Cortisol, Inflammatory Biomarkers May Predict Treatment Response in Schizophrenia

Cortisol and inflammatory biomarkers at the onset of psychosis could be predictors of treatment response, as well as potential targets for the development of novel therapeutic agents, according to a report in Schizophrenia Bulletin posted on March 31.

In a longitudinal study, researchers at the Institute of Psychiatry, Psychology, and Neuroscience at King’s College London collected saliva and blood samples in 68 first-episode psychosis patients and 57 healthy controls at baseline and assessed response to clinician-led antipsychotic treatment after 12 weeks. They repeated biological measurements in 39 patients at the same time they assessed the response. Saliva samples were collected at multiple time points during the day to measure diurnal cortisol levels and cortisol awakening response (CAR); interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-α, and interferon-γ (IFN-γ) levels were analyzed from serum samples.

Patients were divided into nonresponders (n=38) and responders (n=30) to treatment based on information obtained from clinical records, patient face-to-face interviews, and reports from caregivers, using the World Health Organization (WHO) Personal and Psychiatric History Schedule—Follow-Up. The latter is a standardized instrument to record presence and severity of symptoms that has been successfully used in WHO multicenter studies of the incidence and outcome of schizophrenia.

At first onset, nonresponders had markedly lower CAR and higher IL-6 and IFN-γ levels when compared with responders. After 12 weeks, nonresponders showed persistently lower CAR and higher IL-6 and IFN-γ levels when compared with responders.

Both nonresponders and responders had significantly lower CAR than healthy controls, although the difference was greater in the nonresponders.

“The mechanisms linking the blunted CAR and the increased inflammation with poor treatment response at the onset of psychosis could partly be explained by the well-known effects of cortisol and inflammation on monoaminergic pathways and on neuroplasticity,” they wrote. “Notably, it has been recently suggested that the CAR prime the brain for the expected demands of the day and that a blunted CAR predicts less neuroplasticity later in the afternoon, as shown by the response to rapid transcranial magnetic stimulation. Therefore, a blunted CAR in nonresponders may be linked to a lower synaptic plasticity and to a suboptimal brain function, which might ultimately account for the inability of our patients to respond to treatment.”

The study reflects a widening interest in inflammatory blood biomarkers as possible predictors of disease onset and treatment response. At the 2013 International Congress on Schizophrenia Research (ICOSR) in Orlando, Fla., several researchers reported evidence showing that inflammatory blood biomarkers could help distinguish those individuals identified at high risk for psychosis who are likely to convert to active psychosis.

At the conference, Diana Perkins, M.D., M.P.H., a professor of psychiatry at the University of North Carolina, Chapel Hill, reported that in a small sample of subjects from the North American Prodrome Longitudinal Study (NAPLS), laboratory tests analyzing multiple molecules and compounds in peripheral blood distinguished individuals who would go on to convert to psychosis from unaffected controls and from subjects deemed initially at high risk but who did not later develop psychosis.

The biomarker test included compounds reflecting altered immune status and oxidative stress, suggesting that these factors could drive the development of psychosis.

According to Perkins, that’s important because the clinical risk criteria focusing on behavioral symptoms and patient self-reports of subjective experiences identify individuals at elevated risk for psychosis, but less than one-third ultimately develop psychosis. Accurate diagnostic tests could guide clinicians and patients in making choices about preventive interventions.

“There is an emerging story that inflammation is really important,” Perkins said at the ICOSR meeting. “I think these blood tests show promise in helping us to diagnose patients who are already at high risk according to clinical criteria. I don’t think they are going to be useful as a screening tool in the general population, but if you have an individual you are worried about, these tests may be able to help clinicians hone in on who is really at risk.” ■

“Cortisol and Inflammatory Biomarkers Predict Poor Treatment Response in First Episode Psychosis” can be accessed here.