Trends in Psychiatry and Psychotherapy
https://trends.org.br/article/doi/10.1590/2237-6089-2015-0035
Trends in Psychiatry and Psychotherapy
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What can HPA axis-linked genes tell us about anxiety disorders in adolescents?

O que os genes associados ao eixo HPA podem nos dizer sobre os transtornos de ansiedade em adolescentes?

Andressa Bortoluzzi; Carolina Blaya; Eduarda Dias da Rosa; Mariana Paim; Virgínia Rosa; Sandra Leistner-Segal; Gisele Gus Manfro

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Abstract

Introduction: Anxiety disorders (AD) share features of both anxiety and fear linked to stress response. The hypothalamic-pituitary-adrenal (HPA) axis is considered the core biological pathway of the stress system and it is known that an inappropriate response to environmental stimuli may be related to individual genetic vulnerability in HPA-linked genes. Despite the biological plausibility of a relationship between the HPA axis and AD, few studies have investigated associations between genetic polymorphisms linked to the HPA axis and this complex disorder. Objective: To investigate whether AD are associated with genetic polymorphisms in HPA-linked genes in adolescents. Methods: Our study consisted of a cross-sectional evaluation of a community sample comprising a total of 228 adolescents (131 cases of AD). We extracted DNA from saliva and genotyped polymorphisms in HPA-linked genes (FKBP5: rs3800373, rs9296158, rs1360780, rs9470080 and rs4713916; NR3C1: rs6198; CRHR1: rs878886; and SERPINA6: rs746530) with real time polymerase chain reaction (PCR). The instruments used to diagnose and assess the severity of AD were the Schedule for Affective Disorder and Schizophrenia for School-Age Children - Present and Lifetime (K-SADS-PL) and the Screen for Child and Anxiety related Emotional Disorders (SCARED). Results: We failed to detect any associations between AD and genetic polymorphisms in HPA-linked genes (p > 0.05). Conclusion: To our knowledge, this is the first study evaluating these specific polymorphisms in relation to AD in adolescents, which encourages us to design further research on the subject.

Keywords

HPA axis, genetic polymorphisms, anxiety disorder, adolescents

Resumo

Introdução: Os transtornos de ansiedade (TA) compartilham características tanto de ansiedade quanto de medo, ambos associados à resposta ao estresse. O eixo hipotálamo-pituitária-adrenal (HPA) é considerado a principal via biológica do sistema do estresse, e sabe-se que respostas inadequadas aos estímulos ambientais podem estar relacionadas à vulnerabilidade genética individual em genes do eixo HPA. Apesar da plausibilidade biológica de uma relação entre o eixo HPA e os TA, poucos estudos avaliaram a associação entre os polimorfismos genéticos de genes do eixo HPA e esse transtorno psiquiátrico complexo. Objetivo: Investigar, em adolescentes, se os TA estão associados com polimorfismos em genes do eixo HPA. Métodos: Nosso estudo é uma avaliação transversal realizada em uma amostra comunitária de 228 adolescentes (131 casos de TA). Foi extraído DNA de saliva e foram genotipados os polimorfismos do eixo HPA (FKBP5: rs3800373, rs9296158, rs1360780, rs9470080 e rs4713916; NR3C1: rs6198; CRHR1: rs878886; e SERPINA6: rs746530), por reação em cadeia da polimerase (PCR) em tempo real. O diagnóstico e a gravidade dos TA foram avaliados pelo instrumentos The Schedule for Affective Disorder and Schizophrenia for School-Age Children - Present and Lifetime (K-SADS-PL) e Screen for Child and Anxiety related Emotional Disorders (SCARED). Resultados: Não foram encontradas associações entre os TA e os polimorfismos genéticos do eixo HPA (p > 0.05). Conclusão: Segundo nosso conhecimento, este é o primeiro estudo que avaliou, em adolescentes, esses polimorfismos genéticos específicos do eixo HPA e sua relação com os TA, o que nos encoraja a delinear novas pesquisas sobre o assunto.

Palavras-chave

Eixo HPA, polimorfismos genéticos, transtorno de ansiedade, adolescentes

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