Validation of a data collection set for the psychiatric, addiction, sleep and chronobiological assessments of patients with depression: A Delphi study for the SoPsy-depression French national cohort.

OBJECTIVES: Despite international efforts to identify biomarkers of depression, none has been transferred to clinical practice, neither for diagnosis, evolution, nor therapeutic response. This led us to build a French national cohort (through the clinical and research network named SoPsy within the French biological psychiatry society (AFPBN) and sleep society (SFRMS)), to better identify markers of sleep and biological rhythms and validate more homogeneous subgroups of patients, but also to specify the manifestations and pathogeneses of depressive disorders. Before inclusions, we sought to provide a predefined, standardized, and robust set of data to be collected in all centers. METHODS: A Delphi process was performed to achieve consensus through the independent rating of invited experts, the SoPsy-depression co-investigators (n=34). The initial set open for vote included 94 questionnaires targeting adult and child psychiatry, sleep and addiction. RESULTS: Two questionnaire rounds were completed with 94% participation in the first round and 100% participation in the second round. The results of the Delphi survey incorporated the consensus opinion of the 32 members who completed both rounds. Nineteen of the 94 questionnaires achieved consensus at the first round and seventy of 75 at the second round. The five remaining questionnaires were submitted to three experts involved in the steering committee during a dedicated meeting. At the end, 24 questionnaires were retained in the mandatory and 26 in the optional questionnaire set. CONCLUSIONS: A validated data collection set of questionnaires is now available to assess psychiatry, addiction, sleep and chronobiology dimensions of depressive disorders.

Chiari malformation and sleep related breathing disorders.

OBJECTIVE: To estimate the frequency, mechanisms and predictive factors of sleep apnoea syndrome (SAS) in a large group of children and adults with type I (CMI) and II (CMII) Chiari malformation (CM). BACKGROUND: The anatomical and functional integrity of both respiratory circuits and lower cranial nerves controlling the upper airway is necessary for breathing control during sleep. These latter structures may be altered in CM, and a few investigations have reported CM related sleep disordered breathing. METHODS: Forty-six consecutive unrelated patients with CM (40 CMI, six CMII), of which 20 were children (eight males) and 26 were adults (12 males), underwent physical, neurological and oto-rhino-laryngoscopic examination, MRI and polysomnography. RESULTS: SAS was present in 31 (67.4%) of the patients with CM (70% of CMI, 50% of CMII, including mainly children). Sixty per cent of children with CM exhibited SAS, including 35% with obstructive (OSAS) and 25% with central (CSAS) sleep apnoea syndrome. SAS was observed in 73% of CM adults (57.7% OSAS, 15.4% CSAS). Severe SAS was found in 23% of CM adults. Multiple regression analysis revealed that age, type II Chiari and vocal cord paralysis predicted the central apnoea index. CONCLUSION: SAS is highly prevalent in all age groups of patients suffering from CM. CSAS, a rare condition in the general population, was common among the patients with CM in our study. Sleep disordered breathing associated with CM may explain the high frequency of respiratory failures observed during curative surgery of CM. Our results suggest that SAS should be systematically screened for in patients with CM, especially before surgery.

Hypocretin-1 modulates rapid eye movement sleep through activation of locus coeruleus neurons.

The hypocretins (hcrts), also known as orexins, are two recently identified excitatory neuropeptides that in rat are produced by approximately 1200 neurons whose cell bodies are located in the lateral hypothalamus. The hypocretins/orexins have been implicated in the regulation of rapid eye movement (REM) sleep and the pathophysiology of narcolepsy. In the present study, we investigated whether the locus coeruleus (LC), a structure receiving dense hcrtergic innervation, which is quiescent during REM sleep, might be a target for hcrt to regulate REM sleep. Local administration of hcrt1 but not hcrt2 in the LC suppressed REM sleep in a dose-dependent manner and increased wakefulness at the expense of deep, slow-wave sleep. These effects were blocked with an antibody that neutralizes hcrt binding to hcrt receptor 1. In situ hybridization and immunocytochemistry showed the presence of hcrt receptor 1 but not the presence of hcrt receptor 2 in the LC. Iontophoretic application of hcrt1 enhanced the firing rate of LC neurons in vivo, and local injection of hcrt1 into the LC induced the expression of c-fos in the LC area. We propose that hcrt receptor 1 in the LC is a key target for REM sleep regulation and might be involved in the pathophysiological mechanisms of narcolepsy.

Rapid eye movement sleep induction by vasoactive intestinal peptide infused into the oral pontine tegmentum of the rat may involve muscarinic receptors.

In rats, rapid eye movement sleep can be induced by microinjection of either the cholinergic agonist carbachol or the neuropeptide vasoactive intestinal peptide into the oral pontine reticular nucleus. Possible involvement of cholinergic mechanisms in the effect of vasoactive intestinal peptide was investigated using muscarinic receptor ligands. Sleep-waking cycles were analysed after infusion into the oral pontine reticular nucleus of vasoactive intestinal peptide (10 ng in 0.1 microl), carbachol (20 ng), atropine (200 ng) and pirenzepine (50, 100 ng), performed separately or in combination at 15-min intervals. The increase in rapid eye movement sleep due to the combined infusion of vasoactive intestinal peptide and carbachol (+58.7+/-4.6% for 8 h, P<0.05) was not significantly different from that induced by each compound separately. The enhancement of rapid eye movement sleep by vasoactive intestinal peptide was totally prevented by infusion of atropine, but not pirenzepine, a relatively selective M1 antagonist. On their own, none of the latter two compounds affected the sleep-waking cycle. Quantitative autoradiographic studies using [3H]quinuclidinyl benzylate (1 nM) and pirenzepine (0.5 microM) indicated that muscarinic receptors correspond to pirenzepine-insensitive binding sites in the oral pontine reticular nucleus. In vitro, vasoactive intestinal peptide (1-100 nM) significantly increased (+30-40%) the specific binding of [3H]quinuclidinyl benzylate to the oral pontine reticular nucleus in rat brain sections. This effect appeared to be due to an increased density, with no change in affinity, of pirenzepine-insensitive binding sites in this area. These data suggest that pirenzepine-insensitive muscarinic binding sites are involved in the induction of rapid eye movement sleep by vasoactive intestinal peptide at the pontine level in the rat.

Vasoactive intestinal polypeptide microinjections into the oral pontine tegmentum enhance rapid eye movement sleep in the rat.

Rapid eye movement sleep can be elicited in the rat by microinjection of the cholinergic agonist carbachol into the oral pontine reticular nucleus. Intracerebroventricular administration, during the light period, of vasoactive intestinal peptide enhances rapid eye movement sleep in several species. Since this peptide is co-localized with acetylcholine in many neurons in the central nervous system, it was assumed that the oral pontine tegmentum could also be one target for vasoactive intestinal peptide to induce rapid eye movement sleep. This hypothesis was tested by recording the sleep-wakefulness cycle in freely-moving rats injected with vasoactive intestinal peptide or its fragments (1-12 and 10-28) directly into the oral pontine reticular nucleus. when administered into the posterior part of this nucleus, vasoactive intestinal peptide at 1 and 10 ng (in 0.1 microliter of saline), but not its fragments, induced a 2-fold enhancement of rapid eye movement sleep during 4 h, at the expense of wakefulness. At the dose of 10 ng, a significant increase in rapid eye movement sleep persisted for up to 8 h. Moreover, when the peptide was injected into the centre of the positive zone, rapid eye movement sleep was enhanced during three to eight consecutive days. These data provide the first evidence that rapid eye movement sleep can be elicited at both short- and long-term by a single intracerebral microinjection of vasoactive intestinal peptide. Peptidergic mechanisms, possibly in association with cholinergic mechanisms, within the caudal part of the oral pontine reticular nucleus may play a critical role in the long-term regulation of rapid eye movement sleep in rats.

Induction of rapid eye movement sleep by carbachol infusion into the pontine reticular formation in the rat.

Cholinergic regulation of sleep and wakefulness was studied in freely moving rats locally infused with various doses of carbachol into the pontine reticular formation. Induction of REM sleep occurred when carbachol was infused specifically into the posterior oral pontine reticular nucleus (PnO). This effect was observed with 1-10 ng of carbachol, and lasted for at least 6 h. It was antagonized by atropine (100-200 ng) infused into the same site 15 min before carbachol (10 ng), indicating that REM sleep induction resulted from the stimulation of pontine muscarinic receptors. High doses of carbachol (500 ng) did not affect REM sleep but enhanced wakefulness. Cholinergic mechanisms within the PnO may play a critical role in the regulation of REM sleep in the rat.

Non-invasive measurement of haemodynamics during sleep apnoea.

Sleep apnoeas are accompanied by large variations in heart rate (HR) and blood pressure (BP). This nocturnal variability in BP may be involved in the increased cardiovascular morbidity of these patients. Due to the complex interaction between asphyxia, intrathoracic pressure, cardiac function and autonomic activation, the exact haemodynamic mechanisms are unclear. To evaluate the components of the BP surges at resumption of breathing (RB) a non-invasive beat-to-beat measurement was taken of cardiac output (CO) by the pulse contour analysis of the Finapres signal. Six male normotensive patients, free of medication (37-60 y, BMI 26.5-43.0 kg m-2) were studied during polysomnography (apnoea index: 22-69 h-1). Systolic blood pressure rose from 126.5 +/- 1.3 mmHg at beginning apnoea (P1) to 140.4 +/- 1.3 at RB (P < 0.01, ANOVA). During sleep Stages 2 and 3, stroke volume decreased during RB to 96% of P1 value (NS). Due to an opposite change in HR, CO tended to rise at RB to 106% of P1. Computed total peripheral resistance rose during RB to 105% of P1 value (P < 0.011. Therefore, it is concluded that the surge in BP at RB after apnoea is due to concomitant increases in CO and in TPR. Both rises are presumably a consequence of sympathetic nervous activation by the arterial chemoreceptors.

[Verbal fluency and EEG coherence in Alzheimer's disease]. / Fluidité verbale et cohérence EEG dans la maladie d'Alzheimer.

EEG coherence of 16 derivations and a verbal fluency test were evaluated on 25 ambulatory patients suffering from Alzheimer's disease (age: 74 +/- 5.7). The aim of the study was to analyze coherence rate variations from different cortical areas in relation to the performance in the test. Coherence rates of each derivation with the other ones were calculated for four frequency bands from 0.5 to 13.5 Hz. Arithmetic averages of these rates were then calculated to obtain scalp averaged coherence rates. The patients were submitted to a verbal fluency test and divided into two groups according to their test score as compared to normative data: impaired (n = 10) and not impaired (n = 15). Results showed that averaged coherence rates of theta and alpha 1 frequency bands were significantly depressed in the impaired group in comparison with those of the not impaired group. Two cortical areas were concerned with this difference, the left temporo-occipital and frontal zones, in an independent way for the same subject. Moreover, we observed that the patients who where impaired in the verbal fluency test, also presented a significantly greater ancientness of the clinical symptoms as compared to the not impaired patients.

[Nasal obstruction and compliance to nasal positive airway pressure]. / Obstruction nasale et compliance à la ventilation nasale à pression positive.

UNLABELLED: Obstructive sleep apnea syndrome is a very common disease. Nasal continuous positive airway pressure is a useful and efficient treatment but compliance depends on several factors including the degree of nasal obstruction. OBJECTIVES: The aim of this study was to evaluate the effects of surgical correction of nasal obstruction on compliance to nasal continuous positive airway pressure in obstructive sleep apnea syndrome. MATERIAL AND METHODS: This retrospective study (from March 1998 to March 2000) included ten patients suffering from a severe obstructive sleep apnea syndrome (apnea-hypopnea index greater than 30 per hour) treated by nasal continuous positive airway pressure for at least three months and presenting an anatomic nasal obstruction limiting the use of nasal continuous positive airway pressure. Surgical procedures included one septoplasty, two inferior turbinectomies and seven septoplasties with turbinectomies. RESULTS: The post-operative polysomnography showed that surgical correction of nasal obstruction had no effect on obstructive sleep apnea syndrome severity (no significative change of apnea hypopnea index after surgery) but allowed the use of lower nasal continuous positive airway pressure levels (7.1 mmHg after surgery versus 10 mmHg before) and improved compliance to treatment (six compliant patients after surgery versus no compliant patient before). These results were compared with those published in the literature. CONCLUSION: An examination of the nose has to be performed before initiating nasal continuous positive airway pressure. If nasal continuous positive airway pressure cannot be tolerated because of nasal obstruction, surgery is required to improve compliance and tolerance to treatment.

Ambulatory monitoring of blood pressure disturbs sleep and raises systolic pressure at night in patients suspected of suffering from sleep-disordered breathing.

1. The aim of the study was to assess the effect of ambulatory monitoring of blood pressure on sleep and on blood pressure in middle-aged patients. 2. Nine consecutive patients (seven men, two women; mean age 57 years) complaining of snoring and various degrees of excessive daytime somnolence were studied. Five patients were normotensive and four were being treated for hypertension. During one night standard laboratory polysomnography was performed with monitoring of blood pressure by a silent ambulatory monitor and continuous infrared blood pressure by photoplethysmography. 3. Ambulatory blood pressure significantly disturbs sleep architecture, causing EEG arousals in 64% of measurements, and induces a significant rise in blood pressure during systolic pressure measurement by the ambulatory monitor (rise in systolic pressure, 13.7 +/- 15.9 mmHg, P < 0.001; rise in diastolic pressure, 3.7 +/- 8.2 mmHg, P < 0.01). At the time of diastolic measurement, blood pressure had returned to the preinflation value. The rise in systolic blood pressure was higher when an arousal was associated with cuff inflation (P < 0.001). This rise in blood pressure is probably the consequence of sympathetic nervous system activation. 4. We conclude that ambulatory blood pressure recordings of systolic blood pressure during sleep should be interpreted with caution as systolic blood pressure may be significantly increased in patients suspected of suffering from sleep-disordered breathing.

Long-term enhancement of REM sleep by the pituitary adenylyl cyclase-activating polypeptide (PACAP) in the pontine reticular formation of the rat.

In rats, rapid eye movement (REM) sleep can be elicited by microinjection of vasoactive intestinal polypeptide (VIP) into the oral pontine reticular nucleus (PnO). In the present study, we investigated whether this area could also be a REM-promoting target for a peptide closely related to VIP: the pituitary adenylyl cyclase-activating polypeptide (PACAP). When administered into the posterior part of the PnO, but not in nearby areas, of freely moving chronically implanted rats, PACAP-27 and PACAP-38 (0.3 and 3 pmol) induced a marked enhancement (60-85% over baseline) of REM sleep for 8 h that could be prevented by prior infusion of the antagonist PACAP-(6-27) (3 pmol) into the same site. Moreover, injections of PACAP into the centre of the posterior PnO resulted in REM sleep enhancement which could last for up to 11 consecutive days. Quantitative autoradiography using [125I]PACAP-27 revealed the presence in the PnO of specific binding sites with high affinity for PACAP-27 and PACAP-38 (IC50 = 2.4 and 3.2 nM, respectively), but very low affinity for VIP (IC50 > 1 microM). These data suggest that PACAP within the PnO may play a key role in REM sleep regulation, and provide evidence for long-term (several days) mechanisms involved in such a control. PAC1 receptors which have a much higher affinity for PACAP than for VIP might mediate this long-term action of PACAP on REM sleep.

Muscarinic and PACAP receptor interactions at pontine level in the rat: significance for REM sleep regulation.

Cholinergic and PACAPergic systems within the oral pontine reticular nucleus (PnO) play a critical role in REM sleep generation in rats. In this present work, we have investigated whether REM sleep enhancement induced by carbachol (a cholinergic agonist) or PACAP, depends on an interaction between muscarinic and PACAP receptors. This hypothesis was tested by recording sleep-wake cycles in freely moving rats injected into the PnO with PACAP in combination with the muscarinic receptor antagonist atropine, or with carbachol in combination with the PACAP receptor antagonist PACAP6-27. When administered alone, PACAP (3 pmol) or carbachol (110 pmol) induced an enhancement of REM sleep during 8 h (+61%, n = 8; +70%, n = 5), which was totally prevented by infusion of atropine (290 pmol) for PACAP, or of PACAP6-27 (3 pmol) for carbachol. Quantitative autoradiographic studies indicated that (i) PACAP (10-9-10-7 M) induced in the PnO an increase (+35%) of the specific binding of the muscarinic antagonist [3H]quinuclidinyl benzylate, which could be completely prevented by PACAP6-27 (IC50 = 8 x 10-8 M) and (ii) both carbachol and PACAP enhanced [35S]GTP-gamma-S binding in a concentration-dependent manner in the PnO. The maximal increase due to carbachol was significantly higher in the presence (+126%) than in the absence (+102%) of PACAP (0.1 microM). These data showed that interactions between muscarinic and PACAP receptors do exist within the PnO and play a role in the local mechanisms of REM sleep control in the rat.