Genetische Einflüsse und epigenetische Effekte der Hypnotherapie bei der Angsterkrankung

01.07.2018 bis 30.09.2020

Anxiety disorders (AD) are the most common group of mental disorders with a twelve-month prevalence of 14% in the European population 1. The aetiology of anxiety is influenced by genetic (heritability estimates: 30 – 68%) as well as environmental factors, most importantly stressful life events. Stress during critical periods of life - especially during childhood and adolescence - can induce permanent structural and regulatory alterations predisposing to disease vulnerability e.g. disturbed programming of the hypothalamic-pituitary-adrenal (HPA) axis 2-4. The contribution of early life adversities (ELA) to pathopysiological processes which lead to an increased risk for AD later in life, has been consistently described 3, 5-10.
The underlying biological mechanisms are still poorly understood, but evidence is emerging that epigenetic regulation of gene expression is involved in mediating this effect. These epigenetic processes involve DNA methylation. DNA methylation patterns are not as fixed as previously thought 11, but can be influenced by environmental factors and change over time 12. DNA methylation plasticity might therefore play a role in physiological responses as well as in adaptive programming of the genome to a changing environment, especially early in life. In their landmark study, Weaver et al. showed that epigenetic modifications of the glucocorticoid receptor (GR) in the rat hippocampus after exposure to low levels of maternal care triggered life-long differences in stress response 13. Similarly, studies in humans have demonstrated an influence of ELA on epigenetic alterations of the GR in the hippocampus as well as in peripheral blood and saliva 14-25. In addition to the findings for the GR, ELA has been shown to be associated with altered methylation of further genes in humans including BDNF, 5-HTT, ALS2, PTPRN2 and FKBP5 26-32. Moreover, in acutely ill AD patients DNA methylation differences in GAD1 as well as MAOA compared to control individuals were recently identified 33, 34. Further investigations revealed a female-specific interaction between GAD1 methylation status and negative events throughout life 33. Methylation of MAOA in patients was also influenced by life events 34, supporting the hypothesis that epigenetic changes driven by stressful life events contribute to the development of AD. However, none of the human studies published thus far directly linked ELA, epigenetic regulation and anxiety.
Recent evidence suggests that psychotherapeutic interventions provide an excellent setting to investigate environmental influences on biological mechanisms, and in this context it is very interesting to note that first studies reporting epigenetic effects of psychotherapy in AD have been recently published: Roberts et al. found significant alterations in DNA methylation levels of the serotonin transporter gene (5-HTT) in the course of anxiety treatment in children35: Those who responded to cognitive behavior therapy (CBT) showed increased methylation levels at a specific CpG site after treatment, whereas the levels of non-responders decreased significantly. A second study reported similar results for FKBP5: Here, a decrease in DNA methylation during therapy was associated with a strong reduction in symptom severity, whereas an increase in DNA methylation was associated with a weaker response to treatment 36. In addition to the findings in children suffering from anxiety disorder, an epigenetic effect of CBT has also been described in adult anxiety patients: Ziegler et al. detected epigenetic alterations in MAOA associated with response to CBT in adult panic disorder patients 37. Prior to therapy the DNA methylation levels of MAOA were significantly reduced in patients compared to healthy controls. While the DNA methylation levels of responders increased and where no longer significantly different from those of control individuals, the DNA methylation levels of non-responders decreased even further during the co