Lipidomic research provides clues about drug resistance in schizophrenia

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Functional magnetic resonance imaging (MRI) and other brain imaging technologies allow the study of differences in brain activity in people diagnosed with schizophrenia. The image shows two levels of the brain, with areas that were more active in healthy controls than in patients with schizophrenia shown in orange, during an MRI study of working memory. Credits: Kim J, Matthews NL, Park S./PLoS One.

Researchers at Skoltech and the Mental Health Research Center have found 22 lipids in the blood plasma of people with schizophrenia that were associated with an improvement in symptoms over time during treatment. These can help control medication resistance that affects more than a third of patients. The paper was published in the journal Biomolecules.

Studies suggest that up to 34% of people living with schizophrenia may be resistant to two or more antipsychotic medications used to treat the disorder. Individual responses vary widely and there are still no satisfactory biomarkers of treatment response, which can often turn the right medication into a painful and prolonged guessing game.

Recently, researchers have been studying lipids and the important function they are now known to develop in both brain properties and functionality, such as membrane fluidity and permeability, retrograde signaling, neuronal plasticity, and modulation of neurotransmitter release. “Lipidomics is a growing field and many are still unknown and its alteration in disease, which makes lipidomics a promising field for new discoveries, ”says the author of the article, Anna Tkachev, of the Skoltech Center for Neurobiology and Brain Restoration (CNBR).

Anna Tkachev and colleagues measured blood lipid abundance for 322 plasma lipids in 92 people diagnosed with schizophrenia and in hospital treatment. They studied the associations between improving symptoms and individual changes in blood plasma by collecting blood plasma at two different time points: at the beginning and end of a hospital stay that lasted an average of 37 days.

Physicians used the Positive and Negative Syndrome Scale (PANSS) to assess patients ’condition; a higher score corresponds to more severe symptoms, so the researchers looked for a drop in the PANSS score over time. All but one patient showed improvement, but the extent was different. “We found that for patients with a lesser improvement in symptom severity, 22 lipids, including 20 species of triglycerides, increased at the second time, while patients with more improvement did not show the same increase in levels. of lipids, ”the authors write. .

Anna Tkachev points out that there are still many uncertainties about the role of lipids in disease and, in particular, about the role of lipids in schizophrenia. “Normally, in a clinical setting, only total triglycerides in the blood are measured. In our study, we assessed lipids at a more detailed level of individual triglyceride species. The lipids we found significant in our study (triglycerides shorter chain) are not among the most abundant triglycerides, and any variation in their levels would probably remain undetected in the total triglyceride measurement level.Because in the past many studies have focused on total triglyceride levels and not at the detailed level of individual lipid species, it is difficult to say now what these alterations mean, ”she says.

The lipids found by the team appear to be related to metabolic alterations: they have been reported to have been affected by diabetes and non-alcoholic fatty liver disease. “Unfortunately, metabolic abnormalities are common in patients with schizophrenia, and managing these metabolic abnormalities is an important part of managing psychiatric disorder. However, there appears to be a complex interaction between metabolic abnormalities and psychiatric health. ‘these metabolic abnormalities the game in schizophrenia is not well understood and neither is the cause-effect relationship between the two clear,’ explains Tkachev.

Since the researchers studied individual changes in lipid levels and not in baseline lipid levels, 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 of levels. Instead of providing a predictive biomarker, we hope our results can help us understand the underlying mechanisms of disease manifestation and response to treatment, ”says Tkachev.


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More information:
Anna Tkachev et al, Shorter chain triglycerides are negatively associated with improved symptoms in schizophrenia, Biomolecules (2021). DOI: 10.3390 / biom11050720

Citation: Lipidomic research provides clues about drug resistance in schizophrenia (2021, July 6), retrieved July 6, 2021 at https://medicalxpress.com/news/2021-07-lipidomics-clues-drug -resistance-schizophrenia.html

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