Skeletal Muscle DNA Methylation Modifications and Psychopharmacologic Treatment in Bipolar Disorder

Overview

Journal Eur Neuropsychopharmacol

Publisher Elsevier

Specialties Pharmacology
Psychiatry

Date 2019 Oct 23

PMID 31635791

Citations 3

Authors

Kyle J Burghardt

Bradley H Howlett

Elani Sanders

Sabrina E Dass

Zaher Msallaty

Abduallah Mallisho

Berhane Seyoum

Zhengping Yi

Affiliations

Soon will be listed here.

Abstract

Both severe mental illness and atypical antipsychotics have been independently associated with insulin resistance and weight gain. Altered regulation of skeletal muscle DNA methylation may play a role. We aimed to evaluate DNA methylation modifications in human skeletal muscle samples to further understand its potential role in the metabolic burden observed in psychiatric patients and psychopharmacologic treatment. Subjects were included in our study if they had a bipolar diagnosis and were currently treated with a mood stabilizer or atypical antipsychotic. A healthy control group free of psychiatric or physical disease was also included for comparisons. Anthropometric, BMI and hemoglobin A1C (HbA1C%) were measured. Fasting skeletal muscle biopsies were obtained and methylation levels of 5-methycytosine (5-mC), 5-hydroxymethylcytosine (5-hmC) and 5-formylcytosine (5-fC) were measured. Skeletal muscle global methylation of 5-mC and 5-fC were significantly higher in bipolar subjects compared to healthy controls. 5-mC was significantly higher in the AAP group compared to the mood stabilizer group. Significant correlations were observed between 5-fC methylation and HbA1C%. Our findings suggest that psychiatric disease and treatment may influence some methylation measures in the skeletal muscle of patients with bipolar disorder, which may be further influenced by medication treatment.

Citing Articles

DNA methylation and histone modifications associated with antipsychotic treatment: a systematic review.

Marques D, Vaziri N, Greenway S, Bousman C Mol Psychiatry. 2024; 30(1):296-309.

PMID: 39227433 DOI: 10.1038/s41380-024-02735-x.

DNA methylation may partly explain psychotropic drug-induced metabolic side effects: results from a prospective 1-month observational study.

Dubath C, Porcu E, Delacretaz A, Grosu C, Laaboub N, Piras M Clin Epigenetics. 2024; 16(1):36.

PMID: 38419113 PMC: 10903022. DOI: 10.1186/s13148-024-01648-4.

Drug Response-Related DNA Methylation Changes in Schizophrenia, Bipolar Disorder, and Major Depressive Disorder.

Zhou J, Li M, Wang X, He Y, Xia Y, Sweeney J Front Neurosci. 2021; 15:674273.

PMID: 34054421 PMC: 8155631. DOI: 10.3389/fnins.2021.674273.

References

Tse M, Ashbury J, Zwingerman N, King W, Taylor S, Pang S . A refined, rapid and reproducible high resolution melt (HRM)-based method suitable for quantification of global LINE-1 repetitive element methylation. BMC Res Notes. 2011; 4:565. PMC: 3284418. DOI: 10.1186/1756-0500-4-565. View

Caruso M, Ma D, Msallaty Z, Lewis M, Seyoum B, Al-Janabi W . Increased interaction with insulin receptor substrate 1, a novel abnormality in insulin resistance and type 2 diabetes. Diabetes. 2014; 63(6):1933-47. PMC: 4030113. DOI: 10.2337/db13-1872. View

Lockwood L, Youssef N . Systematic Review of Epigenetic Effects of Pharmacological Agents for Bipolar Disorders. Brain Sci. 2017; 7(11). PMC: 5704161. DOI: 10.3390/brainsci7110154. View

Sheehan D, Lecrubier Y, Sheehan K, Amorim P, Janavs J, Weiller E . The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1999; 59 Suppl 20:22-33;quiz 34-57. View

Mill J, Tang T, Kaminsky Z, Khare T, Yazdanpanah S, Bouchard L . Epigenomic profiling reveals DNA-methylation changes associated with major psychosis. Am J Hum Genet. 2008; 82(3):696-711. PMC: 2427301. DOI: 10.1016/j.ajhg.2008.01.008. View

Yatham L, Kennedy S, Parikh S, Schaffer A, Bond D, Frey B . Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018; 20(2):97-170. PMC: 5947163. DOI: 10.1111/bdi.12609. View

Shanely R, Zwetsloot K, Triplett N, Meaney M, Farris G, Nieman D . Human skeletal muscle biopsy procedures using the modified Bergström technique. J Vis Exp. 2014; (91):51812. PMC: 4828068. DOI: 10.3791/51812. View

Burghardt K, Goodrich J, Dolinoy D, Ellingrod V . DNA methylation, insulin resistance and second-generation antipsychotics in bipolar disorder. Epigenomics. 2015; 7(3):343-52. PMC: 4501018. DOI: 10.2217/epi.15.5. View

Burghardt K, Seyoum B, Mallisho A, Burghardt P, Kowluru R, Yi Z . Atypical antipsychotics, insulin resistance and weight; a meta-analysis of healthy volunteer studies. Prog Neuropsychopharmacol Biol Psychiatry. 2018; 83:55-63. PMC: 5817633. DOI: 10.1016/j.pnpbp.2018.01.004. View

10.

Geetha T, Langlais P, Luo M, Mapes R, Lefort N, Chen S . Label-free proteomic identification of endogenous, insulin-stimulated interaction partners of insulin receptor substrate-1. J Am Soc Mass Spectrom. 2011; 22(3):457-66. PMC: 3072570. DOI: 10.1007/s13361-010-0051-2. View

11.

Alladi C, Etain B, Bellivier F, Marie-Claire C . DNA Methylation as a Biomarker of Treatment Response Variability in Serious Mental Illnesses: A Systematic Review Focused on Bipolar Disorder, Schizophrenia, and Major Depressive Disorder. Int J Mol Sci. 2018; 19(10). PMC: 6213157. DOI: 10.3390/ijms19103026. View

12.

DeFronzo R, Tripathy D . Skeletal muscle insulin resistance is the primary defect in type 2 diabetes. Diabetes Care. 2009; 32 Suppl 2:S157-63. PMC: 2811436. DOI: 10.2337/dc09-S302. View

13.

Pillinger T, Beck K, Gobjila C, Donocik J, Jauhar S, Howes O . Impaired Glucose Homeostasis in First-Episode Schizophrenia: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2017; 74(3):261-269. PMC: 6352957. DOI: 10.1001/jamapsychiatry.2016.3803. View

14.

Abdul-Ghani M, DeFronzo R . Pathogenesis of insulin resistance in skeletal muscle. J Biomed Biotechnol. 2010; 2010:476279. PMC: 2860140. DOI: 10.1155/2010/476279. View

15.

Rahimov F, King O, Leung D, Bibat G, Emerson Jr C, Kunkel L . Transcriptional profiling in facioscapulohumeral muscular dystrophy to identify candidate biomarkers. Proc Natl Acad Sci U S A. 2012; 109(40):16234-9. PMC: 3479603. DOI: 10.1073/pnas.1209508109. View

16.

Rimessi A, Pavan C, Ioannidi E, Nigro F, Morganti C, Brugnoli A . Protein Kinase C β: a New Target Therapy to Prevent the Long-Term Atypical Antipsychotic-Induced Weight Gain. Neuropsychopharmacology. 2017; 42(7):1491-1501. PMC: 5436118. DOI: 10.1038/npp.2017.20. View

17.

Swathy B, Banerjee M . Understanding epigenetics of schizophrenia in the backdrop of its antipsychotic drug therapy. Epigenomics. 2017; 9(5):721-736. DOI: 10.2217/epi-2016-0106. View

18.

Grande I, Berk M, Birmaher B, Vieta E . Bipolar disorder. Lancet. 2015; 387(10027):1561-1572. DOI: 10.1016/S0140-6736(15)00241-X. View

19.

Melka M, Laufer B, McDonald P, Castellani C, Rajakumar N, OReilly R . The effects of olanzapine on genome-wide DNA methylation in the hippocampus and cerebellum. Clin Epigenetics. 2014; 6(1):1. PMC: 3895844. DOI: 10.1186/1868-7083-6-1. View

20.

Backlund L, Wei Y, Martinsson L, Melas P, Liu J, Mu N . Mood Stabilizers and the Influence on Global Leukocyte DNA Methylation in Bipolar Disorder. Mol Neuropsychiatry. 2016; 1(2):76-81. PMC: 4996001. DOI: 10.1159/000430867. View