Armando L. Morera-Fumero

S100B and schizophrenia

The research for peripheral biological markers of schizophrenia, although abundant, has been unfruitful. In the last 2 decades, the S100B protein has made its own room in this area of research. S100B is a calcium‐binding protein that has been proposed as a marker of astrocyte activation and brain dysfunction. Research results on S100B concentrations and schizophrenia clinical diagnosis are very consistent; patients with schizophrenia have higher S100B concentrations than healthy controls. The results regarding schizophrenia subtypes and clinical characteristics are not as conclusive. Age of patients, body mass index, illness duration and age at onset have been found to show no correlation, a positive correlation or a negative correlation with S100B levels. With respect to psychopathology, S100B data are inconclusive. Positive, negative and absence of correlation between S100B concentrations and positive and negative psychopathology have been reported. Methodological biases, such as day/night and seasonal variations, the use of anticoagulants to treat biological samples, the type of analytical technique to measure S100B and the different psychopathological scales to measure schizophrenia symptoms, are some of the factors that should be taken into account when researching into this area in order to reduce the variability of the reported results. The clinical implications of S100B changes in schizophrenia remain to be elucidated.

Prognostic Value of Malondialdehyde Serum Levels in Severe Sepsis: A Multicenter Study

Objective The oxidant/antioxidant state in septic patients has only been studied in small series. We wished to determine whether malondialdehyde (MDA) serum levels were associated with severity and 30-day mortality in a large series of patients with sepsis. Methods We performed an observational, prospective, multicenter study in six Spanish Intensive Care Units. Serum levels of MDA were measured in a total of 228 patients (145 survivors and 83 non-survivors) with severe sepsis and 100 healthy controls. Results Serum levels of MDA were higher in severe septic patients than in healthy controls. Non-surviving septic patients had higher MDA values than survivors. MDA serum levels were associated with severity markers (lactic acid, SOFA, APACHE-II) and coagulation indices. Regression analysis showed that MDA serum levels were associated with 30-day survival (Hazard ratio = 1.05; 95% confidence interval = 1.009–1.091; p = 0.016). Receiver operating characteristic analysis showed that the area under curve of MDA serum levels to predict 30-day survival was 0.62 (95% CI = 0.56–0.69; P = 0.002). The risk of death in septic patients with MDA serum levels above 4.11 nmol/mL was higher than in patients with lower values (Hazard Ratio = 2.43; 95% CI = 1.49–3.94; p<0.001). Conclusions The novel findings of our study on severe septic patients, to our knowledge the largest series providing data on the oxidative state, are that elevated MDA serum levels probably represent an unbalanced oxidant state and are related with poor prognosis in patients with severe sepsis.

Role of melatonin in schizophrenia.

Schizophrenia is a chronic mental disease that disturbs several cognitive functions, such as memory, thought, perception and volition. Schizophrenia’s biological etiology is multifactorial and is still under investigation. Melatonin has been involved in schizophrenia since the first decades of the twentieth century. Research into melatonin regarding schizophrenia has followed two different approaches. The first approach is related to the use of melatonin as a biological marker. The second approach deals with the clinical applications of melatonin as a drug treatment. In this paper, both aspects of melatonin application are reviewed. Its clinical use in schizophrenia is emphasized.

Summer/winter changes in serum S100B protein concentration as a source of research variance

BACKGROUND S100B is a calcium binding protein that can be measured in cerebral and extra cerebral biological tissues and fluids. Circadian and seasonal variations have been described in several biological molecules such as melatonin, cortisol and testosterone. Healthy subjects do not have a circadian rhythm of S100B. There is no information on seasonal variations of S100B levels. The aim of this research is to study whether healthy subjects present summer/winter changes in serum S100B protein concentrations. METHODS Ninety-eight subjects were studied in summer, of those, 64 participated in the winter evaluation. Blood was drawn by venipuncture at 09:00 h, 12:00 h and 00:00 h in summer and winter. Serum was separated from blood by centrifugation and stored at -70° until analysis. Serum S100B concentrations were measured by ELISA. RESULTS Serum S100B concentrations were significantly higher in summer than winter (09:00 h: 43.4 ± 24.6 ng/ml vs. 29.3 ± 22.7 ng/ml, p < 0.001; 12:00 h: 42.8 ± 25.0 ng/ml vs. 23.0 ± 22.1 ng/ml, p < 0.001; 00:00 h: 44.5 ± 23.2 ng/ml vs. 28.5 ± 24.6 ng/ml, p < 0.001). Age, gender, body mass index and time points when blood was extracted did not affect serum S100B concentrations neither in summer nor in winter. CONCLUSIONS Our results point to the fact that there is an important difference in serum S100B concentrations between summer and winter. It is strongly advisable to consider this summer/winter difference in serum S100B concentrations when researching into this area.

Low levels of serum total antioxidant capacity and presence at admission and absence at discharge of a day/night change as a marker of acute paranoid schizophrenia relapse

BACKGROUND An oxidant-antioxidant system dysregulation has been described as a schizophrenia pathophysiological base. The total antioxidant capacity (TAC) is one measure of the antioxidant capacity of a system. Day/night concentration changes is a biological characteristic of hormones such as melatonin or cortisol. There is no information about TAC day/night changes in schizophrenia. AIMS Studying the existence of a day/night TAC change in schizophrenia. METHOD Forty-three DSM-IV paranoid schizophrenia inpatients participated in the study. Thirty healthy subjects matched by age and gender acted as control group. Blood was sampled at 12:00 and 00:00h the day after admission and the day before discharge. Serum TAC was measured by the ABTS radical cation technique and expressed in Trolox mmol/L. RESULTS Patients had significantly lower TAC levels at admission and discharge (12:00 and 00:00) than controls. At admission patients had a TAC day/night change, with higher day-time than night-time levels (0.66±0.14 vs 0.60±0.15) as well as healthy subjects (0.83±0.07 vs 0.77±0.11). At discharge patients had a similar TAC level at 12:00 and 00:00 (0.64±0.15 vs 0.63±0.14). CONCLUSION Schizophrenic patients present a deficit of the antioxidant system. The initial presence and the later absence of a day/night change deserves future studies.

P03-317 - Agomelatine facilitates benzodiazepine discontinuation in schizophrenia with severe insomnia

We present the case of a schizophrenic patient with severe insomnia that had a partial response to high doses of benzodiazepines and sedating antipsychotics. Treatment with agomelatine allowed to suspend benzodiazepine treatment and restore quality of sleep. Case report Mr. Y is a 36 year old male patient diagnosed with simple schizophrenia that has complained of insomnia since the age of sixteen. During the last three years the treatment that the patient was following was stable and consisted of 100 mg of diazepam, 300 mg of levomepromazine and 120 mg of clotiapine every night. During the last year 60 mg of duloxetine were added to treat a moderate depression. His mood improved with the prescribed treatment, but eleven months later it worsened. In an attempt to simultaneously treat the mood and the sleep disorder, during a period of 4 days, a dosis of 12.5 mg of aglomelatin at dinner was introduced while the morning dose of duloxetine was reduced to 30mg. On the fifth day, agomelatine was increased to 25 mg at dinner while duloxetine was suspended. The antipsychotic treatment was kept stable while the patient was instructed to reduce 10 mg of diazepam every week until next appointment one month later. In the next appointment the patient had completely suspended diazepam one week before the appointment. The patient referred improved sleep quality and no rebound insomnia. Conclusion Agomelatine may be a valid treatment of insomnia in schizophrenia.

Day/night changes in serum S100B protein concentrations in acute paranoid schizophrenia

ABSTRACT There are day/night and seasonal changes in biological markers such as melatonin and cortisol. Controversial changes in serum S100B protein levels have been described in schizophrenia. We aim studying whether serum S100B levels present day/night variations in schizophrenia patients and whether S100B levels are related to psychopathology. Sixty‐five paranoid schizophrenic inpatients participated in the study. Psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS) at admission and discharge. Blood was drawn at 12:00 (midday) and 00:00 (midnight) hours at admission and discharge. Sixty‐five healthy subjects matched by age, gender and season acted as control group. At admission and discharge patients had significantly higher serum S100B concentrations at midday and midnight than healthy subjects. At admission, patients showed a day/night variation of S100B levels, with higher S100B levels at 12:00 than at 00:00 h (143.7 ± 26.3 pg/ml vs. 96.9 ± 16.6 pg/ml). This day/night difference was not present in the control group. Midday and midnight S100B at admission decreased when compared to S100B at discharge (midday, 143.7 ± 26.3 vs. 83.0 ± 12, midnight 96.9 ± 16.6 vs. 68.6 ± 14.5). There was a positive correlation between the PANSS positive subscale and S100B concentrations at admission. This correlation was not present at discharge. Conclusions: acute paranoid schizophrenia inpatients present a day/night change of S100B serum levels at admission that disappears at discharge. The correlation between serum S100B concentrations and the PANSS positive scores at admission as well as the decrease of S100B at discharge may be interpreted as an acute biological response to the clinical state of the patients. HIGHLIGHTSControversial changes in serum S100B proteins levels have been described in schizophrenia.Acute paranoid schizophrenia inpatients have a S100B serum day/night change at admission that disappears at discharge.The decrease of S100B at discharge may be interpreted as an acute biological response to the clinical state of the patients.

Day/Night and Summer/Winter Changes in Serum Total Antioxidant Capacity

Background: Seasonal and circadian changes are two factors described to affect blood levels of some biological molecules. The Total Antioxidant Capacity (TAC) is one global measure of the antioxidant capacity of a system. There is no agreement about the existence of day/night changes in TAC levels as well as there is no information about seasonal changes in TAC levels. Objective: The aims of this research are studying if there are summer/winter changes in TAC con-centrations or if TAC concentrations have day/night changes. Method: Ninety-eight healthy subjects took part in the summer study of whom 64 participated in the winter one. Blood was sampled at 09:00, 12:00 and 00:00 h. TAC was measured by the ABTS radi-cal cation technique. Results are expressed in mmol/L of trolox equivalents. Results: The subjects had significantly higher TAC levels in summer than winter at the three-time point studied. Summer 09:00 TAC concentration was significantly higher than the 12:00 and 00:00 h concentrations (1.34±0.26 vs 0.83±0.19, 0.75±0.18). Summer TAC 12:00 h concentrations were significantly higher than the 00:00 h concentrations (0.83±0.19 vs. 0.75±0.18). Winter 09:00 TAC concentrations were significantly higher than the 12:00 and 00:00 h concentrations (1.24±0.16 vs. 0.73±0.10, 0.67±0.13). There were no significant differences between the 12:00 and 00:00 h TAC concentrations. Conclusion: Strong methodological biases may be made if the seasonal and circadian changes in se-rum TAC concentration are not taken into account when researching in this area.

A three-month longitudinal study of changes in day/night serum total antioxidant capacity in paranoid schizophrenia

Free radicals and an oxidant/antioxidant imbalance have been involved in the schizophrenia pathophysiology. The total antioxidant capacity (TAC) is a measure of the antioxidant capacity of a system. Day/night changes are a biological characteristic of hormones such as melatonin or cortisol. There is little information about TAC day/night changes in schizophrenia patients. The aim of this research is to study if there are day/night changes in serum TAC levels of schizophrenia patients. Thirty-two DSM-IV schizophrenia paranoid patients were studied. Blood was sampled at 12:00 and 00:00 h at admission, discharge and three months after hospital discharge (TMAHD). TAC results are expressed as mmol of Trolox/L. Patients did not have day/night TAC differences at admission (12:00: 0.67±0.12 vs. 00:00: 0.61±0.14, p>0.14) or discharge (12:00: 0.65±0.15 vs. 00:00: 0.65±0.12, p>0.99). At TMHD, patients had significantly higher TAC levels at midday than midnight (12:00: 0.83±0.10 vs. 00:00: 0.74±0.12, p<0.006) as it has been reported in healthy subjects. There were no significant TAC differences at 12.00 and 00:00 between admission and discharge. At TMAHD, patients had significantly higher TAC levels than at admission and discharge, both at 12:00 and 00:00 h. In conclusion, the absence of day/night serum TAC changes when clinically relapsed and the normalization of day/night serum TAC changes at TMHD can be considered as a biological marker of schizophrenia evolution.

Psychiatric Symptoms and Personality Dimensions in Patients Younger Than 65 Years Admitted for Acute Coronary Syndrome

Instituto de Ciencias de la Salud, Universidad de la Coruña, A Coruña, Spain fibrillation. An update of the 2010 ESC Guidelines for the management of atrial fibrillation developed with the special contribution of the European Heart Rhythm Association Authors/Task Force Members. Eur Heart J. 2012;33: 2719–47. * Corresponding author: E-mail address: manuelp.anguita.sspa@juntadeandalucia.es (M. Anguita). Available online 27 April 2015