What can HPA axis-linked genes tell us about anxiety disorders in adolescents?

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.

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