Feratures of induced brain activity during the analysis of emotional images of carriers of polymorphic variants of genes BDNF and HTR2A

The article presents the results of the study of induced brain activity in carriers of polymorphic variants of the gene of the brain neurotrophic factor BDNF and the gene of the receptor serotonin HTR2A, obtained in the evaluation of stimulatory images of emotionogenic character. The image database used in the work included 573 images assigned to three groups: neutral, positive, negative. 40 people of both sexes aged 19—22 years were examined. The isolation of DNA from the buccal epithelium cells was carried out by PCR (OOO «BiReT», Moscow, Russia). During the genetic analysis, the following DNA sections were analyzed: Neurotrophic factor of the brain BDNF, Serotonin receptor HTR2A. To register the electroencephalogram and evoked potentials (EP) of the brain, a multichannel electroencephalograph Neurovisor-136 (manufactured by ISS, Russia) was used. The recording was carried out unipolarly according to the «5—5» scheme in 128 leads. As a result of the study, it was found that in persons with a heterozygous Val / Met genotype of the cerebral neurotrophic factor BDNF, a more pronounced emotional response to both positive and negative stimuli was observed. For persons with a homozygous Val / Val genotype, a more detailed treatment of the details of the visual image is characteristic. For persons with a dominant homozygous G / G genotype of the HTR2A serotonin receptor gene, weighted decision-making in stimulus analysis is characteristic. In individuals with recessive homozygous genotype A / A HTR2A, evaluating the visual stimulus as negative requires the use of significantly larger brain resources, compared to the carriers of the dominant allele G.

1. Alfimova M.V., Golimbet V.E., Barhatova A.N., Golubev S.A., Korovajceva G.I. Rol' genotip-sredovyh vzaimodeĭstviĭ v razvitii simptomov trevogi i depressii pri stresse, svjazannom s bolezn'ju chlena sem'i [The role of genotype-environment interactions in the development of symptoms of anxiety and depression in stress associated with a family member's illness]. Zhurnal nevrologii i psihiatrii, 2009, no.12, pp. 50—54. (In Rus.).
2. Alfmova M.V., Golimbet V.E. Geny i neirophziologicheskie pokazateli kognitivnykh protsessov: obzor issledovanii [Genes and neurophysiological characteristics of cognitive processes: a review of research]. Zhurnal vysshei nervnoi deyatel'nosti im. I. P. Pavlova, 2011, vol. 61, no. 4, pp. 389—401. (In Rus.).
3. Alfmova M.V., Golimbet V.E., Lebedeva I.S., Korovaitseva G.I., Lezheiko T.V. Vliyanie trevozhnosti i gena COMT na vyzvannye potentsialy mozga i produktivnost' izbiratel'nogo vnimaniya [Effects of anxiety and the COMT gene on cortical evoked potentials and performance effectiveness of selective attention]. Zhurnal Vysshei Nervnoi Deiatelnosti Imeni I P Pavlova, 2014, vol. 64, no. 3, p. 270. Doi:10.7868/s0044467714030034. (In Rus.).
4. Golimbet V.E. Monogennaja model' shizofrenii: smena paradigm [Monogenic model of schizophrenia: a change of paradigms]. Zhurnal nevrologii i psihiatrii, 2016, no. 2, pp. 4—8. doi: 10.17116/jnevro2016116214-8. (In Rus.).
5. Golimbet, V.E., Alfimova M.V., Mitjushina N.G. Polimorfnye varianty gena receptora serotonina (5 HTR2A) i osobennosti lichnosti [Polymorphic variants of the serotonin receptor gene (5 HTR2A) and personality characteristics]. Molecular biology, 2004, I. 83, no. 3, pp. 404—412. (In Rus.).
6. Golimbet V.E., Volel B.A., Dolzhikov A.V., Korovajceva G.I., Isaeva M.I. Associacija polimorfizmov genov receptorov serotonina 5-HTR2A i 5-HTR2C s riskom razvitija depressii u pacientov s ishemicheskoj bolezn'ju serdca [Association of polymorphisms of serotonin 5-HTR2A and 5-HTR2C receptor genes with a risk of depression in patients with coronary heart disease]. Bulletin of Experimental Biology and Medicine, 2013, I. 156, no. 11, pp. 628—631. (In Rus.).
7. Golimbet V.E., Garah Zh.V., Korovajceva G.I., Lezhejko T.V., Zajceva Ju.S., Gurovich I.Ja., Shmukler A.B., Rodionov G.I., Strelec V.B. Svjaz' genov nejrotroficheskogo mozgovogo faktora i perenoschika serotonina s parametrami rannih komponentov vyzvannyh potencialov pri passivnom vosprijatii slov [Relationship between the genes of the neurotrophic brain factor and the serotonin transporter with parameters of the early components of evoked potentials with passive perception of words]. I.P. Pavlov Journal of Higher Nervous Activity, 2016, vol. 66, no. 5, pp. 556—564. (In Rus.).
8. Ermakov P.N., Kovsh E.M., Vorobyeva E.V. Osobennosti vyzvannoj aktivnosti mozga devushek-nositel'nic razlichnyh genotipov po markeru MAOA u-VNTR pri ocenke jemocional'no okrashennyh scen [Features of the evoked brain activity in female carriers of different MAOA -uVNTR genotypes when assessing emotionally charged scenes]. Russian Psychological Journal, 2016, vol. 13, no 4, pp. 232—253. doi: 10.21702/rpj.2016.4.14. (In Rus.).
9. Zainullina A.G., Valiullina A.G., Husnutdinova Je.K. Rol' geneticheskih i sredovyh faktorov riska v formirovanii suicidal'nogo povedenija v hode razvitija [The role of genetic and environmental risk factors in the formation of suicidal behavior in the course of development]. In Malyh S.B., Kovas Ju.V., Gaĭsina D.A. (eds.). Genomics Behavior: Child Development and Education, Tomsk, 2016, pp. 299—331. (In Rus.).
10. Kaluev A.V. BDNF i serotoninovyĭ transporter v patogeneze depressii [BDNF and serotonin transporter in the pathogenesis of depression]. Neurosciences, 2006, vol. 5. no. 7, pp. 31—34. (In Rus.).
11. Kovalenko A.A., Pavlenko V.B. Emocional'naja znachimost' stimula i cherty lichnosti: otrazhenie v patterne vyzvannyh EEG-potencialov [The emotional significance of the stimulus and personality traits: a reflection in the pattern of ERPs]. Nejrofiziologija, 2009, pp. 336—356. (In Rus.).
12. Kovsh E.M. Psihofiziologicheskie i psihologicheskie osobennosti muzhchin i zhenshhin, nositelej polimorfizmov genov MAOA i SOMT, s raznym urovnem agressivnosti. Dissertacija kandidata psihologicheskih nauk [Psychophysiological and psychological characteristics of men and women, carriers of gene polymorphisms MAOA and COMT, with varying levels of aggression. PhD Thesis]. Rostov-on-Don, 2016. 286 p. (In Rus.).
13. Suhodolskaja E.M. Izuchenie allel'nogo polimorfizma genov neĭromediatornyh sistem, associirovannyh s povedencheskimi reakcijami. Dissertacija na soiskanie uchenoj stepeni kandidata biologicheskih nauk [The study of allelic polymorphism of the genes of neurotransmitter systems associated with behavioral responses. Thesis for the degree of candidate of biological sciences. PhD Thesis]. Moscow, 2016. 146 p. (In Rus.).
14. Aas, M., Haukvik, Djurovic, Tesli, Athanasiu, Bjella, T., Hansson, L., Cattaneo, A., Agartz, I., Andreassen, O.A., Melle, I. Interplay between childhood trauma and BDNF val66met variants on blood BDNF mRNA levels and on hippocampus subfields volumes in schizophrenia spectrum and bipolar disorders. Journal of Psychiatric Research, 2014, vol. 59, pp. 14—21.
15. Agartz I., Sedvall G. C., Terenius L., Kulle B., Frigessi A., Hall H. BDNF gene variants and brain morphology in schizophrenia. American Journal of Medical Genetics, 2006, vol. 141, no. 5, pp. 513—523.
16. Brady S.T. Basic Neurochemistry: Principles of Molecular, Cellular and Medical Neurobiology. Academic press, 2012, 1096 p.
17. Barton B., Treister A., Humphrey M., Abedi G., Cramer S.C., Brewer A.A. Paradoxical visuomotor adaptation to reversed visual input is predicted by BDNF Val66Met polymorphism. Journal of Vision, 2014, vol. 14, no. 9, pp. 4. doi: 10.1167/14.9.4 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4125061/
18. Bilder R.M., Volavka J., ál Czobor P., Malhotra A.K., Kennedy J.L., Ni X., Citrome L. Neurocognitive correlates of the COMT Val 158 Met polymorphism in chronic schizophrenia. Biological psychiatry, 2002, vol. 52, no. 7, p. 701—707.
19. Bramon E., Dempster E., Frangou S., McDonald C., Schoenberg P., MacCabe J.H., Walshe M., Sham P., Collier D., Murray R.M. Is there an association between the COMT gene and P300 endophenotypes? European Psychiatry, 2006, vol. 21, p. 70—73.
20. Chen Z.Y., Patel P.D., Sant G., Meng C.X., Teng K.K., Hempstead B.L., et al. Variant brain-derived neurotrophic factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons. The Journal of Neuroscience, 2004, vol. 24, no. 18, pp. 4401—4411.
21. Dai, W., Kaminga, A.C., Wu, X., Wen, S.W., Tan, H., Yan, J., Deng, J., Lai, Z., Liu, A. Brain-Derived Neurotropic Factor Val66Met Polymorphism and Posttraumatic Stress Disorder among Survivors of the 1998 Dongting Lake Flood in China. BioMed Research International, 2017. № 4569698. doi: 10.1155/2017/4569698
22. Delorme A., Makeig S. EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis. Journal of neuroscience methods, 2004, vol. 134, no. 1, pp. 9—21. doi: 10.1016/j.jneumeth.2003.10.009.
23. Dumontheil I., Roggeman C., Ziermans T., Peyrard-Janvid M., Matsson H., Kere J., Klingberg T. Influence of the COMT genotype on working memory and brain activity changes during development. Biological Psychiatry, 2011, vol. 70, p. 222—229.
24. Egan M.F., Kojima M., Callicott J.H., Goldberg T.E., Kolachana B.S., Bertolino A. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell, 2003, vol. 112, no. 2, pp. 257—269.
25. Fan, M., Li, R.H., Hu, M.S., Xiao, L.Y., Zhou, X.D., Ran, M.S., Fang, D.Z. Association of Val66Met polymorphism at brain derived neurotrophic factor gene with depression among Chinese adolescents after Wenchuan earthquake: An 18 months longitudinal study. Physiology and Behavior, 2017, vol. 179, pp. 16— 22.
26. Ji, H., Dai, D., Wang, Y., Jiang, D., Zhou, X., Lin, P., Ji, X., Li, J., Zhang, Y., Yin, H., Chen, R., Zhang, L., Xu, M., Duan, S., Wang, Q. Association of BDNF and BCHE with Alzheimers disease Meta-analysis based on 56 genetic case-control studies of 12,563 cases and 12,622 controls. Experimental and Therapeutic Medicine, 2015, vol. 9., no. 5, pp. 1831—1840.
27. Gatt J.M., Kuan S.A., Dobson-Stone C., Paul R.H., Joffe R.T. Association between BDNF Val66Met polymorphism and trait depression is mediated via resting EEG alpha band activity. Biological Psychology, 2008, vol. 79, no. 2, pp. 275—284.
28. Getzmann S., Gajewski P.D., Hengstler J.G., Falkenstein M., Beste C. BDNF Val66Met polymorphism and goal-directed behavior in healthy elderly — evidence from auditory distraction. Neuroimage, 2013, vol. 64, pp. 290—298. https://doi.org/10.1016/j.neuroimage.2012.08.079.
29. Ho, B.C., Milev, P., O’Leary, D.S., Librant, A., Andreasen, N.C., Wassink, T.H. Cognitive and magnetic resonance imaging brain morphometric correlates of brain-derived neurotrophic factor Val66Met gene polymorphism in patients with schizophrenia and healthy volunteers. Arch. Gen. Psychiatry, 2006, vol. 63, no. 7, pp. 731—740.
30. Laje G., Lally N., Mathews D., Brutsche N., Chemerinski A. Brain-derived neurotrophic factor Val66Met polymorphism and antidepressant efficacy of ketamine in depressed patients. Biological Psychiatry, 2012, vol. 72, no. 11, pp. 27—28.
31. Lebe M., Hasenbring M., Schmieder K. et al. Association of serotonin-1A and -2A receptor promoter polymorphisms with depressive symptoms, functional recovery, and pain in patients 6 months after lumbar disc surgery. Pain, 2013, vol. 154, no. 3, pp. 377—384.
32. Mercader, J.M., Fernández-Aranda, F., Gratacòs, M., Aguera, Z.a, Forcano, L.a, Ribasés, M.df, Villarejo, C., Estivill, X. Correlation of BDNF blood levels with interoceptive awareness and maturity fears in anorexia and bulimia nervosa patients. Journal of Neural Transmission, 2010, vol. 117, no. 4, pp. 505—512.
33. Notaras M., Hill R., van den Buuse M. A role for the BDNF gene Val66Met polymorphism in schizophrenia? A comprehensive review. Neuroscience and Biobehavioral Reviews, 2015, no. 51, pp. 15—30. http:// www.sciencedirect.com/science/article/pii/S0149763414003558.
34. Olofsson J.K., Nordin S., Sequeira H., Polich J. Affective picture processing: an integrative review of ERP findings. Biological psychology, 2008, vol. 77, no. 3, pp. 247—265.
35. Pearson-Fuhrhop K.M., Kleim J.A., Cramer S.C. Brain plasticity and genetic factors. Topics in Stroke Rehabilitation, 2009, vol. 16, no. 4, pp. 282—299.
36. Shimizu E., Hashimoto K., Iyo M. Ethnic difference of the BDNF 196G/A (val66met) polymorphism frequencies: the possibility to explain ethnic mental traits. American Journal of Medical Genetics, 2004, vol. 126B, no. 1, pp. 122—123.
37. Schofield P.R., Williams L.M., Paul R.H., Gatt J.M., Brown K., et al. Disturbances in selective information processing associated with the BDNF Val66Met polymorphism: evidence from cognition, the P300 and fronto-hippocampal systems. Biological Psychology, 2009, vol. 80, no. 2, pp. 176—88.
38. Soltész F., Suckling J., Lawrence P., Tait R., Ooi C., Bentley C., Dodds C.M., Miller S.R., Wille D.R., Byrne M., McHugh S.M., Bellgrove M.A., Croft R.J., Lu B., Bullmore E.T., Nathan P.J. Identification of BDNF Sensitive Electrophysiological Markers of Synaptic Activity and Their Structural Correlates in Healthy Subjects Using a Genetic Approach Utilizing the Functional BDNF Val66Met Polymorphism. PLOS ONE, 2014. https://doi.org/10.1371/journal.pone.0095558.
39. Sujitha S.P., Nair A., Banerjee M. et al. 5-Hydroxytryptamine (serotonin) 2A receptor gene polymorphism is associated with schizophrenia. Indian Journal of Medical Research, 2014, vol. 140, no. 6, pp. 736— 743.
40. Verhagen M., Van Der Meij A.,Van Deurzen P., Janzing J., Arias-Vasquez A., Buitelaar J., Franke B. Meta-analysis of the BDNF Val66Met polymorphism in major depressive disorder: effects of gender and ethnicity. Molecular Psychiatry, 2010, vol. 15, no. 3, pp. 260—271.
41. Vorobyeva, E., Kovsh, E., Yavna, D. Visual evoked potentials elicited by culturally-specific images in women with different levels of hostility. International Journal of Psychophysiology, 2016, vol. 108. pp. 69. doi: 10.1016/j.ijpsycho.2016.07.225.
42. Walitza S., Bové D.S., Romanos M. et al. Pilot study on HTR2A promoter polymorphism, -1438G/A (rs6311) and a nearby copy number variation showed association with onset and severity in early onset obsessive-compulsive disorder. Journal of Neural Transmission, 2012, vol. 119, no. 4, pp. 507—515.