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Salud mental
versión impresa ISSN 0185-3325
Salud Ment vol.29 no.4 México jul./ago. 2006
Artículos originales
Tryptophan and serotonin in blood and platelets of depressed patients: Effect of an antidepressant treatment
1División de Servicios Clínicos, Instituto Nacional de Psiquiatría Ramón de la Fuente; Hospital General, Centro Médico La Raza, Instituto Mexicano del Seguro Social, México D.F.
2Unidad de Investigación Médica en Farmacología, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social México, D.F.
3Servicios Clínicos, Instituto Nacional de Psiquiatría Ramón de la Fuente; Facultad de Medicina, Benemérita Universidad Autónoma de Puebla.
4Servicios Clínicos, Instituto Nacional de Psiquiatría Ramón de la Fuente, México D.F.
5Dirección de Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente, México D.F.
6Doctorado en Ciencias Biológicas, Departamento de Atención a la Salud, CBS, Universidad Autónoma Metropolitana-Xochimilco, México D.F.
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.
Key words: Depression; 5-Hydroxitryptamine; platelet; tryp-tophan; antidepressants
Debido a que las plaquetas tienen un mecanismo de recaptura y almacenamiento de serotonina y acumulan alrededor de 99% del total de la serotonina en sangre, la serotonina plaquetaria se ha empleado como un indicador de la función serotoninérgica sináptica en trastornos psiquiátricos como la depresión. Sin embargo, los estudios que han evaluado la correlación entre la depresión y los cambios en los niveles de serotonina plaquetaria han dado resultados contradictorios.
Por lo que respecta al precursor de la 5-HT, el triptófano (TRP), se ha sugerido que el cambio en los niveles de triptófano plasmático podría ser la causa de las alteraciones en los niveles de 5-HT, tanto en las plaquetas como en el cerebro, y asimismo se ha reportado una disminución de los niveles plasmáticos de TRP en pacientes con depresión.
Respecto al efecto que han ejercido los inhibidores selectivos de la recaptura de serotonina sobre la serotonina plaquetaria, se ha documentado que los inhibidores selectivos de esta recaptura inducen cambios en los niveles plaquetarios de esta amina.
Tomando en cuenta la controversia respecto a los niveles plaquetarios de 5-HT en pacientes deprimidos, y considerando además que a la fecha no se ha caracterizado el efecto de la depresión sobre los niveles de 5-HT y TRP en sangre en sujetos mexicanos, se decidió estudiar los niveles sanguíneos y plaquetarios de serotonina (5-HT) y triptófano (TRP) en pacientes deprimidos, y compararlos con los niveles de estas sustancias en sujetos sanos. Se estudió, además, el efecto del tratamiento antidepresivo con inhibidores selectivos de la recaptura de serotonina (fluoxetina o citalopram) sobre los niveles de 5-HT y TRP sanguíneos en pacientes deprimidos.
Material y métodos
Pacientes deprimidos: Los 30 pacientes incluidos en este estudio (24 mujeres y 6 hombres) se seleccionaron y evaluaron cuidadosamente. Como se consideró la influencia de la estacionalidad, al ingreso de cada paciente al estudio se le buscaba un control, para lo cual se le comparaba con un par por edad y sexo. En el caso de las mujeres, la sujeto control seleccionada se estudiaba ajustando la fase de su ciclo menstrual con el de la paciente en estudio.
Grupo control : El grupo control lo conformaron 30 sujetos sanos con una media de edad de 32.3 ± 10.8 años (24 mujeres y 6 hombres). Se confirmó que no hubieran sufrido ningún trastorno psiquiátrico y se aplicó el SCID-II para descartar cualquier alteración en el eje II. Todos los sujetos se mantuvieron libres de toda medicación durante por lo menos las tres semanas previas al estudio. Los controles mujeres se compararon de acuerdo con la fase del ciclo menstrual de las pacientes.
Después de recibir una explicación minuciosa, todos los sujetos participantes firmaron una carta de consentimiento informado para participar en este estudio. Los pacientes y los controles se examinaron físicamente con datos clínicos y de laboratorio (citometría hemática completa, pruebas bioquímicas, examen general de orina y pruebas de función tiroidea).
Los pacientes deprimidos recibieron, de forma abierta, un tratamiento farmacológico con base en inhibidores selectivos de la recaptura de serotonina (fluoxetina o citalopram) con la intención de lograr una remisión total de la sintomatología depresiva.
Cuando los pacientes presentaban una remisión de los síntomas depresivos, se les tomaba nuevamente una muestra de sangre para cuantificar los niveles sanguíneos y plaquetarios de 5-HT y TRP.
Análisis de 5-HT y TRP: El análisis de 5-HT y TRP en sangre total se realizó de acuerdo con el método descrito por Anderson; cada análisis se cuantificó después por cromatografía de alta efi ciencia (HPLC).
Análisis estadístico: Por medio del análisis de varianza (ANO-VA) de una vía, se determinó la existencia de diferencias estadís ticamente significativas, y se utilizó la prueba de Tuckey HSD como pruebapost hoc. En todos los casos se graficó la media ± el error estándar.
Resultados
Los resultados de laboratorio y gabinete (BHC, química sanguínea, función tiroidea [T3, T4 y TSH], examen general de orina y electroencefalograma) fueron normales, tanto en los pacientes deprimidos como en los sujetos control.
El número de plaquetas, la serotonina sanguínea, el contenido plaquetario de serotonina y la concentración de triptófano no mostraron diferencias en comparación con los sujetos control. Sin embargo, las concentraciones de serotonina sanguínea y plaquetaria fueron significativamente más bajas en pacientes deprimidos después del tratamiento antidepresivo.
Discusión y conclusiones
Las discrepancias entre este estudio y otros reportados en la bibliografía se explican en función de aspectos étnicos, fisiológicos y metodológicos, los cuales se discuten aquí.
El significativo decremento de las concentraciones de serotonina sanguínea y plaquetaria, producido por el tratamiento antidepresivo (fluoxetina o citalopram), puede ser consecuencia de la disminución de la recaptura de 5-HT por las plaquetas.
Considerando los resultados encontrados, podemos concluir que:
Los pacientes mexicanos no mostraron cambios en las concentraciones de serotonina en sangre ni en las plaquetas asociadas con la depresión.
Tampoco se encontraron cambios en las concentraciones de TRP en sangre asociada con la depresión.
El tratamiento con medicamentos antidepresivos inhibidores selectivos de la recaptura de serotonina (fluoxetina o citalopram) se asocian con una disminución de la concentración de serotonina, tanto en sangre como en plaquetas, sin cambio en las concentraciones de triptófano en sangre.
Palabras clave: Depresión; 5-hidroxitriptamina; plaquetas; triptófano; antidepresivos
Acknowledgements
We are thankful for the work of MRS Coral Beedham, who corrected the English version of the manuscript. This work is part of the project of JM to obtain the degree of Doctor in Biological Sciences, at the Universidad Autónoma Metropolitana, Unidad Xochimilco.
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Received: March 29, 2006; Accepted: May 17, 2006
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