Inflammatory marker for schizophrenia treatment resistance, severity

By Liam Davenport, medwireNews Reporter

Levels of the inflammatory marker soluble tumor necrosis factor receptor 1 (sTNFR1) may be associated with severity of symptoms and treatment resistance in schizophrenia, say Brazilian scientists.

The team, led by Cristiano Noto, from São Paolo Federal University, explains: "On the one hand, sTNFR1 might be a consequence of an advanced stage of disease, while on the other hand, it could… mark the acceleration of neuroprogression."

Writing in the Journal of Psychiatric Research, they add: "Alternatively, the presence of heightened sTNFR1 levels might be a confounder that is influenced by general medical comorbidities that are usually more common and severe in late-stage patients."

The researchers took blood samples from 54 chronically medicated schizophrenia outpatients and 118 healthy controls. They measured levels of tumor necrosis factor (TNF)-α alongside those of its receptors, sTNFR1 and sTNFR2.

All schizophrenia patients (mean duration of illness 11.75 years) were being treated with at least one antipsychotic drug, of which 38.5% were using clozapine. Fifty-seven percent of patients were classified as treatment resistant.

The profiles of patients and controls differed: patients were significantly less likely to be female, at 24.1% versus 37.3%; significantly more likely to have an education level of less than 8 years, at 26.9% versus 14.1%; to be single, at 88.2% versus 46.7%; and to smoke, at 42.9% versus 28.2%.

In 69.8% of the sample, TNF-α levels were below the detection limit, and thus could not be compared between the two groups. However, schizophrenia patients were found to have significantly increased sTNFR1 and sTNFR2 levels compared with healthy controls. Levels of both these markers negatively correlated with scores on the Global Assessment of Functioning, at Spearman's rho of -0.377 for sTNFR1 and -0.362 for sTNFR2.

Patients classified as treatment resistant were found to have significantly higher sTNFR1 levels than both treatment-responsive patients and controls. The researchers also observed that sTNFR1 levels positively correlated with nicotine dependence, and were increased in patients with schizophrenia and concomitant depression, as defined by a Calgary Depression Scale for Schizophrenia score of more than 7.

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