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Biomedical subjects

D Koszycki

Publications and source records attributed to D Koszycki.

At least 37 records · Page 2Linked to original sources
PubMed1996

Influence of personality on behavioral response to cholecystokinin-tetrapeptide in patients with panic disorder.

The relationship between personality, as measured by selected clinical scales of the Minnesota Multiphasic Personality Inventory (MMPI) (Hypochondriasis, Depression, Hysteria, Psychasthenia, Social Introversion, and Anxiety) and the Anxiety Sensitivity Index (ASI), and behavioral response to the panicogenic agent cholecystokinin-tetrapeptide (CCK-4) was examined in 29 patients with panic disorder with or without agoraphobia. Significant correlations were found between the MMPI Social Introversion scale and somatic, cognitive, and affective response to CCK-4. Both the MMPI Anxiety scale and the ASI correlated significantly with cognitive response to CCK-4, but not with somatic or affective response. None of the other selected MMPI clinical scales correlated with response to CCK-4. Multiple regression analyses identified the MMPI Social Introversion scale as the best predictor of all three indices of panic-anxiety induced by CCK-4. The results suggest that the relationship between neurotic introversion and sensitivity to CCK requires closer scrutiny.

Adult↗
PubMed1996

MMPI profiles of acute and chronic PTSD in a civilian sample.

In a treatment setting, a group of 165 subjects presenting with either acute or chronic posttraumatic stress disorder (PTSD) were compared to 72 subjects presenting with panic disorder only in order to determine whether the MMPI PTSD assessment strategy developed with Vietnam veterans could be validly used with civilians. Results indicated that the MMPI profile, codetype, diagnostic decision rule, and PK scale developed with samples of Vietnam veterans did not apply well to civilians, especially those presenting with acute PTSD. It is thus recommended that specific assessment strategies be developed for these populations.

Acute Disease↗
PubMed1995

Effect of CI-988 on cholecystokinin tetrapeptide-induced panic symptoms in healthy volunteers.

A randomized, placebo-controlled, double-blind, three-way crossover design was used to evaluate the effectiveness of single oral 100 mg doses of CI-988, a cholecystokinin B (CCKB) antagonist, in attenuating panic symptoms induced by intravenous injection of cholecystokinin-tetrapeptide (CCK-4). Thirty healthy men received the following treatments on three separate occasions: placebo capsules/placebo, placebo capsules/CCK-4, or CI-988 capsules/CCK-4. There was no marked difference in the number, time to onset, or duration of panic symptoms between CI-988/CCK-4 and placebo/CCK-4. There was, however, a 14% difference in sum intensity scores between these treatments that was statistically significant (p = 0.039). The symptoms most affected by CI-988 were cold chills/hot flushes, chest pain/discomfort, and anxiety/fear/apprehension. Panic attack frequency also decreased following CI-988 treatment (8/30 vs. 16/30; p = 0.035). This decrease, amid otherwise modest effects, could be explained by a preferential effect of CI-988 on the subjective experience of anxiety/fear/apprehension. Possible reasons for the relatively modest effects of CI-988 on CCK-4-induced panic symptoms are discussed.

Adult↗
PubMed1994

The panicogenic effects of cholecystokinin-tetrapeptide are antagonized by L-365,260, a central cholecystokinin receptor antagonist, in patients with panic disorder.

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.

Administration, Oral↗
PubMed1994

Effects of flumazenil on cholecystokinin-tetrapeptide-induced panic symptoms in healthy volunteers.

The neuropeptide cholecystokinin-tetrapeptide (CCK-4) has potent anxiogenic action in human and animal subjects. On the basis of prior work which demonstrated that benzodiazepine (BZD) receptor agonists antagonized CCK-induced excitation of rat hippocampal neurons we studied whether BZD receptors mediated the anxiogenic effect of CCK-4. To examine this possibility we determined whether the BZD receptor antagonist flumazenil could antagonize the effects of CCK-4 (50 micrograms) in healthy volunteers. Thirty subjects (10 females; 20 males) were pretreated with flumazenil (2 mg in saline) or placebo (0.9% NaCl in water) 15 min prior to CCK-4 challenge in a randomized double-blind crossover design. Flumazenil had no impact on the behavioral and cardiovascular effects of CCK-4, suggesting that BZD receptors do not mediate the anxiogenic action of CCK-4. The influence of GABA and non-GABA-related mechanisms on response to CCK-4 remains to be considered.

Adult↗
PubMed1994

Imipramine antagonism of the panicogenic effects of cholecystokinin tetrapeptide in panic disorder patients.

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.

Adult↗
PubMed1993

Anxiety sensitivity and response to cholecystokinin tetrapeptide in healthy volunteers.

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.

Adolescent↗
PubMed1992

A dose-ranging study of the behavioral and cardiovascular effects of CCK-tetrapeptide in panic disorder.

Recent animal studies have shown that pretreatment with centrally active cholecystokinin (CCK) antagonists blocks the anxiogenic effects of CCK-tetrapeptide (CCK-4). In order to determine whether pretreatment with these antagonists can block the anxiogenic effects of CCK-4 in patients with panic disorder, a suitable challenge dose of CCK-4 must be selected. Thus, we conducted a dose range study in which patients with panic disorder (n = 29) were challenged with CCK-4 (10, 15, 20, or 25 micrograms) or placebo on two separate occasions, in a balanced incomplete block design. Patients received in random order 10 micrograms (n = 12), 15 micrograms (n = 11), 20 micrograms (n = 12), or 25 micrograms (n = 12) of CCK-4 or placebo (n = 11). CCK-4 induced anxiety and panic responses in a dose-dependent fashion. The incidence of panic attacks following the CCK-4 challenge was 17% (10 micrograms), 64% (15 micrograms), 75% (20 micrograms), and 75% (25 micrograms). None of the patients panicked with placebo. Moreover, a strong linear relationship between CCK-4 and increases in heart rate and diastolic blood pressure was found. The findings of this study suggest that a dose of 20 micrograms of CCK-4 (ED75) might be suitable for efficacy studies of CCKB antagonists and other potential antipanic drugs in patients with panic disorder.

Adolescent↗
PubMed1991

Enhanced sensitivity to cholecystokinin tetrapeptide in panic disorder. Clinical and behavioral findings.

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.

Adult↗
PubMed1991

Comparison of the panicogenic effect of cholecystokinin 30-33 and carbon dioxide in panic disorder.

1. Twenty-two patients who met DSM-III-R criteria for panic disorder received either cholecystokinin 30-33 (25 micrograms i.v.) or 33% carbon dioxide. 2. The principal outcome measures of the study included the number and sum intensity of panic symptoms and the incidence of panic attacks. 3. The incidence of panic attacks tended (P = .07) to be higher with cholecystokinin 30-33 than with carbon dioxide. Nevertheless, patients who panicked within each group did not differ significantly with regard to the number and sum intensity of symptoms or symptom profile. 4. That cholecystokinin 30-33 and 35% carbon dioxide induced panic attacks which were qualitatively and quantitatively similar suggest that these agents might act on distinct systems that have a final common target or a final common mechanism of action.

Adult↗
PubMed1991

Comparison of the effects of cholecystokinin-tetrapeptide and carbon dioxide in health volunteers.

Twenty-six healthy volunteers received either 25 micrograms of cholecystokinin-tetrapeptide (CCK-4) or a mixture of 35% carbon dioxide in oxygen (CO2). DSM-III-R criteria including anxiety, apprehension and/or fear of at least moderate intensity were used to determine the occurrence of a panic attack. Results for the entire sample revealed that CCK-4 produced significantly more intense symptoms than CO2, but not a significantly greater number of symptoms. The incidence of DSM-III-R panic attacks was similar with both substances; 21% (3/14) for CO2 and 17% (2/12) for CCK-4. This study indicates that CCK-4 is at least as potent as CO2 in producing panic symptoms in healthy volunteers and is a useful challenge paradigm for comparative research of pharmacologic agents which possess distinct neurobiologic properties.

Adult↗
PubMed1991

Dose ranging study of the effects of cholecystokinin in healthy volunteers.

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.

Adult↗
PubMed1990

Double-blind comparison of the effects of clonazepam and lorazepam in acute mania.

A double-blind comparison of clonazepam and lorazepam was conducted in 24 patients with acute mania. Patients received either clonazepam or lorazepam alone for 14 days. Treatment with lorazepam produced marked improvement in symptomatology, while treatment with clonazepam failed to demonstrate a significant therapeutic effect. Sixty-one percent of patients responded to treatment with lorazepam, with 38.5% achieving remission. This compares to an 18.2% response rate and 0% remission rate in patients treated with clonazepam. These findings support the usefulness of lorazepam in the treatment of acute mania.

Acute Disease↗
PubMedDate not supplied

[Is cholecystokinin a biological support in panic attacks?].

Cholecystokinin (CCK) is a peptide found high density in the cerebral cortex, the amygdala and the hippocampus of the mammalian brain. Molecular forms of varying amino acid lengths of CCK have been isolated. The sulphated octapeptide (CCK-8S) is the most abundant form and shorter molecular forms are also present in the brain. CCK-8S has been shown to coexist with neurotensin and dopamine in neurons projecting from the ventral tegmental area to the nucleus accumbens, and to a lesser extent in neurons of the substantia nigra projecting to periventricular regions of the caudate. Evidence suggests that CCK acts as a neurotransmitter in the NCS it is synthesized and stored in nerve terminals and cell bodies; it is released by depolarization; it has specific binding sites; it can affect the firing rate of CNS neurons; and its effects can be interfered with by analogues. Studies have found microiontophoretic application of CCK-8S and CCK-4 on cortical and hippocampal neurons to elicit a strong excitatory action. CCK receptors are widely distributed throughout the central nervous system with high densities in the striatum and nucleus accumbens. Considerable effort has been devoted to characterizing the specificity of brain CCK receptors. So far, two types of CCK receptors have been described: CCK-A receptors which have a higher affinity for sulphated CCK-8 than for de-sulphated CCK-8 (CCK-8US), CCK 4 or gastrin, and CCK-B receptors have a high affinity for all of these compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholecystokinin↗