daytime patterns of melatonin levels

P.l.b Basic and clinical neuroscience - Neuroanatomy and neurophysiology • Laboratory tests: liver function test, complete blood count, coagulation profile, renal function tests, fasting and post-prandial blood sugar, serum electrolyte level. • Electroencephalography (EEG): Recordings were performed using 16 channels Nicolet Biomed EEG apparatus under standardized conditions and during hyperventilation. Scalp electrodes were applied according to the standard 10-20 international system. The recording was done using TC: 0.3 Hz, HF: 70 Hz, sensitivity: 10 f-tV/mm and speed: 30mm/sec with bipolar and unipolar connections. Monitoring was done for one hour (on two or three separate sessions depending on the extent of patient cooperation) to record at least three hallucinatory behaviors typical for the patient. Patients have been educated about hallucinatory experiences and agreed about a sign to announce to the doctor at the start and the end of the hallucinatory experience. EEG abnormalities were categorized either focal, regional (contagious channels), multifocal hemispheric or generalized. The timing of the EEG change in relation to the period with hallucination was classified as concordant (when both events occur together), discordant (when both events do not occur together) and serniconcordant (when sometimes there is concordance between the two events and some other times either of them occur separately). EEG findings were classified as positive correlates and negative correlates. A positive EEG correlate was defined by any change against the background that is concordant or semiconcordant and repetitive with the hallucinatory phenomena, whether epileptiform or non epileptiform in nature. Negative correlate is defined when there are no EEG changes or continuous EEG changes or transient EEG changes discordant with the hallucinatory phenomena. Results: Concerning the case group, ten patients had single modality auditory hallucinations, and 5 had multimodaliy hallucinations (auditory hallucinations combined with other modalities; four patients with additional visual and one patient with additional tactile hallucinations). There were no statistically significant differences between the cases and controls as regards the age at onset of paranoid schizophrenia, the age at recruitment, the duration of the disease, sex and antipsychotic therapy. Among the case group, EEG recording during hallucinatory behavior showed positive electrographic correlates in 9 patients (60%) and negative electrographic correlates in 6 patients (40%). EEG findings were epileptiform in 6/15 patients (40%). All the epileptiform EEG were among the group of patients with positive correlates. All EEG findings were either in the frontal or temporal lobe or in both lobes. Of the focal EEG findings, 6/10 patients (60%) had bilateral abnormalities and 4 (40%) had right sided abnormalities. The case group had a statistically significant more EEG abnormalities than the control group (p < 0.05) and 40% of them had epileptiform EEG abnormalities in contrast to none of the control group (p < 0.05). Among the case group, there was no statistically significant correlation between the age of onset of the disease, duration of the disease, sex, type of antipsychotic therapy, modality of hallucination, and EEG findings. Conclusion: A significant number of paranoid schizophrenic patients with hallucinations have EEG correlates and that can help in understanding the pathophysiology of these hallucinations. In addition, it may shed light on the relation between psychosis and epilepsy. References [1] Lee S, Wynn J, Green M, et al. 2006 Quantitative EEG and low resolution electromagnetic tomography (LORETA) imaging of patients with persistent auditory hallucinations. Schizophrenia Research 2006; 83: 111-119.

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[2] Gaser C, Nenadic I, Vo1z lIP, et al. 2004 Neuroanatomy of 'hearing voices': a frontotemporal brain structural abnormality associated with auditory hallucinations in schizophrenia. Cereb Cortex 2004; 14: 91-96. [3] Ishii R, Shinosaki K, Ikejiri Y, et al. Theta rhythm increases in left superior temporal cortex during auditory hallucinations in schizophrenia: a case report. Neuroreport 2000; 11: 3283-3287.

1P.1.b.0021 Night-time/daytime and daytime/daytime patterns of melatonin levels A.L. Morera1 " P. Abreu-Gonzalez2, A. Orozco-Sanmartin 1 , M. Henry 1 , A. Guerra-Reyes 1 , A. Garcia-Hernandez3 , L. Fernandez-Lopez3, C.R. Morales-Garcia4 , E. Diaz-Mesa5 , J. Monzon-Diaz4 . 1 Universidad de La Laguna. Facultad de Medicina, Medicina Interna Dermatologia y Psiquiatria, Santa Cruz de Tenerife, Spain; 2 Universidad de La Laguna. Facultad de Medicina, Fisiologia, Santa Cruz de Tenerife, Spain; 3 Universidad de La Laguna, Enfermeria, Santa Cruz de Tenerift, Spain; 4Hospital Universitario de Canarias, Psiquiatria, Santa Cruz de Tenerift, Spain; 5Hospital Universitario de la Candelaria, Psiquiatria, Santa Cruz de Tenerift, Spain Background: The existence of a circadian rhythm of melatonin (MLT) secretion is well known. Several methodological variables, such as body posture [1] or seasonality [2], bias the results on MLT research. Studying the circadian rhythm of MLT is difficult because of the necessity of frequent sampling. As an alternative method, sampling at 09:00, 12:00 and 24:00 hours has been proposed [3]. The aim of this paper consists of describing serum MLT levels in a sample of healthy subjects. Methods: 24 healthy subjects took part in the study. The study protocol was approved by the Ethical and Research Committee of the University of La Laguna. All subjects gave written informed consent before inclusion. The study was carried out in a week-end in July 2007. After a night of fasting, the subjects arrived at the experimental centre at 08:00 hours, they went to bed and stayed in a supine posture until 09:00 hours, when a sample of blood was extracted by venipuncture. Then, the subjects had breakfast and at 11 :00 hours again they went to bed and stayed in a supine position until 12:00 hours, when a second sample of blood was extracted. At 23:00 hours the subjects went to bed and stayed in supine position. The third blood sample was extracted at 24:00 hours. At 23:00 the eyes of each subject were covered with a mask in order to avoid light contamination. Room light illumination intensity was of 4 lux. Night blood extraction was carried out with the help of a lantern with red light. After each extraction, blood was centrifuged at 3000 rpm for ten minutes; then serum was separated and aliquot in eppendorf tubes. Eppendorf tubes were kept frozen at -30° until biochemical analysis. The biochemical analysis was carried out in one batch. MLT levels were measured using ELISA commercial kits (IBL, Hamburg, Germany). The analyst was blind regarding the time ofblood collection. Statistical analysis was carried out with the Social Statistical Package for the Social Sciences (SPSS, Illinois, Chicago, USA). Time effect on MLT levels were carried out by means of a general linear model for repeated measures. Multiple posterior pair comparisons were carried out taking into account the Bonferroni test correction. Results: MLT level comparisons among 09:00, 12:00 and 24:00 hours is presented in the table. Pairs multiple posterior comparisons corrected by means of the Bonferroni test produced a significant difference at the level of p < 0.0001 among the three time MLT comparisons.

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Conclusions: MLT secretion presents a clear daytime-nighttime pattern. There is also a daytime-daytime pattern of MLT secretion. When researching on MLT a careful selection of blood times sampling should be taken into account.

MLT9 MLT12 MLT24

Mean

Standard deviation

F

6.37 2.40 25.14

4.80 1.54 17.88

0.0001

MLT9: Melatonin level at 09:00 hours; MLT12: Melatonin level at 12.00 hours; MLT24: Melatonin level at 24:00 hours.

References [1] Deacon S, Arendt 1. Posture influences melatonin concentrations in plasma and saliva in humans. Neurosci Lett. 1994;167:191-4. [2] Morera AL, Abreu P. Seasonality of psychopathology and circannual melatonin rhythm. J Pineal Res. 2006;41:279-83. [3] Morera AL. Abreu-Gonzalez P. Henry M. Melatonin as a biological marker in schizophrenia. In: Neuropsychiatric biomarkers, endophonotype, and genes: Promises, advances and challenges. Michael S. Ritsner Ed. Springer. 2009;591--603

Ip.1.b.0031Is diurnal variation in plasma brain-derived neurotrophic factor level sex-related? S. Choi 1 ., J. Ahn1 , S. Bang1 . Psychiatry, Ulsan, South-Korea

1 Ulsan

University Hospital,

Purpose of the study: Diurnal changes of brain-derived neurotrophic factor (BDNF) mRNA and protein contents have been demonstrated in the rat central nervous system [1]. However, there are only two studies at present in the literature investigating a possible BDNF circadian rhythm in human [2,3]. In the present study, we aimed to investigate the presence of a possible diurnal variation of plasma and serum BDNF levels in healthy subjects of both sexes. Methods used: In this study, we included healthy 18 male and 7 female volunteers. Participants were a relatively homogenous set of adults of both sexes, and were requested to adhere to the protocol to minimize the influence of lifestyle variables according to the previous study [3]. In order to investigate the presence of a diurnal rhythm of plasma and serum BDNF, blood from each subject was collected at three different clock times (Le., 09:00h [tIl, 13:00 h ([t2], and 17:00 h [13]), and plasma and serum BDNF level were measured in all samples. BDNF was determined by ELISA method. In previous studies several factors including age, body mass index (BMI), diet, alcohol and smoking have been found to influence peripheral BDNF levels. We have therefore used physician's interview forms and standardized questionnaires (AUDIT: Alcohol Use Disorder Identification Test, FTND: Fagerstrom Test for Nicotine Dependence) to obtain information regarding each subject's history of alcohol and smoking. The BMI index of each participant was calculated. Two-way, repeated-measures ANOYA were carried out to examine the three distinct time of BDNF level, with time and sex being the between-subject factors, followed by Tukey's post hoc testing. Pertinent demographic, BMl, the scores of AUDIT and FTND were entered as covariates. Summary of results containing real data and appropriate statistical assessments: We detected significant diurnal variation in plasma BDNF level in men (F = 5.85; p=0.007), with a trend of

constant decrease during the day. In men, plasma BDNF concentrations (mean±SD, ng/ml) were 2.63±1.45 at 09:00h, 1.74±0.94 at 13:00h and 1.61±1.l6 at 17:00h. Post-hoc comparisons showed the BDNF level significantly decreased between 09:00 and 13:00 h (p=0.025) but not between 13:00 and 17:00 h (p=0.918). In women, no diurnal variation was observed (1.02±0.23 at 09:00 h, 0.94±0.25 at 13:00 h, and 1.03±.0.58 at 17:00 h) in plasma. In addition, we could not found diurnal variation in serum BDNF level in both men (19.60±6.36 at 09:00h, 20.04±5.97 at 13:00h and 19.93±6.48 at 17:00h) and women (13.58±7.06 at 09:00h, 13.18±4.87 at 13:00h and 13.66±3.98 at 17:00h). Conclusions: In conclusion, we demonstrated that sex difference have a specific impact on diurnal variation in plasma BDNF level. We detected significant diurnal variation in plasma BDNF level in men. By contrast, we could not found diurnal variation either in plasma BDNF of women, or in serum BDNF level in both men and women. References [1] Dolci, C., Montaruli, A., Roveda, E., Barajon, 1., Vizzotto, L., Grassi Zucconi, G., Carandente, E, 2003 Circadian variations in expression of the trkB receptor in adult rat hippocampus. Brain Res 994, 67-72. [2] Begliuomini, S., Lenzi, E., Ninni, E, Casarosa, E., Merlini, S., Pluchino, N., Valentino, v., Luisi, S., Luisi, M., Genazzani, AR., 2008 Plasma brain-derived neurotrophic factor daily variations in men: correlation with cortisol circadian rhythm. J Endocrinol 197,429-435. [3] Piccinni, A., Marazziti, D., Del Debbio, A., Bianchi, C., Roncaglia, 1., Mannari, C., Origlia, N., Catena Dell'Osso, M., Massimetti, G., Domenici, L., Dell'Osso, L., 2008 Diurnal variation of plasma brainderived neurotrophic factor (BDNF) in humans: an analysis of sex differences. Chronobiol Int 25, 819-826.

1P.1.b.0041 Ultradian regulations: relationships between sleep EEG power spectra and REM-NREM sleep cycles D. Neu1 " O. Le Bon2 , L. Staner3, P. Linkowski4 . 1Brugmann University Hospital Universite Libre de Bruxelles, Sleep Laboratory and Unit for Chronobiology U78 Department of Psychiatry, Brussels, Belgium; 2Tivoli University Hospital Universite Libre de Bruxelles, Department of Psychiatry, La Louviere, Belgium; 3 Centre Hospitalier Rouffach, Forenap, Rouffach, France; 4 University Clinics of Brussels UL.B., Department ofPsychiatry, Brussels, Belgium Introduction: Links between REMS (Rapid Eye Movement Sleep) and consecutive NREMS (Non-REMS) episode durations were described previously in mice [1], rats [2], cats, monkeys and humans [3]. These relationships are crucial in the understanding of the regulation and neurophysiology of the sleep ultradian alternation. They have been interpreted as a sign of short-term REMS homeostasis, where, according to divergent interpretations, REMS duration determines the duration of the next NREMS episode, or the timing to the next REMS episode. No study so far has used NREMS intensity (Slow Wave Activity, SWA) in these comparisons. The present study is a replication ofthe abovementioned studies, using SWA instead ofNREMS duration in the comparisons. Purpose/Objective: The aim of the present study was to investigate the existing links between quantitative sleep EEG spectral power bands and contiguous REMS and NREMS episodes. The main outcome measure was the relationship between ultradian cycles and slow wave activity (SWA), five other power bands were analyzed descriptively.