IL-6 and TNF-α in unmedicated adults with ADHD: Relationship to cortisol awakening response

Psychoneuroendocrinology. 2017 May:79:67-73. doi: 10.1016/j.psyneuen.2017.02.017. Epub 2017 Feb 20.


There is preliminary evidence that the immune system's cytokines may have impact on ADHD in children. Nevertheless, studies exploring the possible role of pro-inflammatory cytokines in adults with ADHD are lacking. This study aimed to assess differences in serum IL-6 and TNF-α between patients and controls and their possible relationship to resting cortisol. 108 adults with ADHD (DSM-IV), 44 inattentive and 64 combined, age ranging between 18 and 55 years, and 27 healthy controls were included. Major psychiatric disorders and organic comorbidities were excluded. Serum samples for IL-6 and TNF-α and salivary samples to assess cortisol awakening response were collected on the same day. Analysis of variance was applied to study differences in IL-6 and TNF-α between groups. Pearson correlations were used to study associations between IL-6, TNF-α, and CAR. There were no significant differences in serum IL-6 or TNF-α levels between patients and controls or between combined and inattentive patients. Negative associations between IL-6 (r=-0.386, p=0.020), TNF-α (r=-0.372, p=0.023) and cortisol awakening response were found in the inattentive subtype, whereas no association was seen in the combined subtype. A negative correlation between IL-6 and cortisol was also present in the control group (r=-0.44, 0.030). The peripheral pro-inflammatory markers, IL-6 and TNF-α, do not appear to be primarily involved in ADHD in adults, although the role of other inflammatory markers cannot be ruled out. The differences regarding the association between IL-6 and TNF-α and morning cortisol response suggest possible underlying neurobiological differences between the inattentive or combined patients that merit further studies.

Keywords: ADHD; Attention deficit hyperactivity disorder; Cortisol; Cytokines; Il-6; TNF-α.

MeSH terms

  • Adolescent
  • Adult
  • Attention Deficit Disorder with Hyperactivity / blood*
  • Attention Deficit Disorder with Hyperactivity / physiopathology
  • Biomarkers / blood
  • Female
  • Humans
  • Hydrocortisone / analysis*
  • Hypothalamo-Hypophyseal System / physiopathology
  • Interleukin-6 / blood*
  • Male
  • Middle Aged
  • Pituitary-Adrenal System / physiopathology
  • Saliva / chemistry
  • Tumor Necrosis Factor-alpha / blood*
  • Young Adult


  • Biomarkers
  • IL6 protein, human
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Hydrocortisone