Melatonin attenuates antipsychotic metabolic effects: an eight-week randomized, double-blind, parallel-group, placebo-controlled clinical trial.

OBJECTIVE: Second-generation antipsychotics (SGAs) are among the first-line treatments for bipolar disorder and schizophrenia, but have a tendency to generate metabolic disturbances. These features resemble a metabolic syndrome for which a central autonomic imbalance has been proposed that may originate from the hypothalamic suprachiasmatic nuclei. In a clinical trial, we hypothesized that melatonin, a hormone that regulates the suprachiasmatic nucleus, could attenuate SGA-induced adverse metabolic effects. METHODS: In an eight-week, double-blind, randomized, placebo-controlled, parallel-group clinical trial, we evaluated the metabolic effect of melatonin in SGA-treated patients in terms of weight, blood pressure, lipid, glucose, body composition, and anthropometric measures. A total of 44 patients treated with SGAs, 20 with bipolar disorder and 24 with schizophrenia, randomly received placebo (n = 24) or melatonin 5 mg (n = 20). RESULTS: The melatonin group showed a decrease in diastolic blood pressure (5.1 versus 1.1 mmHg for placebo, p = 0.003) and attenuated weight gain (1.5 versus 2.2 kg for placebo, F = 4.512, p = 0.040) compared to the placebo group. The strong beneficial metabolic effects of melatonin in comparison to placebo on fat mass (0.2 versus 2.7 kg, respectively, p = 0.032) and diastolic blood pressure (5.7 versus 5.5 mmHg, respectively, p = 0.001) were observed in the bipolar disorder and not in the schizophrenia group. No adverse events were reported. CONCLUSIONS: Our results show that melatonin is effective in attenuating SGAs' adverse metabolic effects, particularly in bipolar disorder. The clinical findings allow us to propose that SGAs may disturb a centrally mediated metabolic balance that causes adverse metabolic effects and that nightly administration of melatonin helps to restore. Melatonin could become a safe and cost-effective therapeutic option to attenuate or prevent SGA metabolic effects.

Depressive symptomatology is influenced by chronotypes.

BACKGROUND: Rhythm disturbances are a frequent clinical manifestation of depression. In recent years a possible relationship between depression and chronotypes has emerged. Specifically eveningness has been proposed as vulnerability factor. The aim of this study was to describe sleep features of depressed patients according to chronotypes and to explore possible associations with the clinical features of depressive episodes. METHODS: 100 patients diagnosed with Major Depressive Disorder according to the Mini International Neuropsychiatric Interview (MINI) were included (age: 34+/-11.74, range: 18-60 years; female/male:79/21). At admission the Hamilton Rating Scale for Depression (HRSD) was administered. Patients were also administered the Morningness-Eveningness Questionnaire (MEQ), the Epworth Sleepiness Scale, the Athens Insomnia Scale and the Pittsburgh Sleep Quality Index. RESULTS: According to MEQ scores patients were classified in three groups: a) eveningness (n=18), b) neither (n=61) and c) morningness type (n=21). The age was different among chronotypes, being morningness-type patients older. The eveningness-type group showed higher scores in suicidal thoughts, more impaired work and activities, higher paranoid symptoms, higher scores on the anxiety cluster (HRSD), while the morningness-type group showed lower proportion of melancholic symptoms (MINI). We did not find association between sleep parameters and specific chronotypes. LIMITATIONS: The relatively small sample size and the concurrent assessment of chronotypes and depression may have biased our findings. CONCLUSIONS: Our data suggest the idea that chronotypes have an impact on depressive episodes features, with higher severity for the eveningness-type.

Crianza y esquizofrenia

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Abstract: Introduction. Schizophrenia is a chronic psychotic disorder whose prevalence in adults is from 0.5 to 1.5%, and its annual incidence ranks from 0.5 to 5 by each 10,000 inhabitants. Antipsychotic medications have shown to be effective in the treatment of acute psychosis and the prevention of relapse for persons suffering form schizophrenia. However, most of them have not shown to be able to correct fully the alterations in social and labor adjustment. Several studies -refering to the most important advances of the last years regarding this pathology, emphasize the necessity to know which are the psycho-social factors that participate in schizophrenia in order to prevent psychotic relapses and re-hospitalization. Approaches tending to find out the influence of the familiar surroundings have been limited by methodological matters. Although it is certain that attachment has been studied to understand the influence of the raising, in the evolutionary process of the personality and of some mental disorders, little is known about the early parental relations of the schizophrenic. Objectives. 1. To compare the description of the raising made by the schizophrenic patients in remission, with that made by healthy subjects with similar sociodemographic characteristics; 2. To compare the pattern of raising described by the hospitalized schizophrenic patient while presenting acute manifestations of psychosis, with that described once that such manifestations have been controlled; 3. To determine the relation and participation of the dimensions of the raising in regard to schizophrenia and its evolution. Methodology. An explanatory nonexperimental transeccional correlacional causal study was made. The sample was formed by the 23 schizophrenic patients hospitalized in the Instituto Nacional de Psiquiatría during the second semester of 2003, and by a control group formed by 50 healthy subjects with similar socio-demographic characteristics. The schizophrenic patients were evaluated through a clinical history and the application of The Positive and Negative Syndrome Scale (PANSS) and The Parental Bonding Instrument (PBI)(formed by two dimensions: 1. warmth; 2. distance and emotional coldness). These instruments were applied within the first five later days to their hospitalization and within the five previous days to their discharge by improvement. The control group was evaluated only on one occasion. A brief interview was made to collect some sociodemographic data and The Parental Bonding Instrument (PBI) was applied. Results. In order to determine the existing differences in the perception of the paternal and maternal raising between the group of schizophrenic patients in remission and the control group, a t test for independent samples was made. As established in the first hypothesis, significant differences in both groups were found, but only in the dimension paternal of distance and emotional coldness (p = .03) and maternal distance and emotional coldness (p = .000). With the purpose of determining the differences in the perception of the raising by the schizophrenic patients while suffering from acute psychosis and once they were in remission, the punctuation of the paternal and maternal PBI of admission and discharge were compared. In the maternal raising it was observed, in spite that both dimensions scored higher at the discharge, that distance and emotional coldness did not show significant changes. Warmth scored significantly higher at discharge (p = .003). In the case of perception of the parental raising, warmth (p = .001) as will as distance and emotional coldness (p = .02) scored significantly higher at the time of discharge. When analyzing with more detail the items of PBI that showed a significant change with the improvement of acute psychosis, it was observed that in the paternal warmth those were items 5 (p = .008), 7 (p = .021), 11 (p = .015), 12 (p = .049) and 17 (p = .047). As to distance and emotional coldness the items that changed were 16 (p = .002), 18 (p = .004) and 23 (p = .012). In the case of maternal warmth, the items that showed a significant change with the improvement of acute psychosis were 3 (p = .03) and 13 (p = .004). In distance and emotional coldness, only number 14 (p = .015) changed. Of the items of paternal being up that showed a significant change at the time of discharge, it was observed that item 5 had direct relation with the positive symptoms of discharge (p = .03); 7 with the positive symptoms of discharge (p = .01), the general psychopathology of discharge (p = .029) and the total qualification of the PANSS of discharge (p = .012); 11 with the positive symptoms of discharge (p = .04), the general psychopathology of discharge (p = .045) and the total qualification of the PANSS of discharge (p = .037); 12 with the positive symptoms of discharge (p = .003), the general psychopathology of discharge (p = .006) and the total qualification of the PANSS of discharge (p = .009); 18 with the general psychopathology of discharge (p = .041). With respect to the maternal raising it was observed that only number 13 correlated with the positive symptoms of admission (p = .014). In order to determine the relation between these dimensions with the variables and evolution of schizophrenia, a correlation of Pearson was made. In the paternal raising, Warmth (admission) correlated positively with the positive symptoms (admission) (p = .032). Warmth (discharge) was negatively correlated with the positive symptoms (admission) (p = .032) and the number of hospitalizations (p = .034). The paternal Distance and Emotional Coldness (admission) correlated negatively with the age of beginning of the schizophrenia (p = .04), and positively with time of evolution of the disease (p = .048). Distance and emotional coldness (discharge) did not have correlation. With respect to the maternal raising, warmth (admission) was positively correlated with the punctuation of general psychopathology (admission) (p = .032) and the years of study of the patient (p = .026). Distance and Emotional Coldness (admission) did not correlate significantly, nevertheless at the time of discharge did it positively with years of study (p = .03). In order to deter mine if the dimensions of the raising could predict the symptoms of the schizophrenic patient at the time of discharge, a multiple regression analysis was made. It was found that the positive symptoms could be predicted in 41.5% (R2 = .415) through the punctuation of the paternal Distance and Emotional Coldness (admission) (P = .510) and paternal Warmth (discharge) (P = -.622). Negative symptoms were not influenced neither by the paternal raising, nor by the maternal one. The punctuation of the scale of general psychopathology of the PANSS could be predicted in 26.3% (R2 = .263) through maternal warmth (P = -1.01) (discharge) and maternal distance and emotional coldness (P = .805) (discharge). The total qualification of the PANSS at the time of discharge could be predicted in 29.8% (R2 = .298) by maternal warmth (P = .516) (admission) and paternal Warmth (P = -.620) (discharge). The age in with the patient got sick could be predicted though the punctuation of the paternal distance and emotional coldness (P = -.625) (admission) and maternal warmth (P = .5) (discharge) in 44.8% (R2 = .448). The time of evolution could be predicted in 18.2% (R2 = .182) through paternal Distance and Emotional Coldness (P = .427) (admission). The number of hospitalizations was predicted in 37.5% (R2 = .375) by paternal Distance and Emotional Coldness (P = .543) (admission), maternal Warmth (P = -.916) (discharge) and maternal distance and emotional coldness (P = .811) (discharge). The number of days that was committed the patient at the moment of the evaluation could be predicted in 19.6% (R2 = .196) by paternal distance and emotional coldness (P = .484) (admission). Other variables, as the years of study were predicted in 18.6% (R2 = .186) by maternal warmth (P = .474) (admission). Conclusions. The schizophrenic patient in remission had a different perception of their parents than the control group. Schizophrenic patients perceived both parents colder and distant than the control group. In the particular case of first, it was observed that when improving the psychosis, also improved the perception of the raising. This one was related to the psychotic symptoms and other variables of the schizophrenia. These findings indicate the importance of the raising in the evolution of the schizophrenic patient.