Cardiometabolic risk in patients with first-episode schizophrenia spectrum disorders: baseline results from the RAISE-ETP study

JAMA Psychiatry. 2014 Dec 1;71(12):1350-63. doi: 10.1001/jamapsychiatry.2014.1314.


Importance: The fact that individuals with schizophrenia have high cardiovascular morbidity and mortality is well established. However, risk status and moderators or mediators in the earliest stages of illness are less clear.

Objective: To assess cardiometabolic risk in first-episode schizophrenia spectrum disorders (FES) and its relationship to illness duration, antipsychotic treatment duration and type, sex, and race/ethnicity.

Design, setting, and participants: Baseline results of the Recovery After an Initial Schizophrenia Episode (RAISE) study, collected between July 22, 2010, and July 5, 2012, from 34 community mental health facilities without major research, teaching, or clinical FES programs. Patients were aged 15 to 40 years, had research-confirmed diagnoses of FES, and had less than 6 months of lifetime antipsychotic treatment.

Exposure: Prebaseline antipsychotic treatment was based on the community clinician's and/or patient's decision.

Main outcomes and measures: Body composition and fasting lipid, glucose, and insulin parameters.

Results: In 394 of 404 patients with cardiometabolic data (mean [SD] age, 23.6 [5.0] years; mean [SD] lifetime antipsychotic treatment, 47.3 [46.1] days), 48.3% were obese or overweight, 50.8% smoked, 56.5% had dyslipidemia, 39.9% had prehypertension, 10.0% had hypertension, and 13.2% had metabolic syndrome. Prediabetes (glucose based, 4.0%; hemoglobin A1c based, 15.4%) and diabetes (glucose based, 3.0%; hemoglobin A1c based, 2.9%) were less frequent. Total psychiatric illness duration correlated significantly with higher body mass index, fat mass, fat percentage, and waist circumference (all P<.01) but not elevated metabolic parameters (except triglycerides to HDL-C ratio [P=.04]). Conversely, antipsychotic treatment duration correlated significantly with higher non-HDL-C, triglycerides, and triglycerides to HDL-C ratio and lower HDL-C and systolic blood pressure (all P≤.01). In multivariable analyses, olanzapine was significantly associated with higher triglycerides, insulin, and insulin resistance, whereas quetiapine fumarate was associated with significantly higher triglycerides to HDL-C ratio (all P≤.02).

Conclusions and relevance: In patients with FES, cardiometabolic risk factors and abnormalities are present early in the illness and likely related to the underlying illness, unhealthy lifestyle, and antipsychotic medications, which interact with each other. Prevention of and early interventions for psychiatric illness and treatment with lower-risk agents, routine antipsychotic adverse effect monitoring, and smoking cessation interventions are needed from the earliest illness phases.

Publication types

  • Multicenter Study
  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Antipsychotic Agents / adverse effects*
  • Blood Glucose / metabolism
  • Body Composition
  • Cardiovascular Diseases / chemically induced
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / metabolism*
  • Ethnicity
  • Female
  • Humans
  • Insulin / blood
  • Lipids / blood
  • Male
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / chemically induced
  • Metabolic Syndrome / complications
  • Metabolic Syndrome / metabolism*
  • Middle Aged
  • Obesity / complications
  • Overweight / complications
  • Prospective Studies
  • Psychotic Disorders / blood
  • Psychotic Disorders / complications
  • Psychotic Disorders / metabolism*
  • Risk Factors
  • Schizophrenia / blood
  • Schizophrenia / complications
  • Schizophrenia / drug therapy
  • Schizophrenia / metabolism*
  • Sex Factors
  • Time Factors
  • Young Adult


  • Antipsychotic Agents
  • Blood Glucose
  • Insulin
  • Lipids