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Biomedical subjects

G M Van Kempen

Publications and source records attributed to G M Van Kempen.

At least 19 recordsLinked to original sources
PubMed1998

Platelet serotonin, monoamine oxidase activity, and [3H]paroxetine binding related to impulsive suicide attempts and borderline personality disorder.

BACKGROUND: The aim of the present study was to examine the relationship between suicidal behavior and impulsiveness, and more generally borderline personality disorder on the one hand, and platelet indicators of central serotonergic function on the other. METHODS: After a suicide attempt platelet serotonergic measures were obtained from 144 patients with at least one previous attempt. A major DSM-III-R Axis I diagnosis and the use of antidepressants were reasons for exclusion. RESULTS: Platelet monoamine oxidase (MAO) activity was negatively correlated with the personality traits "multi-impulsive behavior" and "disinhibition." In accordance, platelet MAO activity was also lower in patients with less-planned suicide attempts. Platelet serotonin (5-HT) and recidivism were positively correlated with borderline personality disorder, in particular chronic feelings of emptiness. Platelet 5-HT was lower in patients with alcohol abuse. The maximum number of binding sites (Bmax) for paroxetine binding was positively correlated with "sensation seeking." CONCLUSIONS: These findings support the hypothesis that serotonergic involvement in impulsive suicidal behavior is mediated by the relationship between serotonergic function and impulsiveness as personality trait. Other borderline personality traits relevant to recurrent suicidal behavior, in particular chronic feelings of emptiness, appear also related to serotonergic measures.

Adolescent↗
PubMed1998

Pharmacokinetic and pharmacodynamic profile of oral and intravenous meta-chlorophenylpiperazine in healthy volunteers.

meta-Chlorophenylpiperazine (mCPP) is a compound that is frequently used in challenge tests of the serotonergic system. Its human pharmacology is largely unexplored. The objective of this study was to investigate the pharmacokinetic and pharmacodynamic profile of mCPP. Eight female and six male healthy volunteers were included in a randomized, double-blind, double-dummy, three-way crossover design of single-dose intravenous (0.1 mg/kg), oral (0.5 mg/kg), and placebo treatment, with 24-hour follow-up. mCPP showed a large variability in clearance (11-92 mL/hr) and bioavailability (14-108%). Two female subjects dropped out because of headache and dysphoria. During the 27 occasions in which mCPP was administered, autonomic physical symptoms were observed in 23 subjects and disturbances of mood in 6 subjects. Oral and intravenous mCPP caused sudden increases in cortisol levels, prolactin levels, and total scores of the Body Sensation Questionnaire. Administration of mCPP also led to concentration-dependent increases of saccadic peak velocity and adaptive tracking performance and to a decrease of electroencephalographic occipital theta activity. No clinically relevant effects on electrocardiogram, temperature, and blood pressure were found. In conclusion, it is doubtful whether mCPP is a useful compound for challenge tests in view of the large pharmacokinetic variability after intravenous and oral administration. The effects of mCPP are consistent with disinhibition of the central nervous system.

Administration, Oral↗
PubMed1998

Reduction by paroxetine of suicidal behavior in patients with repeated suicide attempts but not major depression.

OBJECTIVE: Suicidal behavior has been associated with reduced central serotonergic function. Because selective serotonin reuptake inhibitors (SSRIs) enhance serotonergic function, the authors studied the efficacy of an SSRI, paroxetine, in the prevention of recurrent suicidal behavior. METHOD: They conducted a 1-year double-blind study comparing paroxetine (40 mg/day) and placebo in 91 patients who had recently attempted suicide for at least a second time. None of the patients had experienced a major depressive episode or had any other major DSM-III-R axis I diagnoses. At least one cluster B personality disorder was present in 74 patients. RESULTS: With adjustment for the number of previous suicide attempts, paroxetine showed significant efficacy in the prevention of recurrent suicidal behavior. Among the patients who had attempted suicide fewer than five times, 12 (36%) in the placebo group (N = 33) and five (17%) in the paroxetine group (N = 30) made a subsequent suicide attempt. Paroxetine was also significantly more effective in patients who met fewer than 15 criteria for cluster B personality disorders than in those who met more than 15 criteria. Overall, paroxetine was not significantly different from placebo in its effect on depressive mood, hopelessness, and anger. However, the data suggest that paroxetine may have some temporary effect in reducing anger. CONCLUSIONS: This study indicates that enhancing serotonergic function with an SSRI may reduce suicidal behavior in a subgroup of patients who have attempted suicide more than once but who do not suffer from major depression.

Adult↗
PubMed1997

Platelet serotonin and [3H]paroxetine binding correlate with recurrence of suicidal behavior.

To distinguish state- from trait-dependent associations between serotonergic function and suicidal behavior, platelet serotonergic measures were repeatedly measured, during a 1-year follow-up, in 106 patients who had recently attempted suicide for at least a second time. A major DSM-III-R axis I diagnosis or use of antidepressants were reasons for exclusion. A higher affinity constant (KD) of platelet [3H]paroxetine binding was related to a higher risk of short-term recurrence of a suicide attempt, suggesting a state relationship. Higher levels of platelet serotonin at baseline were a significant predictor of a recurrent suicide attempt within the year of follow-up, suggesting a trait relationship. These associations held equally within the subgroup of 73 patients with a borderline personality disorder. Neither the maximum number of binding sites (Bmax) of [3H]paroxetine nor platelet monoamine oxidase activity correlated with suicidality. The observed association between indicators of platelet serotonin uptake and suicidal behavior suggests a state- and trait-dependency between suicidality and central serotonergic dysfunction.

Adolescent↗
PubMed1996

Borderline personality, impulsiveness, and platelet monoamine measures in bulimia nervosa and recurrent suicidal behavior.

This study examined the relationship between borderline and impulsive personality traits on the one hand, and monoamine function on the other in 15 women with bulimia nervosa and 15 women with recurrent suicidal behavior. Platelet serotonin (5-HT) and platelet monoamine oxidase (MAO) activity were used as peripheral measures of monoaminergic function. All suicide attempters were diagnosed as having a borderline personality disorder, whereas this diagnosis was less frequent in bulimics. Bulimics with borderline comorbidity resembled recurrent suicide attempters with borderline personality disorder more closely in both psychological (anger, impulsive behavior) and biochemical characteristics (platelet 5-HT) than bulimics without borderline personality disorder. Platelet 5-HT was higher in patients with borderline personality than in normal female controls and was positively correlated with the disposition to experience anger. Impulsive personality traits were consistently negatively correlated with platelet MAO activity. Our findings support the subdivision of bulimics according to the presence of borderline or "multi-impulsive" personality disorder.

Blood Platelets↗
PubMed1996

Hypertonic hemolysis in patients with a mood disorder.

Hypertonic hemolysis was increased in patients with a manic episode (n = 6, mean NaCl concentration in mol/L at which 50% of the erythrocytes was hemolyzed (H50) 3.24 +/- 0.10), compared to healthy controls (n = 12, mean H50 3.43 +/- 0.13) (p < or = 0.02) and patients with a nonaffective psychotic disorder (n = 15, mean H50 3.42 +/- 0.18) (p < or = 0.02). Compared to these two control groups, hypertonic hemolysis was decreased in patients with a severe depressive episode (n = 8, mean H50 3.62 +/- 0.19) (p < or = 0.05 and p < or = 0.02, respectively). Within the total depressed patient group, the patients with an increased genetic vulnerability (n = 8, mean H50 3.68 +/- 0.16) showed a decreased hypertonic hemolysis compared to the other depressed patients (n = 14, mean H50 3.40 +/- 0.16) (p < or = 0.002).

Adolescent↗
PubMed1992

Biochemical measures in patients with a somatoform pain disorder, before, during, and after treatment with amitriptyline with or without flupentixol.

The possible relationship between a number of biochemical parameters and measures of pain and depression was studied in chronic pain patients without a major depression. In a double-blind crossover study, patients were treated with amitriptyline combined with a low dose of flupentixol or placebo. We investigated whether pretreatment biochemical values correlated with initial data on pain and/or depression, or whether they had predictive value for treatment outcome. We also studied systematically the effect of both treatment regimes on the biochemical parameters themselves and their relation to the plasma levels of amitriptyline. From our results, the possible involvement of the serotonin system in somatoform pain disorder is confirmed and no direct relation with the noradrenergic system could be inferred. The lack of involvement of a number of putative, depression-related, biochemical parameters suggests that affective disorders and pain syndromes do not share all mechanisms in common.

Adult↗
PubMed1990

Osmotic behavior of erythrocytes from patients with a major affective disorder. A freeze-fracture electron microscopic study.

Previously we have demonstrated a state-dependent decrease in the number of membrane vesicles in erythrocytes from patients with a major depressive episode. We now report an increase in the number of membrane vesicles during a manic episode as well as a reduction during lithium treatment and we also present data suggesting that the number of erythrocyte membrane vesicles in the affective disorders is dependent on osmotic shrinkage due to the freezing for freeze-etch electron microscopy. Although caution is required since the interrater reliability of the measurement of osmotic strain was insufficient in the mid range where it was tested, we do not think this invalidates the differences in osmotic strain found in the low and high ranges during depressive and manic episodes respectively. These findings warrant the use of more precise techniques in studies of the osmotic behavior of erythrocytes from patients with a major affective disorder.

Adult↗
PubMed1990

Clinical use of the determination of serotonin in whole blood.

Whole blood serotonin (5-hydroxytryptamine, 5-HT) was assayed, and factors possibly influencing 5-HT content were investigated in healthy controls. No significant circadian rhythm or effect of dexamethasone or meals was observed. After use of fluvoxamine, a specific 5-HT reuptake inhibitor, the whole-blood 5-HT concentration of patients was strongly reduced. After treatment with tranylcypromine, an unspecific monoamine oxidase inhibitor (MAOI), the 5-HT content was increased. Determination of whole blood 5-HT in patients treated with fluvoxamine presents a measure of drug compliance. Furthermore, the method may have clinical potential for finding an adequate dose when a 5-HT reuptake inhibitor or an MAOI is used.

Adult↗
PubMed1990

Plasma serotonin.

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Blood Platelets↗
PubMed1989

Serotonin metabolism in migraine.

To investigate systemic serotonin (5-HT) metabolism in migraine, we determined platelet and platelet-free plasma concentrations of 5-HT, its precursors tryptophan and 5-hydroxytryptophan, and its main metabolite 5-hydroxyindoleacetic acid (5-HIAA), as well as the activities of the platelet enzymes monoamine oxidase and phenolsulfotransferase in classic and common migraineurs. Between attacks, migraineurs had lower plasma 5-HT and higher 5-HIAA levels than did healthy controls and patients with tension headache. During migraine attacks, plasma 5-HT levels were substantially higher than during attack-free periods, while 5-HIAA concentrations and platelet enzyme activities were lower. Platelet 5-HT was reduced only during common, but not classic, migraine attacks. We hypothesize that systemic 5-HT metabolism is enhanced in migraineurs during headache-free periods and transiently decreases during attacks, presumably due to a fall in enzymatic degradation. Furthermore, platelet behavior differs during migraine attacks with and without aura, and release of platelet 5-HT cannot (exclusively) be held accountable for the rise of plasma 5-HT during migraine attacks.

5-Hydroxytryptophan↗