Status message

Not the entire site translated, but only to "Journal"

To Study the Relationship of the Polymorphic Variant of the Dopamine-Beta-Hydroxylase rs1611115 (C-1021T) Gene with the Content of Free Fatty Acids in the Blood Serum of Schizophrenic Patients Treated with Haloperidol and Risperidone

Summary
Relevance. According to various authors, the metabolic syndrome is common in more than 50 % of patients with schizophrenia. One of the reasons for the formation of the metabolic syndrome is the excessive content of non-esterified fatty acids (NEFA) in the blood. It is known that antipsychotic therapy in patients with schizophrenia is associated with an increase in the amount of NEFA in the blood serum. Dopamine-beta-hydroxylase (DßH) is an enzyme involved in the metabolism of dopamine and norepinephrine. Some polymorphic variants of the DßH gene are associated with metabolic disorders such as obesity and type 2 diabetes.
Research objective – to study the association between the polymorphic variant of the dopamine-β-hydroxylase (DßH) rs1611115 gene and the content of non-esterified fatty acids in patients with the first episode of paranoid schizophrenia treated with haloperidol and risperidone.
Material and methods. The study included 212 patients (109 male and 103 female patients) with a diagnosis of «paranoid Schizophrenia, follow-up period less than a year» (F 20.09). The age of the patients was 27 ± 6 years. The control group included 132 healthy volunteers. The patients and representatives of the control group were of Caucasian race, were born and lived in the territory of the Trans-Baikal Territory. They were comparable in gender and age.
Human genomic DNA was isolated from whole blood white blood cells. The analysis of rs1611115 was carried out by polymerase chain reaction with electrophoretic detection of products. The content of NEFA in the blood serum was measured using the colorimetric method for determining copper salts. The level of glycerol in the blood serum was determined by an enzymatic photometric test with glycerol-3-phosphate oxidase. The coefficient of NEFA/glycerol, reflecting the degree of utilization of fatty acids, was calculated.
Results. In patients with the first episode of paranoid schizophrenia, an increased content of NEFA in the blood serum was established even before the start of antipsychotic therapy. At the same time, there were no differences in the amount of NEFA and free serum glycerol between carriers of the C/C and C/T + T/T genotypes. Therapy with haloperidol and risperidone was accompanied by an increase in the concentration of NEFA in the blood serum. In patients treated with risperidone, at the 8th week of the study, the content of NEFA in the blood serum did not differ between carriers of the C/C and C/T + T/T genotypes, while, in the group of patients taking haloperidol, at the 8th week of therapy, the concentration of NEFA in the serum of carriers of the C/C genotype was greater than in carriers of the C/T + T/T genotypes. Different effects of haloperidol and risperidone on the content of NEFA and free glycerol in blood serum were found only in carriers of the C/C genotype.
Conclusion. Therapy with haloperidol and risperidone in patients with the first episode of schizophrenia is accompanied by an increase in the content of NEFA in the blood serum. The severity of these changes depends not only on the neuroleptic used, but also on the carrier of the rs1611115 genotypes. Further pharmacogenetic studies are needed to study the metabolic effects of antipsychotics depending on the genetic characteristics of patients in order to develop a personalized approach to therapy.

Contacts
Ozornin A.S.   aozor@yandex.ru https://orcid.org/0000-0003-0560-7138
Govorin N.V.   https://orcid.org/0000-0003-2955-6347
Sakharov A.V. https://orcid.org/0000-0001-8835-6607
Tereshkov P.P. https://orcid.org/0000-0002-8601-3499
Dutova   A.S. https://orcid.org/0000-0001-8285-6061

CITATION: Ozornin A.S., Govorin N.V., Sakharov A.V., Tereshkov P.P., Dutova A.S. The study of the Polymorphic Variant of the Dopamine-Beta-Hydroxylase rs1611115 (C-1021T) Gene with the Content of Free Fatty Acids in the Blood Serum of Schizophrenic Patients Treated with Haloperidol and Risperidone (Results of an original research) // Sovrem. ter. psih. rasstrojstv [Current Therapy of Mental Disorders]. – 2021. – No. 2. – Pр. 2–10. –
DOI: 10.21265/PSYPH.2021.57.2.001 
CONFLICT OF INTEREST: the authors declare no conflict of interest. 
 

 

It appears your Web browser is not configured to display PDF files. Download adobe Acrobat or click here to download the PDF file.

References: 

1.    Naderyan Fe’li S., Yassini Ardekani S.M., Fallahzadeh H. et al. Metabolic syndrome and 10-year risk of cardiovascular events among schizophrenia inpatients treated with antipsychotics // Med J Islam Repub Iran. – 2019. – Vol. 33. – P. 97.
2.    Shojaeimotlagh V., Hashiehbaf A., Karami M. et al. Prevalence of metabolic syndrome in Iranian patients with schizophrenia: A systematic review and meta-analysis // Diabetes Metab Syndr. – 2019. – Vol. 13, no. 1. – Pp. 143–147. 
3.    Gassó P., Arnaiz J.A., Mas S., Lafuente A. et al. Association study of candidate genes with obesity and metabolic traits in antipsychotic-treated patients with first-episode psychosis over a 2-year period // J Psychopharmacol. – 2020. – Vol. 34, no. 5. – Pp. 514–523. 
4.    Tsvetkova M.V., Khirmanov V.N., Zybina N.N. Rol' neeterifitsirovannykh zhirnykh kislot v patogeneze serdechno-sosudistykh zabolevanii // Arterial'naya gipertenziya. – 2010. – T. 16, № 1. – S. 93–103.
5.    Isaeva A.P., Gapparova K.M., Chekhonina Yu.G. i dr. Svobodnye zhirnye kisloty i ozhirenie: sostoyanie problemy // Voprosy pitaniya. – 2018. – № 1 (87). – S. 18–27. – DOI: 10.24411/0042-8833-2018-10002
6.    Gorobets L.N., Bulanov V.S., Vasilenko L.M. i dr. Metabolicheskie rasstroistva u bol'nykh shizofreniei v protsesse terapii atipichnymi antipsikhoticheskimi preparatami // Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. – 2012. – № 9 (112). – S. 90–96. 
7.    Butrova S.A., Dzgoeva F.Kh. Vistseral'noe ozhirenie – klyuchevoe zveno metabolicheskogo sindroma // Ozhirenie i metabolizm. – 2004. – № 1 (1). – S. 10–16.
8.    Rochlani Y., Pothineni N.V., Kovelamudi S. et al. Metabolic syndrome: pathophysiology, management, and modulation by natural compounds // Ther Adv Cardiovasc Dis. – 2017. – Vol. 11 (8). – Pp. 215–225. – DOI: 10.1177/1753944717711379
9.    Cubells J.F., Sun X., Li W. et al. Linkage analysis of plasma dopamine β-hydroxylase activity in families of patients with schizophrenia // Hum Genet. – 2011. – Vol. 130 (5). – Pp. 635–643. – DOI: 10.1007/s00439-011-0989-6
10.    Gonzalez-Lopez E., Vrana K.E. Dopamine beta-hydroxylase and its genetic variants in human health and disease // J Neurochem. – 2020. – Vol. 152 (2). – Pp. 157–181. – DOI: 10.1111/jnc.14893 
11.    Barbitoff Y.A., Serebryakova E.A., Nasykhova Y.A. et al. Identification of Novel Candidate Markers of Type 2 Diabetes and Obesity in Russia by Exome Sequencing with a Limited Sample Size // Genes (Basel). – 2018. – Vol. 9 (8). – P. 415. – DOI: 10.3390/genes9080415
12.    Punchaichira T.J., Mukhopadhyay A., Kukshal P. et al. Association of regulatory variants of dopamine β-hydroxylase with cognition and tardive dyskinesia in schizophrenia subjects // J Psychopharmacol. – 2020. – Vol. 34 (3). – Pp. 358–369. – DOI: 10.1177/0269881119895539
13.    Barrie E.S., Weinshenker D., Verma A. et al. Regulatory polymorphisms in human DBH affect peripheral gene expression and sympathetic activity // Circ Res. – 2014. – Vol. 115(12). – Pp. 1017–1025. – DOI: 10.1161/CIRCRESAHA.116.304398
14.    Braun K., Oeckl J., Westermeier J. et al. Non-adrenergic control of lipolysis and thermogenesis in adipose tissues // J Exp Biol. – 2018. – Vol. 7. – P. 221. – DOI: 10.1242/jeb.165381 
15.    Taher J., Farr S., Adeli K. Central nervous system regulation of hepatic lipid and lipoprotein metabolism // Curr Opin Lipidol. – 2017. – Vol. 28 (1). – Pp. 32–38. – DOI: 10.1097/MOL.0000000000000373
16.    Alekseev V.V. Meditsinskie laboratornye tekhnologii: rukovodstvo po klinicheskoi laboratornoi diagnostike: v 2 t. / pod red. A.I. Karpishchenko. – Izd. 3-e izd., pererab. i dop. – M.: Izd-vo GEOTAR-Media, 2012. – 472 s.
17.    Rifai N., Rifai N., Warnick G.R. Methods for Clinical Laboratory Measurements of Lipid and Lipoprotein Risk Factors. – Washington DC: AACC Press, 1991. – Pp. 324–357.
18.    Tietz N. Fundamentals of Clinical Chemistry. – 3rd ed. – Philadelphia: W.B. Saunders Co., 1987. – Pp. 809–861.
19.    Gorobets L.N., Bulanov V.S., Vasilenko L.M. i dr. Neirolepticheskie metabolicheskie narusheniya pri lechenii antipsikhoticheskimi sredstvami novogo pokoleniya // Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. – 2014. – № 2 (114). – S. 59–68.
20.    Yang X., Sun L., Zhao A. et al. Serum fatty acid patterns in patients with schizophrenia: a targeted metabonomics study // Transl Psychiatry. – 2017. – Vol. 7 (7). – P. e1176. – DOI: 10.1038/tp.2017.152
21.    Zhou X., Long T., Haas G.L. et al. Reduced Levels and Disrupted Biosynthesis Pathways of Plasma Free Fatty Acids in First-Episode Antipsychotic-Naïve Schizophrenia Patients // Front Neurosci. – 2020. – Vol. 14. – P. 784. – DOI: 10.3389/fnins.2020.00784 
22.    Pripachkina E.A., Filev A.P., Govorin A.V. i dr. Soderzhanie v syvorotke krovi neesterifitsirovannykh zhirnykh kislot i glitserola u beremennykh s idiopaticheskoi zheludochkovoi ekstrasistoliei // Zabaikal'skii meditsinskii vestnik. – 2018. – № 1. – S. 110–114. 
23.    Scigliano G., Ronchetti G., Girotti F. Autonomic nervous system and risk factors for vascular disease. Effects of autonomic unbalance in schizophrenia and Parkinson's disease // Neurol Sci. – 2008. – Vol. 29, no. 1. – Pp. 15–21.
24.    Yang J., Chen T., Sun L. et al. Potential metabolite markers of schizophrenia // Mol Psychiatry. – 2013. – Vol. 18, no. 1. – Pp. 67–78. 
25.    Wang C.J., Zhang Z.J., Sun J. et al. Serum free Fatty acids and glucose metabolism, insulin resistance in schizophrenia with chronic antipsychotics // Biol Psychiatry. – 2006. – Vol. 60, no. 12. – Pp. 1309–1313. 
26.    Ward K.M., Yeoman L., McHugh C. et al. Atypical Antipsychotic Exposure May Not Differentiate Metabolic Phenotypes of Patients with Schizophrenia // Pharmacotherapy. – 2018. – Vol. 38, no. 6. – Pp. 638–650.
27.    Dayabandara M., Hanwella R., Ratnatunga S. et al. Antipsychotic-associated weight gain: management strategies and impact on treatment adherence // Neuropsychiatr Dis Treat. – 2017. – Vol. 13. – Pp. 2231–2241. – DOI: 10.2147/NDT.S113099
 

Яндекс.Метрика