Measuring the levels of fatty acids, phospholipids, and sterols in erythrocyte membranes may help predict which high-risk individuals (UHRs) will experience conversion to complete psychosis, new research suggests.
Despite analyzing individually lipids, such as linoleic acid or phospholipids, were somewhat predictive of conversion, only when the three groups were examined together that the researchers were able to significantly predict the conversion of psychosis.
“We believe we can use membrane lipids for personalized medicine in psychiatry, especially in psychosis,” said lead researcher Ariel Frajerman, MD, Center Hospitalier Sainte Anne, Paris, France.
The findings were presented at the virtual congress of the Schizophrenia International Research Society (SIRS) 2021.
New Research Avenue
Frajerman noted that UHR individuals already show some symptoms of psychosis and that between 20% and 40% will experience conversion to complete psychosis in the next 3 years.
“The question is, which ones?” He said.
Membrane lipids are an interesting line of research compared to plasma lipids because erythrocytes have a “life expectancy of 120 days,” so measurements are considered to be more stable over time, Frajerman said. .
Membrane lipids include omega-3, omega-6, and omega-9 polyunsaturated fatty acids; the phospholipids phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine and sphingomyelin; and cholesterol and cholestanol sterols.
“They play a very important role for the biochemical and physical properties of the membrane,” Frajerman said. He noted that his presence is “good … not like plasma.”
Previous attempts to use lipid levels in erythrocyte membranes to predict psychosis conversion yielded conflicting results because of the low number of patients who experienced conversion or because studies focused on specific lipids, he noted.
The researchers examined erythrocytes from a cohort of 61 UHR individuals in France in the ICAAR study. Among participants, 29 experienced conversions and 32 did not.
For the evaluation of erythrocytes, the researchers combined liquid chromatography with mass spectrometry, “which is the gold standard” for lipid analysis, Frajerman said.
Lipid key combination
The results showed a high correlation between the levels of fatty acids, phospholipids and sterols.
As for only fatty acids, the area under the receptor operative characteristic curve (AUC) to predict psychosis conversion was 0.653, which “is not very good,” Frajerman noted.
Linoleic acid alone was a better predictor of psychosis conversion, with an AUC of 0.654. The proportion of cholestanol and cholesterol was not so good, with an AUC of 0.607.
Phospholipids had a similar ability to predict psychosis conversion, with an AUC of 0.645.
The combination of linoleic acid and phospholipids improved the ability to predict psychosis conversion, with an AUC of 0.697. The addition of the cholestanol / cholesterol ratio further improved the predictive power, with an AUC of 0.728 (Pg = .004).
Frajerman noted that his study included 29 patients who experienced a conversion, which “wasn’t much,” but that the cohort is from the same country. This is “important because it has already been shown that long-term diet has an impact on fatty acids, [so there] there will be differences between countries, ”he said.
Limitations of the study include the fact that there was no control group, no dietary data, and no replication cohort. Frajerman said future research will include food questionnaires.
After the presentation, the co-chair of the session, Alexis Cullen, PhD, researcher and honorary professor at the Institute of Psychiatry, Psychology and Neuroscience at King’s College London, London, UK, asked if there was any correlation between the membrane lipids and symptoms.
Frajerman said there was an association between membrane lipid levels at baseline and reduced scores on the social and labor performance assessment scale a year later.
The questions remain
Commenting on the study for Medscape Medical News, David R. Cotter, MD, PhD, Royal College of Surgeons in Ireland and the Center for Education and Research, Beaumont Hospital, Dublin, Ireland, said the findings were “interesting” but need to be replicated.
If replicated, physicians “should consider adding these lipid predictors to protein predictors,” such as the proteomic biomarkers identified in a recent study published a Psychiatry JAMA, said Cotter, who was not involved in the investigation.
He noted that two key questions remain: what is the biological basis of the membrane lipid signature identified in the study and reflects a chronic inflammatory state?
He also commented, said Scott R. Clark, MD, MD, head of psychiatry at Adelaide University, Adelaide, Australia. Medscape Medical News that previous studies have explored associations between lipids and psychosis.
These include a plasma lipid analysis in a large number of children and adolescents from the Avon Longitudinal Study of Parents and Children ia study of high-risk people the cases were followed for 5 years. That study used grouping and machine learning to identify lipid profiles related to the onset of psychosis.
Clark believes there is a potential utility of membrane lipids to personalize attention, focusing on UHR individuals most likely to move on to psychosis. “But I think relationships are more complex and multilipid signatures are likely to be more useful,” he said.
There are “numerous models for predicting psychosis” that combine a number of modes of biological and clinical data, because “all biological predictors have a small effect size and must be combined together to achieve reasonable accuracy.” said Clark.
“Much larger sample sizes are needed to confirm these relationships,” he said. He noted that the National Institute of Mental Health has launched one number of these studies as part of the Accelerating Medicines Partnership. The aim is to identify people at greatest risk and develop specific interventions.
The study’s authors and commentators have not reported any relevant financial relationships.
Congress of the Schizophrenia International Research Society (SIRS) 2021: Abstract 3007124. Presented April 19, 2021.