Metabolic Challenges Occur Early in Schizophrenia

Patients with schizophrenia show signs of metabolic dysfunction early on, researchers reported.

Those having a first schizophrenia spectrum episode were significantly more likely to show a host of cardiovascular and endocrinologic risk factors than the general population of similar age, according to Christoph U. Correll, MD, of North Shore-LIJ Health System in Glen Oaks, N.Y., and colleagues.

Among relatively young patients enrolled in a prospective study of schizophrenia spectrum disorders -- mean age 24 -- half were overweight or obese, nearly 60% had abnormal lipid levels, half had above-normal blood pressure or overt hypertension, and 13% met criteria for metabolic syndrome, they reported online in JAMA Psychiatry.

Although some of these factors were likely related to antipsychotic medications patients had taken, the researchers concluded that the illness itself and associated "unhealthy lifestyles" also played major roles.

"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," Correll and colleagues wrote.

Persons with schizophrenia and related mental disorders show dramatically shorter average lifespans than the general population, with premature cardiovascular death the most common reason, the researchers observed. Rates of obesity are also much greater with schizophrenia; although weight gain is a recognized side effect of many so-called atypical antipsychotic medications, it cannot fully account for the difference. Correll and colleagues wrote that other factors include poverty and "suboptimal medical monitoring and care" were also to blame for the sample's apparent poor physical health.

To get a better handle on these relationships, they analyzed baseline data from an ongoing prospective study called the Recovery After an Initial Schizophrenia Episode-Early Treatment Program (RAISE-ETP), a cluster-randomized trial with a primary purpose of evaluating a multi-component intervention delivered after a first episode in patients 15 to 40 years old.

Out of 404 patients enrolled in the trial, cardiometabolic data at recruitment were available for 394, who served as the sample for the current analysis.

About 70% were male and 55% were white, with an average age of 23.6 (SD 5.0). The mean age at onset of psychotic symptoms was 19. Educational attainment was 12 years or less in two-thirds of the sample.

Prevalences of cardiometabolic risk factors were as follows:

• Smoking history: 50.8%
• Overweight: 26.2%
• Obese: 22.1%
• Prehypertension (120-139 mm Hg systolic/80-89 mmHg diastolic): 39.9%
• Hypertension (≥140 mm Hg/≥90 mm Hg): 10.0%
• Total cholesterol ≥200 mg/dL: 21.0%
• LDL cholesterol ≥130 mg/dL: 17.1%
• Triglycerides ≥170 mg/dL: 16.1%
• Any dyslipidemia: 56.5%
• HbA1c 5.7%-6.4%: 15.4%
• HbA1c >6.4%: 2.9%

In many cases, these rates were higher than were seen in the same general age group in the population-based National Health and Nutrition Examination Survey data.

However, despite the prevalence of cardiovascular abnormalities in the 10%-20% range, only 19 participants -- less than 5% of the total -- were receiving any kind of medication for hypertension, hyperlipidemia, or excess blood glucose.

Statistical analyses indicated that duration of psychiatric illness and exposure to olanzapine (Zyprexa) and quetiapine (Seroquel) were associated with certain risk factors. In particular, patients taking olanzapine tended to have increased triglycerides, serum insulin, and insulin resistance; those on quetiapine had higher ratios of triglycerides to HDL cholesterol.

But drug exposure was clearly not the only contributor to cardiometabolic risk, as patients who had not used any antipsychotic medications were more likely to be obese and to have hypertension (both P<0.05). Also, among those who had received antipsychotics, the mean duration of exposure was less than 7 weeks.

"Taken together, our findings highlight major opportunities for improvement in health care planning and delivery for people with schizophrenia," Correll and colleagues wrote. "There is a need for policy changes that promote the implementation of integrated care, health homes, and accountable care organizations wherein coordinated attention to both physical and mental health care needs will lead to improved health and reduced expenditure."

Limitations to the study included lack of certain cardiometabolic data on some participants, the fact that antipsychotics had been prescribed according to physicians' individual judgment, and an absence of complete medication histories prior to study enrollment for many patients.

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