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Biomedical subjects

J L Abelson

Publications and source records attributed to J L Abelson.

At least 19 recordsLinked to original sources
PubMed1999

Dose response of adrenocorticotropin and cortisol to the CCK-B agonist pentagastrin.

Cholecystokinin (CCK) is an abundant neurotransmitter in brain. Its functional significance in humans is incompletely understood, but it may modulate activity in the hypothalamic-pituitary-adrenal (HPA) axis. To explore this hypothesis, we examined the effects of varying doses (0 to 0.8 microgram/kg) of the CCK-B agonist pentagastrin on adrenocorticotropin (ACTH) and cortisol release in healthy human subjects. We also examined anxiety, heart rate (HR), and blood pressure (BP) responses. Pentagastrin induced large (up to 520% increase over baseline), significant and very rapid, dose-dependent elevations in ACTH and cortisol levels. Significant elevations in HR and BP were seen at all doses, without clear dose-response relationships. Anxious distress and symptom responses were also somewhat dose dependent; but hormonal responses were more robustly linked to pentagastrin dose than to these subjective measures. The HPA axis response to the CCK-B agonist pentagastrin may be a direct pharmacological effect. Further work is needed to determine the mechanisms and the physiological significance of CCK-mediated modulation of the human neuroendocrine stress axis.

Adolescent↗
PubMed1999

Neuroendocrine and psychophysiologic responses in PTSD: a symptom provocation study.

Biological research on post-traumatic stress disorder (PTSD) has focused on autonomic, sympatho-adrenal, and hypothalamo-pituitary-adrenal (HPA) axis systems. Interactions among these response modalities have not been well studied and may be illuminating. We examined subjective, autonomic, adrenergic, and HPA axis responses in a trauma-cue paradigm and explored the hypothesis that the ability of linked stress-response systems to mount integrated responses to environmental threat would produce strong correlations across systems. Seventeen veterans with PTSD, 11 veteran controls without PTSD, and 14 nonveteran controls were exposed to white noise and combat sounds on separate days. Subjective distress, heart rate, skin conductance, plasma catecholamines, ACTH, and cortisol, at baseline and in response to the auditory stimuli, were analyzed for group differences and for patterns of interrelationships. PTSD patients exhibited higher skin conductance, heart rate, plasma cortisol, and catecholamines at baseline, and exaggerated responses to combat sounds in skin conductance, heart rate, plasma epinephrine, and norepinephrine, but not ACTH. The control groups did not differ on any measure. In canonical correlation analyses, no significant correlations were found between response systems. Thus, PTSD patients showed heightened responsivity to trauma-related cues in some, but not all, response modalities. The data did not support the integrated, multisystem stress response in PTSD that had been hypothesized. Individual response differences or differing pathophysiological processes may determine which neurobiological system is affected in any given patient.

Acoustic Stimulation↗
PubMed1999

Effect of alcohol on social phobic anxiety.

OBJECTIVE: Previous research has demonstrated a greater-than-expected association between social phobia and alcohol use disorders. The purpose of this study was to test the hypothesis that drinking alcohol reduces social phobic anxiety. METHOD: Treatment-seeking individuals with social phobia (N = 40) were asked to give two impromptu speeches. Twenty subjects received a placebo alcoholic drink before both speeches, and 20 subjects received a placebo before the first speech, followed by a moderate dose of alcohol before the second speech. Subjective anxiety ratings, heart rate, and cognitions related to social anxiety were used as measures of anxiety. RESULTS: Repeated measures analyses of variance yielded no significant differences in anxiety (subjective, physiological, cognitive) between the alcohol and placebo groups. Current and past drinking habits did not significantly alter the effect of alcohol on anxiety. The belief that one received alcohol was significantly related to levels of subjective anxiety and negative cognitions. CONCLUSIONS: Alcohol does not directly reduce social phobic anxiety. The belief that one received alcohol may reduce social anxiety.

Adult↗
PubMed1998

Defense mechanism changes in successfully treated patients with obsessive-compulsive disorder.

OBJECTIVE: Changes in defense mechanisms after treatment of patients with obsessive-compulsive disorder (OCD) were measured by using an established rating scale. METHOD: Before and after 7-week group behavior therapy, 17 patients with DSM-III-R OCD were assessed with the Defense Style Questionnaire, Yale-Brown Obsessive Compulsive Scale, and Beck Depression Inventory. RESULTS: After behavior therapy the patients evidenced significant decreases in Yale-Brown Obsessive Compulsive Scale scores and significant increases in the use of more adaptive defense mechanisms. There were no significant changes in three maladaptive defense mechanism categories. The improvement in adaptive defenses was independently linked to improvement both in OCD and in depression. CONCLUSIONS: Personality as defined by defense mechanisms may be more amenable to brief behavioral treatment than previously thought. The permanence of these changes must be further assessed.

Adult↗
PubMed1997

Adrenocorticotropic hormone and cortisol responses to corticotropin-releasing hormone: changes in panic disorder and effects of alprazolam treatment.

This study applied the corticotropin-releasing hormone (CRH) stimulation test to patients with panic disorder, before and during treatment with alprazolam, and to control subjects. In contrast to some, but not all prior studies, untreated, nondepressed panic disorder patients failed to show blunted adrenocorticotropic hormone or cortisol responses to CRH. In fact, the responses were subtly enhanced in that they were more rapid than those of controls. After 12 weeks of alprazolam treatment, repeat testing gave results that were indistinguishable from those of controls. Inconsistency among reports of CRH testing in panic disorder may be related to interactions among illness mechanisms, concurrent subthreshold depressive symptoms, the chronic stress of the illness, and hyperresponsiveness of panic patients to the acute stress of experimental manipulations. Pretreatment abnormalities in hypothalamic-pituitary-adrenal axis function appear to resolve with alprazolam treatment. Preliminary observations suggest that pretreatment dysregulation of the hypothalamic-pituitary-adrenal system may predict a more difficult or less satisfactory treatment.

Adrenocorticotropic Hormone↗
PubMed1997

Childhood adversity and vulnerability to mood and anxiety disorders.

Based upon epidemiological surveys, adverse childhood events are proposed to be risk factors for adult depressive and anxiety disorders. However, the extent to which these events are seen in clinical patient populations is less clear. We examined the prevalence of a number of proposed risk factors for depression in 650 patients with mood and anxiety disorders at the time of presentation for treatment in an outpatient subspecialty clinic. Emotional abuse, physical abuse, or sexual abuse (childhood adversity) was found in approximately 35% of patients with major depression and panic disorder, was more common in women than men, and was associated with an earlier onset of symptoms. Childhood adversity was also strongly associated with marital discord/divorce, and psychopathology in a parent, suggesting family discord predisposes to childhood abuse. Furthermore, the association of childhood abuse with parental mental illness suggests that genetic and environmental factors are difficult to separate as etiological factors in vulnerability.

Adult↗
PubMed1996

Hypothalamic-pituitary-adrenal axis activity in panic disorder. 24-hour secretion of corticotropin and cortisol.

BACKGROUND: Oversecretion of corticotropin-releasing hormone and/or dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis may contribute to pathophysiologic processes in panic disorder, but documentation of HPA axis disturbance in panic has been inconsistent. In the current study we examined HPA axis activity in panic disorder over a full circadian cycle, using frequent blood sampling to provide detailed assessment of corticotropin and cortisol secretion. METHODS: Twenty patients with panic disorder and 12 normal control subjects were studied. Blood samples were drawn every 15 minutes for 24 hours and assayed for corticotropin and cortisol levels. RESULTS: Patients with panic disorder had elevated overnight cortisol secretion and greater amplitude of ultradian secretory episodes. Patients who entered the study through clinical referral channels had greater cortisol secretion than those recruited by advertisements. Patients with panic disorder who had a low frequency of panic attacks had elevated daytime corticotropin levels and elevated corticotropin ultradian amplitude. Patients with a high frequency of attacks had shifted corticotropin circadian cycles. CONCLUSIONS: Patients with panic disorder demonstrate subtle alterations in HPA axis activity, characterized by overnight hypercortisolemia and increased activity in ultradian secretory episodes, but HPA axis alterations in panic are modulated by illness severity and treatment seeking. It remains unclear whether HPA axis dysregulation in panic represents a pathogenic defect within the axis itself. Inconsistencies in prior work may reflect the subtlety of the abnormalities seen, differences in clinical characteristics of patients studied, and the use of different probes and measurement contexts.

Activity Cycles↗
PubMed1996

Neuroendocrine responses to laboratory panic: cognitive intervention in the doxapram model.

Doxapram is a respiratory stimulant that appears to be a potent and specific panicogenic agent. It also elicits an abnormal ventilatory response in patients with panic. A replication study confirmed these findings and demonstrated that behavioral and ventilatory responses to doxapram were significantly modified by a psychological intervention designed to cognitively block panic. The replication study provided an opportunity to simultaneously investigate the neuroendocrine effects of the illness, the drug, the drug-induced panic attacks, and the cognitive intervention. Epinephrine (EPI), norepinephrine (NE), growth hormone (GH), adrenocorticotropin (ACTH), and cortisol were studied in patients with panic and control subjects given placebo and doxapram injections after receiving either standard instructions or a brief cognitive intervention. Patients with panic had elevated levels of EPI, ACTH, and cortisol throughout the study. Doxapram had little or no detectable effects on plasma NE, GH, ACTH, and cortisol. Doxapram-induced panic attacks were not associated with elevations in NE, GH, ACTH, or cortisol. Doxapram led to a rapid and very brief rise in plasma EPI, which was small in subjects who did not panic and pronounced in patients who did panic. The cognitive intervention attenuated the EPI response to doxapram, perhaps through its effect on panic, and modified the temporal pattern of ACTH and cortisol secretion. These results suggest that: (1) further study of catecholamine responses within the first few minutes after panic induction is needed; (2) intense panic can occur without significant activation of the hypothalamic-pituitary-adrenal axis; and (3) cognitive factors can modulate neuroendocrine activity in laboratory studies of patients with panic.

Acoustic Stimulation↗
PubMed1996

Reliability and procedural validity of UM-CIDI DSM-III-R phobic disorders.

We evaluate the long-term test-retest reliability and procedural validity of phobia diagnoses in the UM-CIDI, the version of the Composite International Diagnostic Interview, used in the US National Co-morbidity Survey (NCS) and a number of other ongoing large-scale epidemiological surveys. Test-retest reliabilities of lifetime diagnoses of simple phobia, social phobia, and agoraphobia over a period between 16 and 34 months were K = 0.46, 0.47, and 0.63, respectively. Concordances with the Structured Clinical Interview for DSM-III-R (SCID) were K = 0.45, 0.62, and 0.63, respectively. Diagnostic discrepancies with the SCID were due to the UM-CIDI under-diagnosing. Post hoc analysis demonstrated that modification of UM-CIDI coding rules could dramatically improve cross-sectional procedural validity for both simple phobia (K = 0.57) and social phobia (K = 0.95). Based on these results, it seems likely that future modification of CIDI questions and coding rules could lead to substantial improvements in diagnostic validity.

Adolescent↗
PubMed1996

Hypothalamic-pituitary-adrenal axis activity in panic disorder: prediction of long-term outcome by pretreatment cortisol levels.

OBJECTIVE: The authors sought to determine whether hypothalamic-pituitary-adrenal (HPA) axis activity in patients before their treatment for panic disorder can predict follow-up functional status. Although baseline HPA axis disturbances in patients with panic disorder appear to attenuate with treatment, there is evidence that they may be linked to poorer long-term outcomes. METHOD: Follow-up clinical data were obtained for 18 of 20 patients with panic disorder who participated in a detailed study of HPA axis activity in panic, both before and during their treatment with alprazolam. HPA axis assessment included monitoring of adrenocorticotropin and cortisol over a full circadian cycle. The relationships between disability and clinical status at 2-year follow-up and HPA axis overactivity at entry were examined. RESULTS: Mean 24-hour cortisol levels before treatment provided a strong, positive predictor of disability scores at follow-up. Those patients who achieved the treatment goal of medication-free remissions had less evidence of HPA axis overactivity at entry than those who were not in remission. CONCLUSIONS: HPA axis activity before treatment did predict outcome 2 years later. This relationship appears robust and reproducible. Further work is needed to define the neuroendocrine mechanisms underlying the HPA axis markers that are linked to long-term functioning and to determine the biological, psychological, and social processes that link HPA axis disturbance to poorer outcomes.

Adolescent↗
PubMed1994

Pentagastrin infusions in patients with panic disorder. I. Symptoms and cardiovascular responses.

Cholecystokinin (CCK) may mediate human anxiety and animal data suggest that cholecystokinin antagonists could provide an important advance in the treatment of anxiety disorders. The study of CCK receptor systems in psychiatric patients has, however, been severely limited by the lack of available probes. We utilized intravenous infusions of pentagastrin, a selective CCK-B receptor agonist, and studied behavioral and cardiovascular responses in 10 patients with panic disorder and 10 normal controls. Pentagastrin produced substantial symptomatology, including anxiety, and increases in heart rate and blood pressure, in both patients and controls. Patients were more sensitive to the panicogenic effects of the pentagastrin. Panic attacks occurred in 70% of patients and 0% of controls. Patients' symptom responses were very similar to their "typical" panic attacks and to symptoms produced by CCK4. Pentagastrin provides a readily available alternative to CCK4 for studying the CCK receptor system and exploring its involvement in human anxiety.

Adult↗
PubMed1994

Pentagastrin infusions in patients with panic disorder. II. Neuroendocrinology.

Cholecystokinin (CCK) has well-documented anxiogenic effects in animals and normal people, and panicogenic effects in patients with panic disorder, but little is known about its neuroendocrine profile. We examined neuroendocrine responses to intravenous infusions of pentagastrin, a selective CCK-B receptor agonist, in 10 patients with panic disorder and 10 normal control subjects. Pentagastrin potently activated the hypothalamic-pituitary-adrenal (HPA) axis, but did not release growth hormone or any of several vasoactive peptides (neurokinin A, substance P, vasoactive intestinal peptide). The HPA axis response was unrelated to increases in symptoms. Panic patients did not differ from controls in neuroendocrine responses to the CCK agonist. Differential sensitivity to novelty stress accounted for the only patient-control differences in neuroendocrine profiles. The data suggest that CCK may help modulate normal HPA axis activity, but its anxiogenic effects are unrelated to its stimulatory effects on the HPA axis. Pentagastrin provides a safe and readily available probe for further study of CCK receptor systems in humans.

Adrenocorticotropic Hormone↗
PubMed1992

Endocrine, cardiovascular, and behavioral responses to clonidine in patients with panic disorder.

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.

Adrenergic Fibers↗
PubMed1991

Blunted growth hormone response to clonidine in patients with generalized anxiety disorder.

Patients with panic disorder or depression have abnormal responses to the alpha 2-adrenergic receptor partial agonist clonidine. Evidence linking anxiety to noradrenergic dysfunction and the presence of anxiety symptoms in both depression and panic suggest that abnormal responses to clonidine in these disorders could be due to the anxiety symptoms. To explore a possible link between "nonspecific" anxiety symptoms and abnormal responses to clonidine, patients with DSM-III-defined generalized anxiety disorder were given intravenous infusions of clonidine hydrochloride. Responses of plasma growth hormone, 3-methoxy-4-hydroxyphenylglycol, heart rate, blood pressure, and psychological states were determined in 11 patients with generalized anxiety disorder and 14 healthy subjects. Clonidine produced significantly smaller growth hormone responses in patients than in healthy controls. The two groups did not differ in 3-methoxy-4-hydroxyphenylglycol, heart rate, blood pressure, or psychological responses to clonidine. These results are compared with data from similar studies on patients with panic disorder and depression. The blunting of the growth hormone response to clonidine in all three disorders could be due to the presence of generalized anxiety symptoms. Subsensitivity of postsynaptic alpha 2-adrenoreceptors may be present in all three disorders; however, there are alternative interpretations of growth hormone blunting in response to clonidine. Blunting was observed in DSM-III-defined generalized anxiety disorder, whether or not the DSM-III-R criterion of excessive worry was also present.

Adult↗