrenergic agonist. However, the mechanism of this blunted response and the role of hypothalamic-GH dysfunction, if any, remains unclear. To further delineate the status of hypothalamic-GH function in panic disorder, we review the literature and present original data on the GH responses to a number of different chemical and neuroendocrine challenge paradigms. Although stress-mediated increases in GH are thought to be a common correlate of stress in humans, our findings indicate that panic disorder patients have significantly blunted GH responses to clonidine, yohimbine, growth-hormone releasing factor, and caffeine compared to normal control subjects. A similar trend was noted in the delayed rise in GH after glucose challenge. There was no difference in the rate of abnormal GH responses to thyrotropin-releasing hormone in panic disorder compared to normal control subjects. No drug or neuroendocrine challenge, even if associated with marked increases in anxiety, produced a significantly enhanced GH response compared to normal control subjects. These findings provide support for a hyporesponsive hypothalamic-GH system in panic disorder. These observations, combined with preliminary observations from our clinic of short stature in several cases of prepubescent children with anxiety disorders, also underscore the need for assessing early growth patterns in individuals with panic disorder. Strategies for investigating the site(s) of possible neurotransmitter or hypothalamic-GH-somatomedin dysfunction are discussed. [References: 128]
Krystal JH, Leaf PJ, Bruce ML, Charney DS: EFFECTS OF AGE AND ALCOHOLISM ON THE PREVALENCE OF PANIC DISORDER. Acta Psychiatrica Scandinavica 1992; 85(1):77-82. Summary: Findings are reported evaluating the effects of aging and alcoholism histories on the 6-month prevalence rates of panic disorder. The data were collected in 5 communities as part of the Epidemiologic Catchment Area (ECA) study: New Haven, CT; Baltimore, MD; St. Louis, MO; Durham, NC; and Los Angeles, CA. Reanalysis of ECA data provided additional support for a decline in the prevalence of panic disorder among elderly people. In addition, the presence of a history of alcohol abuse or dependence was associated with significantly elevated panic disorder rates in younger individuals, but an earlier decline in panic disorder prevalence with age, regardless of gender. These findings offer preliminary support for neurodevelopmental hypotheses for the onset and outgrowing of panic disorder. They also highlight the impact of alcoholism on the course of panic disorder.
Coplan JD, Liebowitz MR, Gorman JM, Fyer AJ, Dillon DJ, Campeas RB, Davies SO, Martinez J, Klein DF: NORADRENERGIC FUNCTION IN PANIC DISORDER. EFFECTS OF INTRAVENOUS CLONIDINE PRETREATMENT ON LACTATE INDUCED PANIC. Biological Psychiatry 1992; 31(2):135-46. Summary: To assess the role of noradrenergic stimulation during lactate-induced panic, ten patients with panic disorder who panicked during a standard sodium-lactate infusion underwent a repeat infusion following intravenous clonidine pretreatment. Although clonidine significantly lowered prelactate systolic blood pressure, the drug did not significantly lower prelactate anxiety levels, as reflected by the Acute Panic Inventory (API). Clonidine blocked lactate-induced panic in four of ten subjects, a significant effect. Clonidine treatment also significantly attenuated lactate-panic symptoms, as reflected by time to panic and API comparison between trials. Nevertheless, over half the subjects still panicked in response to lactate despite clonidine. This preliminary study suggests that reduction of central noradrenergic activity by clonidine, at least at the dosage levels employed in the current study, only partially attenuates panic response to lactate. Noradrenergic theories of panic may not therefore fully account for lactate panicogenesis.
Zandbergen J, Strahm M, Pols H, Griez EJ: BREATH-HOLDING IN PANIC DISORDER. Comprehensive Psychiatry 1992; 33(1):47-51. Summary: In earlier studies, it was found that exogenous carbon dioxide administration provoked high anxiety in panic disorder (PD) patients, whereas healthy normals and patients suffering from other anxiety disorders were hardly affected. Breath-holding provides a simple method to induce endogenous CO2 accumulation. Fourteen PD patients, 14 patients suffering from other anxiety disorders, and 14 healthy controls were asked to hold their breath as long as possible. Apnea times appeared to be longer in the normal control group than in the other two groups. Using a one-tailed t test, a trend for a difference was found between the PD subjects and other anxiety patients, the PD patients having slightly lower values. No differences were found with respect to increase in anxiety during breath-holding or the ratio of apnea times before and after hyperventilation.
Asnis GM, Wetzler S, Sanderson WC, Kahn RS, van Praag HM: FUNCTIONAL INTERRELATIONSHIP OF SEROTONIN AND NOREPINEPHRINE: CORTISOL RESPONSE TO MCPP AND DMI IN PATIENTS WITH PANIC DISORDER, PATIENTS WITH DEPRESSION, AND NORMAL CONTROL SUBJECTS. Psychiatry Research 1992; 43(1):65-76. Summary: The relationship between norepinephrine (NE) and serotonin (5-hydroxytryptamine; 5HT) functioning was explored in a neuroendocrine challenge paradigm. Ten normal control subjects, 17 patients with major depression, and 22 patients with panic disorder volunteered to participate in this study. Each subject received a challenge with meta-chlorophenylpiperazine (MCPP; 0.25 mg/kg, p.o.), a 5HT agonist, and desmethylimipramine (DMI; 75 mg, i.m.), an indirect NE agonist, in randomized order. The peak-minus-baseline cortisol response to MCPP was used as an indicator of 5HT function, and cortisol response at 75 minutes-minus-baseline to DMI was used as an indicator of NE function. The cortisol responses to DMI and MCPP were found to be highly negatively correlated in the total sample, in particular in the patients with major depression and panic disorder. This finding suggests that the functions (or dysfunctions) of the NE and 5HT systems may not be separate as is usually believed, and that the NE and 5HT disturbances observed in major depression and panic disorder may not be independent. Rather, there may be a joint disturbance of NE-5HT in these disorders.
Beitman BD, Thomas AM, Kushner MG: PANIC DISORDER IN THE FAMILIES OF PATIENTS WITH NORMAL CORONARY ARTERIES AND NON-FEAR PANIC DISORDER. Behaviour Research & Therapy 1992; 30(4):403-6. Summary: Patients with non-fear panic disorder (NFPD) meet DSM-III-R criteria for panic disorder, but do not report subjective fear or anxiety. Although apparently common in medical settings, this controversial group is in need of further diagnostic validation. This study assessed family history of panic disorder in patients with chest pain and normal coronary arteries (CP/NCA) and either NFPD, panic disorder with fear, or no panic. It was hypothesized that the two panic disorder groups would have similar, elevated rates of panic disorder in their first-degree relatives, compared to patients without panic. The results support the hypothesis; about 17% of the first-degree relatives of both NFPD and panic disorder patients were diagnosable with panic disorder according to proband interviews, whereas only 4.6% of the first-degree relatives of patients without panic were so diagnosable. These results support the diagnostic validity of NFPD in CP/NCA patients, because such patients had a family history of panic disorder similar to patients with a more classical panic disorder presentation. The lack of fear symptoms and behavior in NFPD may cause panic disorder to be overlooked as a potential cause of somatic symptoms in patients with no medical explanation for their condition.
Bradwejn J, Koszycki D, Payeur R, Bourin M, Borthwick H: REPLICATION OF ACTION OF CHOLECYSTOKININ TETRAPEPTIDE IN PANIC DISORDER: CLINICAL AND BEHAVIORAL FINDINGS. American Journal of Psychiatry 1992; 149(7):962-4. Summary: Eleven patients with panic disorder were challenged with cholecystokinin tetrapeptide (CCK-4) on two occasions. The effects of CCK-4 were consistent except symptom onset was more rapid with the second injection. Demonstrating that the effects of CCK-4 are reproducible in panic patients opens the doors for studies of the effects of drug treatment on CCK-4-induced panic.
Abelson JL, Glitz D, Cameron OG, Lee MA, Bronzo M, Curtis GC: ENDOCRINE, CARDIOVASCULAR, AND BEHAVIORAL RESPONSES TO CLONIDINE IN PATIENTS WITH PANIC DISORDER. Biological Psychiatry 1992; 32(1):18-25. Summary: We examined adrenergic regulation in patients with panic disorder by challenging 10 patients and 14 age-matched and sex-matched controls with intravenous infusions of clonidine hydrochloride (2 micrograms/kg), an alpha 2-adrenoreceptor agonist. Growth hormone, 3-methoxy-4-hydroxyphenylglycol (MHPG), blood pressure, heart rate, and behavioral (anxiety, sedation) responses were monitored. The data replicated the previously reported finding of blunted growth hormone (GH) responses to clonidine in patients with panic disorder. Reported abnormalities in MHPG, cardiovascular, and behavioral responses of panic patients to clonidine infusion were not replicated. The robustly blunted GH response to clonidine in panic patients supports the adrenergic dysregulation hypothesis of panic disorder, but alternative interpretations of this finding are available and further study is needed.
Pallanti S, Mazzi D: MDMA (ECSTASY) PRECIPITATION OF PANIC DISORDER. Biological Psychiatry 1992; 32(1):91-5. Summary: The authors describe three patients whose panic disorder began during recreational use of MDMA (Ecstasy) and was subsequently complicated by agoraphobic avoidance that continued autonomously after cessation of the drug. Their panic disorder responded well to serotoninergic antidepressant drugs. Theoretical and practical implications are discussed.
Bajwa WK, Asnis GM, Sanderson WC, Irfan A, van Praag HM: HIGH CHOLESTEROL LEVELS IN PATIENTS WITH PANIC DISORDER. American Journal of Psychiatry 1992; 149(3):376-8. Summary: OBJECTIVE: This study was undertaken to help clarify whether the higher cholesterol levels found in patients with panic disorder are a complication of panic disorder only or are associated with any psychiatric disorder. METHOD: The subjects of the study were 30 patients with panic disorder and 30 patients with major depression, diagnosed according to the Structured Interview for DSM-III-R, and 30 normal control subjects. The three groups were matched for sex and age, and none of the subjects had alcohol/drug abuse, abnormal ECGs, or unstable medical conditions. Blood samples were drawn at random times, and serum cholesterol levels were determined. RESULTS: The patients with panic disorder had significantly higher serum cholesterol levels than did the patients with major depression and the normal control subjects. Among the patients with major depression, histories (current or past) of anxiety disorders were associated with significant elevation of serum cholesterol levels. The presence of stable medical conditions was not associated with higher cholesterol levels in any of the three groups of subjects. CONCLUSIONS: Higher cholesterol levels were particularly associated with panic disorder in comparison with major depression. Higher levels of cholesterol in panic disorder are hypothesized to be a result of increased noradrenergic activity, which may be the underlying biological/neurochemical mechanism for symptoms of panic disorder, including anticipatory anxiety.
Kahn RS, van Praag HM: PANIC DISORDER: A BIOLOGICAL PERSPECTIVE. [REVIEW]. European Neuropsychopharmacology 1992; 2(1):1-20. Summary: Panic disorder (PD) was first delineated as a separate diagnostic entity 25 years ago. It is a prevalent disorder that responds well to pharmacological interventions, most notably to antidepressants and benzodiazepines. PD and other psychiatric disorders, such as generalized anxiety disorder and major depression, overlap clinically, but it is unresolved whether they also overlap biologically. Finally, the pathogenesis of PD is still unclear. Theories linking panic to increased sensitivity to CO2 or serotonin are preliminary, while alpha 2-adrenergic dysregulation in panic is still unproven. However, the development of new, selective, receptor agonists and antagonists in combination with imaging techniques may produce some of the answers to the questions raised since. [References: 172]
Satoh K, Fujii I: CURRENT VIEWS ON PANIC DISORDER AND ITS MANAGEMENT IN JAPAN: A NATIONAL SURVEY. Japanese Journal of Psychiatry & Neurology 1992; 46(1):45-53. Summary: In a national random-sample survey, the views of 1,069 practicing clinicians, including internists, surgeons and psychiatrists, on panic disorder were surveyed by using a series of questionnaires. In spite of a high rate of clinical experience and agreements on the symptoms among clinicians, the nature of this disorder, such as a common descriptive diagnosis, and the preferred treatment have not been agreed upon by the Japanese medical community. Furthermore, respondents were questioned as to the preferred treatment for panic disorder, but no treatment was regarded as critical by a majority of clinicians. It is concluded that because of the high potential patient population with panic disorder, clinical research that will provide more adequate diagnosis and treatment for this disorder is necessary in Japan.
Pollack MH, Otto MW, Rosenbaum JF, Sachs GS: PERSONALITY DISORDERS IN PATIENTS WITH PANIC DISORDER: ASSOCIATION WITH CHILDHOOD ANXIETY DISORDERS, EARLY TRAUMA, COMORBIDITY, AND CHRONICITY. Comprehensive Psychiatry 1992; 33(2):78-83. Summary: The rates of comorbid personality disorders in patients with panic disorder are reported to be elevated, have an adverse impact on the response to treatment, and increase the likelihood of relapse on treatment discontinuation. We examined the rates of personality disorders in panic disorder patients in a longitudinal, naturalistic study of panic disorder. Of 100 panic disorder patients studied, 42 met criteria for at least one personality disorder as determined by the Personality Disorder Questionnaire-Revised (PDQ-R). The presence of a personality disorder as determined by the PDQ-R was associated with a past history of childhood anxiety disorders, comorbidity with other anxiety disorders and depression, and a chronic, unremitting course of panic disorder in adulthood. The presence of a personality disorder in these patients was not significantly associated with a history of physical or sexual abuse in childhood. Our findings support the notion that an anxiety diathesis, demonstrated by significant difficulties with anxiety in childhood, influences the development of apparent personality dysfunction in panic patients. In other cases, personality pathology may reflect the presence of comorbid anxiety disorders or depression. The association of personality disorder in panic patients with a more unremitting course of illness underscores the importance of axis II pathology in understanding the longitudinal course of panic disorder.
Buller R, Winter P, Amering M, Katschnig H, Lavori PW, Deltito JA, Klerman GL: CENTER DIFFERENCES AND CROSS-NATIONAL INVARIANCE IN HELP-SEEKING FOR PANIC DISORDER. A REPORT FROM THE CROSS-NATIONAL COLLABORATIVE PANIC STUDY. Social Psychiatry & Psychiatric Epidemiology 1992; 27(3):135-41. Summary: Help-seeking behaviour for treatment of panic disorder was investigated in the sample of the Cross-National Collaborative Panic Study Second Phase. A total of 1168 patients were entered into this trial in 14 countries. Although there were significant center differences in prior treatment and utilization of health services there were also similarities. Treatment had been provided mainly by general practitioners. Drug treatment consisted mostly of prescription of classical tranquilizers and had a longer duration than treatment by psychotherapy. Patients with agoraphobic avoidance, past major depression and longer duration of illness used medical and psychiatric treatment facilities more intensely. Older and more severely disabled subjects were more frequently treated by medical health care providers and were more likely to receive psychotropic drugs. The results indicate that general practitioners carry an important load in the treatment of panic disorders but may need more information about recent development in pharmacotherapy for this condition.
Coplan JD, Gorman JM, Klein DF: SEROTONIN RELATED FUNCTIONS IN PANIC-ANXIETY: A CRITICAL OVERVIEW. [REVIEW]. Neuropsychopharmacology 1992; 6(3):189-200. Summary: The antipanic utility of imipramine and monoamine oxidase inhibitors has led to hypotheses of noradrenergic and/or serotonin (5-HT)-related abnormalities underlying panic disorder (PD) and its agoraphobic complications. Further data support significant antipanic effects for agents with acute 5-HT reuptake blockade effects. It is unlikely that ameliorative effects observed following chronic administration of 5-HT drugs remain 5-HT specific. Despite a range of recently discovered 5-HT receptor subtypes, evidence for a specific receptor abnormality in PD is lacking. Preclinical studies suggest an important role for 5-HT effects in several animal models of anxiety, including separation-induced infant protest responses and respiratory modulation. Induction of anxiety with putative 5-HT agents such as meth-chloro-phenylpiperazine and fenfluramine lend further support to 5-HT involvement in anxiety states. Critical behavioral, physiologic, and neuroendocrine differences between putative 5-HT anxiogens and "classic" panicogens, such as lactate and carbon dioxide are discussed. We propose that 5-HT agents mediate antipanic effects through amelioration of a deranged internal evaluative mechanism along cybernetic lines, rather than simple augmentation or reduction of 5-HT function. [References: 103]
Deci PA, Lydiard RB, Santos AB, Arana GW: ORAL CONTRACEPTIVES AND PANIC DISORDER. Journal of Clinical Psychiatry 1992; 53(5):163-5. Summary: BACKGROUND: There are no published reports of an association between triphasic oral contraceptives and the development of panic disorder. METHOD: The authors describe two cases in which the use of triphasic oral contraceptives in women appear to have precipitated panic disorder. Treatment with the triphasic oral contraceptives was stopped and the patients were followed for 2 years. RESULTS: Both subjects had rapid and total resolution of their panic disorder symptoms following cessation of triphasic oral contraceptive medications. CONCLUSION: Triphasic oral contraceptives in some predisposed women may lead to precipitation of panic disorder.
Goldberg RJ: MEDICAL ASPECTS OF PANIC DISORDER . [REVIEW]. Rhode Island Medicine 1992; 75(5):265-70. Summary: Panic attacks may be due to one or more of a large number of underlying physical or psychiatric disorders. Only when these possible etiologies have been excluded may the diagnosis of panic disorder be established. [References: 67]
Kaplan GB: NEUROBIOLOGICAL ASPECTS OF PANIC DISORDER . [REVIEW]. Rhode Island Medicine 1992; 75(5):247-51. Summary: The limbic system, temporal cortex and the locus coeruleus are important brain regions in the neuroanatomy of panic states. There is evidence for beta- and alpha 2-adrenoreceptor abnormalities and pre- and post-synaptic serotonergic alterations in panic disorder subjects. The anti-panic effects of chronic antidepressant drug treatment may relate to their down-regulation of various components of noradrenergic function and overall enhancement of serotonergic function. The efficacy of benzodiazepine agents in panic disorder and the altered sensitivity of panic patients to benzodiazepine agonists and inverse agonists suggest that alterations in benzodiazepine/GABA receptors may have a role in this disorder. A variety of other pharmacological agents also provoke panic, demonstrating that the biological origins of this disorder are quite diverse and complicated. Most importantly, a variety of new agents that selectively affect different components of these neurotransmitter/receptor systems are being developed. These novel agents offer future promise of greater efficacy with less adverse effects for individuals with panic disorder. [References: 8]
Lydiard RB, Ballenger JC, Laraia MT, Fossey MD, Beinfeld MC: CSF CHOLECYSTOKININ CONCENTRATIONS IN PATIENTS WITH PANIC DISORDER AND IN NORMAL COMPARISON SUBJECTS. American Journal of Psychiatry 1992; 149(5):691-3. Summary: Cholecystokinin concentrations in the CSF of 25 patients with panic disorder and 16 normal comparison subjects were ascertained by radioimmunoassay. The patients with panic disorder had significantly lower CSF concentrations of cholecystokinin, which may reflect increased CNS cholecystokinin receptor sensitivity, reduced numbers of receptors, or a compensatory reduction in cholecystokinin octapeptide secondary to theoretically increased central cholecystokinin tetrapeptide activity.
Starcevic V, Uhlenhuth EH, Kellner R, Pathak D: PATTERNS OF COMORBIDITY IN PANIC DISORDER AND AGORAPHOBIA. Psychiatry Research 1992; 42(2):171-83. Summary: Diagnoses of comorbid disorders were determined in a sample of 54 patients with panic disorder as defined in DSM-III-R. The sample was divided into the following three groups: (1) uncomplicated panic disorder (PDU); (2) panic disorder with mild agoraphobia (PDM); and (3) panic disorder with moderate to severe agoraphobia (PDA). In comparison with patients with PDU, patients with PDA had higher comorbidity rates in general, received multiple comorbid diagnoses more frequently, had a higher prevalence of major depression, dysthymia, social phobia, generalized anxiety disorder, and obsessive-compulsive disorder, and scored higher on most measures of self-rated psychopathology. These findings support the notion that PDA may be a disorder essentially different from PDU.
Andreoli A, Keller SE, Rabaeus M, Zaugg L, Garrone G, Taban C: IMMUNITY, MAJOR DEPRESSION, AND PANIC DISORDER COMORBIDITY. Biological Psychiatry 1992; 31(9):896-908. Summary: Because recent research reports indicated clinical and biological differences in major depression with and without comorbid Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) panic disorder, and as altered immune measures were reported in selected subgroups of depressive patients, we investigated 51 pairs of major depressive episode (MDE) subjects, and gender- and age-matched healthy controls in order to determine if T lymphocytes number and function abnormalities were associated with Panic Disorder comorbidty. We found that those MDE subjects with DSM-III-R panic disorder (PD) had greater numbers of T cells (p less than 0.05) and PHA mitogen (p less than 0.05) responses than depressive patients without PD, as well as increased phytohemagglutinin (PHA) (p less than 0.05) concanavalin A (ConA) (p less than 0.02) mitogen responses compared to their controls. These data suggest that panic disorder comorbidity significantly contributes to the variance of immunologic parameters in major depression and has to be carefully assessed within psychoimmunological studies of psychiatric patients with affective disorders.
Corrigan MH, Gillette GM, Quade D, Garbutt JC: PANIC, SUICIDE, AND AGITATION: INDEPENDENT CORRELATES OF THE TSH RESPONSE TO TRH IN DEPRESSION. Biological Psychiatry 1992; 31(10):984-92. Summary: We investigated the relationship between suicidality, agitation, panic attacks, and the thyrotropin-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH), and tested the hypothesis that panic would account for the association between a reduced TSH response and the other conditions. Twenty-seven euthyroid primary unipolar depressed inpatient women received a TRH test and systematic psychiatric assessment. Panic attacks were insufficient to explain the link between the TSH response and suicidal intent, lethality, and agitation; each condition was independently associated with a lower TSH response. In an additive fashion, copresence of conditions further reduced TSH response. The symptom constellation of panic, agitation, and suicidality in depression may correlate with the greatest reduction in TSH response.
Facchinetti F, Romano G, Fava M, Genazzani AR: LACTATE INFUSION INDUCES PANIC ATTACKS IN PATIENTS WITH PREMENSTRUAL SYNDROME. Psychosomatic Medicine 1992; 54(3):288-96. Summary: A sodium lactate test was performed during the premenstrual phase in 35 women suffering from prospectively confirmed premenstrual syndrome (PMS) and in 16 controls in order to assess whether these patients were sensitive to this test and whether this sensitivity was accounted for primarily by the presence of concomitant panic disorder. Patients with PMS also underwent the Structured Clinical Interview for the DSM-III-R (SCID) to determine the presence of co-morbid anxiety and/or mood disorders. Only 31% of the PMS patients were free from a depressive/anxiety disorder, while nine patients met criteria for panic disorder, and the remaining 15 subjects were diagnosed as having anxiety and/or mood disorders. Lactate infusion induced panic attacks in 22 subjects (62.9%) and two controls (12.5%). Panickers were equally distributed among PMS patients with or without a concurrent anxiety/mood disorder. Although cardiovascular responses to lactate were similar among PMS patients regardless of the presence of concomitant anxiety/mood disorders, both plasma cortisol levels and panic and mood scores were higher during the test in those patients with concomitant panic disorder. These results suggest that PMS patients display an increased sensitivity to lactate, which is not primarily accounted for by the presence of co-morbid panic disorder.
Gann H, Riemann D, Hohagen F, Dressing H, Muller WE, Berger M: THE SLEEP STRUCTURE OF PATIENTS WITH ANXIETY DISORDERS IN COMPARISON TO THAT OF HEALTHY CONTROLS AND DEPRESSIVE PATIENTS UNDER BASELINE CONDITIONS AND AFTER CHOLINERGIC STIMULATION. Journal of Affective Disorders 1992; 26(3):179-89. Summary: This study investigated sleep EEG during placebo and after cholinergic stimulation with RS 86 in 36 healthy subjects, 34 patients with major depression and 20 patients with anxiety disorders. Cholinergic stimulation with RS 86 led to a decrease of slow wave sleep and REM latency. RS 86 had a more profound impact on REM latency in patients with major depression than in healthy controls and patients with anxiety disorders. Six out of 36 healthy controls, three out of 20 patients with anxiety disorders and 24 of 34 patients with depression displayed sleep onset REM periods after cholinergic stimulation. Also effects on REM density and duration of the first REM period were more pronounced in major depression. Even in those patients with anxiety disorders and a secondary major depression no depression-like sleep abnormalities could be provoked. The results underline the usefulness of the cholinergic REM induction test to differentiate patients with major depression from those with other psychiatric disorders. The results can be interpreted as further evidence for the cholinergic-aminergic imbalance model of depression and for the reciprocal interaction model of nonREM-REM regulation.
Schwalberg MD, Barlow DH, Alger SA, Howard LJ: COMPARISON OF BULIMICS, OBESE BINGE EATERS, SOCIAL PHOBICS, AND INDIVIDUALS WITH PANIC DISORDER ON COMORBIDITY ACROSS DSM-III-R ANXIETY DISORDERS. Journal of Abnormal Psychology 1992; 101(4):675-81. Summary: Eighty-two women, presenting as normal-weight bulimics, obese binge eaters, social phobics, and individuals with panic disorder, were compared on anxiety, depression, and substance abuse. All were administered the Anxiety Disorder Interview Schedule-Revised and completed the Michigan Alcohol Screening Test, Drug Abuse Screening Test, and Self-Consciousness Scale. A striking proportion of eating disorder subjects were comorbid for one or more anxiety disorders, the most frequent diagnoses being generalized anxiety disorder and social phobia. The results suggest that the place of anxiety in bulimia nervosa goes beyond that discussed within the context of the anxiety reduction model. Conflicting comorbidity findings among this and prior investigations are noted, however, and discussed in terms of the issue of differential diagnosis between eating and anxiety disorders.
Shavitt RG, Gentil V, Mandetta R: THE ASSOCIATION OF PANIC/AGORAPHOBIA AND ASTHMA. CONTRIBUTING FACTORS AND CLINICAL IMPLICATIONS. General Hospital Psychiatry 1992; 14(6):420-3. Summary: The point prevalence of phobic anxiety disorders was determined in 107 asthmatic outpatients through a standardized psychiatric interview and DSM-III-R diagnostic criteria. Agoraphobia and panic disorder were more prevalent (13.1% and 6.5%, respectively) than in the general population. Contributing factors and the clinical implications of this association are discussed. The recognition of specific anxiety syndromes enhances the efficacy of the treatment of anxious asthmatic patients.
Bystritsky A, Shapiro D: CONTINUOUS PHYSIOLOGICAL CHANGES AND SUBJECTIVE REPORTS IN PANIC PATIENTS: A PRELIMINARY METHODOLOGICAL REPORT. Biological Psychiatry 1992; 32(9):766-77. Summary: Six panic disorder patients and six matched control subjects were studied using a new technique allowing continuous and simultaneous monitoring of physiological responses (blood pressure, heart rate, respiration) and subjective reports of anxiety and panic. This was done before, during, and after CO2 inhalation. Panic patients had significantly higher variability in their heart rate, blood pressure, and breathing rate than the control subjects. They also had irregular breathing patterns with frequent pauses. We identified three different patterns of response to CO2 inhalation in the panic patients. Some patients who panicked on CO2 showed a definite association between changes in physiological responses that preceded their subjective ratings of anxiety; however, others did not show this pattern. The possibility of different physiological mechanisms of panic in different patients is discussed.
Lauer CJ, Krieg JC, Garcia-Borreguero D, Ozdaglar A, Holsboer F: PANIC DISORDER AND MAJOR DEPRESSION: A COMPARATIVE ELECTROENCEPHALOGRAPHIC SLEEP STUDY. Psychiatry Research 1992; 44(1):41-54. Summary: Family studies suggest some common etiological factors in panic disorder and depression. The observation of characteristic depression-like polysomnographic alterations in panic disorder patients would further underline the assumed biological interface between the two psychiatric disorders. In a polysomnographic study of 22 inpatients with panic disorder, 12 inpatients with major depression, and 12 control subjects, we found that both groups of patients had one major feature of depression-like sleep: a shortened rapid eye movement (REM) latency. However, the patterns of the first hours of polysomnography showed more differences than similarities between these psychiatric disorders, indicating that the shortened REM latency apparently is merely a common final pathway of different alterations in sleep regulation. Our findings, therefore, provide more evidence against than for a significant biological interface between panic disorder and depression.
Moreau D, Weissman MM: PANIC DISORDER IN CHILDREN AND ADOLESCENTS: A REVIEW. [REVIEW]. American Journal of Psychiatry 1992; 149(10):1306-14. Summary: OBJECTIVE: Panic disorder has been considered an adulthood disorder that does not occur in children or adolescents. The authors' goals were to critically review the available evidence for panic attacks and/or panic disorder in children and adolescents, to review the limited data on the biological basis of panic disorder as it has been studied in children and adolescents, to discuss the possible treatment approaches for panic disorder in children, and to suggest potential opportunities for further research on panic disorder in children. DATA COLLECTION: Sixty-three articles pertaining to panic disorder in children and adolescents were critically reviewed. These articles included retrospective histories of adults with panic disorder, clinical case reports of children and adolescents with panic disorder, studies of psychiatrically referred children and adolescents, reports from epidemiologic community and school samples of children and adolescents, studies of children and adolescents at risk for psychiatric disorder, reports of panic-like symptoms in pediatric patients, family studies of panic, studies of the biological basis of panic in adults, and studies of treatment for panic. FINDINGS: There is strong evidence that panic disorder occurs in children and adolescents and that its clinical presentation in this population is similar to that found in adults. CONCLUSIONS: Extending the many adult studies of panic disorder to children and adolescents would be extremely fruitful. Like adults with panic disorder, many children and adolescents are brought to emergency and medical clinics for the physical symptoms of unrecognized panic disorder. [References: 63]
Targum SD: CORTISOL RESPONSE DURING DIFFERENT ANXIOGENIC CHALLENGES IN PANIC DISORDER PATIENTS. Psychoneuroendocrinology 1992; 17(5):453-8. Summary: The present study assessed the relation of cortisol response to anxiogenic reactivity during intravenous lactate infusion and oral fenfluramine in 12 panic disorder (PD) patients who responded positively to both challenges and in eight non-reactive control subjects. There was no significant cortisol response difference between the PD patients and the controls during lactate infusion, but there was s significant difference at 120 min during the fenfluramine challenge. These findings are consistent with the possibility that these challenges stimulate different neurobiologic mechanisms and that fenfluramine-precipitated anxiety is more akin to anticipatory or generalized anxiety than to true panic anxiety.
Yeragani VK, Berger R, Pohl R, Srinivasan K, Balon R, Ramesh C, Weinberg P, Berchou R: EFFECTS OF YOHIMBINE ON HEART RATE VARIABILITY IN PANIC DISORDER PATIENTS AND NORMAL CONTROLS: A STUDY OF POWER SPECTRAL ANALYSIS OF HEART RATE. Journal of Cardiovascular Pharmacology 1992; 20(4):609-18. Summary: We studied the effects of yohimbine on heart rate (HR) variability in 13 normal controls and 13 patients with panic disorder. Yohimbine produced a significant increase in SD of HR in standing posture in both patients (p = 0.01) and normal controls (p = 0.025). Panic disorder patients had a significant increase in standing absolute midfrequency (MF) power (0.07-0.15 Hz) after administration of yohimbine (p = 0.002). The ratio of post- to preyohimbine standing MF power (0.07-0.15 Hz) during standing was significantly higher in patients as compared with controls (2.3 +/- 1.08 vs. 1.33 +/- 0.38; p = 0.01), which suggests an increased responsivity of panic disorder patients to the adrenergic effects of yohimbine.
Payeur R, Lydiard RB, Ballenger JC, Laraia MT, Fossey MD, Zealberg J: CSF DIAZEPAM-BINDING INHIBITOR CONCENTRATIONS IN PANIC DISORDER. Biological Psychiatry 1992; 32(8):712-6. Summary: Diazepam-binding inhibitor (DBI) is a neuropeptide that has been detected in the brain and cerebrospinal fluid (CSF). Previous studies have suggested the possible role of DBI as a potential endogenous anxiogenic ligand modulating GABAergic transmission at the benzodiazepine-GABA receptor complex. The measurement of DBI immunoreactivity (DBI-IR) in CSF of panic-disorder patients and normal controls was undertaken to assess whether there were differences in the CSF concentration of this peptide to assess possible relationships with other monoamines and peptides. Lumbar CSF was obtained from 18 panic patients (4 men, 14 women) and 9 controls (5 men, 4 women). As a group, no significant differences were found between panic patients' CSF concentration of DBI-IR (1.12 +/- 0.27 pmol/mL) and normal volunteers (1.23 +/- 0.27 pmol/mL). No gender differences were demonstrated. However, we did find a positive correlation between CSF levels of DBI and CSF corticotropin releasing hormone (CRH) in our panic patients.
Hayward C, Killen JD, Hammer LD, Litt IF, Wilson DM, Simmonds B, Taylor CB: PUBERTAL STAGE AND PANIC ATTACK HISTORY IN SIXTH- AND SEVENTH-GRADE GIRLS. American Journal of Psychiatry 1992; 149(9):1239-43. Summary: OBJECTIVE: Although the incidence of first panic attacks appears to peak during adolescence, little is known about which features of adolescence contribute to the risk of a first panic episode. The purpose of this study was to compare the relative importance of age and pubertal stage in explaining the occurrence of panic attacks in adolescents. METHOD: From a school-based sample of sixth- and seventh-grade girls, 754 subjects completed both a structured clinical interview determining history of one or more panic episodes and a self-assessment of Tanner stages of pubertal development. A multiple logistic regression analysis was performed with panic attack history as the dependent variable and pubertal stage, age, and their interaction as the independent variables. RESULTS: A history of one or more four-symptom panic attacks was found in 5.3% of the girls (N = 40). After age was controlled for, pubertal stage was significantly related to panic attack history. At each age, higher rates of panic attacks were found in the more physically mature girls. CONCLUSIONS: Pubertal stage, after adjustment for the effects of age, appears to predict panic attack occurrence in young adolescent girls. Understanding the link between puberty and panic may offer clues regarding the onset and etiology of panic attacks.
Pohl R, Yeragani VK, Balon R, Lycaki H, McBride R: SMOKING IN PATIENTS WITH PANIC DISORDER. Psychiatry Research 1992; 43(3):253-62. Summary: We compared smoking prevalence in 217 patients with panic disorder with that in 217 age- and sex-matched control subjects who were obtained by telephone survey from the same neighborhoods. Data were obtained for current smoking habits and smoking status at either the onset of illness (patients) or 10 years previously (control subjects). Patients had been ill for 10.6 (SD = 10.0) years. Female patients with panic disorder had a significantly higher smoking prevalence at the onset of their illness than did control subjects 10 years previously (54% vs. 35%). The current smoking prevalence for female patients was also significantly higher than that of control subjects (40% vs. 25%). Male smoking rates did not differ between patients and control subjects. Caffeine use did not appear to explain these findings. These data suggest a link between smoking behavior and panic disorder in women.
Apostolopoulos M, Judd FK, Burrows GD, Norman TR: PROLACTIN RESPONSE TO DL-FENFLURAMINE IN PANIC DISORDER. Psychoneuroendocrinology 1993; 18(5-6):337-42. Summary: The objective of this study was to test the hypothesis that serotonin receptors are hypersensitive in patients with panic disorder. Eleven patients and 12 controls received a single PO dose of 60 mg of dl-fenfluramine at 0900h on a single occasion. Blood samples were collected with an indwelling intravenous catheter at 30-min intervals from 0930h to 1530h and prolactin determined by radioimmunoassay. In both groups, fenfluramine induced a rise in the plasma prolactin concentration from baseline. The patients showed a greater increase in prolactin response than the normal controls. This result is consistent with the hypothesis of increased serotonin receptor function in patients with panic disorder.
Maier W, Minges J, Lichtermann D: ALCOHOLISM AND PANIC DISORDER: CO-OCCURRENCE AND CO-TRANSMISSION IN FAMILIES. European Archives of Psychiatry & Clinical Neuroscience 1993; 243(3-4):205-11. Summary: The co-occurrence of alcoholism and anxiety disorders in epidemiological and clinical samples is well established. Self-medication of anxiety disorder probands with the anxiolytic substance alcohol might be one reason for this association. Common susceptibility factors of both disorders might be alternative explanations. Controlled family studies recruiting probands with panic disorder and alcoholism are powerful tools to answer this question. A family study of this kind, however, is not available. The present study investigated 113 families of probands with either panic disorder or alcoholism or both (but without affective or psychotic disorders) and 80 families of healthy controls in order to estimate the degree of co-occurrence of the two disorders in non-treated samples of relatives and to explore the magnitude of overlap between susceptibility factors of the two disorders. The co-occurrence of the two disorders was relatively rare in all samples of families under study. Overlap of susceptibility factors was demonstrated by an elevated risk of alcoholism in relatives of probands with panic disorder.
Maier W, Lichtermann D, Minges J, Oehrlein A, Franke P: A CONTROLLED FAMILY STUDY IN PANIC DISORDER. Journal of Psychiatric Research 1993; 27 Suppl 1:79-87. Summary: There are only a few family studies in panic disorder. Although there is some evidence that panic disorder is familial, the exact figures of the familial risk for this disorder are at variance across different studies; the impact of comorbidity and of the gender of relatives is also unclear. Family studies in panic disorder controlling for the comorbidity in probands are therefore indicated. This study presents the morbid risks in families of 40 "pure" panic disorder probands (DSM-III-R) without a history of psychotic disorders, major depression or alcoholism compared with families of 80 controls recruited in the general population. The relative frequency of panic disorder (DSM-III-R) in the first-degree relatives of panic disorder probands was 5.7% (the age corrected morbid risk is 7.9%) compared to 1.8% in relatives of healthy controls (age corrected morbid risk 2.3%). Agoraphobia segregated predominantly among female relatives of agoraphobic probands. An increased familial risk of major depression and of alcoholism was also observed. Comorbidity with alcoholism and major affective disorders was excluded in panic disorder probands by definition; therefore, these findings indicate that the etiological factors underlying panic disorder may overlap with those of alcoholism and those of unipolar major depression.
Reich J, Warshaw M, Peterson LG, White K, Keller M, Lavori P, Yonkers KA: COMORBIDITY OF PANIC AND MAJOR DEPRESSIVE DISORDER. Journal of Psychiatric Research 1993; 27 Suppl 1:23-33. Summary: The objective of this report is to determine whether those patients with panic disorder who have current major depression disorder (MDD) differ from those who do not in terms of demographics, comorbid disorders, severity of illness, nature of symptoms of panic attacks and psychosocial functioning. The sample consisted of 182 patients with current or history of panic disorder measured by standardized interview techniques. For analysis these patients were then divided by presence or absence of current MDD. The two groups were not different in age, sex, or marital status, age of onset, or symptom characteristics of panic attacks. However, patients with MDD were more likely to have Social Phobia and Generalized Anxiety Disorder, been hospitalized, made suicide attempts or gestures, have poorer psychosocial functioning, and currently be experiencing panic with more severe symptoms. These findings are discussed in terms of previous literature in the area.
Weissman MM: FAMILY GENETIC STUDIES OF PANIC DISORDER. [REVIEW]. Journal of Psychiatric Research 1993; 27 Suppl 1:69-78. Summary: A review of family and twin studies using specified diagnostic criteria shows the highly familial nature of panic disorder and suggests evidence for a genetic etiology. The population-based lifetime rates of panic disorder cross-nationally range between 1.2/100 and 2.4/100, whereas, the lifetime rates in first-degree relatives of panic probands range between 7.7/100 and 20.5/100. There is evidence from family and twin studies for the separation of panic disorder and generalized anxiety disorder. While there is a substantial comorbidity in individuals between panic disorder and major depression, these two disorders are separate conditions which are independently and specifically transmitted within families. The mode of transmission of panic disorder remains unclear. The high lifetime rates of panic disorder, strong evidence for vertical transmission, and the potential biological markers have increased interest in the application of modern linkage techniques. Several genetic linkage studies of panic disorder are ongoing. [References: 50]
Wittchen HU, Essau CA: EPIDEMIOLOGY OF PANIC DISORDER: PROGRESS AND UNRESOLVED ISSUES. [REVIEW]. Journal of Psychiatric Research 1993; 27 Suppl 1:47-68. Summary: Recent epidemiological studies have consistently shown that panic disorder, according to DSM-III, occurs in adults with a lifetime prevalence of about 2% and a 6-month prevalence of about 1.2%. Panic attacks are relatively common, with a lifetime rate of about 9%. Being female and divorced and separated is associated with higher prevalence of panic disorder. The hazard rates for panic disorder were highest between the ages of 25 and 34 years for females and between the ages of 30 and 44 years for males. Panic disorder frequently co-occurs with other anxiety disorders as well as with a wide range of mental disorders such as depression and substance use disorder. Based on few epidemiological studies, panic disorder has been found to have a chronic course with rare complete remission. Subjects with panic disorder were at an increased risk of social impairment, not getting along with their partners, as well as being financially dependent, and were likely to report fair or poor global physical health, and emotional health. Cases with panic disorder had the most severe psychosocial impairment and the worst outcome as compared to other anxiety disorders. Moreover, they are high users of all types of medical services, including mental health and general medical providers. Although recent epidemiological data, with its improved methodology, have considerably increased our knowledge concerning panic attack, panic disorder and agoraphobia, there are still major questions concerning the etiology, natural history, prevention, or control of panic disorder that need to be answered. Furthermore, since panic disorder has been considered as developing in stages, our current epidemiological knowledge cannot tell us in sufficient detail about the specific role of suggested risk factors in the development of panic disorder through its various stages. [References: 155]
Klein DF: FALSE SUFFOCATION ALARMS, SPONTANEOUS PANICS, AND RELATED CONDITIONS. AN INTEGRATIVE HYPOTHESIS . [REVIEW]. Archives of General Psychiatry 1993; 50(4):306-17. Summary: A carbon dioxide hypersensitivity theory of panic has been posited. We hypothesize more broadly that a physiologic misinterpretation by a suffocation monitor misfires an evolved suffocation alarm system. This produces sudden respiratory distress followed swiftly by a brief hyperventilation, panic, and the urge to flee. Carbon dioxide hypersensitivity is seen as due to the deranged suffocation alarm monitor. If other indicators of potential suffocation provoke panic this theoretical extension is supported. We broadly pursue this theory by examining Ondine's curse as the physiologic and pharmacologic converse of panic disorder, splitting panic in terms of symptomatology and challenge studies, reevaluating the role of hyperventilation, and reinterpreting the contagiousness of sighing and yawning, as well as mass hysteria. Further, the phenomena of panic during relaxation and sleep, late luteal phase dysphoric disorder, pregnancy, childbirth, pulmonary disease, separation anxiety, and treatment are used to test and illuminate the suffocation false alarm theory. [References: 188]
Zandbergen J, van Aalst V, de Loof C, Pols H, Griez E: NO CHRONIC HYPERVENTILATION IN PANIC DISORDER PATIENTS. Psychiatry Research 1993; 47(1):1-6. Summary: Arterial blood gases were measured and base excess calculated in 18 nonpanicking panic disorder (PD) patients, 12 subjects suffering from other anxiety disorders, and 18 normal control subjects. There was neither chronic nor clinically significant acute hyperventilation in either group.
De Cristofaro MT, Sessarego A, Pupi A, Biondi F, Faravelli C: BRAIN PERFUSION ABNORMALITIES IN DRUG-NAIVE, LACTATE-SENSITIVE PANIC PATIENTS: A SPECT STUDY. Biological Psychiatry 1993; 33(7):505-12. Summary: Using single photon emission computed tomography (SPECT) and 99mTc-hexamethylpropyleneamine oxime (HM-PAO), we assessed brain perfusion in seven patients with panic disorder (PD) and in five age-matched normal subjects at rest. No patient had ever received drug treatment for panic. All patients were sensitive to lactate-induced panic. Computed tomography (CT) scans did not reveal any morphological abnormalities of the brain in any of the PD patients. Two indices of cerebral perfusion were calculated; these demonstrated alterations of brain perfusion in the PD group. Significant right-left asymmetry was found in the inferior frontal cortex of the PD patients. We also observed a significant blood flow increase in the left occipital cortex and a significant decrease in the hippocampal regions bilaterally. Although the changes seen in the inferior frontal cortex and occipital cortex may be related to anxiety experienced by the patients during the study, the pattern of hippocampal hypoperfusion appears to be characteristic of panic disorder. This suggests that the hippocampal structures may play an important role in the pathophysiology of panic disorder.
Maddock RJ, Carter CS, Magliozzi JR, Gietzen DW: EVIDENCE THAT DECREASED FUNCTION OF LYMPHOCYTE BETA ADRENORECEPTORS REFLECTS REGULATORY AND ADAPTIVE PROCESSES IN PANIC DISORDER WITH AGORAPHOBIA. American Journal of Psychiatry 1993; 150(8):1219-25. Summary: OBJECTIVE: This study was designed to clarify the nature of the reduced function of the peripheral beta adrenoceptor system observed in panic disorder with agoraphobia. The authors hypothesized that this phenomenon reflected a regulatory and adaptive process. METHODS: Lymphocyte beta adrenoreceptor density and affinity, basal lymphocyte cAMP level, and isoproterenol-stimulated cAMP generation were measured in 27 untreated outpatients with panic disorder with agoraphobia and 24 healthy comparison subjects. Lymphocyte beta receptor attributes were again assessed in patients after 4 weeks of double-blind treatment with adinazolam (slow-release form) or placebo. Panic frequency, agoraphobic symptoms, overall anxiety, and improvement with treatment were assessed with standard rating instruments. RESULTS: Multivariate statistics revealed significantly lower beta receptor density and isoproterenol-stimulated cAMP generation in patients than in comparison subjects. beta receptor density tended to normalize after adinazolam but not after placebo. Pretreatment beta receptor density was lower in treatment responders than nonresponders. Patients with mild agoraphobia had lower cAMP responsivity than patients with moderate or severe agoraphobia. CONCLUSIONS: Decreased function of lymphocyte beta receptors in panic disorder with agoraphobia is expressed as both decreased density and decreased cAMP responsivity. This pattern of changes, and the tendency for receptor density to normalize with treatment, is consistent with an active, regulatory process rather than a structural deficit in the beta receptor system. Preliminary clinical findings suggest that these changes may reflect adaptive processes associated with a favorable clinical course in panic disorder with agoraphobia.
Papp LA, Klein DF, Gorman JM: CARBON DIOXIDE HYPERSENSITIVITY, HYPERVENTILATION, AND PANIC DISORDER. [REVIEW]. American Journal of Psychiatry 1993; 150(8):1149-57. Summary: OBJECTIVE: The purpose of this article is to offer a comprehensive, data-based explanation of the relationship between hyperventilation and panic disorder linking CO2 hypersensitivity, cognitive/behavioral factors, and the respiratory effects of antipanic pharmacologic and psychological treatments. METHOD: The authors conducted a computerized search of MEDLINE for relevant articles. RESULTS: Some panic patients have a chronic, subtle respiratory disturbance. Acute hyperventilation is neither necessary nor sufficient for panic to occur. Respiratory abnormalities in panic patients may adaptively aim at coping with a hypersensitive CO2 chemoreceptor system. Pharmacologic panicogens also stimulate the respiratory system, causing hyperventilation. Triggering this hypersensitive respiratory control mechanism may incite panic. Antipanic medications may reset the receptor threshold. Misattribution and catastrophic interpretation of somatic symptoms or the sense of loss of control may contribute to panic symptoms. Behavioral interventions such as desensitization or breathing retraining may block the full-blown attack. Cognitive strategies through cognitive control of respiration may supplement and accentuate these interventions. CONCLUSIONS: Panic disorder may be due to an inherently unstable autonomic nervous system, coupled with cognitive distress. [References: 108]
Koszycki D, Cox BJ, Bradwejn J: ANXIETY SENSITIVITY AND RESPONSE TO CHOLECYSTOKININ TETRAPEPTIDE IN HEALTHY VOLUNTEERS. American Journal of Psychiatry 1993; 150(12):1881-3. Summary: The authors determined whether fear of anxiety symptoms mediates panicogenic responses to cholecystokinin tetrapeptide (CCK-4) in healthy subjects. Individuals with a preexisting high level of anxiety sensitivity (N = 10) experienced significantly more catastrophic cognitions and fear of somatic symptoms than did subjects with low (N = 9) or medium (N = 17) anxiety sensitivity, but they were not more susceptible to experiencing a panic attack. Thus, cognitive factors do not appear to be critical determinants of CCK-4-induced panic attacks.
Silove D, Manicavasagar V: ADULTS WHO FEARED SCHOOL: IS EARLY SEPARATION ANXIETY SPECIFIC TO THE PATHOGENESIS OF PANIC DISORDER? Acta Psychiatrica Scandinavica 1993; 88(6):385-90. Summary: Although juvenile separation anxiety disorder is maintained to be a predisposing factor to adult panic disorder in DSM-III-R, past research has failed to clarify (a) whether it is separation anxiety per se or school refusal that is the pathogenic risk factor and (b) whether affected youngsters are specifically at risk of developing panic disorder rather than symptoms of general anxiety or phobias in later life. The present study of 74 adults who responded to media publicity found that a measure of early separation anxiety but not a history of school refusal was associated with risk of adult panic disorder according to DSM-III-R criteria. In contrast, separation anxiety scores were not associated with the presence or absence of general anxiety symptoms or phobic-avoidance in adulthood. Subjects with higher separation anxiety scores were more likely to have either a sibling or child with school refusal. Although the present study is limited in its method to mailed survey responses and, in part, to retrospective data, the results do provide additional support for Klein's influential separation anxiety theory of panic disorder.
Stein MB, Chartier M, Walker JR: SLEEP IN NONDEPRESSED PATIENTS WITH PANIC DISORDER: I. SYSTEMATIC ASSESSMENT OF SUBJECTIVE SLEEP QUALITY AND SLEEP DISTURBANCE. Sleep 1993; 16(8):724-6. Summary: To systematically assess sleep complaints in panic disorder (PD), the Pittsburgh Sleep Quality Index (PSQI) was administered to 34 untreated patients with DSM-III-R PD and 34 age-matched healthy controls (HC). PD patients reported significantly more impaired sleep than HC as indicated by higher global index scores on the PSQI (6.9 +/- 2.9 versus 3.1 +/- 2.0; p < 0.0001) and on four of seven of its subscales; sleep was worst among those PD patients with a prior history of major depression. Sixty-eight percent of patients with PD reported moderately or severely impaired sleep compared to only 15% of HC (chi 2 = 17.5, p < 0.0005). Twenty-six percent of PD patients--but none of the HC--complained of frequent awakenings in the preceding month because they "could not breathe comfortably" (Fisher's exact test, p < 0.00625). One-month prevalence of sleep panic in the patients was 18%; lifetime prevalence was 68%. Whereas these findings confirm previous reports of frequent sleep complaints in patients with PD, they also raise the possibility that some of the findings might be trait phenomena attributable to a history of mood disorder.
Graeff FG, Silveira MC, Nogueira RL, Audi EA, Oliveira RM: ROLE OF THE AMYGDALA AND PERIAQUEDUCTAL GRAY IN ANXIETY AND PANIC. [REVIEW]. Behavioural Brain Research 1993; 58(1-2):123-31. Summary: The amygdala (AM) and the periaqueductal gray (PAG) represent the rostral and the caudal pole, respectively, of a longitudinally organized neural system, that is responsible for the integration of behavioral and physiological manifestations of defensive reactions against innate and learned threats. Microinjection of benzodiazepine (BZD) anxiolytics, GABAA receptor agonists or 5-HT receptor antagonists into the AM has anxiolytic effects in conflict tests and other models of conditioned fear, while similar administration of 5-HT or of a 5-HT1A receptor agonist has anxiogenic effects. On the other hand, in the test of electrical stimulation of the PAG, microinjection of 5-HT, 5-HT mimetics, or of drugs that enhance the action of endogenous 5-HT into the same brain area has an antiaversive effect, like BZD and GABAA agonists. Furthermore, microinjection of midazolam, of the NMDA receptor antagonist AP-7, or of the 5-HT1A/1B receptor blocker propranolol increased the exploration of the open arms of the elevated plus-maze, having therefore an anxiolytic effect. These results point to an inhibitory role of the GABA-BZD system in both the AM and the PAG. In contrast, 5-HT seemingly enhances conditioned fear in the AM, while inhibiting unconditioned fear in the PAG. Thus, 5-HT2/1C antagonists reportedly release punished behavior when injected into the AM, whereas they antagonized the antiaversive effect of 5-HT, zimelidine and 5-HT1A/1B receptor blockers in the PAG. Since reported clinical studies revealed that one of such compounds, ritanserin, relieves generalized anxiety but tends to aggravate panic disorder, a relationship may be established between the AM and anxiety and the PAG and panic. [References: 58]
Locatelli M, Bellodi L, Perna G, Scarone S: EEG POWER MODIFICATIONS IN PANIC DISORDER DURING A TEMPOROLIMBIC ACTIVATION TASK: RELATIONSHIPS WITH TEMPORAL LOBE CLINICAL SYMPTOMATOLOGY. Journal of Neuropsychiatry & Clinical Neurosciences 1993; 5(4):409-14. Summary: Computerized EEG activity derived from the temporal lobes was investigated in normal subjects and panic disorder patients with and without depersonalization and/or derealization, in a resting condition and during an odor stimulation task. Panic patients without depersonalization or derealization showed an increase of fast and a decrease of slow activities independent of odor stimulation. Panic patients with depersonalization and/or derealization showed an increase of slow activity and bilateral lack of responsiveness in the fast alpha frequency band during odor stimulation. Findings suggest there are different EEG patterns in the temporal regions of the two different groups of panic patients during rest and activating conditions.
Katerndahl DA, Realini JP: LIFETIME PREVALENCE OF PANIC STATES. American Journal of Psychiatry 1993; 150(2):246-9. Summary: OBJECTIVE: Little is known about the prevalence of panic symptoms that do not meet criteria for panic disorder. This study was conducted to determine the prevalence of panic disorder, panic attacks, and limited-symptom attacks in the general population. METHOD: The authors identified a community-based sample of 1,683 randomly selected adults in 18 census tracts in San Antonio, Tex.; 1,306 of these subjects agreed to be interviewed with the Structured Clinical Interview for DSM-III. Subjects were classified as having panic disorder if they met DSM-III-R criteria, as having panic attacks if they had attacks of four or more panic symptoms but did not have panic disorder, and as having limited-symptom attacks if they had attacks of fewer than four symptoms but no full-blown panic attacks. RESULTS: The crude lifetime prevalence rates were 3.8% for panic disorder, 5.6% for panic attacks, and 2.2% for limited symptom attacks. Women had higher rates of panic disorder and panic attacks than men, but the difference between men and women was not statistically significant for limited-symptom attacks. No statistically significant differences in rates between Hispanic and either non-Hispanic white or black subjects were found. Non-Hispanic white subjects had higher rates of limited-symptom attacks than black subjects. CONCLUSIONS: The prevalence of limited-symptom attacks in this community-based study was 2.2%; black subjects had lower rates than non-Hispanic white subjects. Panic attacks appear to be at least as common as DSM-III-R panic disorder and, like panic disorder, are more common among women.
Bulbena A, Duro JC, Porta M, Martin-Santos R, Mateo A, Molina L, Vallescar R, Vallejo J: ANXIETY DISORDERS IN THE JOINT HYPERMOBILITY SYNDROME. Psychiatry Research 1993; 46(1):59-68. Summary: A case-control study was designed to test the association between joint hypermobility syndrome (JHS), an inherited disorder of collagen synthesis, and anxiety and phobic disorders. One hundred fourteen cases of JHS diagnosed at the rheumatology outpatient clinic of the Hospital del Mar (Barcelona) were compared to 59 control subjects randomly selected from patients seen at the same clinic. Both cases and controls were examined by a psychologist who used the Structured Clinical Interview for DSM-III-R and who was unaware of their medical diagnoses. DSM-III-R diagnoses of panic disorder, agoraphobia, and simple phobia, but not generalized anxiety disorder, dysthymic disorder, or major depression were found to be highly associated with JHS (age- and sex-adjusted odds ratio = 10.7). Mitral valve prolapse (MVP) was present only among JHS cases. Among cases of JHS, subjects with MVP were almost three times more likely to suffer from anxiety than subjects without MVP (odds ratio = 2.95), although the association was not statistically significant. The strong association between panic anxiety and JHS appears to occur at a higher level than the association between panic and MVP, and provides a new basis for further studies on the genetic background of panic-anxiety.
Vazquez A, Jimenez-Jimenez FJ, Garcia-Ruiz P, Garcia-Urra D: "PANIC ATTACKS" IN PARKINSON'S DISEASE. A LONG-TERM COMPLICATION OF LEVODOPA THERAPY. Acta Neurologica Scandinavica 1993; 87(1):14-8. Summary: A series of 31 Parkinson's disease (PD) patients suffering from panic attacks (PA), late in the evolution of their disease, was analyzed from a group of 131 levodopa-treated PD patients. We found that many of motor, sensory, and vegetative symptoms, previously described as complicating phenomena in PD, constituted some of the symptoms of panic disorders. Comparing PA series with the series of PD patients who did not complain of PA, we discovered a clear-cut relationship of PA with the presence of standing/gait troubles (p < 0.001), depression (p < 0.001), and dyskinesias/fluctuations (p < 0.001). The patients of the PA series also presented a more precocious age of PD onset, were put on levodopa therapy earlier, and needed to be treated with higher doses of levodopa than the patients without PA. Finally, we hypothesize that PA could be considered to be a sort of abstinence syndrome from levodopa, because they appears mostly (90.3%) in the OFF phase of fluctuations, and are relieved administering new doses of levodopa or dopaminergic agonists. Nevertheless, we suggest PA are not directly related to the pharmacological properties of levodopa, but to alterations of the noradrenergic systems in the CNS.
Yeragani VK, Pohl R, Berger R, Balon R, Ramesh C, Glitz D, Srinivasan K, Weinberg P: DECREASED HEART RATE VARIABILITY IN PANIC DISORDER PATIENTS: A STUDY OF POWER-SPECTRAL ANALYSIS OF HEART RATE. Psychiatry Research 1993; 46(1):89-103. Summary: We have previously found decreased standard deviations and mean consecutive differences of R-R intervals in panic disorder patients in standing posture, compared with control subjects. In the present study, we used spectral analysis of heart rate variability to examine autonomic function in 21 panic disorder patients and 21 normal control subjects. Patients had a significantly lower standard deviation of heart rate in supine as well as standing postures. Absolute low frequency power (0.01-0.05 Hz) was also significantly lower in panic disorder patients in standing postures. Upon standing, the panic disorder patients had significantly higher relative mid-frequency power (0.07-0.15 Hz). During a standing deep-breathing condition at six breaths per minute, the patients had a significantly decreased absolute and relative mid-frequency (0.07-0.15 Hz) power compared with control subjects. These findings suggest a decrease in cholinergic and a relative increase in adrenergic responsiveness in panic disorder patients compared with control subjects.
Bradwejn J: NEUROBIOLOGICAL INVESTIGATIONS INTO THE ROLE OF CHOLECYSTOKININ IN PANIC DISORDER. [REVIEW]. Journal of Psychiatry & Neuroscience 1993; 18(4):178-88. Summary: Cholecystokinin (CCK) is a neurotransmitter found in high density in the brains of mammals. Microiontophoretic studies showing that benzodiazepines selectively antagonized CCK-induced excitation of rat hippocampal neurons have led to the hypothesis that CCK is an anxiogenic peptide. The hypothesis was supported by demonstrations that CCK-tetrapeptide (CCK4) induces panic attacks in humans. This paper reviews phases of investigations which studied the validity of CCK4 as a panicogenic agent and research strategies for the study of panic disorder using CCK4 as an investigative tool. [References: 76]
Brambilla F, Bellodi L, Perna G, Garberi A, Panerai A, Sacerdote P: LYMPHOCYTE CHOLECYSTOKININ CONCENTRATIONS IN PANIC DISORDER. American Journal of Psychiatry 1993; 150(7):1111-3. Summary: Since cholecystokinin (CCK) is known to be anxiogenic in experimental animals and to induce panic attacks in humans, lymphocyte CCK-8 concentrations were measured in 15 patients with panic disorder and 15 age- and sex-matched healthy subjects. The patients' levels were measured again after a 30-day course of alprazolam therapy, 1.5 mg/day. The CCK-8 concentrations were significantly lower in the patients than in the control subjects and did not change after alprazolam therapy. There was no correlation between the peptide values and levels of anxiety or frequency and severity of panic attacks.
Halle MT, Dilsaver SC: COMORBID PANIC DISORDER IN PATIENTS WITH WINTER DEPRESSION. American Journal of Psychiatry 1993; 150(7):1108-10. Summary: This study investigated the prevalence of comorbid panic disorder in patients with recurrent wintertime episodes of major depression. The subjects were 38 patients (10 male and 28 female) who met the DSM-III-R criteria for major depression with a seasonal pattern (wintertime depression). Diagnoses of panic disorder were made according to the DSM-III-R criteria. Nine (23.7%) of the subjects (four women and five men) met the criteria for panic disorder. Their panic attacks and depressive symptoms had simultaneous onset in the fall or winter and remitted spontaneously in the spring. Patients with winter depression appear to be at high risk for simultaneous panic disorder, consistent with results from studies in which season of illness was not considered.
Savino M, Perugi G, Simonini E, Soriani A, Cassano GB, Akiskal HS: AFFECTIVE COMORBIDITY IN PANIC DISORDER: IS THERE A BIPOLAR CONNECTION? Journal of Affective Disorders 1993; 28(3):155-63. Summary: Although theoretical explanations for comorbidity in panic disorder (PD) abound in the literature, the complex clinical challenges of these patients have been neglected, especially where panic, obsessive-compulsive and 'soft' bipolar (e.g., hypomanic, cyclothymic and hyperthymic) conditions might co-exist. The aim of the present study has been to systematically explore the spectrum of intra-episodic and longitudinal comorbidity of 140 DSM-III-R PD patients--67.1% of whom concomitantly met the criteria for Agoraphobia--and who were consecutively admitted to the ambulatory service of the Psychiatric Clinic of the University of Pisa over a 2-year period. Comorbidity with strictly defined anxiety disorders--i.e., not explained as mere symptomatic extensions of PD--was relatively uncommon, and included Simple Phobia (10.7%), Social Phobia (6.4%), Generalized Anxiety Disorder (3.6%), and Obsessive-Compulsive Disorder (4.2%). Comorbidity with Major Depression--strictly limited to the melancholic subtype--occurred in 22.9%. Comorbidity with Bipolar Disorders included 2.1% with mania, 5% with hypomania, as well as 6.4% with cyclothymia, for a total of 13.5%; an additional 34.3% of PD patients met the criteria for hyperthymic temperament. We submit that such comorbid patterns are at the root of unwieldy clinical constructs like 'atypical depression' and 'borderline personality'. The relationship of panic disorder to other anxious-phobic and depressive states has been known for some time. Our data extend this relationship to soft bipolar disorders. Studies from other centers are needed to verify that the proposed new link is not merely due to referral bias to a tertiary university setting.
Garvey MJ, Black DW: AN ASSOCIATION BETWEEN THE LYSOSOMAL ENZYME NAG AND URINARY FREE CORTISOL AND PLATELET IMIPRAMINE BINDING. Journal of Psychiatric Research 1993; 27(3):241-5. Summary: Urinary levels of the lysosomal enzyme N-acetyl-beta-glucosaminidase (NAG) were significantly correlated to levels of 24-hour urinary free cortisol in a group of panic disordered patients. In a separate study of healthy controls NAG levels showed a trend toward association with platelet imipramine binding density. A hypothesis is proposed that NAG levels may be proportional to the density of postsynaptic serotonin receptors.
Horwath E, Johnson J, Hornig CD: EPIDEMIOLOGY OF PANIC DISORDER IN AFRICAN-AMERICANS. American Journal of Psychiatry 1993; 150(3):465-9. Summary: OBJECTIVE: The authors investigated the prevalence and clinical characteristics of panic disorder among African-Americans and whites in a community study. METHOD: A total of 4,287 African-American and 12,142 white subjects were interviewed at five sites as part of the Epidemiologic Catchment Area study. Panic disorder and other diagnoses were made using the National Institute of Mental Health Diagnostic Interview Schedule and DSM-III criteria. RESULTS: The lifetime prevalence of panic disorder was 1.2% among African-Americans and 1.4% among whites, a nonsignificant difference. Comparisons between African-Americans and whites on age at onset, years with panic disorder, and suicide attempts revealed no significant differences. Rates of individual panic symptoms in African-American and white subjects with panic disorder were similar, although African-Americans reported a higher mean number of symptoms during their worst episode. Among subjects with comorbid panic disorder, African-Americans and whites had similar rates of major depression, alcohol abuse, drug abuse, obsessive-compulsive disorder, agoraphobia, somatization disorder, and schizophrenia. Patterns of treatment seeking among African-American and white panic subjects were similar, with the exception that African-Americans were significantly less likely to seek help from a mental health professional in private practice. CONCLUSIONS: On the basis of these findings, the authors conclude that panic disorder in the community is similar among African-Americans and whites with respect to lifetime prevalence, age at onset, years of disorder, symptom distribution, suicide attempts, and comorbidity with other psychiatric disorders. Differences in the diagnosis and treatment of panic disorder by race are not due to differences in the prevalence or nature of the disorder.
Starcevic V, Uhlenhuth EH, Kellner R, Pathak D: COMORBIDITY IN PANIC DISORDER: II. CHRONOLOGY OF APPEARANCE AND PATHOGENIC COMORBIDITY. Psychiatry Research 1993; 46(3):285-93. Summary: Ages of onset and the sequence of appearance of panic disorder (PD) and comorbid conditions were determined in a sample of 54 patients with the principal DSM-III-R diagnosis of PD. The onset of PD was earlier in patients with moderate to severe agoraphobia (AG) than in panic patients without AG. Patients with alcohol abuse and drug abuse before the onset of PD also had a tendency to develop PD earlier, which suggests that these conditions might have specifically predisposed to PD. All comorbid disorders, except for major depression, were more likely to precede the onset of PD so that, more often than not, PD appeared as a chronologically secondary condition. However, it was found that only for primary substance abuse such a temporal relationship might denote etiologic relatedness to PD, because of the reduced temporal distance between the onset of primary substance abuse and secondary PD.
Swinson RP, Cox BJ, Rutka J, Mai M, Kerr S, Kuch K: OTONEUROLOGICAL FUNCTIONING IN PANIC DISORDER PATIENTS WITH PROMINENT DIZZINESS. Comprehensive Psychiatry 1993; 34(2):127-9. Summary: Fifteen panic disorder patients with prominent dizziness underwent audiologic, caloric, and vestibuloocular reflex activity testing and were compared with normal controls. There were no abnormalities detected on audiologic and caloric tests. Compared with normal controls, panickers with dizziness showed a greater discrepancy between eye and head movements on vestibulo-ocular reflex activity in the dark. Panickers with prominent dizziness did not differ from a second control group of panickers with severe heart palpitations on a number of psychological tests. The results did not support the hypothesis that organic dizziness is etiologically important in the causation of panic or agoraphobia, but do suggest that vestibuloocular reflex activity should be further studied in panic disorder.
Chignon JM, Lepine JP, Ades J: PANIC DISORDER IN CARDIAC OUTPATIENTS. American Journal of Psychiatry 1993; 150(5):780-5. Summary: OBJECTIVE: Continuing the long history of interest in the relation of anxiety disorders to cardiovascular function and symptoms, this study investigated the level of anxiety and prevalence of panic disorder in cardiac patients and the possible associations between specific abnormal ECG results and a diagnosis of panic disorder. METHOD: Consecutive patients referred for ambulatory ECG recordings were assessed with the seven anxiety items of the Hospital Anxiety and Depression Scale. Then, 50 patients with scores higher than 8 (the anxious group) were interviewed with the Schedule for Affective Disorders and Schizophrenia--Lifetime Version Modified for the Study of Anxiety Disorders (SADS-LA). RESULTS: Of the 50 anxious patients (26 male and 24 female) interviewed with the SADS-LA, 62% (N = 31) met the DSM-III-R criteria for panic disorder. Patients with panic disorder had a higher mean maximal heart rate and a shorter P-R interval than patients without panic disorder. Unlike the patients without panic disorder, the patients with panic disorder showed no correlation between maximal heart rate and minimal P-R interval. CONCLUSIONS: The rate of panic disorder was high in the patients referred for ECG. Moreover, the prevalence of panic disorder was similar in the patients with and without ECG abnormalities, indicating that in anxious patients the presence of panic disorder does not rule out organic cardiac disease. On the other hand, the higher maximal heart rate and shorter P-R interval of the panic patients may be attributable to hypersensitivity of beta-adrenergic receptors in panic disorder.
Kendler KS, Neale MC, Kessler RC, Heath AC, Eaves LJ: PANIC DISORDER IN WOMEN: A POPULATION-BASED TWIN STUDY. Psychological Medicine 1993; 23(2):397-406. Summary: Previous studies based on probands from clinical samples suggest that panic disorder aggregates strongly in families and may be due to a highly penetrant single major locus. In this study we examine panic disorder as assessed at blind, structured psychiatric interview in 2163 women from a population-based twin registry. DSM-III-R diagnoses were assigned at a narrow and at a broad level both by clinician review and by computer algorithm. The familial aggregation of panic disorder in this sample was only modest. The relatively small number of affected individuals prevented a definitive resolution of competing genetic and non-genetic models of familial transmission. Although there was some inconsistency across diagnostic approaches, most results suggested that the familial aggregation of panic disorder was due largely to genetic factors. Using a multifactorial-threshold model, the best estimates of the heritability of liability ranged from 30 to 40%. From a familial perspective, panic disorder with phobic avoidance appears to represent a more severe form of the syndrome than panic disorder without avoidance. Our results, which suggest that in the general population panic disorder is only a moderately heritable condition, are at variance with results from several previous investigations based on clinically ascertained samples.
Spinhoven P, Onstein EJ, Sterk PJ, Le Haen-Versteijnen D: HYPERVENTILATION AND PANIC ATTACKS IN GENERAL HOSPITAL PATIENTS. General Hospital Psychiatry 1993; 15(3):148-54. Summary: The 2-week prevalence of panic attacks according to DSM-III-R criteria was assessed in 102 general hospital patients with unexplained somatic symptoms suggestive of the hyperventilation syndrome (HVS). Thirty-six patients were classified as panickers. In comparison to nonpanickers, panickers reported more severe panic and hyperventilation symptoms and state anxiety during anxiety episodes in daily life and also obtained higher scores on measures for depression, generalized anxiety, agoraphobic anxiety, and agoraphobic avoidance. During the Hyperventilation Provocation Test, panickers reported more panic and hyperventilation symptoms and state anxiety and also rated their symptoms to be more similar to those occurring in daily life than nonpanickers. However, no differences were observed between panickers and nonpanickers in base excess values or in minute respiratory volume, respiratory rate, or fraction of end-tidal carbon dioxide during the resting, hyperventilation, and recovery phase. It is concluded that the prevalence of panic attacks in this group of patients is relatively high and that medical specialists must be more attentive to the occurrence of panic attacks or panic disorder in general hospital patients with unexplained somatic symptoms suggestive of HVS.
Stein MB, Enns MW, Kryger MH: SLEEP IN NONDEPRESSED PATIENTS WITH PANIC DISORDER: II. POLYSOMNOGRAPHIC ASSESSMENT OF SLEEP ARCHITECTURE AND SLEEP CONTINUITY. Journal of Affective Disorders 1993; 28(1):1-6. Summary: This study assessed the EEG sleep of 16 patients with panic disorder who did not currently meet criteria for major depression in comparison to 16 age-comparable healthy controls. Patients with panic disorder had remarkably normal sleep, with only a modest reduction in total sleep time (374 +/- 46 min vs. 399 +/- 36 min) and delta sleep (11.4 +/- 6.2% vs. 16.4 +/- 6.6%) noted. Contrary to expectation, impairment in sleep maintenance and continuity was not found in the patients with panic disorder. We conclude (a) sleep in non-depressed patients with panic disorder is fairly unremarkable, and does not resemble that classically described for depressed patients, and (b) excessive arousability is not a characteristic feature of sleep in panic disorder.
Sheehan DV, Raj BA, Trehan RR, Knapp EL: SEROTONIN IN PANIC DISORDER AND SOCIAL PHOBIA. [REVIEW]. International Clinical Psychopharmacology 1993; 8 Suppl 2:63-77. Summary: The role of serotonin in psychiatry has been the focus of speculation for several decades. The literature since 1966 is reviewed (and referenced) and five organizing questions are identified: (1) What are the major hypotheses regarding the involvement of the serotonin system in panic disorder? (2) Is there a serotonin system defect associated with panic disorder? (3) Is a serotonin system defect the cause of panic disorder? (4) Are the 5-HT1A agonists and the 5-HT2 antagonists effective in this condition? (5) Are serotonin selective uptake inhibitors (SSUIs) effective in panic disorder via the serotonin system or some other mechanism? Though the role of the serotonin system in panic disorder and social phobia is uncertain there is increasing agreement that SSUIs effectively treat panic disorder but further double-blind placebo-controlled studies are needed. [References: 160]
Tancer ME, Stein MB, Uhde TW: GROWTH HORMONE RESPONSE TO INTRAVENOUS CLONIDINE IN SOCIAL PHOBIA: COMPARISON TO PATIENTS WITH PANIC DISORDER AND HEALTHY VOLUNTEERS. Biological Psychiatry 1993; 34(9):591-5. Summary: The growth hormone (GH) response to intravenous administration of clonidine hydrochloride (2 micrograms/kg) was assessed in 16 patients with DSM-III-R social phobia, 13 patients with DSM-III-R panic disorder, and 31 healthy controls. Compared to the healthy volunteers, both social phobic and panic-disorder patients had significantly blunted GH increments after clonidine. The social phobic patients demonstrated a similar degree of GH "blunting" to clonidine as did the patients with panic disorder.
Gorman JM, Papp LA, Coplan J, Martinez J, Liebowitz MR, Klein DF: THE EFFECT OF ACETAZOLAMIDE ON VENTILATION IN PANIC DISORDER PATIENTS. American Journal of Psychiatry 1993; 150(10):1480-4. Summary: OBJECTIVE: Patients with panic disorder are behaviorally hypersensitive to CO2 inhalation and may also be biologically hypersensitive. A report by Mathew et al. showed, however, that administration of the carbonic anhydrase inhibitor acetazolamide, which is believed to increase brain CO2 level, did not cause panic in panic disorder patients. The authors of the present study noted that respiratory frequency did not increase in the earlier experiment and wondered whether respiratory stimulation occurred during acetazolamide administration, as would be expected if CO2 level increases significantly. METHOD: Ten patients with panic disorder and six normal control subjects received injections of acetazolamide, 1 g i.v., as per the Mathew et al. protocol, during breath by breath measurement of both tidal volume and frequency of respiration. RESULTS: Three patients had panic attacks, one before receiving acetazolamide, one during the injection, and one 2 minutes after injection. Only the last of these attacks appeared possibly attributable to acetazolamide. None of the control subjects panicked. Neither patients nor control subjects exhibited meaningful change in tidal volume, respiratory frequency, or minute ventilation, and both groups experienced a trend toward significant decrease in overall levels of anxiety and dyspnea after acetazolamide injection. CONCLUSIONS: The authors replicated the earlier finding that acetazolamide is not panicogenic in patients with panic disorder but also showed that at the dose given, there is no meaningful effect on ventilation. If acetazolamide does affect CO2 levels it does so in a way that does not stimulate ventilation. Therefore, the acetazolamide injection results of Mathew et al. and of the present study do not challenge hypotheses linking panic attacks to hypersensitive respiratory control mechanisms.
Schmidt SM, Zoega T, Crowe RR: EXCLUDING LINKAGE BETWEEN PANIC DISORDER AND THE GAMMA-AMINOBUTYRIC ACID BETA 1 RECEPTOR LOCUS IN FIVE ICELANDIC PEDIGREES. Acta Psychiatrica Scandinavica 1993; 88(4):225-8. Summary: The GABAA receptor subunits are candidate genes for panic disorder because the receptor is the site of action for the anxiolytic effects of the benzodiazepines. We tested for linkage between a tetranucleotide repeat polymorphism at the GABAA beta 1 locus, located on chromosome 4p13-p12, and panic disorder defined by DSM-III-R criteria in 5 Icelandic pedigrees. Both a narrow affection status (definite panic disorder and agoraphobia) and a broad one (including probable cases of these disorders) were tested. With the narrow definition, at a recombination fraction of 0.00, the lod scores in the 5 pedigrees ranged from -3.240 to +0.063, the total score across all 5 pedigrees being -8.299. With the broad definition at the same recombination fraction, the individual lod scores ranged from -2.614 to -0.489, with the total being -8.089. Thus, linkage between panic disorder/agoraphobia and the GABAA beta 1 locus in these pedigrees is exceedingly unlikely.
Weissman MM, Wickramaratne P, Adams PB, Lish JD, Horwath E, Charney D, Woods SW, Leeman E, Frosch E: THE RELATIONSHIP BETWEEN PANIC DISORDER AND MAJOR DEPRESSION. A NEW FAMILY STUDY. Archives of General Psychiatry 1993; 50(10):767-80. Summary: OBJECTIVE: The comorbidity between panic disorder and major depression (MDD) in individuals has been amply documented. However, data from family studies to determine whether panic disorder and MDD aggregate separately or together in families have been inconclusive, in part because of the absence of studies with the full range of proband groups. This report presents results from a family study with the necessary mutually exclusive groups: panic disorder without MDD, panic disorder with MDD, MDD without panic disorder, and normal controls. METHODS: Diagnostic information was obtained from 193 probands and 1047 of their adult relatives with the Schedule for Affective Disorders and Schizophrenia--Lifetime Version for Anxiety Disorders by direct interview, and/or from multiple informants, without knowledge of proband diagnoses. Best-estimate diagnoses were based on all available information by clinicians independently of data collection and without knowledge of probands' and other relatives' status. RESULTS: Findings indicated the specific and independent transmission of panic disorder and MDD, the separation of panic disorder from MDD, and the nonfamilial nature of late-onset MDD. The pattern of results was unaffected by the use of different diagnostic criteria, number of informants, interview status of relatives, presence of substance abuse or agoraphobia or the sequence of MDD and panic disorder in probands, or whether probands were selected from treatment clinics or community sample. CONCLUSIONS: We conclude that panic disorder and MDD are separate disorders with substantial co-occurrence in individuals, and that panic comorbid with MDD is not a single, distinct disorder. Finally, we illustrate an approach to examining comorbidity in family data through analysis of mutually exclusive, parallel diagnoses in probands and relatives.
Guthrie SK, Grunhaus L, Pande AC, Hariharan M: NORADRENERGIC RESPONSE TO INTRAVENOUS YOHIMBINE IN PATIENTS WITH DEPRESSION AND COMORBIDITY OF DEPRESSION AND PANIC. Biological Psychiatry 1993; 34(8):558-61. Summary: Adrenergic response following infusions of yohimbine or normal saline was evaluated in 9 control subjects, 8 patients suffering from a major depressive episode (MDE), and 12 patients suffering from concurrent MDE and panic disorder (MDE + P). Blood was drawn at -20, 0, 5, 10, 20, 45, and 90 min following the infusions, and assayed for norepinephrine (NE) and 3-methoxy-4-hydroxy-phenyl glycol (MHPG). Although the patient groups exhibited higher baseline NE concentrations, and a greater NE area under the plasma concentration versus time curve (AUC0-90) during the yohimbine infusion, the differences were not statistically significant. Baseline NE was significantly correlated with the NE AUC0-90 in all three groups, suggesting that, although the NE system may be dysregulated in the MDE and MDE + P patients, the NE system still appears to respond somewhat predictably following a challenge, even though the actual magnitude of response may vary.
Maddock RJ, Gietzen DW, Goodman TA: DECREASED LYMPHOCYTE BETA-ADRENORECEPTOR FUNCTION CORRELATES WITH LESS AGORAPHOBIA AND BETTER OUTCOME IN PANIC DISORDER. Journal of Affective Disorders 1993; 29(1):27-32. Summary: Previous studies have demonstrated reduced function of peripheral beta-adrenoreceptors in panic disorder with agoraphobia (PDA). We recently reported that decreased lymphocyte beta-receptor function was associated with milder agoraphobia and better treatment response in PDA. We now report on lymphocyte beta-receptor function in 12 additional patients with PDA. Lower cyclic AMP responses to isoproterenol were significantly correlated with milder agoraphobia and better response to naturalistic treatment. Lower beta-receptor density tended to correlate similarly with agoraphobia and treatment response. These findings further support the hypothesis that decreased peripheral beta-receptor function in PDA reflects an adaptive process associated with greater resistance to agoraphobia and greater capacity for recovery with treatment.
Friedman BH, Thayer JF, Borkovec TD, Tyrrell RA, Johnson BH, Columbo R: AUTONOMIC CHARACTERISTICS OF NONCLINICAL PANIC AND BLOOD PHOBIA. Biological Psychiatry 1993; 34(5):298-310. Summary: Autonomic characteristics of nonclinical panic and blood phobia were compared using spectral analysis of the electrocardiogram (EKG), as well as more conventional cardiovascular measures. The cardiovascular responses of 11 subjects who reported recent occurrence of frequent severe panic attacks, and 10 subjects who reported intense somatic reactions to the sight of blood (including episodes of syncope) were recorded during a variety of laboratory tasks (quiet rest, reaction time/shock avoidance, face immersion, and combined reaction time/face immersion). Results suggest distinct autonomic patterns in the groups. Panickers showed (a) higher heart rate and reduced heart-rate variability (b) aberrant associations among cardiovascular measures, and (c) dominant sympathetic control of heart rate coupled with diminished vagal tone. Blood phobics generally displayed an opposite pattern. The relevance of these findings to the etiology of panic and blood phobia, as well as to biological models of anxiety disorders in general, is discussed.
Braune S, Albus M, Frohler M, Hohn T, Scheibe G: PSYCHOPHYSIOLOGICAL AND BIOCHEMICAL CHANGES IN PATIENTS WITH PANIC ATTACKS IN A DEFINED SITUATIONAL AROUSAL. European Archives of Psychiatry & Clinical Neuroscience 1994; 244(2):86-92. Summary: A group of 27 patients with panic disorder with or without agoraphobia were compared with 10 control subjects before stress exposure. No statistically significant differences between patients and controls were found for the cardiovascular parameters. Skin conductance level and skin conductance reaction were significantly higher in the patient group. They also showed higher self-ratings in behavioural symptoms associated with anxiety. There were statistically significant higher venous plasma levels of norepinephrine in patients than in controls, although the epinephrine levels were similar. The number of binding sites of alpha 2-receptors and the affinity of 3H-yohimbine to the alpha 2-receptors on intact thrombocytes was statistically significantly lower in patients compared to controls. Significant differences between the gender groups of patients and controls were found for electrodermal activity and epinephrine levels. These data add further evidence to an overshooting activation of the noradrenergic pathway in patients with panic disorder, possibly based on a dysregulation of alpha 2-receptor.
Dick CL, Bland RC, Newman SC: EPIDEMIOLOGY OF PSYCHIATRIC DISORDERS IN EDMONTON. PANIC DISORDER. Acta Psychiatrica Scandinavica, Supplementum 1994; 376:45-53. Summary: A random sample of 3258 adult household residents of Edmonton, Alberta, Canada were interviewed by trained lay interviewers using the Diagnostic Interview Schedule (DIS), which gives DSM-III diagnostic data on each individual interviewed. This paper reports results for panic disorder. Panic disorder was found to affect women primarily (female:male morbidity risk 2.2:1). The mean age of onset (first symptom) was 19.3 years for men and 21.5 years for women. Rarely did symptoms first occur after the age of forty. The lifetime prevalence rate was 1.7% for women and 0.8% for men and the lifetime morbidity risk was 3.7% for females and 1.7% for males. All twelve panic symptoms were found to be highly specific for panic disorder. Women complained of more (means = 8.0) symptoms than men (means = 6.0). On average 7.3 symptoms were reported. Those with panic disorder showed increased lifetime prevalence rates for major depressive episode (73.4%), alcohol abuse/dependence (54.2%), drug abuse/dependence (43%) and phobia (44.2%). Altogether, 90.4% of those with panic disorder also met criteria for another DSM-III diagnosis, which was 2.7 times the rate in those who did not have panic disorder.
Marazziti D, Rotondo A, Martini C, Giannaccini G, Lucacchini A, Pancioli-Guadagnucci ML, Diamond BI, Borison R, Cassano GB: CHANGES IN PERIPHERAL BENZODIAZEPINE RECEPTORS IN PATIENTS WITH PANIC DISORDER AND OBSESSIVE-COMPULSIVE DISORDER. Neuropsychobiology 1994; 29(1):8-11. Summary: Peripheral benzodiazepine (BDZ) receptors were investigated through the binding of the specific ligand 3H-PK-11195 to platelet membranes, in 17 patients suffering from panic disorder (PD) and in 16 patients affected by obsessive-compulsive disorder (OCD). The results, showing that the density (Bmax) of peripheral BDZ receptors was significantly lower in patients with PD than in controls or OC patients, suggest that the number of platelet BDZ receptors varies with different anxiety disorders and that perhaps this marker may be beneficial in differentiating some subtypes of these disorders.
Schlegel S, Steinert H, Bockisch A, Hahn K, Schloesser R, Benkert O: DECREASED BENZODIAZEPINE RECEPTOR BINDING IN PANIC DISORDER MEASURED BY IOMAZENIL-SPECT. A PRELIMINARY REPORT. European Archives of Psychiatry & Clinical Neuroscience 1994; 244(1):49-51. Summary: Single photon emission tomography (SPECT) imaging of the central benzodiazepine receptor (BZr) became possible with the newly developed ligand 123I-IOMAZENIL. The BZr binding was investigated in ten patients with panic disorder (PP) compared to ten epileptic patients (EP). Panic patients had lower IOMAZENIL uptake rates in the frontal, occipital and temporal cortex than EP indicating the involvement of the BZr complex in panic disorder.
Starcevic V, Fallon S, Uhlenhuth EH, Pathak D: COMORBIDITY RATES DO NOT SUPPORT DISTINCTION BETWEEN PANIC DISORDER AND GENERALIZED ANXIETY DISORDER. Psychopathology 1994; 27(6):269-72. Summary: Groups of patients with principal diagnosis of panic disorder (n = 54) and generalized anxiety disorder (n = 49) were compared on the basis of their comorbidity with other mental disorders. The rates and patterns of comorbidity were similar, except for comorbid simple phobia and past drug abuse. This finding was interpreted as failing to support a notion that there is essential distinction between panic disorder and generalized anxiety disorder.
Stuppy WP, Shipko S: THE DICHOTOMY OF ALEXITHYMIA AND PANIC DISORDER. [REVIEW]. International Journal of Psychosomatics 1994; 41(1-4):30-3. Summary: This manuscript presents a novel model of psychophysiologic markers for the stress response. The hypothesis describes what we believe is a human analogue of the physiologic changes described in animal models of inescapable shock. This is bolstered by laboratory and clinical data derived from patients with stress-related functional gastrointestinal disorders. The idea explains the clinical findings of simultaneous analgesia and somatization in alexithymics. The implications for understanding the physiologic relationship between panic disorder and functional bowel disorders in the context of the stress response is discussed along with novel treatment strategies for these disabling conditions. [References: 21]
Yeragani VK, Srinivasan K, Pohl R, Berger R, Balon R, Ramesh C: EFFECTS OF NORTRIPTYLINE ON HEART RATE VARIABILITY IN PANIC DISORDER PATIENTS: A PRELIMINARY STUDY USING POWER SPECTRAL ANALYSIS OF HEART RATE. Neuropsychobiology 1994; 29(1):1-7. Summary: Previous reports on heart rate variability suggest that, compared to controls, panic disorder patients have a higher relative mid-frequency (MF) (0.07-0.15 Hz) power in standing posture and that they also have a greater increase in standing MF power after the administration of yohimbine. We studied the effects of nortriptyline, a tricyclic antidepressant, on HR variability measures in 13 panic disorder patients before and after successful treatment. There was a highly significant increase in supine and standing HR (p = 0.00001) while there was a significant decrease of standing absolute and relative MF power (p = 0.009 and 0.0001 respectively). This uncontrolled preliminary study suggests a decrease in sympathetic activity related to nortriptyline treatment in addition to its anticholinergic effects.
Gorman JM, Papp LA, Coplan JD, Martinez JM, Lennon S, Goetz RR, Ross D, Klein DF: ANXIOGENIC EFFECTS OF CO2 AND HYPERVENTILATION IN PATIENTS WITH PANIC DISORDER. American Journal of Psychiatry 1994; 151(4):547-53. Summary: OBJECTIVE: Previous studies have indicated that patients with panic disorder are more likely than normal subjects to have acute panic attacks during inhalation of CO2, but methodological objections have been raised. In this study the authors attempted to address three of these methodological problems by ensuring that raters who assessed whether panic attacks occurred were blind to subjects' diagnoses, by randomizing the order of administration of 5% CO2 and hyperventilation, and by challenging a greater number of subjects with 7% CO2. METHOD: Patients with panic disorder and normal subjects underwent 20-minute inhalations of 5% CO2 and 7% CO2 and 15 minutes of room-air hyperventilation. Ratings of panic/no panic during each condition were made separately by an assessor blind to diagnosis and by the subject. Scores on four panic rating scales were also recorded before and after each intervention. RESULTS: Room-air hyperventilation caused panic attacks in a small number of patients; the difference in panic rate between patients and comparison subjects was statistically significant by the subjects' but not by the raters' assessment. Panic rates during 5% CO2 and 7% CO2 were significantly greater among the patients by both assessments; the panic rate was greatest during 7% CO2. Order of administration did not significantly affect panic rates for hyperventilation and 5% CO2. CONCLUSIONS: Panic patients were clearly more sensitive to the anxiogenic effects of CO2 than comparison subjects, and CO2 was a more potent anxiogenic stimulus than room-air hyperventilation. Seven percent CO2 discriminated best between patients and comparison subjects and should be the focus of further research.
Grunhaus L, Pande AC, Brown MB, Greden JF: CLINICAL CHARACTERISTICS OF PATIENTS WITH CONCURRENT MAJOR DEPRESSIVE DISORDER AND PANIC DISORDER. American Journal of Psychiatry 1994; 151(4):541-6. Summary: OBJECTIVE: This study was designed to test the hypothesis that patients with both major depressive disorder and panic disorder exhibit more clinical symptoms and have a more protracted course of illness than patients with major depressive disorder only. METHOD: The authors compared standardized clinical evaluations (from Schedule for Affective Disorders and Schizophrenia interviews) of 119 patients with major depressive disorder only and 57 patients with major depressive disorder and concurrent panic disorder. Clinical and demographic variables were included. RESULTS: The patients with both disorders reported symptoms of major depressive disorder earlier in life and also required treatment and hospital admission earlier in life. Many clinical features during the index episode were significantly more severe in the patients with both disorders. A logistic regression identified a "panic index" consisting of the symptoms of somatic anxiety, phobia, indecisiveness, and feelings of inadequacy. Scores on this index allowed proper classification of patients to either of the two diagnostic groups with high reliability. CONCLUSIONS: In major depressive disorder, the presence of panic disorder is suggestive of a more severe and precocious form of illness.
van Megen HJ, Westenberg HG, den Boer JA, Haigh JR, Traub M: PENTAGASTRIN INDUCED PANIC ATTACKS: ENHANCED SENSITIVITY IN PANIC DISORDER PATIENTS. Psychopharmacology 1994; 114(3):449-55. Summary: The effects of pentagastrin, a synthetic analogue of the cholecystokinin tetrapeptide (CCK4), were studied in 15 patients with panic disorder and 15 healthy controls. Three different intravenous dosages of pentagastrin (0.1, 0.3 and 0.6 microgram/kg) and saline were investigated. Subjects were randomly allocated to two of the four treatment groups and tested on two separate occasions, 1 week apart, using an unbalanced double-blind incomplete block design. The mean panic rate with pentagastrin was 55% (12/22) for patients and 5% (1/22) for controls. None of the subjects panicked with saline. The frequency of panic attacks between the three pentagastrin doses in patients was not different. One control subject had a panic-like attack at the highest dose of pentagastrin. These findings concur with previous studies on the panicogenic effect of CCK4 and pentagastrin and suggest a greater sensitivity for CCK receptor agonists in patients suffering from panic disorder than in healthy controls.
Clark DB, Hirsch BE, Smith MG, Furman JM, Jacob RG: PANIC IN OTOLARYNGOLOGY PATIENTS PRESENTING WITH DIZZINESS OR HEARING LOSS. American Journal of Psychiatry 1994; 151(8):1223-5. Summary: This study compared 50 patients presenting to an otolaryngology clinic with a complaint of dizziness and 50 patients presenting with hearing loss on questionnaire measures of panic, phobic avoidance, generalized anxiety, and depression. Clinical and laboratory evaluations of vestibular and audiological complaints were also completed. Twenty percent of the group with dizziness and none of the group with hearing loss reported symptoms that met DSM-III-R criteria for panic disorder. Patients with dizziness and peripheral vestibulopathy had more symptoms of phobic avoidance, generalized anxiety, and depression than patients with confirmed hearing loss.
Koenigsberg HW, Pollak CP, Fine J, Kakuma T: CARDIAC AND RESPIRATORY ACTIVITY IN PANIC DISORDER: EFFECTS OF SLEEP AND SLEEP LACTATE INFUSIONS. American Journal of Psychiatry 1994; 151(8):1148-52. Summary: OBJECTIVE: This study examined cardiac and respiratory activity in panic disorder patients and healthy comparison subjects during sleep, when the effects of anxious cognition and expectancy set are minimized. METHOD: Heart rate, respiratory rate, end-tidal PCO2, and oxygen saturation were recorded for 11 panic disorder patients and 12 comparison subjects before and during sleep and before and after infusions of sodium lactate and a saline control. RESULTS: Panic disorder patients had higher oxygen saturations than comparison subjects before sleep onset and during sleep stages 0 and 2 before any infusions. The two groups did not differ on other respiratory variables and heart rate. Panic disorder patients responded to lactate infusions during stage 3-4 sleep with greater increases in heart rate and oxygen saturation, and possibly in respiratory rate and end-tidal PCO2, than comparison subjects. The saline control infusion had little effect. CONCLUSIONS: These findings suggest that panic disorder patients have greater cardiac and respiratory reactivity than healthy comparison subjects during sleep, when the influence of cognitive factors is minimal or absent.
Yeragani VK, Srinivasan K, Balon R, Ramesh C, Berchou R: LACTATE SENSITIVITY AND CARDIAC CHOLINERGIC FUNCTION IN PANIC DISORDER. American Journal of Psychiatry 1994; 151(8):1226-8. Summary: Using spectral analysis of the continuous time series signal before and during lactate and placebo infusions, the authors studied heart rate variability in six patients with panic disorder and nine normal comparison subjects. The decrease in high-frequency (0.20-0.50 Hz) power and the increase in sympathovagal ratios (mid-frequency [0.07-0.15 Hz] to high-frequency powers) after the administration of intravenous sodium lactate were significantly greater in the patients than in the normal subjects after correction of the values for the amount of lactate infused. This result suggests an exaggerated cardiac vagal withdrawal in patients with panic disorder during lactate infusions.
van Megen HJ, den Boer JA, Westenberg HG: ON THE SIGNIFICANCE OF CHOLECYSTOKININ RECEPTORS IN PANIC DISORDER. [REVIEW]. Progress in Neuro-Psychopharmacology & Biological Psychiatry 1994; 18(8):1235-46. Summary: Interest in the biological aspects of panic disorder has been focussed mainly on the noradrenergic and serotonergic systems in the brain. Recently evidence has been found that Cholecystokinin (CCK) receptors in the Central Nervous System (CNS) may be involved in panic disorders. This hypothesis is based on the results of animal electrophysiological studies, animal models of anxiety and on challenge test using CCK fragments in humans. In this review, the studies evaluating the putative involvement of CCK, and especially CCK-B receptors, in panic disorder will be discussed. [References: 36]
Bradwejn J, Koszycki D: IMIPRAMINE ANTAGONISM OF THE PANICOGENIC EFFECTS OF CHOLECYSTOKININ TETRAPEPTIDE IN PANIC DISORDER PATIENTS. American Journal of Psychiatry 1994; 151(2):261-3. Summary: Eleven panic disorder patients who panicked in response to exogenous cholecystokinin tetrapeptide (CCK-4) were rechallenged after chronic treatment with imipramine. In the rechallenge the patients displayed a marked reduction in the number and intensity of panic symptoms, duration of symptoms, frequency of panic attacks, and cardiovascular responsiveness. This study demonstrates that imipramine can antagonize the panicogenic effects of CCK-4.
Brown TA: FAMILIAL AGGREGATION OF PANIC IN NONCLINICAL PANICKERS. Behaviour Research & Therapy 1994; 32(2):233-5. Summary: Despite several methodological difficulties inherent in the nonclinical panic literature, some researchers have highlighted the consistent finding that a greater proportion of panickers than nonpanickers report a history of panic in first-order relatives to be supportive of the validity of nonclinical panic research findings. However, in all of these studies, familial aggregation differences have been evaluated via panickers' and nonpanickers' self-reports of familial panic history. Given evidence that questionnaire assessment of panic results in substantial false positives (Brown & Cash, 1989, Journal of Anxiety Disorders, 3, 139-148), it was hypothesized that familial aggregation differences could be largely attributable to this phenomenon as well. Consistent with this hypothesis, as in prior studies, a significantly greater proportion of panickers than nonpanickers reported first-order relatives who experienced panic; however, panickers and nonpanickers also differed in their reports of close male friends and close female friends who had experienced panic. On the basis of these data, potential caveats to prior conclusions concerning familial aggregation differences between nonclinical panickers and nonpanickers are discussed as are methodological considerations for future nonclinical panic research.
Goisman RM, Warshaw MG, Peterson LG, Rogers MP, Cuneo P, Hunt MF, Tomlin-Albanese JM, Kazim A, Gollan JK, Epstein-Kaye T, et al: PANIC, AGORAPHOBIA, AND PANIC DISORDER WITH AGORAPHOBIA. DATA FROM A MULTICENTER ANXIETY DISORDERS STUDY. Journal of Nervous & Mental Disease 1994; 182(2):72-9. Summary: In a cross-sectional investigation of the properties of DSM-III-R panic disorder (PD), panic disorder with agoraphobia (PDA), and agoraphobia without history of panic disorder (AWOPD), we analyzed demographic, descriptive, comorbidity, treatment, and course data for 562 subjects with PD, PDA, or AWOPD in a multicenter anxiety-disorders study. In general, AWOPD subjects had the worst functioning and PD subjects the best, as measured by length of intake episodes, education attained, likelihood of receiving financial assistance, depressive comorbidity, and likelihood of having experienced 8 weeks symptom-free. Panic disorder with agoraphobia was the most common disorder and emerged as a condition intermediate in severity between the other two. Treatments received varied little by diagnosis. Most subjects received medication, usually benzodiazepines. Psychodynamic psychotherapy was the most frequently received psychosocial treatment; cognitive and behavioral approaches were less common. Subjects classified with AWOPD were the most likely to have received exposure therapies.
Pauls DL, Leckman JF, Cohen DJ: EVIDENCE AGAINST A GENETIC RELATIONSHIP BETWEEN TOURETTE'S SYNDROME AND ANXIETY, DEPRESSION, PANIC AND PHOBIC DISORDERS. British Journal of Psychiatry 1994; 164(2):215-21. Summary: Analyses were undertaken to examine whether a wide range of psychiatric disorders, including anxiety, affective, substance abuse and psychotic disorders, represent variant manifestations of Tourette's syndrome (TS). Previous studies have suggested that chronic tics (CT) and obsessive-compulsive disorder (OCD) are variant expressions of TS since both CT and OCD are elevated among relatives of TS probands. In the current study, no other psychiatric disorder was significantly elevated among the relatives who did not have TS, CT or OCD when compared with a control sample. These findings are not consistent with the hypothesis that a wide range of psychiatric and behavioural disorders are variant expressions of TS.
Sagduyu K: THE ETIOLOGY OF PANIC DISORDER: A REVIEW OF CURRENT RESEARCH. [REVIEW]. Missouri Medicine 1994; 91(2):90-3. Summary: During the last decade, there has been extensive research toward understanding the etiology and developing a treatment approach for panic disorder. This is a review and summary of issues related to proposed current biological mechanisms in an attempt to define the etiology of panic disorder. It also emphasizes the need for further studies. [References: 45]
Sivaramakrishnan K, Alexander PJ, Saharsarnamam N: PREVALENCE OF PANIC DISORDER IN MITRAL VALVE PROLAPSE: A COMPARATIVE STUDY WITH A CARDIAC CONTROL GROUP. Acta Psychiatrica Scandinavica 1994; 89(1):59-61. Summary: This study investigated the relationship between mitral valve prolapse (MVP) and panic disorder (PD), by comparing the prevalence of PD in 33 patients with MVP and 27 patients with haemodynamically insignificant atrial septal defect or patent ductus arteriosus. MVP was diagnosed using standard echocardiographic criteria and the presence of mental disorder was assessed blindly with the help of the Schedule for Affective Disorders and Schizophrenia. DSM-III criteria were used to diagnose PD. The two groups did not differ in age and sex; 12.1% of MVP patients and 3.7% of cardiac controls had PD (NS). Although the prevalence of PD in our sample of MVP patients was considerably higher than the prevalence of PD in the general population, this need not necessarily indicate a causal relationship between MVP and PD and may be due to studying a hospital-based sample. The absence of any significant difference in prevalence of PD between MVP patients and a carefully selected cardiac control group drawn from the same setting argues against any special relationship between PD and MVP.
Newman SC, Bland RC: LIFE EVENTS AND THE 1-YEAR PREVALENCE OF MAJOR DEPRESSIVE EPISODE, GENERALIZED ANXIETY DISORDER, AND PANIC DISORDER IN A COMMUNITY SAMPLE. Comprehensive Psychiatry 1994; 35(1):76-82. Summary: A community survey was conducted in Edmonton, Alberta, Canada, in which 3,070 respondents completed the Diagnostic Interview Schedule (DIS) and the Life Events Scale (LES) of Paykel. During the year before the interview, there were 222, 234, and 38 cases of major depressive episode (MDE), generalized anxiety disorder (GAD), and panic disorder (PD), respectively, where individuals may have had more than one disorder. It was not possible to time the onset of the disorder relative to the occurrence of life events, and so correlations, no casual relationships, were examined. The LES score showed an increasing trend across disorder categories defined as follows: MDE and GAD both absent; MDE absent and GAD present; MDE present and GAD absent; and MDE and GAD both present. A similar trend was observed for most of the LES subscales studied, but only in the case of events classified as "entrance," "undesirable," and "marital" was there statistical significance. The results suggest that stressful life events are correlated with both MDE and GAD, that individuals with MDE only tend to have a greater burden of stressful events and comorbid disorders than persons with GAD only, and that the presence of both disorders is associated with an even greater level of stress and number of comorbid disorders. The similar patterns across LES subscales suggest that MDE and GAD are not related to specific types of live events, at least not those covered by the LES questionnaire.
Spinhoven P, Ros M, Westgeest A, Van der Does AJ: THE PREVALENCE OF RESPIRATORY DISORDERS IN PANIC DISORDER, MAJOR DEPRESSIVE DISORDER AND V-CODE PATIENTS. Behaviour Research & Therapy 1994; 32(6):647-9. Summary: Point prevalence and lifetime prevalence of respiratory disorders were assessed in 100 panic disorder (PD), 100 major depressive disorder (DD) and 100 V-code (VC) patients. Both current and past frequency of respiratory diseases were significantly higher in PD patients in comparison to VC patients, while no significant differences in point and lifetime prevalence between PD and DD or DD and VC patients were observed. It is hypothesized that a disturbed respiratory physiology may have differential effects depending upon the nature of the disorder and the appraisal by the patient.
Labbate LA, Pollack MH, Otto MW, Langenauer S, Rosenbaum JF: SLEEP PANIC ATTACKS: AN ASSOCIATION WITH CHILDHOOD ANXIETY AND ADULT PSYCHOPATHOLOGY. Biological Psychiatry 1994; 36(1):57-60. Summary: The authors examine whether the presence of sleep panic attacks identifies a subgroup of panic disorder patients. Subjects (n = 95) were consecutive patients with panic disorder participating in the MGH longitudinal study of panic disorder. Patients were evaluated with structured interviews to establish adult anxiety and affective disorders, and the presence of childhood anxiety disorders. Patients were queried whether they had ever experienced at least one panic attack during sleep. Patients with a history of sleep panic had significantly higher rates of comorbid generalized anxiety disorder (p < 0.01), social phobia (p < 0.03), and major depression (p < 0.005). The trend was toward longer length of illness (p < 0.09) and were more likely to have a history of an anxiety disorder during childhood (p < 0.005). The presence of sleep panic attacks may delineate a subgroup of panic disorder patients with early difficulties with anxiety, and comorbid mood and anxiety disorders as adults.
Bradwejn J, Koszycki D, Couetoux du Tertre A, van Megen H, den Boer J, Westenberg H: THE PANICOGENIC EFFECTS OF CHOLECYSTOKININ-TETRAPEPTIDE ARE ANTAGONIZED BY L-365,260, A CENTRAL CHOLECYSTOKININ RECEPTOR ANTAGONIST, IN PATIENTS WITH PANIC DISORDER. Archives of General Psychiatry 1994; 51(6):486-93. Summary: BACKGROUND: We investigated whether the selective brain cholecystokinin (CCKB) receptor antagonist, L-365,260, could antagonize the panicogenic effects of CCK-tetrapeptide (CCK-4) in patients with panic disorder. DESIGN: The study employed a double-blind, placebo-controlled, two-period crossover design. Patients (N = 29) received a single oral dose of L-365,260 (10 or 50 mg) or placebo 90 minutes prior to injection of CCK-4. After a 1-week washout period, patients received a different dose of L-365,260 or placebo according to a balanced incomplete block design. RESULTS: The 50-mg dose of L-365,260 was superior to placebo in reducing the number (P < .01) and sum intensity (P < .001) of symptoms induced with CCK-4. Panic attack frequency following CCK-4 injection was 88% for patients receiving placebo, 33% for those receiving the 10-mg dose, and 0% for those receiving the 50-mg dose. The difference between the effects of the 50-mg dose and placebo was statistically significant (P = .002). Increases in heart rate following CCK-4 injection were markedly reduced with both the 50-mg (P < .0001) and 10-mg (P < .01) doses compared with placebo. CONCLUSION: These data suggest that CCKB receptors are an important site of action of exogenous CCK-4. It will be important to determine in future studies the efficacy of CCKB receptor antagonists as antipanic agents.
Cox BJ, Direnfeld DM, Swinson RP, Norton GR: SUICIDAL IDEATION AND SUICIDE ATTEMPTS IN PANIC DISORDER AND SOCIAL PHOBIA. American Journal of Psychiatry 1994; 151(6):882-7. Summary: OBJECTIVE: Using the original National Institute of Mental Health Epidemiologic Catchment Area (ECA) suicide questions in a clinical setting and including a comparison group of patients with social phobia, the authors attempted to replicate the finding of Weissman and associates of a greater risk of suicidal ideation and suicide attempts associated with panic disorder. METHOD: One hundred six patients with panic disorder and 41 patients with social phobia answered the five ECA suicide questions and completed a psychometric assessment package at an anxiety disorders clinic. RESULTS: Thirty-three (31%) of the patients with panic disorder and 14 (34%) of the patients with social phobia reported suicidal ideation in the past year, but only one of the patients with panic disorder and two of the patients with social phobia actually made suicide attempts in the past year. Nineteen (18%) of the patients with panic disorder and five (12%) of the patients with social phobia reported making suicide attempts at other times in their lives. Patients who had made past suicide attempts were significantly more likely to report previous psychiatric hospitalizations and past treatment for depression than were patients who had never attempted suicide. CONCLUSIONS: These results are consistent with the findings of Weissman and associates that a large proportion of individuals with panic disorder report suicidal ideation. However, many patients with social phobia also reported suicidal ideation, and few individuals in either diagnostic group had actually made recent suicide attempts. Although 12%-18% of the patients reported lifetime suicide attempts, there is evidence to suggest that these were in the context of depressive symptoms.
Marriott PF, Greenwood KM, Armstrong SM: SEASONALITY IN PANIC DISORDER. Journal of Affective Disorders 1994; 31(2):75-80. Summary: Following a clinical observation of increased anxiety symptoms and mood changes during winter in panic disorder patients, the Seasonal Pattern Assessment Questionnaire (SPAQ) was completed by 133 patients. Global Seasonality Scores (GSS), and the prevalence of Seasonal Affective Disorder (SAD), were significantly higher than reported in general population studies. Seasonal changes were also found in anxiety and panic attacks. These findings suggest the possibility of a common aetiology for panic disorder and SAD, that seasonality may be a far more general phenomenon in psychopathology, and that light therapy may be a useful treatment for some panic disorder patients.
Eaton WW, Kessler RC, Wittchen HU, Magee WJ: PANIC AND PANIC DISORDER IN THE UNITED STATES. American Journal of Psychiatry 1994; 151(3):413-20. Summary: OBJECTIVE: The goal of this study was to determine the prevalence of DSM-III-R panic disorder and to describe its correlates. METHOD: The study was part of the National Comorbidity Survey, the first psychiatric epidemiologic survey of the entire U.S. population and the first to use DSM-III-R criteria for diagnosis. The 8,098 survey respondents, aged 15-54 years, were given the Composite International Diagnostic Interview. For this report, the data on panic were analyzed, and from them the prevalence of panic disorder and related experiences in the U.S. population was estimated. RESULTS: About 15% of the survey respondents reported the occurrence of a panic attack over their lifetimes, and 3% reported a panic attack in the preceding month. About 1% met the DSM-III-R criteria for panic disorder in the month preceding the interview. Panic attacks and panic disorder had a bimodal age distribution and were associated with female sex and lower educational achievement. Fifty percent of the survey respondents with panic disorder reported no symptoms of agoraphobia. The pattern of prevalence of correlated sociodemographic factors was similar for persons with panic attacks, panic disorder, and panic disorder with agoraphobia. CONCLUSIONS: There appears to be no obvious threshold for the diagnosis of panic disorder. Panic disorder and agoraphobia, although highly comorbid, also occur separately.
Hoffman DL, O'Leary DP, Munjack DJ: AUTOROTATION TEST ABNORMALITIES OF THE HORIZONTAL AND VERTICAL VESTIBULO-OCULAR REFLEXES IN PANIC DISORDER. Otolaryngology - Head & Neck Surgery 1994; 110(3):259-69. Summary: Patients with panic disorder often describe dizziness as a disturbing symptom, with more severe episodes reported than in other psychiatric populations. Nineteen patients diagnosed as having a panic disorder were tested for vestibulo-ocular (VOR) abnormalities with the Vestibular Autorotation Test (VAT), a computerized test of the high-frequency (2 to 6 Hz) VOR. The patients were unselected for the presence or absence of balance disorders. Results showed VOR abnormalities, relative to a normal population, in the horizontal and/or vertical VORs of all 19 patients. Vestibulo-ocular reflex asymmetries were commonly present. Because the VAT tested the VOR over a frequency range encountered during common daily activities, the observed abnormalities could result in a perceptually moving visual field (oscillopsia). We hypothesize that the resulting experience of a visual-vestibular disturbance--perhaps in a biologically or psychologically predisposed individual--is catastrophically misinterpreted, leading to more bodily symptoms and anxiety. These could then contribute to more misinterpretation in a positive feedback sense, ultimately leading to a panic attack.
Judd FK, Apostolopoulos M, Burrows GD, Norman TR: SEROTONERGIC FUNCTION IN PANIC DISORDER: ENDOCRINE RESPONSES TO D-FENFLURAMINE. Progress in Neuro-Psychopharmacology & Biological Psychiatry 1994; 18(2):329-37. Summary: 1. Prolactin and cortisol responses to d-fenfluramine were measured in 16 patients with DSM-III-R panic disorder and 14 normal controls. 2. Patients showed a greater mean prolactin response than controls but the difference between groups was not statistically significant (P > 0.05, MANOVA). 3. No consistent differences were observed between patients and controls with respect to cortisol responses (P > 0.05, MANOVA). 4. The results do not support the hypothesis of hypersensitive post-synaptic serotonin receptors in patients with panic disorder. 5. Studies in larger groups are necessary to confirm the trend and to explore receptor subtype sensitivity.
Goldstein RB, Weissman MM, Adams PB, Horwath E, Lish JD, Charney D, Woods SW, Sobin C, Wickramaratne PJ: PSYCHIATRIC DISORDERS IN RELATIVES OF PROBANDS WITH PANIC DISORDER AND/OR MAJOR DEPRESSION. Archives of General Psychiatry 1994; 51(5):383-94. Summary: BACKGROUND: Panic disorder and major depression (MDD) are both highly familial disorders that co-occur in individuals but do not cosegregate in families. Evidence concerning their familial aggregation with other psychiatric disorders, including phobias, substance abuse, and antisocial personality, has been contradictory. In part, the contradictory findings may be due to failure to account for the effects of proband comorbidity on risks in relatives. METHODS: A family study of 1047 adult first-degree relatives of 193 probands in four diagnostic groups (panic disorder without MDD, panic disorder plus MDD, early-onset MDD, and screened normal controls) was used to determine the range of psychiatric disorders associated with panic disorder and MDD and the effects of proband comorbidity on the rates of disorders in relatives. RESULTS: Compared to relatives of normal controls, relatives of probands with panic disorder or panic disorder and MDD showed significantly increased risks of panic disorder, but relatives of probands with early-onset MDD did not. After proband comorbidity was controlled for, relatives of probands with panic disorder were also at a significantly increased risk for social phobia but not for any other psychiatric disorders. Relatives of probands with early-onset MDD were at significantly increased risk for MDD, dysthymia, abuse of or dependence on alcohol and other drugs, and antisocial personality disorders but not for any other psychiatric disorders. CONCLUSIONS: We conclude that panic disorder is a specific familial entity that is not associated with a broad range of other anxiety or other psychiatric disorders, with the possible exception of social phobia. Dysthymia, substance abuse, and antisocial personality appear to be on the spectrum of early-onset MDD.
Asmundson GJ, Stein MB: VAGAL ATTENUATION IN PANIC DISORDER: AN ASSESSMENT OF PARASYMPATHETIC NERVOUS SYSTEM FUNCTION AND SUBJECTIVE REACTIVITY TO RESPIRATORY MANIPULATIONS. Psychosomatic Medicine 1994; 56(3):187-93. Summary: We examined the effects of hyperventilation and other manipulations of respiratory pace on parasympathetic nervous system function and subjective reactivity in 15 patients with panic disorder, 15 patients with social phobia, and 15 healthy control subjects. After a 30-minute rest period subjects completed a 2.5-minute trial of each of hypoventilation, normoventilation, and hyperventilation. Trials were separated by a 3 minute inter-trial interval. Incidence of panic attacks, symptom severity, vagal tone, heart rate, end-tidal carbon dioxide level, and respiratory frequency were measured throughout. Resting physiological measures did not differ between groups. Each respiratory manipulation resulted in the expected physiological changes (e.g., hyperventilation attenuated vagal tone), however, groups did not exhibit differential physiological reactivity to the manipulations. There were no panic attacks reported during either the hypoventilation or normoventilation phases; however, two social phobic subjects (13.3%) and two panic disorder patients (13.3%) reported panic attacks during hyperventilation. Although both groups of anxiety patients reported greater severity of hyperventilation-induced symptoms than did control subjects, symptom severity did not correlate significantly with vagal tone or heart rate. These results suggest that parasympathetic function is unlikely to be aberrant in PD patients and that diminished parasympathetic activity is not sufficient for the experience of panic attacks.
Stein MB, Asmundson GJ, Ireland D, Walker JR: PANIC DISORDER IN PATIENTS ATTENDING A CLINIC FOR VESTIBULAR DISORDERS. American Journal of Psychiatry 1994; 151(11):1697-700. Summary: In a study of the prevalence of panic and other anxiety disorders in persons with complaints of dizziness, 87 patients referred to a clinic for vestibular disorders completed self-rating measures of anxiety and depression; 32 also underwent a structured diagnostic interview. Thirteen (14.9%) of the patients met the DSM-III-R criteria for panic disorder, agoraphobia, or both. They rated themselves as much more disabled by their dizziness than the patients with no psychiatric disorder. Panic disorder was equally prevalent among patients with and without vestibular disease. In some cases panic disorder may provide an explanation for the dizziness, whereas in others it may be a comorbid condition compounding the disability attributable to the vestibular disorder.
Wagner KD, Berenson AB: NORPLANT-ASSOCIATED MAJOR DEPRESSION AND PANIC DISORDER. Journal of Clinical Psychiatry 1994; 55(11):478-80. Summary: BACKGROUND: Norplant is a long-acting subdermal implant system that is widely used for contraception. The implant releases a continuous dose of levonorgestrel, a synthetic progestin. Although oral contraceptives are associated with depression and panic disorder, no cases have been reported of psychiatric disorders secondary to the use of Norplant. METHOD: Two women, aged 18 and 29 years, are described who developed major depression and panic disorder while using the Norplant system. RESULTS: These women who had no prior psychiatric history developed major depression and panic disorder 1 to 2 months after insertion of Norplant system capsules. The symptoms worsened over the course of a year. Following removal of Norplant, the symptoms of depression and anxiety resolved within 1 month. CONCLUSION: The progesterone content of oral contraceptives has been linked to major depression and panic disorder. Since Norplant is a progestin-only preparation, it is likely that some women will develop these disorders. These cases illustrate the importance of careful follow-up for adolescents and adults who select Norplant for contraception. Patients should be informed about the possible occurrence of psychiatric disorders. When evaluating new onset of depression and panic disorder in adolescent and adult women, it is important to inquire about Norplant insertion.
Perna G, Marconi C, Battaglia M, Bertani A, Panzacchi A, Bellodi L: SUBCLINICAL IMPAIRMENT OF LUNG AIRWAYS IN PATIENTS WITH PANIC DISORDER. Biological Psychiatry 1994; 36(9):601-5. Summary: Lung function was assessed in 17 panic patients and 20 healthy controls. Panic patients had abnormal values for some dynamic lung volumes, namely Peak Expiratory Flow Rate (PEFR), Expiratory Flow at 75% of Vital Capacity (FEF75) and Maximum Mid-Expiratory Flow Rate (MMEF). Such functional abnormalities might indicate subclinical obstruction of lung airways, possibly relevant to the mechanisms related to panic disorder (PD).
Stewart W, Breslau N, Keck PE Jr: COMORBIDITY OF MIGRAINE AND PANIC DISORDER. Neurology 1994; 44(10 Suppl 7):S23-7. Summary: Clinical and epidemiologic evidence suggests that migraine co-occurs with psychopathology, including specific anxiety disorders. To examine this association, survey data from a population-based study of more than 10,000 respondents were used to determine if individuals with a history of panic attacks were at greater risk of having specific headaches in the week preceding an interview. Four types of headache were defined. Of these, only migraine was strongly associated with panic attacks. Given the high prevalence of both migraine and panic attacks and evidence that they often co-occur, treatment implications are discussed for this comorbidity.
Stein MB, Asmundson GJ: AUTONOMIC FUNCTION IN PANIC DISORDER: CARDIORESPIRATORY AND PLASMA CATECHOLAMINE RESPONSIVITY TO MULTIPLE CHALLENGES OF THE AUTONOMIC NERVOUS SYSTEM. Biological Psychiatry 1994; 36(8):548-58. Summary: Panic disorder has been widely hypothesized to be associated with dysfunction of the autonomic nervous system. In this study, 24 patients with panic disorder and 26 healthy control subjects took part in a broad battery of autonomic function tests, each designed to stress the autonomic nervous system in a particular fashion. Testing consisted of postural challenge, isometric exercise, cold pressor, and Valsalva maneuver. Dependent measures included heart rate, vagal tone, blood pressure, respiratory frequency, end-tidal CO2 levels, and plasma norepinephrine and epinephrine levels. The testing procedures reliably produced changes in autonomic output in the expected directions, but patients with panic disorder were not found to differ from healthy controls in their cardiorespiratory or plasma catecholaminergic responses. This pattern of normal autonomic responsivity in the patients with panic disorder was evident across multiple test conditions with varying autonomic demand characteristics, thereby supporting the integrity of autonomic regulatory systems in this illness. These data run counter to a simple notion of autonomic dysfunction in panic disorder.
Andrade L, Eaton WW, Chilcoat H: LIFETIME COMORBIDITY OF PANIC ATTACKS AND MAJOR DEPRESSION IN A POPULATION-BASED STUDY. SYMPTOM PROFILES. British Journal of Psychiatry 1994; 165(3):363-9. Summary: BACKGROUND. The co-occurrence of panic disorder and major depression in the same individual is common. A question to be answered is whether the comorbid disorder is a distinct one or may resemble one or other disorder. In this paper we examine whether the comorbid disorder is a distinct condition. METHOD. We examined the symptom profiles and rates of comorbidity of panic attacks and DIS/DSM-III major depressive disorder in a population-based sample from four sites of the National Institute of Mental Health (NIMH) Epidemiologic Catchment Area Program (n = 12,668). RESULTS. The co-occurrence of panic attacks and major depression over the lifetime was 11 times higher than expected by chance (OR = 11.4, 95% CI 9.5 to 13.6). Subjects with both panic and depression had worse symptoms than those who had only one disorder. However, the pattern of symptoms was remarkably similar, after overall severity was taken into account. Depressive symptoms associated with more severe forms of depression (e.g. guilt, suicidal thoughts or attempts, and motor disturbance) were more frequent in the comorbid group. CONCLUSIONS. These findings may indicate a worse severity when the two disorders occur in the same individual.
Aoki Y, Fujihara S, Kitamura T: PANIC ATTACKS AND PANIC DISORDER IN JAPANESE NON-PATIENT POPULATION: EPIDEMIOLOGY AND PSYCHOSOCIAL CORRELATES. Journal of Affective Disorders 1994; 32(1):51-9. Summary: To investigate the prevalence rates of panic disorder and panic attacks in the general population of Japan, a set of questionnaires were administered to 207 people aged 18 or over, who were then interviewed. Seven (3.4%) had experienced one or more unexpected panic attacks in their lifetime. Two subjects (1.0%) had had panic disorder (DSM-III-R), and five (2.4%) had had panic attacks not meeting the criteria for panic disorder. Seventy percent of the persons with panic disorder or panic attacks had sought medical care. There was comorbidity with agoraphobia in two cases, and with major depression in five. Harsh discipline, frequent quarrel, between parents, and serious illness before the age of 16 were more frequent in individuals suffering from panic attacks, compared to those without.
Schweitzer R: TACHYCARDIA AND PANIC ATTACKS. Australian Family Physician 1994; 23(9):1784-7. Summary: This case taught me the importance of listening closely to the patient's history, and not just jumping in and accepting an old diagnosis. It also showed me how patients can effect change in their lives, that even when patients are seemingly crippled by panic, anxiety, stress, and with a history of sexual abuse as a child, that person can effect meaningful change in their life and reclaim their life from the effects of these problems.
Iny LJ, Pecknold J, Suranyi-Cadotte BE, Bernier B, Luthe L, Nair NP, Meaney MJ: STUDIES OF A NEUROCHEMICAL LINK BETWEEN DEPRESSION, ANXIETY, AND STRESS FROM [3H]IMIPRAMINE AND [3H]PAROXETINE BINDING ON HUMAN PLATELETS. Biological Psychiatry 1994; 36(5):281-91. Summary: We measured platelet [3H]imipramine and [3H]paroxetine binding in patients with major depression (n = 11), dysthymia (n = 9), generalized anxiety (n = 18) and panic disorder (n = 10), and in healthy controls (n = 13). The [3H]imipramine binding capacity (Bmax) was lower in all patient groups; [3H]paroxetine binding was reduced in anxiety disorders, however, decreases in depression and dysthymia were not significant. There were no differences in the affinity constant (Kd) for either radioligand. We also examined the effects of examination stress on platelet binding in medical students. Compared to after vacation, when binding was similar to controls, [3H]imipramine (n = 19) and [3H]paroxetine (n = 14) Bmax values were significantly decreased during examinations and similar to patient values. Examinations were also associated with an increase in plasma cortisol levels. These findings suggest that there is a neurochemical link between depression, anxiety, and stress, and that disturbances in neurochemical functioning may be associated with specific symptomatology, independent of psychiatric diagnosis.
Chen YW, Dilsaver SC: COMORBIDITY OF PANIC DISORDER IN BIPOLAR ILLNESS: EVIDENCE FROM THE EPIDEMIOLOGIC CATCHMENT AREA SURVEY. American Journal of Psychiatry 1995; 152(2):280-2. Summary: OBJECTIVE: The authors' goal was to determine the rate of comorbid panic disorder in individuals with bipolar disorder. METHOD: They used the Epidemiologic Catchment Area survey database to determine the prevalence of comorbid panic disorder in individuals with unipolar depression, those with bipolar disorder, and comparison subjects without bipolar or unipolar disorder. RESULTS: The lifetime prevalence of panic disorder among subjects with bipolar disorder was 20.8%; among subjects with unipolar depression it was 10.0%, and among comparison subjects it was 0.8%. CONCLUSIONS: Individuals with bipolar disorder have a particularly high risk of comorbid panic disorder. The evaluation of patients with bipolar disorder should include screening for panic disorder.
Reschke AH, Mannuzza S, Chapman TF, Lipsitz JD, Liebowitz MR, Gorman JM, Klein DF, Fyer AJ: SODIUM LACTATE RESPONSE AND FAMILIAL RISK FOR PANIC DISORDER. American Journal of Psychiatry 1995; 152(2):277-9. Summary: OBJECTIVE: The authors used the family study method to test the hypothesis that sodium lactate response defines two subtypes of panic disorder. METHOD: Rates of panic disorder in 142 first-degree relatives of patients who responded to sodium lactate, 88 first-degree relatives of patients who did not respond to sodium lactate, and 231 first-degree relatives of never mentally ill subjects were compared. RESULTS: No difference in familial transmission of panic disorder was found between the two patient groups. CONCLUSIONS: The findings do not support the notion that panic disorder subtypes are associated with lactate sensitivity.