J P Macher

Hospital Rouffach, Alsace, France

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Publications (122)353.53 Total impact

  • European Neuropsychopharmacology - EUR NEUROPSYCHOPHARMACOL. 01/2006; 16.
  • European Neuropsychopharmacology - EUR NEUROPSYCHOPHARMACOL. 01/2006; 16.
  • European Neuropsychopharmacology - EUR NEUROPSYCHOPHARMACOL. 01/2006; 16.
  • European Neuropsychopharmacology - EUR NEUROPSYCHOPHARMACOL. 01/2006; 16.
  • European Neuropsychopharmacology - EUR NEUROPSYCHOPHARMACOL. 01/2006; 16.
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    ABSTRACT: Regional brain iron levels of two patients with haemochromatosis and severe restless legs syndrome (RLS) were assessed using R2' magnetic resonance imaging (MRI) sequences in both patients and in nine healthy controls. R2' relaxation rates in the patients were decreased in the substantia nigra, red nucleus, and pallidum when compared with the controls. These results indicate that local brain iron deficiency may occur in patients with haemochromatosis and suggest a role for brain iron metabolism in the pathophysiology of RLS.
    Journal of Neurology Neurosurgery & Psychiatry 08/2005; 76(7):1009-10. · 4.92 Impact Factor
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    ABSTRACT: Cyamemazine (Tercian) is an antipsychotic drug with anxiolytic properties. Recently, an in vitro study showed that cyamemazine possesses high affinity for serotonin 5-HT(2A) receptors, which was fourfold higher than its affinity for dopamine D(2) receptors (Hameg et al. 2003). The aim of this study is to confirm these previous data in vivo in patients treated with clinically relevant doses of Tercian. Eight patients received 37.5, 75, 150 or 300 mg/day of Tercian depending on their symptomatology. Dopamine D(2) and serotonin 5-HT(2A) receptor occupancies (RO) were assessed at steady-state plasma levels of cyamemazine with positron emission tomography (PET), using [(11)C]raclopride and [(11)C]N-methyl-spiperone, respectively. The effective plasma level of the drug leading to 50% of receptor occupancy was estimated by fitting RO with plasma levels of cyamemazine at the time of the PET scan. Cyamemazine induced near saturation of 5-HT(2A) receptors (RO=62.1-98.2%) in the frontal cortex even at low plasma levels of the drug. On the contrary, occupancy of striatal D(2) receptors increased with plasma levels, and no saturation was obtained even at high plasma levels (RO=25.2-74.9%). The effective plasma level of cyamemazine leading to 50% of D(2) receptor occupancy was fourfold higher than that for 5-HT(2A) receptors. Accordingly, individual 5-HT(2A)/D(2) RO ratios ranged from 1.26 to 2.68. No patients presented relevant increased prolactin levels, and only mild extrapyramidal side effects were noticed on Simpson and Angus Scale. This in vivo binding study conducted in patients confirms previous in vitro findings indicating that cyamemazine has a higher affinity for serotonin 5-HT(2A) receptors compared to dopamine D(2) receptors. In the dose range 37.5-300 mg, levels of dopamine D(2) occupancy remained below the level for motor side effects observed with typical antipsychotics and is likely to explain the low propensity of the drug to induce extrapyramidal side effects.
    Psychopharmacology 08/2005; 180(2):377-84. · 4.06 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    Sleep Medicine 06/2005; 6(3):225-9. · 3.49 Impact Factor
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    ABSTRACT: Indirect observations suggest that dopamine function may be altered in depressed patients, notably in bipolar patients. The purpose of this study was to assess the dopamine receptor sensitivity at the hypothalamic-pituitary level in 19 drug-free DSM-IV major depressed patients: 10 bipolar depression (BP), 9 unipolar depression (UP), compared with 15 sex and age matched hospitalized controls (HC). We evaluated the multihormonal responses to the dopamine agonist apomorphine (APO, 0,75 mg SC) in order to obtain an indirect index of dopaminergic neurotransmission at the post synaptic level. We also examined, in the same subjects, prolactin (PRL) response to 8AM and 11PM protirelin challenges (TRH, 200μg IV) and cortisol response to dexamethasone suppression test (DST, 1 mg orally). No significant difference in cortisol, ACTH and GH values was found between controls, UP and BP patients (i.e. at baseline and in response to apomorphine test). However, BP had lower APO-induced PRL suppression than HC (P=0.0003) and UP (P=0.04). Taken together these results suggest that decreased APO-induced PRL suppression in bipolar depressed patients is not due to deficiency of pituitary lactrophs and/or increased HPA axis activity, but may reflect altered post synaptic receptor sensitivity D2 in the tuberoinfundibular dopamine system.
    Annales Medico-psychologiques - ANN MEDICO-PSYCHOL. 01/2005; 163(5):399-404.
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    ABSTRACT: 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.
    Neurophysiologie Clinique/Clinical Neurophysiology 01/2005; 34(6):293-300. · 2.55 Impact Factor
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    ABSTRACT: This is a review of our research on dopamine receptor D3 (DRD3) gene polymorphism in psychiatric patients. We found that heterozygosity at a diallelic Ball polymorphic site in the first exon of the DRD3 gene was associated with schizophrenia, as did another group (Mant et al., 1994). However others did not reproduce our findings and raised doubts about a possible role of the DRD3 in schizophrenia. More recently, we found that homozygosity for allele 2 at the same site was associated with lower cortisol and ACTH responses to apomorphine. We had also previously reported lower ACTH and cortisol responses to apomorphine in paranoid schizophrenics compared to controls (Mokrani et al., in press). This suggests that DRD3 polymorphisms might be associated with functional differences that could secondarily influence the expression of schizophrenia, in spite of the lack of clear association with schizophrenia. More generally, classical association studies may be limited in their power to prove or disprove minor gene effects in schizophrenia because the disorder is heterogeneous and various genes may have additive effects in different patients. Biological measures that are closer to gene effects may be a better way to test candidate genes than the association with a complex clinical phenotype.
    Human Psychopharmacology Clinical and Experimental 10/2004; 10(1):19 - 24. · 2.10 Impact Factor
  • European Neuropsychopharmacology - EUR NEUROPSYCHOPHARMACOL. 01/2004; 14.
  • European Neuropsychopharmacology - EUR NEUROPSYCHOPHARMACOL. 01/2004; 14.
  • European Neuropsychopharmacology - EUR NEUROPSYCHOPHARMACOL. 01/2004; 14.
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    ABSTRACT: To investigate the effects of apomorphine on the frequency of periodic limb movements during sleep (PLMS) and on sleep architecture. 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. 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. 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.
    Neurophysiologie Clinique/Clinical Neurophysiology 09/2003; 33(4):180-4. · 2.55 Impact Factor
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    ABSTRACT: In the present study, we investigated the effects of a single and a repeated (5 days) administration of naftidrofuryl, a serotonin 5-HT2 receptor inhibitor having neuroprotective properties, on functional brain physiology in male healthy elderly subjects, using quantitative electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Twelve subjects aged 60 +/- 3.8 years completed the quantitative EEG study, where the effects of 400 and 600 mg were assessed, and 12 other subjects (aged 56 +/- 4.7 years) completed the fMRI study, where the effect of 400 mg was assessed on the brain activation induced by the continuous performance test (CPT). Naftidrofuryl induced a transient reduction in alpha activity followed by a specific synchronisation of the 9.5- to 11-Hz EEG activity most pronounced after repeated administration. Such regimen also increased the CPT-induced brain activation visualized by way of fMRI. The results of the present study can be interpreted at the functional level that naftidrofuryl induced an improved level of vigilance or an increased capacity of alertness in healthy elderly subjects.
    Neuropsychobiology 02/2003; 48(3):160-8. · 2.37 Impact Factor
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    ABSTRACT: This study was aimed at investigating the relationships between sleep EEG abnormalities and hypothalamo pituitary adrenal (HPA) and hypothalamo pituitary thyroid (HPT) disturbances in major depressive disorder. Post dexamethasone (DXM) cortisol levels and the dual TSH response to 08:00 h and 23:00 h TRH administration were determined after a 2 weeks wash-out period in a group of 113 DSM-IV major depressed patients (72 females aged 44.3+/-13.0 and 41 males aged 45.7+/-11) who were consecutively admitted to undergo sleep EEG recordings. Post-DXM cortisolemia, 08:00 and 23:00 post-TRH TSH values, time spent in rapid eye movement sleep (REMS), in slow wave sleep (SWS), and in stage 2 as well as time awake after sleep onset were introduced in a principal component (PC) analysis. The four 3 PC scores explaining up to 74% of the data set were further calculated for each patients and used in a cluster analysis. A three-cluster solution was retained. Controlling for the effects of age and gender, patients belonging to these three clusters could clearly be differentiated on the basis of their neuroendocrine responses and on their sleep EEG profiles. Compared to the two other clusters, cluster I (n=26) patients showed the most severe sleep continuity disturbances. Post-DXM cortisol escape and sleep architecture disturbances (consisting of a shortening of REMS latency and a decreased SWS) identified patients belonging to cluster II (n=39). Patients in cluster III (n=48) had the lowest TSH response to TRH and the less marked sleep EEG alteration. Clinical or demographic variables were unable to differentiate the three clusters. Our results suggest that different biological dysfunctions could each underlie particular neuroendocrine and sleep EEG disturbances in major depression.
    Journal of Psychiatric Research 01/2003; 37(1):1-8. · 4.09 Impact Factor
  • Schizophrenia Research - SCHIZOPHR RES. 01/2003; 60(1):51-51.
  • European Neuropsychopharmacology - EUR NEUROPSYCHOPHARMACOL. 01/2003; 13.
  • José Haba-Rubio, Luc Staner, Jean Paul Macher
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    ABSTRACT: 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.
    Sleep Medicine 12/2002; 3(6):517-20. · 3.49 Impact Factor

Publication Stats

1k Citations
353.53 Total Impact Points

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Institutions

  • 1987–2005
    • Hospital Rouffach
      Alsace, France
  • 1998
    • Catholic University of Louvain
      Walloon Region, Belgium
  • 1996
    • University of Santiago, Chile
      CiudadSantiago, Santiago, Chile