Features of omega-3/omega-6 fatty acid metabolism in children with epileptic encephalopathies and autism spectrum disorders

Authors

  • L.G. Kyrylova SI «Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova of the NAMS of Ukraine», Kyiv, Ukraine
  • О.О. Yuzva SI «Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova of the NAMS of Ukraine», Kyiv, Ukraine
  • O.O. Miroshnikov SI «Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova of the NAMS of Ukraine», Kyiv, Ukraine

DOI:

https://doi.org/10.15574/PP.2022.90.31

Keywords:

autism spectrum disorders, epileptic seizures, essential fatty acids, monounsaturated fatty acids, unsaturated fatty acids, fatty acid unsaturation index

Abstract

Purpose - to study the level of the serum fatty acids in children with autism spectrum disorders (ASD); to compare omega-6/omega-3 ratio depending of the clinical manifestation epileptic encephalopathy (EE) and ASD  and electroencephalography data (EEG).

Materials and methods. The study examined 101 children aged 2-6 years (mean age 4.02±0.95 years) with clinical manifestations ASD, who had been treated in a neuropsychiatric unit of the SI «Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova of the NAMS of Ukraine». According to the clinical features of epileptic encephalopathies and ASD, EEG monitoring data formed three groups: the group 1 - 35 children with clinical manifestations of ASD but without epileptic seizures and epileptiform changes in the EEG; the group 2 - 32 children with cognitive disintegration, clinical manifestations of ASD in which parents and health professionals did not note or noted a single history of epileptic seizures, but with epileptiform changes in the EEG; the group 3 - 34 children with clinical manifestations of ASD in which parents or health professionals have noted epileptic seizures and epileptiform changes in the EEG. In all children the level of blood fatty acids was determined by gas-liquid chromatography.

Results. Indicators of fatty acid concentration indicate that the serum of children showed a significantly low level of omega-3 polyunsaturated fatty acids (PUFA) and saturation of omega-6 po PUFA in all groups of children. The level of concentration of the main metabolites of essential fatty acids reflects the imbalance due to deficiency of essential linolenic acid and its metabolite - docosapentaenoic acid, especially in children with ASD and epileptiform changes in the EEG (group 2), (p<0.01). Among the omega-6 PUFA found a high content of essential linoleic acid and its metabolite - arachidonic acid, which causes the total excess of this group of PUFA, more pronounced in the groups 1 and 2.

The level of index of unsaturated fatty acids in children from the group 1 was 10.1, in children from the group 2 - 9.8, and in the group 3 - 9.3. The obtained results of the assessment of the unsaturation index reflect the lower level of index of unsaturated fatty acids in children of the group 3 who have manifestations of ASD and epileptic seizures compared to other groups (p<0.05, r=0.99).

Conclusions. The data is a reliable evidence that children with ASD, epileptic seizures and epileptiform changes in the EEG have higher levels of omega-6 PUFA and arachidonic acid and omega-3 and docosahexaenoic acid deficiency. The most pronounced imbalance in both the ratio of omega-6 / omega-3 and arachidonic acid / docosahexaenoic acid in the group of children with ASD and epileptiform changes in the EEG. These results may support the theory of changes in the properties of the phospholipid membrane and ion channels of nerve cells and require further study using electron microscopy.

The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies.

No conflict of interests was declared by the authors.

References

American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (Fifth ed.). Arlington, VA: American Psychiatric Publishing. https://doi.org/10.1176/appi.books.9780890425596

Anagnostou E, Taylor MJ. (2011). Review of neuroimaging in autism spectrum disorders: what have we learned and where we go from here? Mol Autism. 2: 4. https://doi.org/10.1186/2040-2392-2-4; PMid:21501488 PMCid:PMC3102613

ASD. (2013). A Guide to DSM-5: Autism Spectrum Disorders. Medscape.com.

ASD. (2015). Autistic spectrum disorders (epidemiology revive). National Academy of Sciences. US.

Bell JG, MacKinlay EE, Dick JR et al. (2004). Essential fatty acids and phospholipase A2 in autistic spectrum disorders. Prostaglandins Leukot Essent Fatty Acids. 71 (4): 201-204. https://doi.org/10.1016/j.plefa.2004.03.008; PMid:15301788

Boland LM, Drzewiecki MM et al. (2009). Inhibitory effects of polyunsaturated fatty acids on Kv4 / KChIP potassium channels. Am j Physiol. 296: C1003-C1014. https://doi.org/10.1152/ajpcell.00474.2008; PMid:19261906 PMCid:PMC2681380

Breyer RM, Bagdassarian CK, Myers SA, Breyer MD. (2001). Prostanoid receptors: subtypes and signaling. Annu Rev Pharmacol Toxicol. 41: 661-690. https://doi.org/10.1146/annurev.pharmtox.41.1.661; PMid:11264472

Brigandi S et al. (2015). Autistic Children Ehibit Decreased Levels of Essential Fatty Acids in Red Blood Cells. Int J Mol Sci. 16: 1061-1074. https://doi.org/10.3390/ijms160510061; PMid:25946342 PMCid:PMC4463632

Canitano R, Zappella M. (2006). Autistic epileptiform regression. Funct Neurol. 21 (2): 97-101.

Casanova MF, Buxhoeveden DP, Switala AE, Roy E. (2002). Minicolumnar pathology in autism. Neurology. 58: 428-432. https://doi.org/10.1212/WNL.58.3.428; PMid:11839843

CDC. (2014). CDC estimates 1 in 68 children has been identified with autism spectrum disorder. URL: https://www.cdc.gov/media/releases/2014/p0327-autism-spectrum-disorder.html.

DeMar JC Jr, Lee HJ et al. (2006). Brain elongation of linoleic acid is a negligible source of the arachidonate in brain phospholipids of adult rats. Biochim Biophys Acta. 1761: 1050-1059. https://doi.org/10.1016/j.bbalip.2006.06.006; PMid:16920015

Guizy M, David M et al. (2008). Modulation of the atrial specific Kv1.5 channel by the n-3 polyunsaturated fatty acid, alpha-linolenic acid. J Mol Cell Cardiol. 44: 323-335. https://doi.org/10.1016/j.yjmcc.2007.11.004; PMid:18155022

Hartley-McAndrew M et al. (2010). Autism spectrum disorders: correlation between aberrant behavior. EEG abnormalities and seizures. https://doi.org/10.4081/ni.2010.e10; PMid:21577334 PMCid:PMC3093215

Kanemura H et al. (2013). Can EEG characteristics predict development of epilepsy in autistic children? Eur J Pediatr Neurol. 17: 232-237. https://doi.org/10.1016/j.ejpn.2012.10.002; PMid:23122323

Kazuyuki Nakamura, Hirofumi Kodera, Tenpei Akita et al. (2013). De Novo Mutations in GNAO1, Encoding a Gαo Subunit of Heterotrimeric G Proteins, Cause Epileptic Encephalopathy. Am J Hum Genet. 93 (3): 496-505. https://doi.org/10.1016/j.ajhg.2013.07.014; PMid:23993195 PMCid:PMC3769919

King BH. (2015). Promising forecast for autism spectrum disorders. Journal of the American Medical Association. 313 (15): 1518-1519. https://doi.org/10.1001/jama.2015.2628; PMid:25898047

Kumaraku А et al. (2015). Epilepsy in autism spectrum disorders. EJPN-journal.

Lawrence GD. (2010). The fats of life: essential fatty acids in health and disease. New Brunswick: Rutgers University Press. https://doi.org/10.36019/9780813549194

Legler DF, Bruckner M et al. (2010). Prostaglandin E2 at new glance: novel insights in functional diversity offer therapeutic chances. Int J Biochem Cell Biol. 42 (2): 198-201. https://doi.org/10.1016/j.biocel.2009.09.015; PMid:19788928

Mazahery H, Stonehouse W et al. (2017). Relationship between Long Chain n-3 Polyunsaturated Fatty Acids and Autism Spectrum Disorder: Systematic Review and Meta-Analysis of Case-Control and Randomised Controlled Trials. Nutrients. 9 (2): 155. https://doi.org/10.3390/nu9020155; PMid:28218722 PMCid:PMC5331586

Mostafa GA, Al-Ayadhi LY. (2015). Reduced levels of plasma polyunsaturated fatty acids and serum carnitine in autistic children: Relation to gastrointestinal manifestations. Behav. Brain Funct. 11: 4. https://doi.org/10.1186/s12993-014-0048-2; PMid:25757041 PMCid:PMC4332725

Muhin KYu, Petruhin AS, Holin AA. (2011). Epilepticheskie entsefalopatii i shozhie sindromyi u detey. M. ArtServis Ltd. 680: 396-426.

Mukhin KYu. (2012). Cognitive epileptiform disintegration: definition, diagnosis, therapy. Russian journal of child neurology. 7 (1): 3-20.

Mulligan CK, Trauner DA. (2014). Incidence and Behavioral Correlates of Epileptiform Abnormalities in Autism Spectrum Disorders. J of Autism and Dev Disord. 44 (2): 452-458. https://doi.org/10.1007/s10803-013-1888-6; PMid:23872941

Nabbout R, Dulac O. (2003). Epileptic encephalopathies: a brief overview. J Clin Neurophysiol. 20 (6): 393-397. https://doi.org/10.1097/00004691-200311000-00002; PMid:14734929

Partela N et al. (2016). Omega-3 and Omega-6 Polyunsaturated Fatty Acid Level and Correlation with Symptoms in Children with Attention Deficit Hyperactivity Disorder, Autism Spectrum Disorder and Typically Developing Controls.PLOS ONE. 11: 5. https://doi.org/10.1371/journal.pone.0156432; PMid:27232999 PMCid:PMC4883772

Sugimoto Y, Narumiya S. (2007). Prostaglandin E receptors. J Biol Chem. 282 (16): 11613-11617. https://doi.org/10.1074/jbc.R600038200; PMid:17329241

Tostes MH, Polonini HC et al. (2013). Fatty acid and phospholipase A2 plasma levels in children with autism. Trends Psychiatry Psychother. 35: 76-80. https://doi.org/10.1590/S2237-60892013000100009; PMid:25923188

Tuchman R, Hirtz D, Mamounas LA. (2013). NINDS epilepsy and autism spectrum disorders workshop report. Neurology. 29; 81 (18): 1630-1636. https://doi.org/10.1212/WNL.0b013e3182a9f482; PMid:24089385 PMCid:PMC3806917

Valvo G et al. (2015). Temporal lobe connects regression and macrocephaly to autism spectrum disorders. Eur Child Adolesc Psychiatry: 1-9. https://doi.org/10.1007/s00787-015-0746-9; PMid:26224585 PMCid:PMC4820486

Yang X et al. (2011). Effects of fatty acid unsaturation numbers on membrane fluidity and α-secretase-dependent amyloid precursor protein processing. Neurochem Int. 58 (3): 321-329. https://doi.org/10.1016/j.neuint.2010.12.004; PMid:21184792 PMCid:PMC3040984

Yasuhara A. (2010). Corelation between EEG abnormalities and symptoms of autism spectrum disorder (ASD). Brain Dev. 32: 791-798. https://doi.org/10.1016/j.braindev.2010.08.010; PMid:20826075

Yehuda S, Rabinovitz S, Mostofsky DI. (1999). Essential fatty acids are mediators of brain biochemistry and cognitive functions. J Neurosci Res. 56: 565-570. https://doi.org/10.1002/(SICI)1097-4547(19990615)56:6<565::AID-JNR2>3.0.CO;2-H

Young G, Conquer J. (2005). Omega-3 fatty acids and neuropsychiatric disorders. Reprod Nutr Dev. 45: 1-28. https://doi.org/10.1051/rnd:2005001; PMid:15865053

Published

2022-06-30