Biomedical subjects

Luc Staner

Publications and source records attributed to Luc Staner.

17 recordsLinked to original sources

PubMed2006

Effects of acamprosate on sleep during alcohol withdrawal: A double-blind placebo-controlled polysomnographic study in alcohol-dependent subjects.

BACKGROUND: Sleep disturbances are frequently encountered in alcohol-dependent patients. Drugs improving sleep during abstinence from alcohol may play an important role in the recovery process. METHODS: In the present study, the effects of acamprosate, a drug successfully used in maintaining abstinence following alcohol withdrawal, were assessed by polysomnographic recordings. A parallel double-blind placebo-controlled study was conducted in 24 male DSM-IV alcohol-dependent subjects aged 35.9+/-1.2 years. Treatments (2 tablets of 333 mg acamprosate vs placebo t.i.d.) were initiated 8 days before alcohol withdrawal and continued during the 15 days following alcohol withdrawal. Polysomnographic assessments were recorded during acute withdrawal (the first 2 nights following withdrawal) and during postwithdrawal abstinence (the last 2 nights of the trial). RESULTS: Results show that, compared with placebo, acamprosate decreased wake time after sleep onset and increased stage 3 and REM sleep latency (all treatment effects with a p < 0.05 significance). Withdrawal effects themselves were also demonstrated as sleep efficiency (p < 0.01) and total sleep time (p < 0.05) were lower in abstinence nights versus withdrawal nights, whereas no significant treatment x withdrawal effect could be evidenced. Acamprosate was well tolerated during the entire course of the study. CONCLUSIONS: The present study shows that acamprosate ameliorates both sleep continuity and sleep architecture parameters classically described as disturbed in alcohol-dependent patients. From a clinical perspective, it suggests that an 8-day acamprosate prewithdrawal treatment is well tolerated and can attenuate the sleep disturbances engendered by alcohol withdrawal in alcohol-dependent subjects.

Acamprosate↗

PubMed2006

Surrogate outcomes in neurology, psychiatry, and psychopharmacology.

A surrogate outcome can be defined as an outcome that can be observed sooner, at lower cost, or less invasively than the true outcome, and that enables valid inferences about the effect of intervention on the true outcome. There is increasing interest in the use of surrogate outcomes of treatment efficacy measurement in investigational drug trials. However, the significance of surrogate markers of treatment outcome in neurology and psychiatry has not yet been sufficiently demonstrated. Few such markers have been adequately "validated, " that is, shown to predict the effect of the treatment on the clinical outcome of interest. In this article, evidence that would support the validation of such markers is discussed. Biomarkers used during early clinical development programs of new psychotropic compounds are considered in the contexts of Parkinson's disease, affective disorder, and schizophrenia. The particular case of neuroprotective trials is exemplified by Parkinson's disease, where a biomarker substituting for a clinical measure of progression could be considered as a surrogate treatment outcome.

Animals↗

PubMed2005

Next-day residual effects of hypnotics in DSM-IV primary insomnia: a driving simulator study with simultaneous electroencephalogram monitoring.

RATIONALE: Most studies that investigated the next-day residual effects of hypnotic drugs on daytime driving performances were performed on healthy subjects and after a single drug administration. OBJECTIVES: In the present study, we further examine whether the results of these studies could be generalised to insomniac patients and after repeated drug administration. METHOD: Single and repeated (7 day) doses of zolpidem (10 mg), zopiclone (7.5 mg), lormetazepam (1 mg) or placebo were administered at bedtime in a crossover design to 23 patients (9 men and 14 women aged 38.8+/-2.0 years) with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) primary insomnia. Driving tests were performed 9-11 h post-dose. RESULTS: Results showed that treatment effects were evidenced for subjective sleep, for driving abilities, and for electroencephalogram (EEG) recorded before (resting EEG) and during the driving simulation test (driving EEG). Compared to placebo, zopiclone increased the number of collisions and lormetazepam increased deviation from speed limit and deviation from absolute speed, whereas zolpidem did not differentiate from placebo on these analyses. EEG recordings showed that in contrast to zolpidem, lormetazepam and zopiclone induced typical benzodiazepine-like alterations, suggesting that next-day poor driving performance could relate to a prolonged central nervous system effect of these two hypnotics. CONCLUSION: The present results corroborate studies on healthy volunteers showing that residual effects of hypnotics increase with their half-lives. The results further suggest that drugs preserving physiological EEG rhythms before and during the driving simulation test 9-11 h post-dose, such as zolpidem, do not influence next-day driving abilities.

Adult↗

PubMed2005

Periodic limb movements and sleepiness in obstructive sleep apnea patients.

BACKGROUND AND PURPOSE: The aim of this study was to assess the possibility that periodic limb movements during sleep (PLMS) could play an additive role in the sleepiness associated with obstructive sleep apnea syndrome (OSAS) before treatment, or could account for residual sleepiness in successfully CPAP-treated patients. PATIENTS AND METHODS: In order to test this hypothesis, we compared objective sleepiness, assessed by the Multiple Sleep Latency Test (MSLT) and subjective sleep propensity, assessed by the Epworth Sleepiness Scale (ESS), in a clinical series of 57 patients consecutively diagnosed with OSAS (apnea/hypopnea index, 53.3+/-26.15), before and after 1 year of treatment with CPAP. RESULTS: Twenty-two patients (38.5%) had significant PLMS (at least 5 PLMS/h of sleep; mean 52.9+/-53.9) in absence of apneas (with CPAP). The two groups (with and without PLMS) were similar in gender distribution, BMI, apnea/hypopnea index or CPAP level. Patients with PLMS were older than those without PLMS. Sleepiness measurements following OSAS diagnosis and after 1 year of CPAP treatment were similar in patients PLMS compared to those without significant PLMS. There was no correlation in the PLMS patient group between the PLM index, Epworth Sleepiness Scale score and mean latency in the MSLT. CONCLUSION: In this study we did not find a link between PLMS and increased objective or self-evaluated sleepiness in OSAS patients, before or after treatment with CPAP.

Body Mass Index↗

PubMed2005

Inverse association between Slow Wave Activity per cycle and the number of ultradian sleep cycles per night in healthy humans.

OBJECTIVE: Comparisons of sleep Slow Wave Activity (SWA) during successive sleep cycles rely on the assumption that SWA in a given cycle is independent of the number of ultradian cycles present in a night. This assumption was evaluated here. METHODS: Twenty-six healthy controls with no medical, sleep or psychiatric disorders were selected among 84 candidates and their sleep was recorded at home across 2 consecutive nights after two habituation nights. RESULTS: In comparison with nights with less cycles, nights with more cycles showed significantly more REMS but not more NREMS. No correlation was found between the number of cycles and the integrated SWA per night (epochs visually scored as NREMS). However, inverse correlations were found between the number of cycles and the SWA per cycle. This was significant on both nights in Cycle 1 and strong trends were found for the two subsequent cycles on Night 2. Comparable results were found after removal of nights containing suspected Skipped First REMS episodes. CONCLUSIONS: The SWA in a cycle was found to be inversely correlated to the number of cycles in the first 3 cycles in at least one of the two analyzed nights. SIGNIFICANCE: Differences in the number of cycles per night are a potential bias in the comparisons of SWA per cycles.

Activity Cycles↗

PubMed2005

Suicide attempts and family history of suicide in three psychiatric populations.

The influence of a family history of suicide on suicide attempt rate and characteristics in depression, schizophrenia, and opioid dependence was examined. One hundred sixty inpatients with unipolar depression, 160 inpatients with schizophrenia, and 160 opioid-dependent patients were interviewed. Overall, a family history of suicide was associated with a higher risk for suicide attempt, with high-lethality method, with repeated attempts, and with number of attempts, while the interaction between family history and diagnostic group was not significant. Thus, a positive family history of suicide was a risk factor for several suicide attempt characteristics independent of psychiatric diagnosis.

Adult↗

PubMed2005

Sleep disturbances, psychiatric disorders, and psychotropic drugs.

Brain neurotransmitter dysfunctions involved in the pathophysiological processes of psychiatric disorders are likely to be reflected by concomitant alterations in sleep continuity and architecture. Since the corrective effects of psychotropic drugs on dysfunctional neurotransmission systems can be evidenced through polysomnographic recordings, one may consider sleep as a kind of "window" on the neurobiology of psychiatric disorders. During the last 10 years, major breakthroughs in our understanding of sleep-wake mechanisms have provided some indications on how psychotropic drugs could influence the sleep-wake cycle. In this review, recent inroads into the understanding of sleep regulatory neural mechanisms are introduced and discussed in terms of the effects of psychotropic drugs. The relationship between the pathophysiological process of a disease, its consequence on sleep, and the corrective effect of a psychotropic drug are exemplified by two psychopathological states: substance withdrawal and major depression. One may conclude that polysomnographic recordings are a unique noninvasive tool to analyze brain functioning, and are particularly well suited to evaluating the objective effects of new psychotropic drugs.

Animals↗

PubMed2004

What is the clinical significance of periodic limb movements during sleep?

UNLABELLED: To understand better the clinical impact of periodic limb movements during sleep (PLMS) we analysed data from 51 patients who, following an adaptation night, presented a PLMS index > 5 during two consecutive nocturnal polysomnographic recordings. In the morning following each recording patients completed a questionnaire including five visual analogic scales (VAS): (1) I did not sleep well/I slept very well. (2) I feel very sleepy/I do not feel sleepy at all. (3) I feel very tired/I feel very dynamic. (4) Physically, I do not feel fit/physically, I feel fit. (5) Psychologically, I do not feel fit/psychologically, I feel fit. We compared the responses to these questions with the PLMS index, first inter-individually, then intra-individually between nights. RESULTS: The inter-individual analysis did not show correlations between the PLMS index and the questions (1) and (2). We found a significant correlation between the PLMS index and the questions (3) (r = -0.29; P < 0.05), (4) (r = -0.30; P < 0.05) and (5) (r = -0.39; P < 0.01). For the intra-individual analysis, we did not find correlations between the PLMS index and questions (1)-(3), but found a significant correlation with questions (4) (r = -0.28; P < 0.05) and (5) (r = -0.36; P < 0.01). CONCLUSION: PLMS per se, or the sleep changes induced by them, seem to be associated with decreased physical and psychological fitness on awakening.

Adult↗

PubMed2004

Comparative effects of duloxetine and desipramine on sleep EEG in healthy subjects.

RATIONALE: Antidepressants are known to modify human sleep patterns. OBJECTIVES: Duloxetine is a new antidepressant with a mechanism of action involving reuptake inhibition of both serotonin (5-HT) and norepinephrine (NE). In this study, the effects of two dosing regimens of duloxetine on sleep electroencephalography (EEG) were investigated at steady-state plasma concentrations in young, healthy, male subjects. METHODS: Placebo (n=12), desipramine (50 mg BID; n=12) and two regimens of duloxetine (80 mg QD, n=6; or 60 mg BID, n=6) were compared in a randomized, double-blind, three-period crossover study, each treatment being administered from day 1 to day 7. Sleep polygraphic recordings took place at baseline (day -1) and day 6 of each period. The Leeds sleep evaluation questionnaire (LSEQ) was also administered on the morning of day 7. RESULTS: Both regimens of duloxetine produced a significant increase in the onset latency of REM sleep as well as a significant mean decrease in total REM sleep duration. Desipramine exhibited comparable effects. When compared to placebo, sleep continuity was significantly reduced with desipramine and duloxetine 60 mg BID whereas a significant improvement was observed with duloxetine 80 mg QD. On the LSEQ, duloxetine 80 mg QD produced a significant improvement in the "getting to sleep" subscale compared to placebo, whereas desipramine demonstrated a significant reduction (worsening) in the "quality of sleep" score versus placebo. CONCLUSIONS: The two dose regimens of duloxetine (80 mg QD and 60 mg BID) produced a REM sleep pattern comparable to that of most antidepressant medications. Duloxetine 80 mg QD appeared to exhibit less impact upon sleep quality than duloxetine 60 mg BID in healthy subjects.

Adolescent↗

PubMed2003

Acute low single dose of apomorphine reduces periodic limb movements but has no significant effect on sleep arousals: a preliminary report.

STUDY OBJECTIVES: To investigate the effects of apomorphine on the frequency of periodic limb movements during sleep (PLMS) and on sleep architecture. DESIGN: Nine patients presenting PLMS (including eight patients with restless legs syndrome) underwent three consecutive night sleep recordings. They received a single dose of 0.5 mg subcutaneous apomorphine at bedtime the third night. RESULTS: When computing PLMS during four 2-h periods of sleep, a significant period by apomorphine-effect was demonstrated, with a marked reduction of PLMS during the first 4 h post-injection (P < 0.01). No significant differences were found in sleep macroarchitecture between the three recorded nights, excepted a slight reduction in sleep latency during the third night (P < 0.05). Despite the decreased number of PLMS after apomorphine injection, there were significant changes neither in the total number of arousals nor in the index of arousals per hour of sleep. CONCLUSION: Our results add further support to the dopaminergic hypothesis in the generation of PLMS. The persistence of arousals suggests that they are not simply the consequence of PLMS but a primary phenomenon, not related with the dopaminergic system.

Apomorphine↗

PubMed2003

Sleep microstructure around sleep onset differentiates major depressive insomnia from primary insomnia.

In the present study we investigate whether alterations of sleep propensity or of wake propensity are implicated in sleep initiation disturbances encountered in major depressive insomnia and in primary insomnia. For this purpose, the time course of electroencephalogram (EEG) power density during the period preceding sleep onset and during the first non-rapid eye movement (REM) period was examined in three age and gender matched groups of 10 women and 11 men (healthy controls, primary insomniacs and depressive insomniacs). In contrast to healthy controls and depressive insomniacs, patients with primary insomnia did not experience a gradual decrease of their alpha and beta1 power during the sleep onset period and had a lower delta activity in the 5 min preceding sleep onset. Compared with the two other groups, depressive patients exhibit less dynamic changes in slow wave activity during the first non-REM period. The present results suggest that hyperarousal (high 'Process W') may mainly be implicated in the sleep initiation difficulties of primary insomniacs whereas the homeostatic sleep regulation process seems to be partially maintained. In our major depressed patients, the sleep initiation disturbances appeared to relate to a lower sleep pressure (low 'Process S') rather than to hyperarousal. This study supports the idea that different mechanisms are implicated in sleep disturbances experienced by primary insomniacs and major depressive insomniacs.

Adult↗

PubMed2003

Double-blind, placebo-controlled study of the efficacy of trazodone in alcohol post-withdrawal syndrome: polysomnographic and clinical evaluations.

Alcohol detoxification is accompanied by sustained difficulties in sleep initiation and maintenance. These difficulties are thought to be an important cause of relapse to alcohol use. However, the treatment of sleep problems with hypnotic drug is made difficult by cross-tolerance between benzodiazepines and alcohol. In this report, we evaluated the capacity of trazodone (TRZ), a second-generation antidepressant with anxiolytic and sedative properties, to increase the sleep efficiency in alcohol-dependent patients after detoxification. Sixteen patients completed the TRZ (n = 8) or the placebo (PL; n = 8) treatment arms. Polysomnographies were performed at baseline, after the 1st drug dose, and after 4 weeks of treatment. The main outcome was sleep efficiency. Secondary outcomes included changes in other sleep parameters, Hamilton Depression Rating and Clinical Global Impression scales. Sleep efficiency was increased in the TRZ group when it was computed after sleep onset, both immediately after 1st administration of the drug and after 4 weeks of treatment. No benefit was observed in the PL group. Sleep improvement under TRZ also included the number of awakenings, intermittent wake sleep time, and non-rapid eye movement sleep. Hamilton and Clinical Global scales were better for the TRZ group. TRZ is thus a potential option in the treatment of alcohol post-withdrawal insomnia.

Adolescent↗

PubMed2002

A dimensional impulsive-aggressive phenotype is associated with the A218C polymorphism of the tryptophan hydroxylase gene: a pilot study in well-characterized impulsive inpatients.

Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the biosynthesis of serotonin, and association and linkage studies of its variants in suicidal and impulsive-aggressive behavior have brought conflicting results. This pilot study was designed to investigate whether TPH A218C genotypes could be associated with impulsive behavioral tendencies (IBTs) in consecutively admitted nonpsychotic nonorganic inpatients. Patients (20 females and 34 males; age, 38.8 +/- 11.8) did not differ from healthy nonimpulsive controls (16 females and 11 males; age, 35.2 +/- 10.2) regarding TPH genotypes, but in the patients, the number of IBT was related to the presence of the 218C allele. It was concluded that impulsive-aggressive behavior may be associated with the TPH genotype in well-characterized impulsive patients and that the present results stress the importance of considering impulsiveness-aggressiveness in studies investigating the relationship between suicidal behavior and TPH genotypes.

Adult↗

PubMed2002

Serotonergic function and suicidal behavior in schizophrenia.

Recent studies suggest that altered serotonergic (5-HT) function, as assessed by lower prolactin (PRL) response to fenfluramine (FEN), a specific 5-HT releaser and uptake inhibitor, is associated with suicidal behavior in either depressed and personality disordered patients. The purpose of this study was to investigate, in schizophrenic patients, the relationship between suicidal behavior and PRL response to D-fenfluramine (D-FEN). A D-FEN test was performed in 18 healthy controls and 33 drug-free DSM-IV schizophrenic patients (12 with a history of suicide attempts, 21 without it). Schizophrenic patients with a history of suicide attempts showed a lower PRL response to D-FEN (Delta PRL) compared to schizophrenic patients without such history (P<0.04) and also compared to healthy controls (P<0.0003). Delta PRL did not differentiate schizophrenic patients without suicide attempts and controls. These findings could not be explained by PRL basal hormonal levels, age, sex, menstrual status, demographic or clinical characteristics. These results suggest that PRL response to D-FEN is a marker of suicidal tendencies also in schizophrenia, supporting the hypothesis that a dysfunction in serotonergic function is associated with suicidal behavior regardless of the psychiatric diagnosis.

Adult↗

PubMed2002

Positive association of dopamine D2 receptor polymorphism with bipolar affective disorder in a European Multicenter Association Study of affective disorders.

Convincing evidence for a genetic component in the etiology of affective disorders (AD), including bipolar affective disorder (BPAD) and unipolar affective disorder (UPAD), is supported by traditional and molecular genetic studies. Most arguments lead to the complex inheritance hypothesis, suggesting that the mode of inheritance is probably not Mendelian but most likely oligogenic (or polygenic) and that the contribution of genes could be moderate or weak. The purpose of the present European multicenter study (13 centers) was to test the potential role in BPAD and UPAD of two candidate dopaminergic markers, DRD2 and DRD3, using a case-control association design. The following samples were analyzed for DRD2: 358 BPAD/358 control (C) and 133 UPAD/ 133 C subjects, and for DRD3: 325 BPAD/ 325 C and 136 UPAD/136 C subjects. Patients and controls were individually matched for sex, age ( plus minus five years) and geographical origin. Evidence for significant association between BPAD and DRD2 emerged, with an over-representation of genotype 5-5 (P=0.004) and allele 5 (P=0.002) in BPAD cases compared to controls. No association was found for DRD2 in UPAD, and for DRD3 neither in BPAD or UPAD. Our results suggest that the DRD2 microsatellite may be in linkage disequilibrium with a nearby genetic variant involved in the susceptibility to BPAD. Our large European sample allowed for replicating of some previous reported positive findings obtained in other study populations.

Alleles↗

PubMed2002

Periodic arousals or periodic limb movements during sleep?

Periodic limb movements during sleep (PLMS), frequently found in polysomnograms, are often accompanied by arousals. The relationship is not clear, however, because PLMS can occur before, after or simultaneous to the electromyographic (EMG) activation. We describe the case of a patient who presents PLMS during two of three consecutive recording nights, and periodic arousals without motor activation on the other night. We conclude that, at least in some patients with a periodic limb movement disorder, there exists an underlying arousal disorder that produces periodic activation and deactivation of the cerebral cortex.

Journal Article↗

PubMed2002

EEG source identification: frequency analysis during sleep.

This article deals with a new approach in sleep characterization that combines EEG source localisation methods with standard frequency analysis of multielectrode EEGs. First, we describe the theoretical methodology and the benefits that we get from a three-dimensional image (LORETA) of the cerebral activity related to a frequency band. Then, this new application is used as signal-processing technique on sleep EEG recordings obtained from young male adults using four frequency bands (delta 0.5-3.5 Hz, theta 4.0-7.5 Hz, alpha 8.0-12.5 Hz and beta 13.0-32.0 Hz) in different sleep stages. Finally, we show that the obtained results are highly consistent with other physiological assessments (standard EEG mapping, functional magnetic resonance imaging, etc.), but give us more realistic additional information on the generators of electromagnetic cerebral activity.

Adult↗