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R J Verkes,
H J Gijsman,
M S Pieters,
R C Schoemaker,
S de Visser,
M Kuijpers,
E J Pennings,
D de Bruin,
G Van de Wijngaart,
J M Van Gerven,
A F Cohen
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ABSTRACT: (+/-) 3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") has been shown to cause long term damage to serotonergic cerebral neurons in animals. The neurotoxic effects in humans are less clear and little is known about the functional consequences, although some studies suggest memory impairment. Given the widespread use of MDMA, our lack of knowledge raises concerns.
We investigated, in humans, the relation between past use of ecstasy and cognitive performance as well as serotonergic function. Methods: Two groups of 21 males with moderate and heavy recreational use of MDMA, respectively, and a control group of 20 males without use of MDMA were compared. All were from the same subculture. Reaction time, direct recall, and recognition were assessed. Serotonergic function was measured by the neuro-endocrine response to a placebo-controlled, crossover challenge with dexfenfluramine.
Ecstasy users showed a broad pattern of statistically significant, but clinically small, impairment of memory and prolonged reaction times. Heavy users were affected stronger than moderate users. Release of cortisol but not of prolactin after dexfenfluramine administration was significantly reduced in both groups of ecstasy users compared with the controls. Analyses of covariance showed that likely confounding variables including recent exposure to ecstasy, psychosocial profiles and use of other drugs did not explain the differences found between the groups.
These results provide further evidence that use of ecstasy may be associated with impairment of memory and of serotonergic function. These findings are compatible with neurotoxicity of ecstasy as shown in animals.
Psychopharmacologia 02/2001; 153(2):196-202. · 4.08 Impact Factor
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Neuropsychopharmacology 11/1999; 21(4):597. · 7.99 Impact Factor
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ABSTRACT: Depressive mood and impulsive-aggressive behavior are relevant to suicidal behavior and have been associated with decreased central serotonergic function. Impulsive behavior and aggression have also been related to abnormal glucose metabolism. To investigate these relationships further, blood serotonin (5-HT), blood glucose measures (glycated hemoglobin (HbA1C) and fructosamine) and self-reported depressive symptoms and anger 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. Intra-individual variations in blood 5-HT were inversely correlated with variations in depressive mood, self-depreciation, and anger, and positively with variations in fructosamine. Intra-individual variations of HbA1c or fructosamine were not correlated with mood. Mean blood 5-HT levels per patient were positively correlated with mean scores of depression and self-depreciation. The contrast between the intra-individual and the inter-individual correlations may reflect a difference between short- vs. long-term effects. The results do support an association between serotonergic function and mood, but not between glucose metabolism and mood, in recurrent suicide attempters.
Psychiatry Research 10/1998; 80(3):239-48. · 2.52 Impact Factor
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Nederlands tijdschrift voor geneeskunde 06/1998; 142(18):1046-7.
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ABSTRACT: 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.
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.
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."
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.
Biological Psychiatry 06/1998; 43(10):740-6. · 8.28 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
American Journal of Psychiatry 05/1998; 155(4):543-7. · 12.54 Impact Factor
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Journal of Clinical Psychopharmacology 11/1997; 17(5):430-2. · 4.10 Impact Factor
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ABSTRACT: 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.
Psychopharmacologia 08/1997; 132(1):89-94. · 4.08 Impact Factor
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ABSTRACT: 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.
Biological Psychiatry 09/1996; 40(3):173-80. · 8.28 Impact Factor
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ABSTRACT: The circadian activity rhythm was assessed over a one-week period using a wrist-worn activity monitor in 59 patients with a history of recurrent suicide attempts. In 40 of these patients a second recording was made 6 months later. Platelet serotonin (5-HT) and monoamine oxidase-B activity (MAO) were measured. Suicidal ideation, borderline personality disorder and impulsiveness were associated with the absence of a clear 24-hour periodicity in motor activity. Depressive mood and hopelessness were associated with a less regular bed-in time and a lower daytime activity. Platelet 5-HT as well as MAO correlated negatively with the amplitude of the circadian activity rhythm. Our results support the suggested link between suicidality, altered circadian activity and serotonergic function.
Acta Psychiatrica Scandinavica 02/1996; 93(1):27-34. · 4.22 Impact Factor
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ABSTRACT: Fifteen bulimic women (BN) and 19 healthy female controls (CO) were studied. The subjects were cross-over treated with either fluoxetine (FXT) or placebo during 4 days. They received, in randomized order, a breakfast containing pure carbohydrate (CHO) or a protein-rich (PROT) breakfast following day 3 and 4 of each treatment period. Twenty-nine different food items were offered for lunch. The fasting serum glucose and insulin concentrations and the fasting plasma tryptophan (Trp)/large neutral amino acid (LNAA) ratio were slightly higher in BN. The changes of these metabolic parameters in response to a CHO or PROT breakfast were similar in both groups. Across breakfast type, the plasma (Trp)/(LNAA) ratio at 120 min after breakfast was higher in BN. Total caloric intake at lunchtime was less in BN. In CO, less carbohydrate was selected at lunchtime following the CHO breakfast, an effect that was abolished by FXT. Breakfast type or FXT did not have any apparent effect on food intake at lunchtime in BN. This might indicate that bulimic subjects are less sensitive to serotoninergic stimuli than control subjects.
Biological Psychiatry 12/1995; 38(10):659-68. · 8.28 Impact Factor
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ABSTRACT: The choice of treatment for patients with cancer of the esophagus and cardia is controversial. Since overall survival is poor, the most important aim of treatment should be improvement of the main complaint: the inability to eat. In a retrospective analysis of 265 patients, referred to the University Hospital in Leiden, The Netherlands, comparisons were made between palliative effects of surgical resection (N = 92) and irradiation (N = 128). Several methods of comparing surgery with irradiation are possible: (1) all surgical patients vs. all irradiated patients; (2) only those surgical patients who survived the operation (N = 70) vs. all irradiated patients (N = 128); and (3) survivors after resection (N = 70) vs. only those irradiated patients treated with "curative" radiation (N = 62). Analysis of prognostic factors showed that in both surgical and irradiated patients, the only statistically significant factor was the (dis)ability to eat. Criteria to be considered to make individual recommendations for either treatment are presented.
Journal of Surgical Oncology 09/1991; 47(4):225-9. · 2.10 Impact Factor
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ABSTRACT: A group of 127 patients with esophageal cancer treated with radiotherapy at different dose levels was retrospectively analysed. It was found that 70.5% of the patients showed improvement of dysphagia and that 54% remained palliated with respect to food passage until their death. The two major prognostic variables with respect to the palliative effect on dysphagia as well as survival were the passage score and the radiation dose. Patients with severe dysphagia (PASS 0 or 1) had a median actuarial DFI and SURV of 3.7 and 6.4 months, respectively, in contrast to 16.0 and 8.7 months for patients who were able to use (semi)solid food (PASS 2 and 3). The median actuarial DFI and SURV of patients treated with a relatively low dose (less than 50 Gy in 5 weeks) were 2.5 and 4.8 months, respectively, compared to 10.1 and 8.3 months, respectively, for patients treated with a relatively high dose.
Radiotherapy and Oncology 06/1988; 12(1):15-23. · 5.58 Impact Factor
