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Biomedical subjects

H M van Praag

Publications and source records attributed to H M van Praag.

At least 19 recordsLinked to original sources
PubMed1992

Serotonin denervation enhances responsiveness of presynaptic dopamine efflux to acute clozapine in nucleus accumbens but not in caudate-putamen.

Clozapine alters mesolimbic dopamine (DA) function but spares nigrostriatal DA function in laboratory animals, but the underlying mechanism is unknown. In the present study, acute intraperitoneal injection of clozapine (5-40 mg/kg) increased extracellular DA levels in nucleus accumbens (Acb) and caudate-putamen (CPu) of awake, freely moving rats as measured by in vivo brain microdialysis, without anatomic selectivity. However, in serotonin (5HT)-denervated rats acute clozapine preferentially enhanced DA levels in Acb as compared to CPu. Since (i) up-regulation of 5HT receptors on DA neurons may result from 5HT denervation, (ii) clozapine has potent anti-5HT action, and (iii) 5HT receptors are more dense in Acb than CPu, these data appear to add additional weight to previous suggestions that a serotonergic mechanism may partly underlie clozapine's mesolimbic selectivity.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Suicide and violence associated with panic attacks.

Several studies have indicated that patients with panic attacks have a higher rate of suicide attempts as well as deaths from suicide. Additionally, several investigators have presented case reports of individuals manifesting suicidal and violent behaviors directly and temporally associated with panic attacks. We report on four additional cases and suggest that these findings may explain, in part, the increased rate of suicidal behavior among patients with panic attacks found by some investigators. Furthermore, these case reports offer preliminary evidence that the relationship between violent behavior and the panic state may be clinically significant and deserving of further elucidation.

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

Cortisol response to intramuscular desipramine in patients with major depression and normal control subjects: a replication study.

The authors conducted a double-blind study evaluating the cortisol response to 75 mg of desipramine (DMI), administered intramuscularly to 20 patients with major depressive disorder (MDD) and 20 age- and sex-matched normal control subjects. A blunted placebo-corrected cortisol response to DMI was found in MDD patients in comparison with the normal control subjects. Since the behavioral/side effect and pharmacokinetic profiles of DMI were similar for patients with MDD and normal control subjects, these findings suggest that patients with MDD have an underlying biological insensitivity of the hypothalamic-pituitary-adrenal axis to DMI. It is hypothesized that these findings are consistent with a norepinephrine deficit, an alpha 1-adrenergic receptor insensitivity, or both. Further use of DMI as a neuroendocrine probe for the noradrenergic system is indicated.

Adolescent↗
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↗
PubMed1992

About the centrality of mood lowering in mood disorders. Plenary Lecture ECNP Congress, Monte Carlo, October 1991.

5-HT disturbances in depression (as exemplified by lowered CSF 5-HIAA) are not syndrome specific but related to components of the depressive syndrome, specifically to increased anxiety and aggression. These 5-HT disturbances are probably core pathogenetic processes not derivative features. I hypothesized that in this subtype of depression, i.e. in "5-HT related depression", the key psychopathological disturbances are dysregulation of anxiety and aggression, while mood lowering is a "by-product". Based on this hypothesis it was predicted that agents which ameliorate anxiety and/or aggression via harmonization of 5-HT ergic transmission will, in addition, exert overall antidepressant effect in "5-HT related depression". The study of the relative "weight" of the various psychopathological components of depression is a basic exercise in understanding the nature of that condition and could, as such, greatly facilitate the goal-directed search for new and innovative antidepressants.

Affect↗
PubMed1992

Panic disorder: a biological perspective.

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.

Humans↗
PubMed1992

High cholesterol levels in patients with panic disorder.

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.

Adult↗
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

Activation of 5-HT3 receptor by 1-phenylbiguanide increases dopamine release in the rat nucleus accumbens.

The serotonin-3 (5-HT3) agonist 1-phenylbiguanide (0.1-1.0 mM in perfusate) caused a robust, dose-dependent enhancement of extracellular dopamine content in nucleus accumbens as measured by in vivo microdialysis. This action was antagonized by co-perfusion of the 5-HT3 antagonists zacopride and GR38032F (1 mM in perfusate). Similar effects were observed in 5-HT-denervated rats. These findings suggest that there is a potent modulation of dopamine (DA) release in the nucleus accumbens mediated via 5-HT3 receptors, which appear to be located presynaptically on DA terminals of the mesolimbic DA pathway.

3,4-Dihydroxyphenylacetic Acid↗
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↗
PubMed1991

Correlates of risk of suicide in violent and nonviolent psychiatric patients.

OBJECTIVE: This study was designed to identify variables that correlate with the risk of suicide in two patient groups that differ mainly in their level of expressed aggression. METHOD: Twenty-eight psychiatric patients with a history of violent behavior who were in a forensic psychiatric facility were tested and compared to 28 psychiatric inpatients without a history of violence who were admitted to a large municipal hospital. Measures used included a battery of self-report questionnaires, with acceptable reliability and validity, that provided indices of risk of suicide, risk of violence, impulsivity, anger, anxiety, and various mood states. RESULTS: The two groups, matched on demographic variables and overall risk of suicide, differed significantly on the measured risk of violence. The two groups showed similar patterns of correlations between risk of suicide and such variables as risk of violence, anger, fear, state and trait anxiety, lack of impulse control, suspiciousness, and rebelliousness. They differed in the correlation between suicide risk and depression. In the nonviolent patients there was a high correlation between risk of suicide and sadness; in the violent patients there was no correlation between these variables. CONCLUSIONS: The low correlation between sadness and risk of suicide in the violent patients, and the low prevalence of affective disorder diagnoses in these patients compared to other patients, suggests that suicidal risk should be managed differently in highly violent patients than in others.

Adult↗