Serum ghrelin is positively associated with physiological anxiety but negatively associated with pathological anxiety in humans: Data from a large community-based study

The orexigenic hormone ghrelin is being increasingly recognized as a stress hormone being involved in anxiety regulation. In animals, ghrelin effects on, and responses to acute stress differed from those in chronic stress, an animal model for anxiety and depression. In humans, elevated ghrelin levels were reported in pathological anxiety (e.g. panic disorder). However, no reports exist on physiological anxiety in mentally healthy subjects. In addition, reports on generalized anxiety symptoms, both in mentally healthy subjects (e.g. worrying) or in adult patients, are lacking. Total serum ghrelin was determined in 1666 subjects of a population-based cross-sectional study (‘LIFE’). The 7-item Generalized Anxiety Disorder Scale (GAD-7), detecting also other anxiety disorders, was administered. For multiple linear regression analyses, 1091 subjects were finally included. Serum ghrelin and GAD-7 scores were positively but not significantly associated in the total group (ß=0.00025, standardized β = 0.039, 95%CI: −0.00006;0.0006;p = 0.144), in subjects with no more than mild anxiety, there was a significant positive association (GAD-7 ≤9: n = 1061, 97.25%, β = 0.00032; standardized β = 0.060; 95%CI: 0.000023;0.00062;p = 0.036). In contrast, there was a negative association in subjects with anxiety symptoms above the GAD-7 cut-off (GAD-7 ≥10: n = 30, 2.75%, ß=−0.003, standardized β = −0.462; 95% CI:−0.006;0.0001;p = 0.045). Ghrelin levels were only numerically (p = 0.23) higher in subjects with clinically relevant anxiety symptoms (963.5 ± 399.6 pg/ml; mean±SD) than in those without (901.0 ± 416.4 pg/ml). In conclusion, the positive association between ghrelin and no more than mild anxiety is an initial indication for a role for ghrelin in the regulation of physiological anxiety in humans. This association and the opposed association in pathological anxiety resemble findings in animals showing diverging ghrelin effects in acute and chronic stress.