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Biomedical subjects

S Wetzler

Publications and source records attributed to S Wetzler.

At least 19 recordsLinked to original sources
PubMed1992

Effect of m-chlorophenylpiperazine on plasma arginine-vasopressin concentrations in healthy subjects.

It has been demonstrated convincingly that ACTH and prolactin release are under the stimulatory control of serotonin (5-hydroxytryptamine, 5HT). Recent animal studies suggest that stimulation of 5HT activity also induces the release of arginine-vasopressin (AVP). More specifically, m-chlorophenylpiperazine (MCPP), a 5HT agonist widely used to examine 5HT receptor responsivity in human subjects, has been found to induce AVP release in rodents. This study examined whether MCPP increased plasma AVP levels in healthy human subjects. MCPP was administered orally to 17 healthy subjects in a placebo-controlled design in doses of 0.25 and 0.5 mg/kg. AVP was measured twice hourly over a 210 min period after administration of capsules. MCPP did not significantly alter AVP levels as compared to placebo. However, female subjects had significantly lower plasma AVP levels than males. Since it has been suggested that MCPP-induced AVP release in animals is due to stimulation of 5HT1c receptors, the fact that MCPP did not induce the release of AVP in humans suggests that either MCPP is not a potent 5HT1c agonist or that AVP is not released by stimulation of 5HT(1c) receptors in human subjects. The observation of gender differences in plasma AVP levels suggests that this factor should be taken into account in future studies of AVP secretion in plasma.

Adult↗
PubMed1992

A dose-response study of intravenous m-chlorophenylpiperazine in normal subjects.

A placebo-controlled dose-response study of the direct serotonin receptor agonist m-chlorophenylpiperazine (MCPP), intravenously infused over 90 s in 0.06 and 0.08 mg/kg doses, was conducted in nine normal male subjects. Cortisol, prolactin, MCPP serum levels and behavioral responses were measured over a 210-min period. Both doses caused significant cortisol and prolactin release and were associated with significantly greater behavioral effects as compared to placebo. Though the two doses were associated with different MCPP serum levels, they did not significantly differ in their hormonal and behavioral effects.

Adult↗
PubMed1992

Prevalence of personality disorders in patients with major depression and dysthymia.

The authors administered the Structured Clinical Interview for DSM-III-R Axis I (SCID-P) and Axis II (SCID-II) Disorders to 197 patients with major depression, 63 patients with dysthymia, and 32 patients with both major depression and dysthymia ("double depression"). Fifty percent of major depressive patients, 52% of dysthymic patients, and 69% of patients with double depression were diagnosed as having at least one personality disorder. Patients with a personality disorder had higher scores on the Beck Anxiety and Depression Inventories. The most commonly diagnosed personality disorders were from the anxious/fearful cluster, most notably avoidant and dependent personality disorders.

Adult↗
PubMed1992

Functional interrelationship of serotonin and norepinephrine: cortisol response to MCPP and DMI in patients with panic disorder, patients with depression, and normal control subjects.

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.

Adult↗
PubMed1991

m-Chlorophenylpiperazine as a probe of serotonin function.

m-Chlorophenylpiperazine (mCPP) is the most extensively used probe of serotonin function in psychiatry. This article reviews its in vitro and in vivo properties in animals, normal human subjects, and psychiatric patients. mCPP is a safe, reliable, direct 5-hydroxytryptamine (5HT) agonist, which may be used to evaluate 5HT receptor sensitivity. It causes a consistent, dose-dependent elevation of ACTH, cortisol, and prolactin levels in both animals and humans, as well as increased body temperature in man. It also causes a variety of behavioral effects, depending on the population studied. These effects are probably 5HT receptor-related, although specific 5HT receptor subtype mechanisms have not yet been established. mCPP may be considered an important addition to armamentarium of 5HT receptor probes, which is especially useful until more selective 5HT receptor agonists have been tested.

Adrenocorticotropic Hormone↗
PubMed1991

The MCPP challenge test in schizophrenia: hormonal and behavioral responses.

In a neuroendocrine challenge paradigm, the present study investigated responses of schizophrenic patients to m-chlorophenylpiperazine (MCPP), a serotonin (5-hydroxytryptamine, 5HT) agonist. In an oral dose of 0.25 mg/kg, MCPP was administered in a placebo-controlled double-blind design to male schizophrenic patients (n = 7) and normal male controls (n = 8). Behavioral (Positive and Negative Syndrome Scale; PANSS) and hormonal (cortisol, prolactin) variables were measured over the subsequent 210 min. The schizophrenic patients experienced an overall exacerbation of psychopathology on MCPP as compared with placebo (p less than 0.05), with specific worsening of PANSS-positive symptoms (p less than 0.025) and PANSS activation (p less than 0.001). In addition, the schizophrenic patients showed significantly lower cortisol (p less than 0.05) and prolactin (p less than 0.05) responses than the normal subjects. The schizophrenic patients had lower peak MCPP blood levels than the normal subjects, although this difference was not statistically significant. The findings are discussed in terms of 5HT receptor(s) sensitivity and the pharmacokinetics of MCPP in schizophrenia.

Adult↗
PubMed1991

Serotonin receptor sensitivity and aggression.

This study investigated the relationship between increased serotonin (5-hydroxytryptamine, 5HT) receptor sensitivity and human aggression. A low oral dose of meta-chlorophenylpiperazine (MCPP), a postsynaptic 5HT receptor agonist, was administered in a placebo-controlled design to depressed (n = 22) and panic disorder (n = 20) patients classified with or without signs of outwardly directed aggression, patients with a history of suicide attempts (inwardly directed aggression) (n = 11), and normal controls (n = 19). Hormones under 5HT control were measured at 30-min intervals. Results were as follows: (1) MCPP did not induce or reduce anger, (2) patients with outwardly directed aggression did not have significantly greater MCPP-induced cortisol or prolactin release than did patients without signs of outwardly directed aggression, (3) patients with a history of suicide attempts did not have significantly greater MCPP-induced cortisol or prolactin release than did normal controls, and (4) MCPP-induced hormone release was unrelated to measures of aggression.

Adult↗
PubMed1991

Pituitary hormone responses to meta-chlorophenylpiperazine in panic disorder and healthy control subjects.

The present study reports adrenocorticotropic hormone (ACTH) and prolactin responses after oral administration of 0.25 mg/kg of the serotonin agonist, meta-chlorophenylpiperazine (MCPP), in patients with panic disorder (PD) and in healthy subjects. MCPP blood levels were similar for the two groups, but almost twice as high in males as in females. Female patients had augmented ACTH and prolactin release as compared to healthy females, while ACTH and prolactin release in male patients was similar to that of male controls. These results suggest that female PD patients have hypersensitive serotonin receptors. Moreover, they indicate that pharmacokinetic gender differences may affect challenge studies, and that different doses may be required to study neuroendocrine responses in males and females.

Adrenocorticotropic Hormone↗
PubMed1990

Five percent carbon dioxide challenge: valid analogue and marker of panic disorder?

The administration of 5% carbon dioxide (CO2) to patients with panic disorder (PD) induces a behavioral response similar to a naturally occurring panic attack. This article reviews the literature on the nature and incidence of this response. We conclude that the 5% CO2 challenge test is a valid and useful laboratory analogue of naturally occurring panic attacks, and shows promise as a marker to identify a subset of PD patients. Though further research on reliability, validity, and dose-response effects must be conducted, the CO2 challenge test provides important information regarding the phenomenology of panic states.

Administration, Inhalation↗
PubMed1990

Effects of m-chlorophenylpiperazine in normal subjects: a dose-response study.

m-Chlorophenylpiperazine (MCPP), a direct 5HT receptor agonist, was administered orally to 20 normal subjects in two doses (0.25 and 0.5 mg/kg) in a placebo-controlled design. Behavioral responses; ACTH, cortisol, prolactin and MCPP blood level; temperature and pulse rate were measured over a 210-min period after administration of tablets. Non-linear dose-response relationships between MCPP and ACTH, cortisol and prolactin response were found. On the higher dose, a significant increase in the number of physical symptoms was also noted and three subjects (15%) had a panic attack, while one subject (5%) had a panic attack on the lower dose. No effects on other behavioral variables, pulse rate and temperature were found using either dose. These findings attest to the usefulness of MCPP as a challenge agent to assess 5HT receptor hypersensitivity when given at a low oral dose (i.e. around 0.25 mg/kg), and to assess 5HT receptor hyposensitivity when given at higher oral doses (i.e. around 0.5 mg/kg).

Adrenocorticotropic Hormone↗
PubMed1990

Effects of serotonin antagonists on m-chlorophenylpiperazine-mediated responses in normal subjects.

The serotonin (5HT) agonist, m-chlorophenylpiperazine (MCPP), has been used as a challenge agent to assess central 5HT receptor sensitivity in normal subjects and patients with panic disorder, obsessive-compulsive disorder, and major depression. Adrenocorticotropin, cortisol, and prolactin responses to MCPP were among the variables measured. MCPP's usefulness as a probe of 5HT receptors, however, hinges on its 5HT selectivity. To address MCPP's selectivity for 5HT, this study tested whether two different 5HT antagonists, methysergide (4 mg p.o.) and metergoline (4 mg p.o.), could block the hormonal and behavioral effects of MCPP (0.5 mg/kg p.o.) in 10 normal male subjects in comparison to placebo. Both 5HT antagonists abolished the prolactin release to MCPP. Metergoline, the antagonist with the more potent 5HT binding affinity, significantly blocked MCPP's effect on cortisol release as compared to placebo, and methysergide showed a nonsignificant trend to that effect. MCPP alone did not have a significant effect on behavioral variables, perhaps explaining why neither 5HT antagonist affected these measures. The findings from this study suggest that both MCPP-induced prolactin release and cortisol release are indeed 5HT-mediated effects.

Administration, Oral↗
PubMed1990

Psychological test characteristics of depressed and panic patients.

This study compared the psychological test performance of patients with major depression (MD) (n = 23), patients with panic disorder (PD) (n = 20), and normal subjects (n = 24). Results indicated that scores of normal subjects were significantly less pathological than those of both patient groups on almost all psychological test scales, but that the test performance of the two patient groups did not differ. The only difference between the two patient groups was on the level of self-reported and observer-rated depression. Both patient groups exhibited significant personality pathology, and the rate of personality disorders diagnosed by the Millon Clinical Multiaxial Inventory (MCMI) (base rate greater than 84) was 73% for PD patients and 86% for MD patients. The problems of assessing personality during episodes of MD and PD and the possible overdiagnosis of personality disorders by the MCMI are discussed.

Adult↗
PubMed1990

The Millon Clinical Multiaxial Inventory (MCMI): a review.

This article reviews research conducted to date on the Millon Clinical Multiaxial Inventory (MCMI), a self-report test of psychopathology. The composition of the test and its theoretical basis are described. Data regarding its internal psychometric structure are reviewed. Finally, the article summarizes the research on the validity of the MCMI.

Adaptation, Psychological↗
PubMed1990

Diagnosis of personality disorders by the Millon Clinical Multiaxial Inventory.

The diagnostic efficiency of the Millon Clinical Multiaxial Inventory (MCMI) was examined with regard to the diagnosis of DSM-III axis II personality disorders by practicing psychiatrists. The MCMI displayed fairly good sensitivity but poor specificity and predictive power regarding the diagnosis of any personality disorder. Two possible explanations were offered: a) axis I psychopathology inflates scores on the MCMI personality disorder scales and causes an overdiagnosis of personality disorders by the test; or b) there is an under-recognition of axis II personality disorders (especially in the context of obvious axis I psychopathology) by the average practicing clinician.

Adjustment Disorders↗