Lipidomics study reveals schizophrenic patients’ resistance to antipsychotic drugs

Scientists from Skoltech and the Mental Health Research Center discovered 22 lipids in the blood plasma of schizophrenia patients that were linked to slower symptom improvement over time. These can be used to track medication resistance, which affects almost one-third of patients.

Schizophrenia Concept. Image Credit: My Ocean Production/Shutterstock.com

The study was published in the Biomolecules journal.

According to studies, up to 34% of persons with schizophrenia can develop resistance to two or more antipsychotic drugs used to treat the illness. Individual reactions vary widely, and there are currently no reliable biomarkers of therapy response, making the selection of proper medicine an unpleasant and time-consuming guessing game.

Researchers have recently focused their attention on lipids and the critical role they play in brain characteristics and functions, such as retrograde signaling, membrane fluidity and permeability, neurotransmitter release modulation, and neuronal plasticity.

Lipidomics is a growing field, and a lot remains unknown about lipid metabolism and its alteration in disease, which makes lipidomics a promising field for new discoveries.”

Anna Tkachev, Study Lead Author, Skoltech Center for Neurobiology and Brain Restoration

Tkachev and her team examined the blood lipid abundances of 322 blood plasma lipids in 92 people with schizophrenia who were undergoing inpatient treatment.

They looked at the links between symptom improvement and individual changes in blood plasma lipid levels by taking blood samples at two different times: at the start and end of a hospital stay that lasted an average of 37 days.

Doctors assessed the patients’ condition using the Positive and Negative Syndrome Scale (PANSS)—a higher score indicates more severe symptoms; therefore, researchers were looking for a decrease in PANSS score over time.

All except one of the patients improved, but to varying degrees. “We discovered that at the second time point, 22 lipids, including 20 triglyceride species, were elevated in patients with the least improvement in symptom severity, but patients with the most improvement did not show the same increase in lipid levels,” the scientists write.

Anna Tkachev points out that a lot is still unknown regarding the role of lipids in disease, and specifically the role of lipids in schizophrenia.

Typically, in a clinical setting, only total triglycerides are measured in the blood. In our study, we assessed lipids at a more detailed level of individual triglyceride species. The lipids we find significant in our study (shorter chain triglycerides) are not among the most abundant triglycerides, and any variation in their levels would probably remain undetected at the level of total triglyceride measurement.”

Anna Tkachev, Study Lead Author, Skoltech Center for Neurobiology and Brain Restoration

“Because many studies in the past have focused on total triglyceride levels and not detailed level of individual lipid species, it is difficult to say for now what these alterations signify,” added Tkachev.

The lipids discovered by the team appear to be linked to metabolic changes: they have been linked to diabetes and non-alcoholic fatty liver disease.

Metabolic abnormalities are, unfortunately, common in patients suffering from schizophrenia, and managing these metabolic abnormalities is an important part of managing the psychiatric disorder. However, there seems to be a complex interplay between metabolic abnormalities and psychiatric health. The role these metabolic abnormalities play in schizophrenia is not well understood, and the cause-effect relationship between the two is unclear as well.”

Anna Tkachev, Study Lead Author, Skoltech Center for Neurobiology and Brain Restoration

Since the researchers were looking at individual changes in lipid levels and not the levels of lipids at baseline, their results cannot be used for a predictive model of treatment response.

“Our results show that different levels of symptom improvement are associated with different alterations in lipid levels. Rather than providing a predictive biomarker, we hope that our results can help further the understanding of the underlying mechanisms of disease manifestation and treatment response,” concluded Tkachev.