Chronic low-grade peripheral inflammation is associated with ultra resistant schizophrenia. Results from the FACE-SZ cohort

Eur Arch Psychiatry Clin Neurosci. 2019 Dec;269(8):985-992. doi: 10.1007/s00406-018-0908-0. Epub 2018 May 28.


A high rate of patients with schizophrenia (SZ) does not sufficiently respond to antipsychotic medication, which is associated with relapses and poor outcomes. Chronic peripheral inflammation has been repeatedly associated with schizophrenia risk and particularly to poor responders to treatment as usual with cognitive impairment in SZ subjects. The objective of present study was to confirm if ultra resistance to treatment in schizophrenia (UTRS) was associated to chronic peripheral inflammation in a non-selected sample of community-dwelling outpatients with schizophrenia. Participants were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia and received a thorough clinical assessment, including recording of current treatment. Current psychotic symptomatology was evaluated by the Positive and Negative Syndrome scale for Schizophrenia (PANSS). UTRS was defined by current clozapine treatment + PANSS total score ≥ 70. Functioning was evaluated by the Global Assessment of Functioning scale. High sensitivity CRP (hs-CRP) was measured for each participant as a proxy to define peripheral low-grade inflammation. 609 stabilized community-dwelling SZ subjects (mean age = 32.5 years, 73.6% male gender) have been included. 60 (9.9%) patients were classified in the UTRS group. In multivariate analyses, UTRS has been associated independently with chronic peripheral inflammation (OR = 2.6 [1.2-5.7], p = 0.01), illness duration (0R = 1.1 [1.0-1.2], p = 0.02) and impaired functioning (OR = 0.9 [0.9-0.9], p = 0.0002) after adjustment for age, sex, current daily tobacco smoking, metabolic syndrome and antidepressant consumption. Peripheral low-grade inflammation is associated with UTRS. Future studies should explore if anti-inflammatory strategies are effective in UTRS with chronic low-grade peripheral inflammation.

Keywords: Functioning; Inflammation; Resistant schizophrenia.

MeSH terms

  • Adult
  • Antipsychotic Agents / therapeutic use*
  • C-Reactive Protein / analysis
  • Cohort Studies
  • Female
  • Humans
  • Inflammation / complications*
  • Male
  • Metabolic Syndrome / complications
  • Psychiatric Status Rating Scales
  • Schizophrenia / complications
  • Schizophrenia / drug therapy*
  • Treatment Failure


  • Antipsychotic Agents
  • C-Reactive Protein