The interaction between the endocrine system and inflammation is crucial pathogenesis of depression. Our study aimed at exploring the possible relationship between sex hormones and growth differentiation factor-15 (GDF-15), a common indicator of inflammation in male patients with major depressive disorder (MDD). Methods: GDF-15 levels of 121 male MDD patients were compared with 105 healthy subjects with the help of a Cobas 8000 automatic chemiluminescence immunoanalyzer. Results: (1) MDD patients showed higher GDF-15 levels, a lower testosterone (T) level and testosterone/estradiol ratio (T/E2 ratio) than healthy subjects (all p < 0.05). (2) Serum T levels and the T/E2 ratio were inversely associated with GDF-15 serum levels (all p < 0.05). (3) HAMD-24 scores were positively correlated with the levels of GDF-15 (p < 0.01), but not with T levels, estradiol (E2) levels, and the T/E2 ratio (all p > 0.05). Conclusion: The high level of GDF-15 was correlated with a low T/E2 ratio and T deficiency in male MDD patients. The above results demonstrate that up-regulation of serum GDF-15 and down-regulation of T and T/E2 ratio may be correlated with the occurrence and severity of depression. So, changing the level of GDF-15 by regulating the proportion of sex hormones may play a key role in the prognosis and treatment of depression.

Background: Elevated levels of growth differentiation factor (GDF)-15 and reduced levels of testosterone have been linked to depressive disorder, but whether they are also linked to suicidal ideation in patients with depression is unclear. Methods: This retrospective study involved 301 patients ≥ 22 years old hospitalized for depression between July 2018 and November 2020 at Renmin Hospital of Wuhan University, of whom 120 had suicidal ideation. Serum levels of GDF-15 and testosterone were compared between patients with or without suicidal ideation. Results: GDF-15 levels were significantly higher among patients with suicidal ideation than among those without, regardless of whether testosterone levels were above or below the median of 314 ng/dL. In multivariate logistic regression involving all patients, serum GDF-15 level was associated with low testosterone level (P=0.001). Among patients with testosterone < 314 ng/dL, an increase of 1 standard deviation in serum GDF-15 level translated to a 1.3-fold increase in the risk of suicidal ideation (P=0.007). This relationship was not observed in all population or patients with testosterone levels ≥ 314 ng/dL. Conclusion: High serum GDF-15 level may be associated with an increased risk of suicidal ideation in patients with depression, and this association appears to be partly mediated by low testosterone levels.

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 is not fully understood. We observed the correlation between serum T/E ratio and circulating GDF15 in male 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-V (SCID), and male healthy controls (n = 137). Serum levels of testosterone, estradiol, and depression risk biomarkers (thyroid hormone, lipids, hs-CRP, Tenascin-C [TNC], GDF15, KLF4, Gas6, and sgp130) were measured. The associations among log-transformed T/E ratio and these biomarkers 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 ratio was 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.