Profiling of lipidomics before and after antipsychotic treatment in first-episode psychosis

Leppik, Liisa; Parksepp, Madis; Janno, Sven; Koido, Kati; Haring, Liina; Vasar, Eero; Zilmer, Mihkel

doi:10.1007/s00406-018-0971-6

Cited by 38 publications

(37 citation statements)

References 47 publications

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“…Although the samples used herein and in other studies were different, the findings taken together reinforce the potential role of SM in schizophrenia pathobiology and response to treatment. In agreement, one study found decreased SM levels in serum of antipsychotic-näive FEP patients; and the level of SM was decreased after 7 months of antipsychotic treatment (Leppik et al, 2019). These findings suggest that SM might be a potential biomarker for FEP and antipsychotic response, as we have hypothesized here.…”

Section: Discussionsupporting

confidence: 90%

“…Among all lipid classes, we noted that PCs were largely affected in our study. Accordingly, Leppik and colleagues (Leppik et al 2019) found a decrease in 16 PCs in antipsychotic-näive first-episode psychosis. After 7 months, the authors reported that some PCs were up-regulated by antipsychotics, and these effects may be associated with modulation of the inflammatory pathways.…”

Section: Discussionmentioning

confidence: 97%

“…Particularly, phospholipids have a crucial role in the structure of neuronal membranes and appear to be associated with the pathobiology of schizophrenia (Horrobin, 1998). Furthermore, studies have suggested that changes in lipids can be associated with an increased breakdown of membrane phospholipids, and pro-inflammatory state, suggesting that the modulation of lipid homeostasis is a potential target for the improvement of schizophrenia symptoms (Keshavan et al 2003;Leppik et al 2019;Wood, 2014Wood, , 2019. Thus, lipidomic changes may have a potential for disease-state or predictive biomarkers for schizophrenia, or a predictive lipidic signature for antipsychotic response in schizophrenia (Aquino et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Changes in the blood plasma lipidome associated with response to atypical antipsychotic treatments in schizophrenia

Almeida

Alexandrino

Aquino

et al. 2020

Preprint

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Atypical antipsychotics are widely used to manage schizophrenia symptoms. However, these drugs can induce deleterious side effects, such as MetS, which are associated with an increased cardiovascular risk to patients. Lipids play a central role in this context, and changes in lipid metabolism have been implicated in schizophrenia's pathobiology. Furthermore, recent evidence suggests that lipidome changes may be related to antipsychotic treatment response.The aim of this study was to evaluate the lipidome changes in blood plasma samples of schizophrenia patients before and after 6 weeks of treatment with either risperidone, olanzapine, or quetiapine. Liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis showed changes in the levels of ceramides (Cer), glycerophosphatidic acids (PA), glycerophosphocholines (PC), phosphatidylethanolamines (PE), phosphatidylinositols (PI), glycerophosphoglycerols (PG), and phosphatidylserines (PS) for all treatments. However, the treatment with risperidone also affected diacylglycerides (DG), ceramide 1-phosphates (CerP), triglycerides (TG), sphingomyelins (SM), and ceramide phosphoinositols (PI-Cer). Moreover, specific lipid profiles were observed that could be used to distinguish poor and good responders to the different antipsychotics. As such, further work in this area may lead to lipid-based biomarkers that could be used to improve the clinical management of schizophrenia patients.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Changes in the blood plasma lipidome associated with response to atypical antipsychotic treatments in schizophrenia

Almeida

Alexandrino

Aquino

et al. 2020

Preprint

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“…There is also a growing awareness of the important function lipids are now known to play in both the properties and functionality of the brain, such as membrane fluidity and permeability, retrograde signaling, neural plasticity, and neurotransmitter release modulation [ 6 , 7 ]. Studies of blood plasma lipid alteration in psychiatric disorders, in particular, have been numerous over the past decade [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ], with blood being a relatively easy sample type to procure for studies and most relevant for potential future biomarker implementations. Indeed, this area of research shows promise, evidenced by the distinct pattern of schizophrenia-associated lipid alterations being reported in the literature.…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, this area of research shows promise, evidenced by the distinct pattern of schizophrenia-associated lipid alterations being reported in the literature. Among other lipid compounds, the lipid classes most robustly associated with the disorder are ether phospholipids (such as plasmanyl-/plasmenyl- phosphatidylcholine and plasmanyl-/plasmenyl- phosphatidylethanolamine) [ 9 , 11 , 12 , 13 , 14 , 24 ] and acylcarnitines [ 8 , 10 , 15 , 25 , 26 ]. Associations with ether phospholipids and acylcarnitines have also been reported for other psychiatric disorders, such as major depressive disorder [ 19 , 20 , 21 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

Shorter Chain Triglycerides Are Negatively Associated with Symptom Improvement in Schizophrenia

et al. 2021

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Schizophrenia is a serious mental disorder requiring lifelong treatment. While medications are available that are effective in treating some patients, individual treatment responses can vary, with some patients exhibiting resistance to one or multiple drugs. Currently, little is known about the causes of the difference in treatment response observed among individuals with schizophrenia, and satisfactory markers of poor response are not available for clinical practice. Here, we studied the changes in the levels of 322 blood plasma lipids between two time points assessed in 92 individuals diagnosed with schizophrenia during their inpatient treatment and their association with the extent of symptom improvement. We found 20 triglyceride species increased in individuals with the least improvement in Positive and Negative Syndrome Scale (PANSS) scores, but not in those with the largest reduction in PANSS scores. These triglyceride species were distinct from the rest of the triglyceride species present in blood plasma. They contained a relatively low number of carbons in their fatty acid residues and were relatively low in abundance compared to the principal triglyceride species of blood plasma.

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Lipid Alteration Signature in the Blood Plasma of Individuals With Schizophrenia, Depression, and Bipolar Disorder

et al. 2023

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ImportanceNo clinically applicable diagnostic test exists for severe mental disorders. Lipids harbor potential as disease markers.ObjectiveTo define a reproducible profile of lipid alterations in the blood plasma of patients with schizophrenia (SCZ) independent of demographic and environmental variables and to investigate its specificity in association with other psychiatric disorders, ie, major depressive disorder (MDD) and bipolar disorder (BPD).Design, Setting, and ParticipantsThis was a multicohort case-control diagnostic analysis involving plasma samples from psychiatric patients and control individuals collected between July 17, 2009, and May 18, 2018. Study participants were recruited as consecutive and volunteer samples at multiple inpatient and outpatient mental health hospitals in Western Europe (Germany and Austria [DE-AT]), China (CN), and Russia (RU). Individuals with DSM-IV or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses of SCZ, MDD, BPD, or a first psychotic episode, as well as age- and sex-matched healthy controls without a mental health–related diagnosis were included in the study. Samples and data were analyzed from January 2018 to September 2020.Main Outcomes and MeasuresPlasma lipidome composition was assessed using liquid chromatography coupled with untargeted mass spectrometry.ResultsBlood lipid levels were assessed in 980 individuals (mean [SD] age, 36 [13] years; 510 male individuals [52%]) diagnosed with SCZ, BPD, MDD, or those with a first psychotic episode and in 572 controls (mean [SD] age, 34 [13] years; 323 male individuals [56%]). A total of 77 lipids were found to be significantly altered between those with SCZ (n = 436) and controls (n = 478) in all 3 sample cohorts. Alterations were consistent between cohorts (CN and RU: [Pearson correlation] r = 0.75; DE-AT and CN: r = 0.78; DE-AT and RU: r = 0.82; P &lt; 10−38). A lipid-based predictive model separated patients with SCZ from controls with high diagnostic ability (area under the receiver operating characteristic curve = 0.86-0.95). Lipidome alterations in BPD and MDD, assessed in 184 and 256 individuals, respectively, were found to be similar to those of SCZ (BPD: r = 0.89; MDD: r = 0.92; P &lt; 10−79). Assessment of detected alterations in individuals with a first psychotic episode, as well as patients with SCZ not receiving medication, demonstrated only limited association with medication restricted to particular lipids.Conclusions and RelevanceIn this study, SCZ was accompanied by a reproducible profile of plasma lipidome alterations, not associated with symptom severity, medication, and demographic and environmental variables, and largely shared with BPD and MDD. This lipid alteration signature may represent a trait marker of severe psychiatric disorders, indicating its potential to be transformed into a clinically applicable testing procedure.

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Profiling of lipidomics before and after antipsychotic treatment in first-episode psychosis

Cited by 38 publications

References 47 publications

Changes in the blood plasma lipidome associated with response to atypical antipsychotic treatments in schizophrenia

Changes in the blood plasma lipidome associated with response to atypical antipsychotic treatments in schizophrenia

Shorter Chain Triglycerides Are Negatively Associated with Symptom Improvement in Schizophrenia

Lipid Alteration Signature in the Blood Plasma of Individuals With Schizophrenia, Depression, and Bipolar Disorder

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