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Wim J Riedel

Publications and source records attributed to Wim J Riedel.

15 recordsLinked to original sources
PubMed2006

Effects of 5-HT on memory and the hippocampus: model and data.

5-Hydroxytryptamine (5-HT) transmission has been implicated in memory and in depression. Both 5-HT depletion and specific 5-HT agonists lower memory performance, while depression is also associated with memory deficits. The precise neuropharmacology and neural mechanisms underlying these effects are unknown. We used neural network simulations to elucidate the neuropharmacology and network mechanisms underlying 5-HT effects on memory. The model predicts that these effects are largely dependent on transmission over the 5-HT1A and 5-HT3 receptors, which regulate the selectivity of retrieval. It also predicts differential memory deficit profiles for 5-HT depletion and overactivation. The latter predictions were confirmed in studies with healthy and depressed participants undergoing acute tryptophan depletion or ipsipirone challenge. The results suggest that the memory impairments in depressed subjects may be related to 5-HT undertransmission, and support the notion that 5-HT1A agonists ameliorate memory deficits in depression.

Animals↗
PubMed2005

Drug testing in blood: validated negative-ion chemical ionization gas chromatographic-mass spectrometric assay for enantioselective measurement of the designer drugs MDEA, MDMA, and MDA and its application to samples from a controlled study with MDMA.

BACKGROUND: The enantiomers of the designer drugs 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA) differ in their pharmacologic and toxicologic potency. The aim of this study was to develop an assay for measuring these enantiomers in small plasma volumes and to analyze samples from a controlled study with MDMA. METHODS: The analytes were extracted from < or = 0.2 mL of plasma by mixed-mode solid-phase extraction. After derivatization with S-(-)-heptafluorobutyrylprolyl chloride, the resulting diastereomers were separated by gas chromatography (HP-5MS) within 17 min and detected by mass spectrometry in the negative-ion chemical ionization mode. The method was fully validated and applied to samples from a controlled study in which a single dose of racemic MDMA (75 mg) was administered. RESULTS: The derivatized enantiomers were well separated and detected with good sensitivity. The assay was linear (per enantiomer) at 1-50 microg/L for MDA and 5-250 microg/L for MDMA and MDEA. Analytical recovery, accuracy, repeatability, and intermediate precision data were within required limits. Extraction yields were 82.1%-95.3%. In the study samples, concentrations of R-(-)-MDMA significantly exceeded those of S-(+)-MDMA. Their ratios (R vs S) were always >1.0 and increased over time. Concentrations of S-(+)-MDA exceeded those of R-(-)-MDA, their ratios (R vs S) also increasing over time but remaining <1.0. CONCLUSIONS: This assay enables sensitive, reliable, and fast enantioselective measurement of MDA, MDMA, and MDEA in small volumes of plasma. The controlled study data confirm previous findings of MDMA and MDA enantiomer ratios (R vs S) increasing over time after ingestion of racemic MDMA.

3,4-Methylenedioxyamphetamine↗
PubMed2005

Acute tryptophan depletion in depressed patients treated with a selective serotonin-noradrenalin reuptake inhibitor: augmentation of antidepressant response?

BACKGROUND: It has frequently been demonstrated that experimental lowering of serotonin (5-HT) neurotransmission by acute tryptophan depletion (ATD) induces a transient depressed mood in 50-60% of patients treated with a selective serotonin reuptake inhibitor (SSRI) who are in remission from depression. In unmedicated depressed patients, ATD has no immediate effect on symptoms. The effects in currently depressed medicated patients have not been investigated. METHODS: Fourteen currently depressed patients (seven patients treated with a selective serotonin-noradrenalin reuptake inhibitor (SSNRI); seven other treatment, non-SSNRI) received ATD in a double-blind, crossover design. Different strengths of the ATD mixture (aimed at 50% and 90% reduction of tryptophan) were used on separate days. Psychiatric symptoms were assessed at both sessions prior to, at +6.5 h, and at +24 h after ATD. RESULTS: The ATD mixtures induced the expected reductions of plasma tryptophan levels. Full but not partial depletion improved mood and other psychiatric symptoms at +24 h in patients who received SSNRI treatment, as indicated by clinical ratings and self-report. Subjective sleep quality also improved. CONCLUSIONS: The effects of ATD on psychiatric symptoms in currently depressed patients are remarkably different from the results in recently remitted SSRI-treated patients. ATD in currently depressed patients treated with serotonergic antidepressants possibly provides important information about the mechanism of action of SSRIs.

Adrenergic Uptake Inhibitors↗
PubMed2005

Specific serotonergic reuptake inhibition impairs vigilance performance acutely and after subchronic treatment.

Subchronic treatment with the selective serotonergic reuptake inhibitors (SSRIs) fluoxetine, venlafaxine and paroxetine, but not sertraline, were previously shown to specifically impair vigilance performance. The current study was designed to compare the vigilance effects of subchronic treatment with the SSRIs sertraline and citalopram in healthy volunteers, according to a placebo-controlled, double-blind, three-way cross-over design. Twenty-four healthy subjects, aged 30-50 years, of whom 21 completed the study, underwent three treatment periods of 2 weeks in which they received sertraline (50 mg on days 1-8, 100 mg on days 8-15), citalopram (20 mg on days 1-8, 40 mg on days 8-15) and placebo. Treatment periods were separated by 14 days washout periods. Vigilance performance was assessed through a 45-min Mackworth Clock Test at days 1, 8 and 15 of each treatment period. It was found that citalopram impaired vigilance performance acutely after the first 20 mg dose and subchronically after 40 mg daily doses. By contrast, no vigilance impairment was found during sertraline treatment. Sertraline is the only SSRI studied so far with no detrimental effects on vigilance. This may be due to the affinity of sertraline for the dopamine reuptake site. Because citalopram is the most specific SSRI showing this effect, it is concluded that the SSRI-induced decrement of vigilance performance is specifically associated with serotonergic reuptake inhibition.

Adult↗
PubMed2005

The effects of high-dose and low-dose tryptophan depletion on mood and cognitive functions of remitted depressed patients.

It has frequently been demonstrated that acute tryptophan depletion (ATD) induces a transient depressed mood in some patients who are in remission from depression. However, the effects of ATD on cognitive processes in remitted depressed patients have not been investigated. The aim of the present study was to investigate the effects of different extents of depletion on mood and cognitive tasks involving neutral and emotional stimuli. Twenty patients in remission or in partial remission from depression received ATD in a double-blind, crossover design. Mood was assessed at both sessions before, at +6.5 h and +24 h after depletion. Cognitive assessment in both sessions started at +4.75 h, and also before and after the whole procedure. The ATD mixtures induced the expected reductions of plasma tryptophan levels. High-dose ATD induced a depressive response in a subsample of patients and impaired the processing of positive information independent of mood change. Attention for neutral stimuli (Stroop interference) improved in a dose-dependent manner. ATD may affect mood and cognition via different pathways: one implicated in mood regulation and the processing of emotional information, and one for the processing of neutral information. The first pathway may be more important for discriminating vulnerability to impaired serotonin function. The comparison of the effects of high-dose and low-dose ATD is useful for those studies aiming to investigate the relationships among 5-HT, mood and cognition.

Adolescent↗
PubMed2005

Memory function in women with premenstrual complaints and the effect of serotonergic stimulation by acute administration of an alpha-lactalbumin protein.

Serotonergic hypofunction may underlie at least part of the symptoms that are experienced by women with premenstrual complaints, including memory deficits. In the current study we investigated changes in memory functions in the premenstrual phase compared to the early postmenstrual phase in 16 women with premenstrual complaints. In addition, the effect of an acute serotonergic stimulation by administration of an alpha-lactalbumin protein on premenstrual memory performance was assessed using a double-blind placebo-controlled crossover design. It was found that both short-term and long-term memory for words (30-word learning task) and abstract figures (abstract visual learning task) were mildly impaired in the premenstrual phase. Administration of alpha-lactalbumin during the premenstrual phase could only partially attenuate the memory performance decrements that are seen in the premenstrual phase. Specifically, alphalactalbumin improved long-term memory for abstract figures, but not for words. There were no effects of menstrual phase or alpha-lactalbumin on planning functions (computerized Tower of London). The data suggest that serotonergic hypofunction may play a role in premenstrual memory decline, but serotonergic mechanisms cannot fully account for observed cognitive changes in the premenstrual phase.

Adolescent↗
PubMed2003

Tryptophan modulation and cognition.

The interest in the function of the serotonergic system in relation to cognition stems from three sources: (1) the association of depression, cognitive dysfunction and 5-HT dysregulation; (2) the association of drug-induced 5-HT dysregulation and cognitive dysfunction; and (3) the association of cognitive performance and serotonergic function per se. We performed several experiments in subjects at risk for cognitive impairment and in healthy volunteers, in which 5-HT was manipulated by means of either tryptophan depletion or tryptophan loading. The results show that tryptophan and cognitive performance are associated in a complex non-linear fashion. Dissociations are observed between cognitive functions: tryptophan depletion impairs memory consolidation but improves focussed attention; as well as between subject groups: tryptophan depletion impairs problem solving in healthy 1st degree relatives of bipolar depressed patients but improves it in healthy volunteers without such a family history. It was demonstrated that the mood- and memory effects of tryptophan-depletion were specifically mediated by the depletion of tryptophan and also that the observed memory and cognitive deficits were emotionally biased in a manner consistent with depressive symptoms. We conclude that experimental manipulations of tryptophan mediate temporal and frontal cognitive functions such as memory consolidation and working memory respectively, in an opposite manner.

Cognition↗
PubMed2002

Neuroendocrine response to meta-chlorophenylpiperazine and ipsapirone in relation to anxiety and aggression.

The aim of this study was to establish the association of trait anxiety and anger with hormonal responses to acute challenges with two different 5-HT agonists in a mixed group of patients with depressed mood. Fifteen patients and 16 normal controls received single oral doses of 0.5 mg/kg meta-chlorophenylpiperazine (MCPP), a 5-HT(2C) agonist, and 10 mg of ipsapirone, a 5-HT(1A) agonist, according to a double-blind, placebo-controlled, cross-over design. Dutch-adapted versions of the Spielberger Trait-Anxiety Inventory and the Spielberger Trait-Anger Scale administered assessed at study entry. Hormonal responses, expressed as drug-placebo differences, to MCPP and ipsapirone (changes in cortisol, ACTH and prolactin) were measured. Blood levels of MCPP and ipsapirone were also measured. MCPP and ipsapirone elevated cortisol, ACTH and prolactin. In the patient group, there was a significant correlation between trait anxiety and the cortisol response to MCPP. No significant correlations between the ACTH and prolactin responses to MCPP and levels of anxiety/anger were observed in the patients. No significant correlations could be established between levels of anxiety/anger and hormonal responses to ipsapirone. This study provided evidence for an association between measures of anxiety/aggression and the hormonal response to MCPP. Thus, in subjects with depressed mood, high levels of anxiety suggest a higher probability of 5-HT(2C) disturbances.

Adolescent↗
PubMed2002

Plasma, oral fluid and sweat wipe ecstasy concentrations in controlled and real life conditions.

In a double-blind placebo controlled study on psychomotor skills important for car driving (Study 1), a 75 mg dose of +/- 3,4-methylenedioxymethamphetamine (MDMA) was administered orally to 12 healthy volunteers who were known to be recreational MDMA-users. Toxicokinetic data were gathered by analysis of blood, urine, oral fluid and sweat wipes collected during the first 5h after administration. Resultant plasma concentrations varied from 21 to 295 ng/ml, with an average peak concentration of 178 ng/ml observed between 2 and 4h after administration. MDA concentrations never exceeded 20 ng/ml. Corresponding MDMA concentrations in oral fluid, as measured with a specific LC-MS/MS method (which required only 50 microl of oral fluid), generally exceeded those in plasma and peaked at an average concentration of 1215 ng/ml. A substantial intra- and inter-subject variability was observed with this matrix, and values ranged from 50 to 6982 ng/ml MDMA. Somewhat surprisingly, even 4-5h after ingestion, the MDMA levels in sweat only averaged 25 ng/wipe. In addition to this controlled study, data were collected from 19 MDMA-users who participated in a driving simulator study (Study 2), comparing sober non-drug conditions with MDMA-only and multiple drug use conditions. In this particular study, urine samples were used for general drug screening and oral fluid was collected as an alternative to blood sampling. Analysis of oral fluid samples by LC-MS/MS revealed an average MDMA/MDEA concentration of 1121 ng/ml in the MDMA-only condition, with large inter-subject variability. This was also the case in the multiple drug condition, where generally, significantly higher concentrations of MDMA, MDEA and/or amphetamine were detected in the oral fluid samples. Urine screening revealed the presence of combinations such as MDMA, MDEA, amph, cannabis, cocaine, LSD and psilocine in the multiple-drug condition.

Adult↗
PubMed2002

Differential residual effects of zaleplon and zopiclone on actual driving: a comparison with a low dose of alcohol.

STUDY OBJECTIVES: To compare residual effects of zaleplon 10 mg, zopiclone 7.5 mg, and placebo, and a social dose of alcohol on car driving, memory, and psychomotor performance. DESIGN: Two-part placebo controlled, crossover study. Part 1 was single blind, Part 2 double blind. SETTING: University research institute. PARTICIPANTS: Thirty healthy volunteers (15 men and 15 women, mean age 32 +/- 7 years) INTERVENTIONS: In Part 1 alcohol and alcohol-placebo drinks were administered around noon. In Part 2 single oral doses of zaleplon 10 mg, zopiclone 7.5 mg and placebo were administered at bedtime. MEASUREMENT AND RESULTS: A highway driving test, laboratory tests of word learning, critical tracking and divided attention, and subjective assessments of sleep, mood, and effects of treatments on driving. Driving started 40 minutes after a second alcohol dose in Part 1, and 10 hours after drug intake in Part 2. The results demonstrated that alcohol, at average plasma concentrations of approximately 0.030 g/dl, significantly impaired performance in all tests. Zaleplon's residual effects did not differ significantly from those of placebo in any test. In contrast, zopiclone had significant residual effects on driving, divided attention, and memory. The magnitude of impairment in the driving test observed the morning after zopiclone 7.5 mg was twice that observed with alcohol. CONCLUSION: Zaleplon 10 mg has no residual effects on driving when taken at bedtime, 10 hours before driving. In contrast, zopiclone 7.5 mg can cause marked residual impairment. Patients should be advised to avoid driving the morning after zopiclone administration.

Acetamides↗
PubMed2002

Modulation of the critical flicker fusion effects of serotonin reuptake inhibitors by concomitant pupillary changes.

RATIONALE: Serotonin reuptake inhibitors (SSRIs) have been attributed CNS-activating properties based on their ability to elevate the Critical Flicker Fusion (CFF) threshold. However, such an interpretation may be questioned since CFF elevations may also be due to SSRI-induced increases in pupil diameter. OBJECTIVES: The effect of pupillary changes on CFF assessment following SSRI administration was investigated in a double blind, crossover study. METHODS: During three periods of 15 days, 21 healthy men and women (30-50 years) received sertraline (50 mg on days 1-8, 100 mg on days 9-15), citalopram (20 mg on days 1-8, 40 mg on days 9-15) and placebo. Assessments were done on days 1, 8 and 15 and consisted of pupillary measurements and CFF assessments with and without pupillary control (a 2-mm artificial pupil) using the Leeds Psychomotor Tester. RESULTS: Both SSRIs induced an acute and steady increase in pupil diameters. CFF thresholds were depressed following acute administration of sertraline and citalopram, but this was only apparent when a control was made for the pupillary changes. No CFF effects were seen at day 8, but CFF was again reduced at day 15, with and without control for pupil size. CONCLUSIONS: Mydriasis masked the detrimental effects of both SSRIs on CFF during the acute assessments. Our results raise questions regarding the validity of the assessment of the behavioural toxicity of SSRIs based on CFF measurements without ample control for pupil size, especially when these concern acute measurements.

Adult↗
PubMed2002

Atypical cognitive profile in patients with depression after myocardial infarction.

BACKGROUND: We evaluated the cognitive profile of 48 patients with major depression following their first myocardial infarction (MI). METHODS: The cognitive performance of the patients was compared with the performance of 48 non-depressed MI patients and 48 healthy controls. RESULTS: Depressed MI patients performed slower on a simple cognitive speed related measure compared with non-depressed MI patients and healthy controls. Attention and speed-related aspects of cognitive functioning were not affected. Surprisingly, (depressed) MI patients showed even better performances with respect to memory function. LIMITATION: No patients with non-MI-related depression were included. CONCLUSIONS: The cognitive profile of major depression after MI differs from that of non-cardiac-related depressive disorder, as described in the literature. This may reflect a different etiology of post MI depression from non-cardiac-related depression.

Adult↗
PubMed2002

Tryptophan, mood, and cognitive function.

In separate experiments we investigated the duration of the effects of acute tryptophan depletion (ATD) on mood and cognition. The results showed that ATD's effects consist of lowering of mood only in subjects with a family history of unipolar depression. A specific impairment of memory consolidation was seen in all subjects. In subjects without any vulnerability for mood disorders, performance on so-called 'frontal tasks,' measuring higher attentional functions tended to improve after ATD. The effects of ATD on mood and cognition were manifest as long as biochemical indices of low tryptophan remained low. In conclusion, ATD is a model for impairment of memory, next to being a model of mood disorders in vulnerable subjects. Moreover, ATD could be used as a challenge to demonstrate individual vulnerability of the serotonergic system.

Affect↗
PubMed2002

Additional dopamine reuptake inhibition attenuates vigilance impairment induced by serotonin reuptake inhibition in man.

There is evidence for a specific impairment of human vigilance following enhancement of serotonergic activity by antidepressant drugs. In the present study, we investigated the putative role of serotonergic-dopaminergic interactions in diminished vigilance by comparing the attentional effects of sertraline, a selective serotonin reuptake inhibitor (SSRI) with additional mild dopamine stimulating effects, with those of paroxetine, a SSRI without dopamine activity, using a placebo-controlled, double-blind, three-way cross-over design. Twenty-one (of 24) healthy middle-aged subjects completed the three treatment periods of 2 weeks in which sertraline (50 mg, days 1-7; 100 mg, days 8-14), paroxetine (20 mg, days 1-7; 40 mg, days 8-14) and placebo were administered. Vigilance (Mackworth Clock Test), selective (Stroop, Dichotic Listening) and divided attention (Dichotic Listening) were assessed at baseline and on days 7 and 14 of each treatment period. Selective and divided attention were unaffected by SSRI treatment. Subchronic administration of paroxetine impaired vigilance performance at each investigated dose. Sertraline did not produce a significant decline in vigilance performance, presumably due to its concomitant effects on dopamine activity, counteracting the negative effects of serotonin on dopamine neurotransmission. It is concluded that a serotonergically mediated reduction of dopamine activity plays an important role in the reduction of human vigilance following SSRI administration.

Adult↗