tetragastrin and Anxiety-Disorders

Although the epidemiology, neurobiology, and treatment of anxiety disorders have received considerable attention in the child and adult literature, they have not received the same consideration in the geriatric population. This disparity is remarkable given the prevalence and associated costs of these disorders that can persist into late life. Further, although a considerable amount is known about these disorders in younger age groups, it is unclear whether the phenomenology of anxiety evolves over the course of the aging process. Thus, conclusions drawn based on younger populations of anxious adults may not hold true for older cohorts. This article reviews issues of epidemiology, phenomenology, neurobiology, and medical comorbidity, as well as pharmacologic and psychotherapeutic treatments in older adults.

Topics: Adult; Aged; Antidepressive Agents; Anxiety Disorders; Brain; Cognitive Behavioral Therapy; Female; Humans; Male; Middle Aged; Tetragastrin

Topics: Animals; Anxiety; Anxiety Disorders; Cholecystokinin; gamma-Aminobutyric Acid; Humans; Sincalide; Tetragastrin

Topics: Animals; Anxiety; Anxiety Disorders; Cholecystokinin; Humans; Panic Disorder; Receptors, Cholecystokinin; Tetragastrin

Benzodiazepine effects on cholecystokinin tetrapeptide (CCK-4)-induced panic attack (PA) in humans are incompletely characterized, in particular on the neurofunctional level. This work explores the effects of lorazepam on brain activity and behavioral and physiological symptoms related to CCK-4-induced PA in healthy volunteers. Twenty-one male volunteers received 1 mg of lorazepam or placebo orally, 2 hours before an injection of 0.9% saline solution followed by 50 µg of CCK-4 during functional magnetic resonance imaging (fMRI) and heart rate recording. Panic attacks were defined using the panic symptom scale (PSS). In addition, the Y1-STAI (state anxiety) and the Bond & Lader Visual Analogue Scale (VAS) were used. Eleven subjects were classified as panickers. CCK-4 induced behavioral anxiety and cardiovascular effects along with cerebral activation in anxiety-related brain regions. Overall, lorazepam did not significantly modify the anxiogenic and cardiovascular effects of CCK-4. Regarding CCK-4-induced brain activation, lorazepam did not reduce activity in the insulae and cingulate gyrus of panickers. One milligram of lorazepam was not sufficient to reverse strong panicogenic effects, but decreased brain activity in the case of mild anxiety.

Topics: Adult; Anti-Anxiety Agents; Anxiety; Anxiety Disorders; Attention; Cerebral Cortex; Cross-Over Studies; Gyrus Cinguli; Heart Rate; Humans; Lorazepam; Magnetic Resonance Imaging; Male; Panic; Panic Disorder; Psychiatric Status Rating Scales; Tetragastrin; Young Adult

Panic attacks induced by administration of cholecystokinin tetrapeptide (CCK-4) have been evaluated as a valuable tool to investigate the neurobiological mechanisms involved in panic anxiety. The rationale to study the effects of natriuretic peptides on the CCK-4 response is derived from observations that atrial natriuretic peptide (ANP) is released during panic attacks in humans and has anxiolyticlike actions in various animal models.. A double-blind, placebo-controlled design was conducted in 9 patients with panic disorder and 9 similar healthy control subjects. After pretreatment with an infusion of 150 microg of ANP or placebo in random order, each subject received 50 microg of CCK-4. Psychopathological parameters as well as physiological measures were sampled before and after CCK-4 administration.. After pretreatment with ANP, the number of CCK-4-induced panic attacks decreased from 8 to 6 in patients and from 5 to 2 in controls. Acute Panic Inventory ratings were significantly reduced in patients after ANP vs placebo pretreatment. Infusion of ANP significantly curtailed the CCK-4-induced release of corticotropin in patients. Heart rate variability analysis indicated a sympathetic stimulation by CCK-4 that was inhibited by ANP in patients and controls.. The present study indicates that ANP exerts anxiolyticlike effects on CCK-4-stimulated anxiety attacks in patients with panic disorder. In addition, ANP produced an inhibition of the hypothalamopituitary-adrenocortical system and sympatholytic effects.

Topics: Adrenocorticotropic Hormone; Adult; Anti-Anxiety Agents; Anxiety Disorders; Area Under Curve; Atrial Natriuretic Factor; Blood Pressure; Double-Blind Method; Female; Heart Rate; Humans; Hydrocortisone; Male; Panic Disorder; Placebos; Prospective Studies; Tetragastrin

This article examines the effect of baseline anxiety, anxiety sensitivity and dysfunctional attitudes on the response to cholecystokinin tetrapeptide (CCK-4) in healthy volunteers. CCK-4 and placebo were administered to 14 subjects in a double-blind manner. Four volunteers experienced a panic attack after CCK-4 administration. Those subjects who panicked had significantly higher baseline scores on dysfunctional attitudes. Dysfunctional thought patterns appeared also to predict number of symptoms and experience of cognitive and affective symptoms during injection. Baseline anxiety as well as anxiety sensitivity predicted reactions to placebo but not panic responses to CCK-4. Results suggest that a general tendency towards erroneous interpretation of information has some role in mediating the panicogenic effects of CCK-4, and also interpersonal sensitivity may constitute a vulnerability factor for panic. Psychological factors that have been considered more specific to panic disorder, namely high state and trait anxiety as well as anxiety sensitivity, appeared mainly to determine general reactions to a threatening situation.

Topics: Adult; Anxiety Disorders; Cognition Disorders; Double-Blind Method; Female; Gastrointestinal Agents; Humans; Male; Panic Disorder; Placebos; Tetragastrin

The authors tested the prediction of temporal cortex activation during experimentally induced anxiety by using positron emission tomography and the [15O]H2O bolus-subtraction method to determine regional cerebral blood flow (CBF) changes in normal volunteers challenged with a bolus injection of cholecystokinin tetrapeptide (CCK4).. Eight right-handed healthy subjects (five male, three female; mean age, 26.4 years) underwent four 60-second [15O]H2O scans separated by 15-minute intervals; each scan followed an intravenous bolus injection of either saline (placebo) or CCK4 (50 micrograms). Each subject received CCK4 once, as the first or second bolus, in a random-order, placebo-controlled, double-blind fashion. Two of the three placebo conditions were nominally identical, and the remaining placebo was used to control for anticipatory anxiety. Magnetic resonance imaging scans were obtained for subsequent anatomical correlation of blood flow changes.. CCK4, but not placebo, elicited a marked anxiogenic response, reflected by robust increases in subjective anxiety ratings and heart rate. CCK4-induced anxiety was associated with 1) robust and bilateral increases in extracerebral blood flow in the vicinity of the superficial temporal artery territory and 2) CBF increases in the anterior cingulate gyrus, the claustrum-insular-amygdala region, and the cerebellar vermis.. Some of the temporopolar cortex CBF activation peaks previously reported in humans in association with drug- and non-drug-induced anxiety, as well as the increase in regional CBF in the claustrum-insular-amygdala region, may be of vascular and/or muscular origin.

Topics: Adult; Anxiety Disorders; Cerebrovascular Circulation; Double-Blind Method; Female; Humans; Magnetic Resonance Angiography; Male; Oxygen Radioisotopes; Panic Disorder; Placebos; Regional Blood Flow; Subtraction Technique; Temporal Lobe; Tetragastrin; Tomography, Emission-Computed

We studied the action of cholecystokinin tetrapeptide (CCK-4) in patients with panic disorder and normal controls. Subjects received, in random order, one injection of CCK-4 and one injection of placebo (saline) on two separate days in a double-blind crossover design. Two doses of CCK-4, 50 and 25 micrograms, were administered to two different samples of subjects. The panic rate with 50 micrograms of CCK-4 was 100% (12/12) for patients and 47% (7/15) for controls. The panic rate with 25 micrograms of CCK-4 was 91% (10/11) for patients and 17% (2/12) for controls. Nine percent of patients compared with 0% of controls panicked with placebo. These findings concur with previous reports of a panicogenic effect of CCK-4 and suggest that patients with panic disorder are more sensitive to the panicogenic effect of the peptide than are normal controls.

Topics: Adult; Anxiety Disorders; Cholecystokinin; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Middle Aged; Panic; Placebos; Tetragastrin

Cholecystokinin-tetrapeptide (CCK-4) and placebo were injected to 11 panic disorder patients. CCK-4 induced a panic attack identical to spontaneous panic attacks in all patients; placebo did not induce any attacks. The role of CCK-4 in anxiety disorders is discussed.

Topics: Adult; Anxiety Disorders; Clinical Trials as Topic; Double-Blind Method; Fear; Female; Gastrins; Humans; Male; Middle Aged; Panic; Tetragastrin

The effects of GB-115 dipeptide, a retroanalog of endogenous CCK-4, on the behavioral indices in "elevated plus maze" (EPM) test and on the content of biogenic amines in the brain structures after discontinuation of a chronic administration of benzodiazepine (BZ) derivatives phenazepam (2.0 mg/kg, i.p.) and diazepam (4.0 mg/kg, i.p.) have been studied in outbred and inbred MR/MNRA rats. It is established that, in 24-48 h following BZ withdrawal, GB-115 dipeptide administered in doses of 0.1 and 0.5 mg/kg, i.p., produced an anxiolytic effect in all animals, which was manifested by increasing the stay time and number of entries in EPM. In the striatum of outbred rats, GB-115 increased DOPAC (+25%) and DA (+31.6%) levels that were decreased during diazepam withdrawal syndrome. The obtained results showed the GB-115 efficiency in attenuating the anxiety caused by BZ withdrawal.

Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; Animals, Outbred Strains; Anti-Anxiety Agents; Anxiety Disorders; Behavior, Animal; Benzodiazepines; Brain Chemistry; Diazepam; Dipeptides; Disease Models, Animal; Dopamine; Exploratory Behavior; Male; Maze Learning; Rats; Substance Withdrawal Syndrome; Tetragastrin; Tranquilizing Agents

In order to elucidate the impact of psychological factors on panic severity the correlation between baseline anxiety and panic response to cholecystokinin-tetrapeptide (CCK-4), an established model of human anxiety, was investigated in 33 healthy volunteers. Baseline anxiety was assessed with the State-Trait-Anxiety-Inventory (STAI). Trait and state anxiety did not differ between panickers and nonpanickers nor were they correlated with panic severity. In conclusion, psychological factors are not major determinants for the subjective panic response to CCK-4 thus emphasising the importance of neurobiological factors.

Topics: Adult; Anxiety; Anxiety Disorders; Brain; Causality; Drug Resistance; Fear; Humans; Male; Neuropsychological Tests; Panic Disorder; Predictive Value of Tests; Tetragastrin

Trait dissociation might influence the response to panicogens in normal controls. The behavioral effects of 25 microg of cholecystokinin tetrapeptide (CCK-4) were studied in 18 healthy men, nine each with high or low trait dissociation. Subjects with high trait dissociation showed a significantly lower increase of acute dissociative, anxiety and panic symptoms compared with subjects with low trait dissociation. Trait dissociation should be assessed in further behavioral challenge studies as a potentially important covariate.

Topics: Adult; Anxiety Disorders; Gastrointestinal Agents; Health Status; Humans; Male; Panic Disorder; Severity of Illness Index; Tetragastrin

This study examined the relationship between the Symptom Checklist 90 (SCL-90), Maudsley Personality Inventory (MPI) and cholecystokinin 4 (CCK4)-induced intracellular calcium response in T cells. Fifty-two normal volunteers were 37 males and 15 females; they ranged in age from 23 to 44 years. Measures included CCK4-induced intracellular calcium response in T cells, SCL-90 scores, and MPI. Paranoid ideation and interpersonal sensitivity in SCL-90 showed a significant negative association with CCK4-induced intracellular calcium response. Absent were sex differences and extroversion and neuroticism correlations. There were no significant differences between men and women in SCL-90 or MPI scores. There was no correlation among extroversion and neuroticism and CCK4-induced intracellular calcium response. CCKB receptor function might play a role in paranoid ideation and interpersonal sensitivity.

Topics: Adult; Anxiety Disorders; Calcium; Calcium Channels; Extraversion, Psychological; Female; Humans; Introversion, Psychological; Male; Personality Disorders; Personality Inventory; Receptor, Cholecystokinin B; Receptors, Cholecystokinin; T-Lymphocytes; Tetragastrin

Topics: Anxiety Disorders; Carbon Dioxide; Comorbidity; Depressive Disorder; Female; Humans; Lactates; Menstrual Cycle; Panic Disorder; Premenstrual Syndrome; Tetragastrin

Topics: Anxiety Disorders; Fear; Gastrins; Humans; Panic; Pentagastrin; Receptors, Cholecystokinin; Tetragastrin