Profiling of Acylcarnitines in First Episode Psychosis before and after Antipsychotic Treatment

Abstract

Acylcarnitines (ACs) have been shown to have a potential to activate pro-inflammatory signaling pathways and to foster the development of insulin resistance. The first task of the current study was to study the full list of ACs (from C2 to C18) in first episode psychosis (FEP) patients before and after antipsychotic treatment. The second task was to relate ACs to inflammatory and metabolic biomarkers established in the same patient cohort as in our previous studies. Serum levels of ACs were determined with the AbsoluteIDQ p180 kit (BIOCRATES Life Sciences AG, Innsbruck, Austria) using the flow injection analysis tandem mass spectrometry ([FIA]-MS/MS) as well as liquid chromatography ([LC]-MS/MS) technique. Identification and quantification of the metabolites was achieved using multiple reactions monitoring along with internal standards. The comparison of ACs in antipsychotic-naïve first-episode psychosis (FEP) patients (N = 38) and control subjects (CSs, N = 37) revealed significantly increased levels of long-chain ACs (LCACs) C14:1 (p = 0.0001), C16 (p = 0.00002), and C18:1 (p = 0.000001) in the patient group. These changes of LCACs were associated with augmented levels of CARN palmitoyltransferase 1 (CPT-1) (p = 0.006). By contrast, the level of short-chain AC (SCAC) C3 was significantly reduced (p = 0.00003) in FEP patients. Seven months of antipsychotic drug treatment ameliorated clinical symptoms in patients (N = 36) but increased significantly their body mass index (BMI, p = 0.001). These changes were accompanied by significantly reduced levels of C18:1 (p = 0.00003) and C18:2 (p = 0.0008) as well as increased level of C3 (p = 0.01). General linear model revealed the relation of LCACs (C16, C16:1, and C18:1) to the inflammatory markers (epidermal growth factor, IL-2, IL-4, IL-6), whereas SCAC C3 was linked to the metabolic markers (leptin, C-peptide) and BMI. FEP was associated with an imbalance of ACs in patients because the levels of several LCACs were significantly higher and the levels of several SCACs were significantly reduced compared with CSs. This imbalance was modified by 7 months of antipsychotic drug treatment, reversing the levels of both LCACs and SCACs to that established for CSs. This study supports the view that ACs have an impact on both inflammatory and metabolic alterations inherent for FEP.

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

“…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 .…”

“…Regarding antipsychotics, studies have suggested that these drugs may compensate for or reverse lipid pathway dysregulation related to the early stage of the disorder 55,59,63 . Furthermore, fatty acid metabolism and cholesterol biosynthesis have been identified by gene expression studies as key elements in antipsychotic treatment response 64,65 .…”

Function, Detection and Alteration of Acylcarnitine Metabolism in Hepatocellular Carcinoma

“…There are also a small number of studies used GC-MS [88]. In recent years, LC-MS has become the most popular techniques for acylcarnitine detection [89,90,91,92,93]. Reversed-phase liquid chromatography (RPLC), hydrophilic interaction liquid chromatography (HILIC), ion chromatography, and capillary electrophoresis are different options for acylcarnitine separation.…”

Characterizing acyl-carnitine biosignatures for schizophrenia: a longitudinal pre- and post-treatment study

“…Carnitine and acyl-carnitine supplementation have also been used in the treatment of various illnesses (e.g., Alzheimer’s disease, peripheral arterial disease, and celiac disease) for decades with the primary function of regulating cellular bioenergetics 19,20 . Furthermore, accumulated evidence indicates that alterations of carnitines may contribute to certain mental illnesses, including depression 21 , autism spectrum disorder 22 , and schizophrenia 23 . In particular, several recent studies have reported that schizophrenia is associated with an imbalance in redox or oxidative stress status.…”

“…In addition, acetyl-carnitine and levocarnitine 26,27 supplementation therapies have been used to target carnitine deficiency observed in individuals with schizophrenia. Available evidence suggest that acyl-carnitines impact insulin sensitivity, lipid metabolism, inflammatory response, as well as bioenergetic functions 23,28 . Based on these foregoing evidence, we believe acyl-carnitines play an essential role in the pathoetiology of schizophrenia.…”