Characterisation of three polymorphisms of the tryptophan hydroxylase 2 gene in a sample of Colombian population with major depressive disorder / Caracterización de tres polimorfismos del gen de la triptófano hidroxilasa 2 en una muestra de población colombiana con trastorno depresivo mayor

ABSTRACT Objective: Identify whether rs11179000, rs136494 and rs4570625 polymorphisms of the tryptophan hydroxylase 2 gene, are associated with a major depressive disorder in a sample of the Colombian population. Methods: Case-control study was conducted in which a comparison was made between subjects diagnosed with major depressive disorder at some point in adulthood or active symptoms at the time of evaluation, and subjects with no psychiatric disease. Subjects were studied in the Department of Psychiatry, Faculty of Medicine and the Institute of Genetics at the National University of Colombia. Polymorphisms were genotyped using Taqman probes in real time PCR. As well as studying the association between major depressive disorder and these single nucleotide polymorphisms (SNPs), the association with other factors previously associated with depression were also analysed. Results: No statistically significant association between genotypic and allelic frequencies of each polymorphism and major depressive disorder was found. Association between sex and complication during pregnancy/childbirth and major depressive disorder was observed. Association between sex and complication during pregnancy/childbirth and major depres sive disorder was observed. Conclusions: There was no association between any polymorphism and major depressive disorder.

RESUMEN Objetivo: Identificar si los polimorfismos rs11179000, rs136494 y rs4570625 del gen de la triptófano hidroxilasa 2 están asociados a trastorno depresivo mayor en una muestra de población colombiana. Métodos: Estudio de casos y controles en el que se comparó a sujetos con trastorno depresivo mayor diagnosticado en algún momento de la vida adulta o con síntomas activos en el momento de la valoración y sujetos sin enfermedad psiquiátrica. Se estudió a los sujetos en el Departamento de Psiquiatría de la Facultad de Medicina y en el Instituto de Genética de la Universidad Nacional de Colombia. Se genotipificaron los polimorfismos usando reacción en cadena de la polimerasa en tiempo real y sondas Taqman. Además de buscar asociación entre trastorno depresivo mayor y estos polimorfismos de un solo nucleótido, se exploró asociación con otros factores relacionados previamente con depresión. Resultados: No se encontró asociación estadísticamente significativa entre las frecuencias genotípicas o alélicas de cada polimorfismo y el trastorno depresivo mayor. Se observó asociación entre sexo y complicaciones durante el embarazo/parto y trastorno depresivo mayor. Conclusiones: No se halló asociación entre polimorfismo alguno y el trastorno depresivo mayor.

[Characterisation of three polymorphisms of the tryptophan hydroxylase 2 gene in a sample of Colombian population with major depressive disorder]. / Caracterización de tres polimorfismos del gen de la triptófano hidroxilasa 2 en una muestra de población colombiana con trastorno depresivo mayor.

OBJECTIVE: Identify whether rs11179000, rs136494 and rs4570625 polymorphisms of the tryptophan hydroxylase 2 gene, are associated with a major depressive disorder in a sample of the Colombian population. METHODS: Case-control study was conducted in which a comparison was made between subjects diagnosed with major depressive disorder at some point in adulthood or active symptoms at the time of evaluation, and subjects with no psychiatric disease. Subjects were studied in the Department of Psychiatry, Faculty of Medicine and the Institute of Genetics at the National University of Colombia. Polymorphisms were genotyped using Taqman probes in real time PCR. As well as studying the association between major depressive disorder and these (single nucleotide polymorphisms (SNPs), the association with other factors previously associated with depression were also analysed. RESULTS: No statistically significant association between genotypic and allelic frequencies of each polymorphism and major depressive disorder was found. Association between sex and complication during pregnancy / childbirth and major depressive disorder was observed. Association between sex and complication during pregnancy / childbirth and major depressive disorder was observed. CONCLUSIONS: There was no association between any polymorphism and major depressive disorder.

Maternal separation during nursing alters basal neuroendocrine levels in juvenile and adult rats.

INTRODUCTION: Work with different animal models including that of maternal separation during nursing has shown that early adverse experiences such as abuse, maternal abandonment and psychosocial stress may favor the development of various psychopathologies. However, several neuroendocrine changes have not been completely described yet.  OBJECTIVE: To establish whether maternal separation during nursing modifies the basal levels of neurohormones such as corticosterone, ACTH, oxytocin and vasopressin in juvenile and adult rats (aged 35 and 90 days, respectively).  MATERIALS AND METHODS: Wistar rats were separated from their mothers for two periods of 3 hours per day during the 21 days of nursing. Once these rats had reached 35 and then 90 days of age, blood samples were taken from both the separated and control groups to obtain serum for immunoenzymatic assays and measure the levels of each of the hormones.  RESULTS: Concentrations of corticosterone were higher in control adult females in comparison with the rest of the groups and lower in the control adult males. Those of ACTH were higher in the separated young males and females than in the adult groups. Oxytocin levels were significantly higher in the separated adult females in comparison with the other groups and significantly lower in the adult males. With respect to vasopressin, the separated groups had lower concentrations than the young and adult control groups.  CONCLUSIONS: These results show that the early stress to which rats were submitted produced changes in the basal responses of the hypothalamic-pituitary-adrenal axis, that these responses were distinct in males and females and that they also differed according to age.

La separación materna durante la lactancia altera los niveles basales del sistema neuroendocrino en ratas adolescentes y adultas / Maternal separation during nursing alters basal neuroendocrine levels in juvenile and adult rats

Introducción. En diversos modelos animales, incluido el de la separación materna durante la lactancia, se ha demostrado que las experiencias tempranas adversas, como el maltrato, el abandono materno y el estrés psicosocial, pueden favorecer el desarrollo de algunas enfermedades mentales, pero no se han descrito completamente varios de los cambios que se producen en el sistema neuroendocrino. Objetivo. Determinar si la separación materna durante la lactancia modificaba los niveles basales de neurohormonas como la corticosterona, la corticotropina (ACTH), la oxitocina y la vasopresina (ADH), en ratas jóvenes (35 días) y adultas (90 días). Materiales y métodos. Se separaron ratas Wistar de sus madres durante dos periodos de tres horas diarias a lo largo de los 21 días de lactancia. A los 35 y 90 días se tomaron muestras de los grupos de las ratas de control y de las separadas de la madre, para obtener el suero y posteriormente medir cada una de las hormonas mediante un ensayo inmunoenzimático. Resultados. Las concentraciones de corticosterona fueron mayores en las hembras adultas de control que en el resto de los grupos, y menores en los machos adultos de control. Las de ACTH fueron mayores en los machos y hembras jóvenes separadas de la madre que en los grupos de adultos. Los niveles de oxitocina fueron significativamente mayores en las hembras adultas separadas de la madre que en los otros grupos y significativamente menores en los machos adultos. En cuanto a la vasopresina, los grupos separados de la madre tuvieron concentraciones menores, en comparación con los grupos de jóvenes y adultos de control. Conclusiones. Estos resultados muestran que el estrés temprano al que fueron sometidas las ratas, produjo cambios en las respuestas del eje hipotálamo-hipófisis-suprarrenal, las cuales variaron según el sexo y la edad.

Introduction: Work with different animal models including that of maternal separation during nursing has shown that early adverse experiences such as abuse, maternal abandonment and psychosocial stress may favor the development of various psychopathologies. However, several neuroendocrine changes have not been completely described yet. Objective: To establish whether maternal separation during nursing modifies the basal levels of neurohormones such as corticosterone, ACTH, oxytocin and vasopressin in juvenile and adult rats (aged 35 and 90 days, respectively). Materials and methods: Wistar rats were separated from their mothers for two periods of 3 hours per day during the 21 days of nursing. Once these rats had reached 35 and then 90 days of age, blood samples were taken from both the separated and control groups to obtain serum for immunoenzymatic assays and measure the levels of each of the hormones. Results: Concentrations of corticosterone were higher in control adult females in comparison with the rest of the groups and lower in the control adult males. Those of ACTH were higher in the separated young males and females than in the adult groups. Oxytocin levels were significantly higher in the separated adult females in comparison with the other groups and significantly lower in the adult males. With respect to vasopressin, the separated groups had lower concentrations than the young and adult control groups. Conclusions: These results show that the early stress to which rats were submitted produced changes in the basal responses of the hypothalamic-pituitary-adrenal axis, that these responses were distinct in males and females and that they also differed according to age.

Efecto de la alopregnanolona sobre la ansiedad en ratas con separación materna durante la lactancia / The effect of allopregnanolone on anxiety induced in rats separated from their young during breastfeeding

Antecedentes. La relación madre-hijo y el cuidado parental al recién nacido son fundamentales en el desarrollo fisiológico y emocional de los individuos. Evidencias asocian el estrés temprano con el desarrollo de enfermedades mentales. El modelo de separación materna durante la lactancia (SMDL) se ha utilizado para inducir estrés temprano en ratas y estudiar efectos a largo plazo. Diversos estudios han encontrado que, en ratas separadas de sus madres, disminuyen los niveles del receptor GABA-A y esos bajos niveles están asociados a comportamientos ansiosos. Objetivo. Evaluar el efecto de la alopregnanolona, un neuroesteroide agonista del receptor GABA-A, sobre la ansiedad inducida por SMDL. Materiales y métodos. Se utilizaron 30 ratas Wistar dividas en dos grupos, uno control y uno experimental (SMDL). La SMDL se realizó desde el día postnatal 1 hasta el día postnatal 21, durante 180 minutos en la mañana y 180 minutos en la tarde. Desde el día 22 los sujetos se alojaron en cajas por sexo y tratamiento y continuaron su desarrollo normal hasta el día 60, en el que se hizo la inyección con alopregnanolona y la prueba comportamental en el laberinto en cruz elevado. Resultados. El estrés crónico causado por la SMDL afecta el comportamiento de los individuos, perfil comportamental que varía dependiendo del sexo. Se encontró que los machos presentan comportamientos más ansiosos que las hembras, las cuales a su vez muestran más actividad locomotora y exploración Conclusiones. Al aplicar alopregnanolona el repertorio comportamental varía en los animales con SMDL; estos resultados sugieren que la alopregnanolona, a través de su unión al receptor GABA-A, puede llegar a revertir los efectos de la separación materna, sobre los comportamientos relacionados con ansiedad.

Background. The mother-child relationship and parental care for the newborn are fundamental in individuals' physiological and emotional development. Evidence-based research associates early stress with the development of mental illnesses. Maternal separation during lactation (MSDL) models have been used to induce early stress in rats and for studying the long-term effects of such intervention. Several studies have found decreased GABA-A receptor levels in separated rats from their mothers and such low levels have been associated with anxious behaviour. Objective. Assessing the effect of allopregnanolone (a GABA-A receptor neurosteroid agonist) on MSDL-induced anxiety. Materials and methods. Thirty Wistar rats were divided into two groups: control and experimental (MSDL). SMDL occurred for 180 minutes in the morning and 180 minutes in the afternoon. Subjects were housed in boxes by gender and treatment following day 22 and their normal development was allowed to continue until day 60 when they were injected with allopregnanolone and underwent a behavioural test in an elevated plus maze (EPM). Results. Chronic stress induced by MSDL affected individuals' behaviour, their behavioural profile varying according to their gender. Males exhibited more anxious behaviour than females who engaged in more locomotive and exploratory activity. Conclusions. MSDL animals' behavioural repertoire varied due to the allopregnanolone injection, suggesting that the effect of allopregnanolone due to GABA-A receptor interaction could reverse the effects of maternal separation on anxiety-related behaviour.