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Efeito de poliformismos genéticos do gene HSD11b1 sobre o risco para desenvolver depressão na população brasileira / Effect of HSD11b1 gene polymorphisms on the risk of developing depression in the Brazilian populationDrumond, Fernanda Viana Figaro 19 September 2017 (has links)
A depressão tem sido considerada uma das principais causas de incapacidade e caracteriza-se pela a presença de humor triste e perda de interesse ou prazer, acompanhada de alterações somáticas e cognitivas que afetam significativamente a capacidade de funcionamento do indivíduo. Evidências sugerem que o hormônio relacionado ao estresse, o cortisol, está envolvido na fisiopatologia da depressão em adultos. Isso pode estar relacionado com estresse precoce durante o desenvolvimento inicial, o que poderia levar a uma maior vulnerabilidade para desenvolver depressão e risco de tentativa de suicídio na fase adulta. O cortisol tem sua liberação mediada pelo eixo hipotálamo-hipófise-adrenal (HPA) e a alteração deste eixo pode afetar significativamente a biodisponibilidade do cortisol circulante. É comprovado também que fatores ambientais e genéticos permeiam a causa da depressão e o eixo HPA tem sido implicado na fisiopatologia de transtornos depressivos. O gene HSD11B1 que codifica a enzima 11?-hidroxiesteróide desidrogenase tipo1 que é a responsável por converter cortisona em cortisol permeia a função do eixo HPA. Com isso, polimorfismos genéticos no gene HSD11B1 podem afetar o risco para desenvolver depressão e o risco de suicídio. O objeto foi avaliar se genótipos e haplótipos do gene HSD11B1 estão associados com risco de depressão, com a gravidade dos sintomas e com o comportamento suicida, considerando o estresse precoce como um fator ambiental. Foram incluídos 107 pacientes depressivos e 67 pacientes saudáveis incluídos como controles. Todos os sujeitos foram submetidos a uma avaliação psicométrica com a Escala MINI, escala GRID-HAMD21, Questionário de Traumas Infantis CTQ e Escala Beck de Ideação Suicida. Foi encontrada associação significativa com o polimorfismo rs11119328 nos genótipos para risco aumentado de pelo menos uma tentativa de suicídio (OR: 12,53, p = 0,045) E uma associação de genótipos variantes do polimorfismo rs11811440 com humor eutímico para tratamento farmacológico otimizado (OR: 0,05, P = 0,027). Concluímos que os polimorfismos do gene HSD11B1 podem ser biomarcadores relevantes para detectar indivíduos geneticamente vulneráveis a desenvolver depressão e a cometer suicídio. / Depression has been considered one of the main cause of disability and is characterized by the presence of sad mood and loss of interest or pleasure, accompanied by somatic and cognitive changes that significantly affect the ability of the individual to function. Evidence suggests that the stress-related hormone, cortisol, is involved in the pathophysiology of depression in adults. This may be related to adverse experiences in childhood during early development, which could lead to increased vulnerability to developing depression and suicide attempt risk in adulthood. Cortisol has its release mediated by the hypothalamic-pituitary-adrenal axis (HPA) and the alteration of this axis can significantly affect the bioavailability of the circulating cortisol. It is also proven that environmental and genetic factors permeate the cause of depression and the HPA axis has been implicated in the pathophysiology of depressive disorders. The HSD11B1 gene encoding the 11?-hydroxysteroid dehydrogenase type 1 enzyme that is responsible for converting cortisone to cortisol permeates HPA axis function. Thus, genetic polymorphisms in the HSD11B1 gene may affect the risk of developing depression and the risk of suicide. The objective was to evaluate if genotypes and haplotypes of the HSD11B1 gene are associated with risk of depression, with severity of symptoms and with suicidal behavior, considering early stress as an environmental factor. We included 107 depressive patients and 67 healthy patients included as controls. All subjects underwent a psychometric evaluation with the MINI Scale, GRID-HAMD21 Scale, Child Trauma Questionnaire CTQ and Beck Scale of Suicidal Ideation. It was found a significant association with rs11119328 polymorphism in genotypes at increased risk of at least one suicide attempt (OR: 12.53, p = 0.045) and an association of rs11811440 polymorphism genotypes with euthymic humor for optimized pharmacological treatment (OR: 0.05, P = 0.027). We conclude that HSD11B1 gene polymorphisms may be relevant biomarkers for detecting genetically vulnerable individuals to develop depression and commit suicide.
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Rolle von Single-Nukleotid-Polymorphismen der 11beta-Hydroxysteroid-Dehydrogenase in Bezug auf den Glucocorticoidstoffwechsel im Knochen – Einfluss auf den supprimierten Cortisolspiegel und die Knochendichte bei Osteoporosepatienten / Genetic polymorphisms in 11ß-hydroxysteroid dehydrogenase HSD11B1 influence dexamethasone suppressed cortisol levels as possible pathogenetic factor of bone mineral density in osteoporosis patientsMergler-Etmanski, Michael Helmut 13 February 2019 (has links)
No description available.
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siRNA-basierte Studien zu der physiologischen Funktion des Transkriptionsfaktors Runx2 in humanen Osteoblasten / siRNA-based studies regarding physiological function of transcription factor Runx2 in human osteoblastsPeiffer, Kai-Henrik 09 May 2012 (has links)
No description available.
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Personality and the HPA-axis in Association with Postpartum DepressionIliadis, Stavros I January 2016 (has links)
Postpartum depression is a psychiatric disorder affecting a substantial proportion of newly delivered women, and remains a significant cause of childbirth-related morbidity. The aim of the present thesis was to examine psychological, endocrine and genetic aspects of postpartum depression in a large, population-based sample of women in Uppsala, Sweden. All included studies were undertaken as parts of the BASIC-project, a longitudinal study on psychological wellbeing during pregnancy and the postpartum period. Study participants were screened for depressive symptoms in pregnancy week 17 and 32 as well as at six weeks and six months postpartum, mainly by use of the Swedish version of the Edinburgh Postnatal Depression Scale (EPDS). Furthermore, personality was assessed with the Swedish universities Scale of Personality (SSP) in pregnancy week 32. Evening cortisol levels in saliva were measured in pregnancy week 36 and at six weeks postpartum. Blood samples were obtained to measure corticotropin-releasing hormone levels (CRH) and to perform genetic analyses. The results of this thesis demonstrate that neuroticism is a strong and independent predictive factor of depressive symptoms at six weeks and six months postpartum, and has a significant mediatory role in the association between a single nucleotide polymorphism in the hydroxysteroid (11-beta) dehydrogenase 1 gene (HSD11B1) and postpartum depression. Furthermore, women with postpartum depressive symptoms present with a dysregulated hypothalamic-pituitary-adrenal axis activity in terms of elevated cortisol levels postpartum, as well as elevated CRH levels in mid-gestation. In conclusion, this thesis develops current knowledge on several attributes of postpartum depression. Further studies are required to replicate and expand on these results, which would further contribute to early identification of women at risk of postpartum depression and adoption of proper interventions that may moderate the short- and long-term consequences of the disorder.
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Lokální steroidogeneze v periferních tkáních a její regulace / Local steroidogenesis in peripheral tissues and its regulationLangová, Veronika January 2018 (has links)
The innate and adaptive immune processes are modulated by hormones including glucocorticoids and by microbiota. The exact mechanisms underlying the microbial and hormonal contributions to this control are not completely clear. Present study is therefore focused to crosstalk between microbiota and de novo biogenesis or local regeneration of glucocorticoids. In particular, the study analysed the effect of commensal microbiota on expression of genes encoding steroidogenic enzymes (Star, Cyp11a1, Hsd3b1, Cyp21a1, Cyp11b1) and regeneration of glucocorticoids (Hsd11b1) in adrenal glands, colon, spleen and mesenteric lymph nodes using conventional and germ-free mice. The expression of all 5 components of steroidogenesis was identified only in the adrenal gland and colon, whereas the lymphoid organs expressed predominantly Star, Cyp11a1 and Hsd3b1 indicating the ability to produce only progesterone but not corticosterone. Microbiota decreased the expression of Star in all studied tissues but the expression of other genes was insensitive to microbiota or did not respond homogenously depending on the tissue and gene. Hsd11b1 expression was upregulated by microbiota in the spleen but not in other tissues. Similarly, the in vitro treatment of immune cells isolated from mesenteric lymph nodes by microbial...
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