The Biomarkers That May Predict Antipsychotic Treatment Response


Stress and inflammation biomarkers have been identified that might help predict whether people with psychosis will respond to existing antipsychotic medication. The findings could help clinicians distinguish individuals at greatest risk of not responding, which could aid the search for improved medications and personalised treatment plans.

The discovery was made by researchers from the National institute for Health Research (NIHR) Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust (SLaM) and King’s College London.

Roughly three percent of people in England have at least one episode of psychosis throughout their lives, and in any given year, one new case of psychosis is diagnosed for every 2,000 people. Only half of patients with psychosis respond to current medications and there is still a lack of knowledge surrounding the factors causing this lack of response.

Lowered Cortisol Awakening Response

For the study, saliva and blood samples were taken from 68 patients presenting with early psychosis and 57 healthy controls. In order to establish whether symptoms had improved following the first course of antipsychotic medication, responses to treatment were measured at the beginning of the study and 12 weeks later.

Those who did not respond to early treatment showed lower levels of cortisol awakening response (CAR). CAR refers to an increase of around 50 percent in levels of cortisol 20-30 minutes after waking in the morning.

Individuals at the onset of psychosis typically show increased levels of cortisol throughout the day but a blunted CAR.

The study also found higher levels of inflammatory markers, in particular IL-6 and IFN-γ, among those who did not respond to treatment. These differences in cortisol and inflammatory biomarkers were found to persist over the first 12 weeks of treatment.

Dr Valeria Mondelli from the NIHR Maudsley Biomedical Research Centre at SLaM and King’s, which also funded the study, said:

“Stress plays a recognised role in the onset of psychosis, so the biomarkers highlighted in our study could hold great potential for identifying those people less likely to respond to antipsychotic medicines. By pinpointing patients with high inflammation and abnormal levels of cortisol at the outset, we may be able to develop medications and personalised treatment plans which target these biomarkers.

Fewer Subsequent Episodes

Psychosis is a term used to indicate mental health disorders that present with symptoms like hallucinations, such as hearing voices, or delusions, unshakeable beliefs based on the person’s altered perception of reality, which may not correspond to the way others see the world.

Psychotic episodes are present in conditions such as schizophrenia and bipolar disorder.

In most cases, psychosis develops during late adolescence (15 or above) or adulthood. Treatment involves a combination of antipsychotic medication, psychological therapies and social support. Many people with psychosis go on to lead ordinary lives, and for about 60 percent of people, the symptoms disappear within 12 months from onset.

However, for others, treatment is less straightforward, and many do not respond to the initial antipsychotic treatment prescribed by their doctor. Early response to antipsychotic medication is known to be associated with better outcomes and fewer subsequent episodes, and intervening early with effective treatments is therefore important.

  1. Valeria Mondelli, Simone Ciufolini, Martino Belvederi Murri, Stefania Bonaccorso, Marta Di Forti, Annalisa Giordano, Tiago R. Marques, Patricia A. Zunszain, Craig Morgan, Robin M. Murray, Carmine M. Pariante, and Paola Dazzan. Cortisol and Inflammatory Biomarkers Predict Poor Treatment Response in First Episode Psychosis. Schizophr Bull March 31, 2015 doi:10.1093/schbul/sbv028

Last Updated on January 26, 2024