Blood-Based Lipidomics Approach to Evaluate Biomarkers Associated With Response to Olanzapine, Risperidone, and Quetiapine Treatment in Schizophrenia Patients

Aquino, Adriano; Alexandrino, Guilherme L.; Guest, Paul C.; Augusto, Fábio; Gomes, Alexandre F.; Murgu, Michael; Steiner, Johann; Martins-de-Souza, Daniel

doi:10.3389/fpsyt.2018.00209

Cited by 24 publications

(13 citation statements)

References 39 publications

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“…Therefore, changes in lipids have been associated with the pathophysiology of schizophrenia. Specifically, alterations related to fatty acids and ketone bodies 55 , 56 , phospholipids 57 , 58 sphingolipids 59 , total lipids, triglycerides and cholesterol esters were observed in schizophrenia patients 60 – 62 .…”

Section: Resultsmentioning

confidence: 98%

Ubiquitin–proteasome system, lipid metabolism and DNA damage repair are triggered by antipsychotic medication in human oligodendrocytes: implications in schizophrenia

Seabra

Almeida

Reis‐de‐Oliveira

et al. 2020

Sci Rep

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Schizophrenia is a chronic, severe and disabling psychiatric disorder, whose treatment is based on psychosocial interventions and the use of antipsychotic drugs. While the effects of these drugs are well elucidated in neuronal cells, they are still not so clear in oligodendrocytes, which play a vital role in schizophrenia. Thus, we aimed to characterize biochemical profiles by proteomic analyses of human oligodendrocytes (MO3.13) which were matured using a protocol we developed and treated with either haloperidol (a typical antipsychotic), clozapine (an atypical antipsychotic) or a clozapine + d-serine co-treatment, which has emerged lately as an alternative type of treatment. this was accomplished by employing shotgun proteomics, using nanoeSi-Lc-MS/MS labelfree quantitation. Proteomic analysis revealed biochemical pathways commonly affected by all tested antipsychotics were mainly associated to ubiquitination, proteasome degradation, lipid metabolism and DNA damage repair. Clozapine and haloperidol treatments also affected proteins involved with the actin cytoskeleton and with EIF2 signaling. In turn, metabolic processes, especially the metabolism of nitrogenous compounds, were a predominant target of modulation of clozapine + d-serine treatment. in this context, we seek to contribute to the understanding of the biochemical and molecular mechanisms involved in the action of antipsychotics on oligodendrocytes, along with their possible implications in schizophrenia. Abbreviations ACC Anterior cingulate cortex ACN Acetonitrile ACTB Beta-actin CNPase 2′,3′-Cyclic-nucleotide-3-phosphodiesterase COPS8 COP9 signalosome complex subunit 8 DIA Data-independent acquisition DLPFC Dorsolateral prefrontal cortex DMEM Dulbecco's modified eagle medium DTT Dithiothreitol eIF2 Eukaryotic initiation factor-2

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Section: Resultsmentioning

confidence: 98%

Ubiquitin–proteasome system, lipid metabolism and DNA damage repair are triggered by antipsychotic medication in human oligodendrocytes: implications in schizophrenia

Seabra

Almeida

Reis‐de‐Oliveira

et al. 2020

Sci Rep

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“…Our study also identified lower PC lipids in the skeletal muscle of AAP-treated patients compared to mood stabilizer patients. Previous work has demonstrated that antipsychotics may have effects on peripheral blood and brain PC levels in humans [16,18,19,30,32,46]. Findings from these studies suggest that AAPs may increase peripheral PC levels following treatment compared to healthy controls, psychiatric controls or first-episode AAP- naïve patients.…”

Section: Discussionmentioning

confidence: 94%

“…In vivo studies in rodent models have demonstrated that some antipsychotics, but not all, increase the synthesis of peripheral and central nervous system polyunsaturated fatty acids [40]. This is supported by several peripheral blood lipidomic studies within humans that suggest antipsychotics alter, and often increase, most fatty acid species after treatment ranging from four to 12 weeks [18,19,30,41]. In contrast, Albaugh and colleagues demonstrated that short-term treatment with olanzapine, an AAP associated with a higher rate of insulin resistance and weight gain caused a reduction in free fatty acids within gastrocnemius muscle tissue, which may be supported by our findings here [42].…”

Section: Discussionmentioning

confidence: 99%

“…Given the multiple critical roles that lipids play in cellular mechanisms, the lipidome may aid in understanding the efficacy and side effects of AAP treatment. To this end, several studies have investigated lipidomic changes in peripheral blood samples from various clinical populations treated with AAPs [18,19,27,28,29,30,31]. These studies have demonstrated that AAPs can influence the peripheral lipidome of several lipid species, which may be correlated to treatment efficacy or side effects.…”

Section: Introductionmentioning

confidence: 99%

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Atypical Antipsychotics and the Human Skeletal Muscle Lipidome

et al. 2018

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Atypical antipsychotics (AAPs) are a class of medications associated with significant metabolic side effects, including insulin resistance. The aim of this study was to analyze the skeletal muscle lipidome of patients on AAPs, compared to mood stabilizers, to further understand the molecular changes underlying AAP treatment and side effects. Bipolar patients on AAPs or mood stabilizers underwent a fasting muscle biopsy and assessment of insulin sensitivity. A lipidomic analysis of total fatty acids (TFAs), phosphatidylcholines (PCs) and ceramides (CERs) was performed on the muscle biopsies, then lipid species were compared between treatment groups, and correlation analyses were performed with insulin sensitivity. TFAs and PCs were decreased and CERs were increased in the AAP group relative to those in the mood stabilizer group (FDR q-value <0.05). A larger number of TFAs and PCs were positively correlated with insulin sensitivity in the AAP group compared to those in the mood stabilizer group. In contrast, a larger number of CERs were negatively correlated with insulin sensitivity in the AAP group compared to that in the mood stabilizer group. The findings here suggest that AAPs are associated with changes in the lipid profiles of human skeletal muscle when compared to mood stabilizers and that these changes correlate with insulin sensitivity.

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“…Moreover, given the side effects of antipsychotic medications, there has been a significant drop in medication usage by patients, which can only worsen the symptoms and, therefore, the mental health of the patients. Thus far, we were able to generate panels of lipid [11] and protein biomarkers [12], which may be implemented as biochemical tests for the prediction of a successful drug response. Proteomic signatures have also been used to build a diagnostic test for schizophrenia [13], which was even commercialized, but later discontinued.…”

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confidence: 99%