Hormonal Dynamics Effect of Serum Insulin-Like Growth Factor I and Cortisol/Dehydroepiandrosterone Sulfate Ratio on Symptom Severity of Major Depressive Disorder

J Clin Psychopharmacol. Jul/Aug 2019;39(4):367-371. doi: 10.1097/JCP.0000000000001071.


Background: Insulin-like growth factor I (IGF-I) is a neurotrophic factor produced by the hypothalamic-pituitary-somatotropic axis and is considered a potential contributor to the pathology of major depressive disorder (MDD). Although it is known that the hypothalamic-pituitary-adrenal axis and cortisol are involved in the pathology of MDD, the association with dehydroepiandrosterone sulfate (DHEAS) remains unclear. The current study sought to clarify the relationship between these hormones and the pathology of MDD.

Methods: Subjects were 91 Japanese patients with a diagnosis of MDD. Serum IGF-I, cortisol, and DHEAS were measured. Samples were taken before breakfast after overnight fasting. Depressive symptoms were assessed using the Hamilton Rating Scale for Depression (HAM-D).

Results: Subjects included 59 men and 32 women with an average age of 44.1 ± 13.1 years (mean ± SD). The blood IGF-I level was 152.0 ± 50.0 ng/mL, the cortisol level was 10.1 ± 4.6, and the DHEAS level was 201.3 ± 112.7 μg/dL. The mean HAM-D score was 13.9 ± 9.0. Serum IGF-I levels were not correlated with cortisol. Higher IGF-I, cortisol, and cortisol/DHEAS ratios were associated with higher HAM-D scores (adjusted R = 0.240, P < 0.001), and higher IGF-I and cortisol were associated with higher melancholic or suicide subscores (adjusted R = 0.200, P < 0.001; adjusted R = 0.273, P < 0.001).

Conclusions: Our findings suggest that hormonal dysregulation of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-somatotropic axes may be related to the symptom severity of MDD, melancholia, and suicide-related factors.

MeSH terms

  • Adult
  • Dehydroepiandrosterone Sulfate / blood*
  • Depressive Disorder, Major / blood*
  • Depressive Disorder, Major / physiopathology*
  • Female
  • Humans
  • Hydrocortisone / blood*
  • Hypothalamo-Hypophyseal System / physiopathology
  • Hypothalamus / physiopathology
  • Insulin-Like Growth Factor I / analysis*
  • Male
  • Middle Aged
  • Pituitary-Adrenal System / physiopathology


  • Dehydroepiandrosterone Sulfate
  • Insulin-Like Growth Factor I
  • Hydrocortisone