Altered Circulating GDF-15 Level Predicts Sex Hormone Imbalance in Major Depressive Disorder

Abstract Background: It has been hypothesized that higher growth differentiation factor 15 (GDF15) level and lower testosterone/ estradiol (T/E) ratio are associated with major depressive disorder (MDD), yet the underlying effect of serum GDF15 on hinting the T/E ratio imbalance are not fully understood. We observed the correlations between serum T/E ratio and circulating GDF15 in depressed cohort. Methods: The sample consisted of participants (aged 18~65 years) from the Renmin Hospital of Wuhan University with MDD (n=412) defined according to a Structured Clinical Interview for DSM-IV (SCID), and healthy controls (n=137). Serum levels of testosterone, estradiol, and depression risk indicators (thyroid hormone, lipids, hs-CRP, Tenascin-C [TNC], GDF15, KLF4, Gas6, and sgp130) were measured. The associations among loge-transformed T/E ratio and these indicators were analyzed using univariate correlation analysis, category analyses, and linear regression adjusting for standard risk factors. Results: Of the sample, 36.89% had lower T/E ratio (<10:1) and 10.20% had higher T/E ratio (>20:1). After multivariable adjustment, T/E ratios were negatively associated with GDF15 (-0.095 [95% CI -0.170~-0.023] standard deviation [SD] change per SD increase in lg[T/E], P=0.015) and inversely related to TNC (-0.085 [95% CI -0.167~0.003] standard deviation [SD] change per SD increase in lg[T/E], P=0.048). Serum T/E ratio was negatively associated with GDF15 level in both FT3, TSH and HDL strata, whereas this association was not observed in TNC. In T/E ratio strata analyses, there is a significant and negative correlation among T/E ratio and GDF15 in depressive patients with sex hormone imbalance, yet this relationship was not investigated in patients with sex hormone balance. Conclusion: In our community-based observation, circulating GDF-15 level was greatly and inversely associated with serum T/E ratio, indicating that higher GDF-15 alerts sex hormone imbalance in patients with MDD.Trial registration: All subjects did not provide written informed consent due to the using the remaining specimens.