Using antipsychotic medications to treat individuals with schizophrenia has long challenged clinicians. Up to 34% of people with schizophrenia can be resistant to two or more antipsychotic medications, says Anna Tkachev, a researcher at the Skoltech Center for Neurobiology and Brain Restoration, a private research institute in Moscow.

In recent years, Tkachev and other scientists have focused on the study of lipids, as experts have learned the important functions they play in the properties and functionality of brains – such as membrane fluidity and permeability, retrograde signaling, neural plasticity, and neurotransmitter release modulation.1

Lipidomics, as the field of study is known, is a growing and promising area for new pharmacological discoveries. New schizophrenia treatments are one possibility.

Schizophrenia Treatment Approaches

According to the American Psychiatric Association, schizophrenia is one of the top 20 causes of disability globally. Lifetime prevalence is thought to be about 0.7% and the disorder is linked with increased mortality. While schizophrenia is considered a serious mental illness, it is treatable.2 (More on symptoms and diagnostic criteria for schizophrenia).

In guidelines released in 2020, the American Psychiatric Association offers an approach that incorporates evidence-based treatment with a patient’s preferences and goals. Recommendations include both pharmacological and non-pharmacological approaches. Among the pharmacological approaches are antipsychotic medications with monitoring for effectiveness and side effects and continuation of the medications for those whose symptoms have improved.

Antipsychotics are thought to work by changing the effect of certain brain chemicals (dopamine, serotonin, noradrenaline, acetylcholine) that can play a role in behavior, mood or emotions.3 (More on treatment guidelines for schizophrenia.)

Lipid Levels Linked to Schizophrenia Symptoms

Tkachev and her team measured the blood lipid abundances for 322 blood plasma lipids, looking at 92 people with diagnosed schizophrenia and in hospital for treatment. They collected samples of plasma at the beginning and end of hospital stays that averaged 37 days. The team used the Positive and Negative Syndrome Scale (PANSS) to evaluate the condition of the patients, looking for an expected drop in PANSS score, since a higher score reflects more severe symptoms.

Their major finding: In patients with the least improvement in symptoms, 22 lipids, including 20 triglyceride species, were increased at the second time point. Those who had improvement in symptoms in the second time point did not have that same increase in lipid levels.1

Using Lipids to Monitor Schizophrenia Treatment

Tkachev explained to Psycom Pro, “We were not comparing levels of these lipids at the same time point in different patient groups but were comparing the changes in lipid levels in the same individual through time. It turns out that these changes in lipid levels depended on whether or not the individual showed larger or smaller symptom improvement.”

As for the clinical application, Tkachev cautions, “These findings cannot be used to predict treatment response.” To do that, one would need the lipid measurement before and after treatment to be able to use the information adequately. In their research, she points outs, the patients had already undergone treatment.

In the future, however, these findings and their application might be used to monitor treatment for schizophrenia. Tkachev says she is not sure of the practical value “since clinicians can assess the patient’s treatment response directly.” However, lab tests for specific lipid levels, for instance, ”could provide complementary information about the patient’s health state that could be useful for the clinicians, potentially.”

Other salient points: “The significant lipid turned out to be triglycerides, but these were specific types of triglycerides – they had shorter carbon chains in their fatty acid residues,” notes Tkachev. “Importantly, these results would have remained undetected if a standard lipid test was used, such as a total triglycerides test which is routinely used in clinical practice.”

Metabolic Links to Schizophrenia

Tkachev also notes that individuals with schizophrenia often have multiple metabolic comorbidities, such as obesity and cardiovascular diseases. And while lifestyle choices could explain some co-occurring medical illnesses, the lipid ”signature” they found in the study seems to be linked also with certain abnormalities metabolically. For instance, triglycerides have been linked to diabetes and non-alcoholic fatty liver disease. She says the findings in her study could be related to the metabolic abnormalities induced by the antipsychotic treatment, affecting the response and reflecting the interplay between psychiatric disorders and metabolic abnormalities.

In another study, the researchers have found that psychiatric patients have a distinct lipid profile separating them from healthy individuals. That research is as yet unpublished, she says.

Schizophrenia and Lipidomics: Supporting Research

Other researchers are looking to lipidomics as an avenue to improving the management of schizophrenia.

Brazilian researchers, for example, evaluated 54 people with schizophrenia treated with antipsychotics for 6 weeks. Treatment led to significant improvements in 34 subjects, but no improvement for 20 subjects. They then looked at plasma samples taken before therapy (using liquid-chromatography tandem mass spectrometry (LC-MS/MS) and identified, respectively, 38, 10, and 52, compounds linked with the olanzapine (Zyprexa, others), risperidone (Risperdal), and quetiapine (Seroquel) treatment groups that could be used to distinguish responders from non-responders.4

The Brazilian researchers noted limitations, such as retroactive analysis and small sample size, and note that future research with larger sample sets could lead to the development of a molecular test to help psychiatrists decide the best treatment for each patient. They concluded that their study “provides the groundwork for development of objective clinical tests that can be used to help psychiatrists in the choice of treatments for individuals presenting with acute schizophrenia in line with personalized medicine objectives.”4

 

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Last Updated: Oct 20, 2021