Superoxide dismutase and cytokines in chronic patients with schizophrenia: association with psychopathology and response to antipsychotics

Psychopharmacology (Berl). 2009 May;204(1):177-84. doi: 10.1007/s00213-008-1447-6. Epub 2009 Jan 13.


Objective: Both schizophrenia and oxidative stress have been associated with immune system abnormalities in interleukin-2 and -6 (IL-2; IL-6) and increases in superoxide dismutase (SOD) activity. These abnormalities may improve during antipsychotic drug treatment that reduces symptoms in schizophrenic patients.

Materials and methods: Subjects included 30 healthy controls (HC) and 78 schizophrenic (SCH) in-patients who were randomly assigned to 12 weeks of double-blind treatment with risperidone 6 mg/day or haloperidol 20 mg/day. Ratings using the Positive and Negative Syndrome Scale (PANSS) were correlated with blood SOD and serum IL-2 levels.

Results: SCH patients who were medication-free for 2 weeks had greater SOD, IL-2, and IL-6 levels than HC. At baseline, these SOD elevations were associated with higher PANSS total scores and the IL-2 elevations with lower PANSS positive symptom scores. The SOD and IL-2 levels in the SCH were also positively correlated. After treatment, PANSS positive symptoms and both SOD and IL-2 showed a significant decrease, but IL-6 showed no change. The SOD and IL-2 reductions were correlated with the reductions in PANSS total score, and SOD reductions also correlated with positive subscore reductions. Females showed these associations more strongly than males.

Conclusion: Our results suggest that the dysregulation in the cytokine system and oxidative stress in patients with schizophrenia is implicated in clinical symptoms and is improved at least partially with antipsychotic treatment. The stronger associations in females deserve further study and confirmation.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antipsychotic Agents / therapeutic use*
  • Chronic Disease
  • Double-Blind Method
  • Female
  • Haloperidol / therapeutic use
  • Humans
  • Interleukin-2 / blood*
  • Interleukin-6 / blood*
  • Male
  • Middle Aged
  • Oxidative Stress
  • Risperidone / therapeutic use
  • Schizophrenia / blood*
  • Schizophrenia / drug therapy*
  • Schizophrenia / physiopathology
  • Sex Factors
  • Superoxide Dismutase / blood*
  • Time Factors
  • Treatment Outcome


  • Antipsychotic Agents
  • Interleukin-2
  • Interleukin-6
  • Superoxide Dismutase
  • Haloperidol
  • Risperidone