ABSTRACT
Abstract: Platelets llave serotonin (5-HT) uptake and storage mechanisms similar to those from neurons. In addition, they represent nearly 99% of blood 5-HT concentration. For these characteristics, platelets are considered useful biomarkers of the serotonergic synaptic neurotransmission, particularly in psychiatric disturbances such as depression. However, most studies which have evaluated platelet 5-HT concentrations in depression have not shown similar findings. It has been suggested that changes in plasma tryptophan (TRP) concentrations might modify 5-HT concentration in the brain, as well as in platelets. Likewise, decreased plasma concentrations of TRP have been found in depressed patients, and the selective 5-HT reuptake inhibitors (SSRIs) induce changes in platelet 5-HT concentration. Considering the controversy surrounding platelet 5-HT concentrations in depressed patients, and the fact that blood 5-HT and TRP have not been studied in the Mexican population, we decided to study 5-HT and tryptophan concentrations in blood and platelets from depressed and control Mexican subjects to evaluate a possible correlation with the severity of depression. The effect of fluoxetine and citalopram treatment on blood and platelet 5-HT and TRP concentrations in depressed patients was also studied. Material and methods Depressed patients The patients of this study were carefully selected and evaluated. Scales based on semi-structured interviews were applied (MINI and SCID-II) by clinical investigators to reduce any possible bias in patient selection. The influence of the seasonal variability on the 5-HT or TRP blood concentrations was controlled by pairing depressed patients and healthy subjects according to age, gender and, in the case of women, menstrual cycle phase. Patients with a complete remission of depression symptoms (defined as a score not higher than 5 points in the Hamilton's scale, and lower than 7 points in Beck's scale) were asked for a blood sample to measure platelet and blood concentrations of 5-HT and TRP. The patients were weighted before the treatment and after their improvement. Control subjects The control group was integrated by 30 healthy subjects, 24 women and 6 men, with an average age of 32.3 ± 10.8 years. Participants were recruited from the overall Mexican population, interviewed by a psychiatrist, and evaluated with the structured interview MINI and the SCID-II, all these to discard any psychiatric diagnose. None of them had received any pharmacological treatment during the three weeks prior to the study. Control and depressed women were paired according to their menstrual cycle phase. All participants received a detailed explanation of the study, and those who voluntarily accepted the stipulations signed an informed consent document. Control and patient subjects were clinically examined and studied with routine laboratory tests (blood count, blood chemistry, urinalysis, and thyroid function test). Blood sample procedures 5-HT and TRP measurements in total blood preparation were carried out according to the method described by Anderson, and were quantified by high performance liquid chromatography (HPLC). Statistical analysis The differences were statistically determined through an analysis of variance (ANOVA), with the assistance of the SPSS 12.00 (Statistical Software by SPPS Inc.). Results Results from laboratory tests, such as blood count, blood chemistry, thyroid function (T3, T4 and TSH) and urinalysis were normal in depressed subjects, as well as in healthy volunteers. Platelet number, blood 5-HT concentration, platelet content of 5-HT, and blood tryptophan concentration showed no significant differences in depressed patients in comparison to control subjects. 5-HT values in blood and platelet were significantly lower than the initial concentrations in patients after antidepressant treatment. Discussion and conclusions Discrepancies between our study and those found in the literature can be explained with three different approaches: ethnical, physiological, and methodological, as is further discussed. The significant decrease produced by the antidepressant treatment in blood and platelet serotonin concentration may be a consequence of the action of SSRIs, due to a 5-HT diminished uptake by the platelet. Considering our results, we conclude that: Blood and platelet 5-HT concentrations were not different between depressed patients and healthy volunteers. Blood TRP concentrations were not different between depressed patients and healthy volunteers. SSRIs (fluoxetine or citalopram) used in the treatment of depressed patients induced a significant decrease in blood and platelet content of 5-HT, and had no effect in TRP concentrations. Based on these results, neither blood/platelet 5-HT nor blood tryptophan concentrations seem to be good biological markers of depressive patients status. However, 5-HT, but not tryp-tophan, might be a reference point for pharmacological treatment effect.
resumen está disponible en el texto completo
ABSTRACT
El placebo es cualquier procedimiento médico que brinde un efecto curativo por su intención terapéutico y no por su naturaleza específica. Es un fenómeno que ha estado presente a lo largo de la historia de la medicina; sin embargo, el interés en su estado surgió con la aparición de los ensayos clínicos controlados, hace aproximadamente 40 años. Desde entónces se ha observado que su efecto es potente y que puede emplearse en un gran número de padecimientos, entre ellos, los transtornos depresivos. Las características de los sujetos susceptibles a responder al placebo, son variables e inespecíficas. Se ha intentado analizar el fenómeno "placebo" por medio del estudio de las características de los pacientes que responden a él, para determinar si hay elementos específicos del sujeto o de su padecimiento, que puedan predecir una respuesta. Estos datos se han obtenido de estudios farmacológicos controlados en los que se administra placebo a un grupo de pacientes, previamente al tratamiento activo, en forma ciega o bien en forma doble ciega, y se le compara con el otro grupo que recibió un tratamiento activo. Con el fin de obtener más información sobre los pacientes deprimidos que responden al placebo, en este trabajo analizamos las características individuales y el tipo de padecimiento de los sujetos que respondieron a una semana de tratamiento con placebo oral, antes de iniciar un estudio farmacológico, comparando estas características con las de los sujetos que no respondieron. Se evauaron 45 pacientes con el diagnóstico de depresión mayor, de acuerdo con el DSM-III, que aceptaron participar en el estudio y que obtuvieron una calificación mínima de 18 puntos en la Escala de Depresión de Hamilton. Se consideró que habían respondido al placebo si al final de la semana, bajaba la calificación en esta escala, por lo menos en un 50%, o bien, si quedaba por debajo de los 18 puntos. Además se aplicaron la Escala de Depresión de Carroll y el MMPI. Quince pacientes respondieron al placebo y 30 no respondieron...