Role of HPA Axis and Cytokines in Adolescent Depression and Suicide: A Postmortem Brain Study

  • Ghanshyam Pandey, University of Illinois at Chicago, United States
  • Xinguo Ren, University of Illinois at Chicago, United States
  • Hooriyah Rizavi, University of Illinois at Chicago, United States
  • Jawed Fareed, Loyola University Medical Center, United States
  • Debra Hoppensteadt-Moorman, Loyola University Medical Center, United States
  • Rosalinda Roberts, University of Alabama at Birmingham, United States
  • Robert Conley, Eli Lilly and Company, United States
  • Yogesh Dwivedi, University of Illinois at Chicago, United States
  • Objective: Stress and depression are major risk factors for suicide and it has been shown that both are associated with abnormalities of hypothalamic-pituitary-adrenal (HPA) axis and increased levels of proinflammatory cytokines. In this study we examined if HPA axis components and proinflammatory cytokines are altered in teenage suicide brain.

    Methods: We determined the protein expression levels of glucocorticoid receptors (GR) mineralocorticoid receptors (MR) corticotrophin releasing factor (CRF) and CRF receptor-1 (CRF-R1) and CRF-R2 as well as the levels of proinflammatory cytokines interlukin-1β (IL-1β) and tumor neurosis factor α (TNF-α) in the prefrontal cortex (PFC) obtained from 28 teenage suicide victims and 28 matched normal control subjects using Western blot and ELISA method respectively.

    Results: We found that the protein expression levels of GR but not MR were significantly decreased in the PFC and amygdala but not hippocampus of teenage suicide victims compared with normal controls. On the other hand we found that the level of CRF were significantly increased in PFC and amygdala and CRF-R1 receptor were significantly decreased in the PFC of teenage suicide victims as compared to normal control subjects. The levels of pro-inflammatory cytokines, IL-1β and TNF-α were significantly increased in two areas of PFC Brodmann area 10 (BA-10) and BA-8 of teenage suicide victims compared with matched normal control subjects.

    Conclusions: These results suggest that abnormal HPA axis feedback mechanism may be related to decreased GR expression. Increased serum proinflammatory cytokines in depressed patients may be an index of similar increases in the brain.