1. На главную
  2. Электронные версии
  3. Журнал высшей нервной деятельности им. И.П. Павлова
  4. T. 72, № 4, 2022

Журнал высшей нервной деятельности им. И.П. Павлова, 2022, T. 72, № 4, стр. 471-486

Влияние стресса и генетической предрасположенности на симптомы психопатологии

Г. Г. Князев 1, *, А. В. Бочаров 1, 2, А. Н. Савостьянов 1, 2, 3, Е. А. Прошина 1

1 Федеральное государственное бюджетное научное учреждение “Научно-исследовательский институт нейронаук и медицины”
Новосибирск, Россия

2 Новосибирский государственный университет
Новосибирск, Россия

3 Федеральный исследовательский центр институт цитологии и генетики СО РАН
Новосибирск, Россия

* E-mail: knyazev@physiol.ru

Поступила в редакцию 31.10.2021
После доработки 04.04.2022
Принята к публикации 26.04.2022

Аннотация

Литературные данные свидетельствуют о том, что присутствие S-аллеля гена транспортера серотонина (5-HTTLPR) связано с повышенным риском развития депрессии у лиц, которые в недалеком прошлом испытывали влияние стресса. Однако существует много работ, в том числе метаанализов, в которых подобная ассоциация не подтверждается. Несогласованность результатов можно отчасти объяснить тем, что связь между полиморфизмом 5-HTTLPR, стрессовыми жизненными событиями и симптомами психических расстройств может быть не столь прямой и очевидной. В данной работе мы провели анализ механизмов взаимодействия полиморфизма 5-HTTLPR с уровнем стрессовых жизненных событий в их влиянии на возникновение симптомов психических расстройств через промежуточные переменные, в качестве которых рассматривались показатели коннективности сетей покоя и способы регуляции эмоций. Было выявлено, что реакции мозга на повышенный уровень стресса не отличаются у носителей разных аллелей гена транспортера серотонина, но у носителей LL-генотипа эти реакции могут понижать вероятность возникновения депрессии, а у носителей S-аллеля, наоборот, ее провоцировать. Это различие объясняется тем, что у носителей LL-генотипа наблюдается тенденция к переосмыслению стрессовых ситуаций в менее негативном свете, что препятствует возникновению психопатологии, тогда как у носителей S-аллеля реакция на стресс сопровождается появлением повторяющихся навязчивых мыслей и тщетных попыток подавить их, что в конечном итоге может привести к депрессии.

Ключевые слова: 5-HTTLPR, депрессия, стресс, регуляция эмоций, подавление, переоценка, руминации, ЭЭГ, сети покоя

Список литературы

  1. Дорошева Е.А., Князев Г.Г. Психометрические свойства трех опросников регуляции эмоций. Современные проблемы клинической психологии и психологии личности. 2017. 193–198.

  2. Abbott A. Psychiatric genetics: the brains of the family. Nature. 2008. 454: 154–157.

  3. Ahlfors S.P., Han J., Belliveau J.W., Hamalainen M.S. Sensitivity of MEG and EEG to source orientation. Brain Topogr. 2010. 23: 227–232.

  4. Aldao A., Nolen-Hoeksema S., Schweizer S. Emotion regulation strategies across psychopathology: A meta-analytic review. Clinical psychology review. 2010. 30: 217–237.

  5. Antypa N., Van der Does A.J.W. Serotonin transporter gene, childhood emotional abuse and cognitive vulnerability to depression. Genes, Brain and Behavior. 2010. 9: 615–620.

  6. Arango V., Huang Y.Y., Underwood M.D., Mann J.J. Genetics of the serotonergic system in suicidal behavior. J. Psychiatr. Res. 2003. 37: 375–386.

  7. Baron R.M., Kenny D.A. The moderator–mediator variable distinction in social psychological research: Conceptual, strategic, and statistical considerations. Journal of Personality & Social Psychology. 1986. 51: 1173–1182.

  8. Beck A.T., Steer R.A., Brown G.K. Manual for the Beck Depression Inventory-II. San Antonio, TX: Psychological Corporation. 1996.

  9. Beevers C.G., Pacheco J., Clasen P., McGeary J.E., Schnyer D. Prefrontal morphology 5-HTTLPR polymorphism and biased attention for emotional stimuli. Genes Brain Behav. 2010. 9: 224–233.

  10. Beevers C.G., Wells T.T., Ellis A.J., McGeary J.E. Association of the serotonin transporter gene promoter region (5-HTTLPR) polymorphism with biased attention for emotional stimuli. J Abnorm Psychol. 2009. 118: 670–681.

  11. Ben-Simon E., Podlipsky I., Arieli A., Zhdanov A., Hendler T. Never resting brain: simultaneous representation of two alpha related processes in humans. PLoS ONE. 2008. 3: e3984.

  12. Beusenberg M., Orley J. World Health Organization. A user’s guide to the Self-reporting Questionnaire (SRQ). Geneva: Division of Mental Health World Health Organization. 1994.

  13. Bosker F.J., Hartman C.A., Nolte I.M., Prins B.P., Terpstra P., Posthuma D., van Veen T., Willemsen G., DeRijk RH., de Geus E.J., Hoogendijk W.J., Sullivan P.F., Penninx B.W., Boomsma D.I., Snieder H., Nolen W.A. Poor replication of candidate genes for major depressive disorder using genome-wide association data. Mol Psychiatry. 2010. 16: 516–532.

  14. Brookes M.J., Liddle E.B., Hale J.R., Woolrich M.W., Luckhoo H., Liddle P.F., Morris P.G. Task induced modulation of neural oscillations in electrophysiological brain networks. NeuroImage. 2012. 63: 1918–1930.

  15. Brookes M.J., Woolrich M., Luckhoo H., Price D., Hale J.R., Stephenson M.C., Barnes G.R., Smith S.M., Morris P.G. Investigating the electrophysiological basis of resting state networks using magnetoencephalography. Proc Natl Acad Sci U S A. 2011. 108: 16783–16788.

  16. Butler E.A., Egloff B., Wilhelm F.H., Smith N.C., Erickson E.A., Gross J.J. The social consequences of expressive suppression. Emotion. 2003. 3: 48–67.

  17. Caspi A., Hariri A.R., Holmes A., Uher R., Moffitt T.E. Genetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits. Am J Psychiatry. 2010. 167: 509–527.

  18. Caspi A., Sugden K., Moffitt T.E., Taylor A., Craig I.W., Harrington H., McClay J., Mill J., Martin J., Braithwaite A., Poulton R. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science. 2003. 301: 386–389.

  19. Chen J.L., Ros T., Gruzelier J.H. Dynamic changes of ICA derived EEG functional connectivity in the resting state. Hum Brain Mapp. 2012. 34: 852–868.

  20. Clarke H., Flint J., Attwood A.S., Munafo M.R. Association of the 5-HTTLPR genotype and unipolar depression: a meta-analysis. Psychol Med. 2010. 40: 1767–1778.

  21. Clasen P.C., Wells T.T., Knopik V.S., McGeary J.E., Beevers C.G. 5-HTTLPR and BDNF Val66Met polymorphisms moderate effects of stress on rumination. Genes, Brain and Behavior. 2011. 10(7): 740–746.

  22. Dannlowski U., Konrad C., Kugel H., Zwitserlood P., Domschke K., Schoning S., Ohrmann P., Bauer J., Pyka M., Hohoff C., Zhang W., Baune B.T., Heindel W., Arolt V., Suslow T. Emotion specific modulation of automatic amygdala responses by 5-HTTLPR genotype. NeuroImage. 2010. 53: 893–898.

  23. De Pasquale F., Marzetti L. Temporal and spectral signatures of the default mode network. Magnetoencephalography Berlin Heidelberg: Springer-Verlag. 2014. p. 451–476.

  24. Dolan M., Anderson I.M., Deakin J.F.W. Relationship between 5-HT function and impulsivity and aggression in male offenders with personality disorders. The British Journal of Psychiatry. 2001. 178(4): 352–359.

  25. Doppelmayr M., Klimesch W., Pachinger T., Ripper B. Individual differences in brain dynamics: important implications for the calculation of event-related band power. Biol Cybern. 1998. 79: 49–57.

  26. Duncan L.E., Keller M.C. A critical review of the first ten years of candidate gene-by-environment interaction research in psychiatry. Am J Psychiatry. 2011. 168: 1041–1049.

  27. Efron B., Tibshirani R.J. An introduction to the bootstrap. Boca Raton, FL: CRC Press. 1993.

  28. Forman S.D., Cohen J.D., Fitzgerald M., Eddy W.F., Mintun M.A., Noll D.C. Improved assessment of significant activation in functional magnetic resonance imaging (fMRI): use of a cluster-size threshold. Magn Reson Med. 1995. 33: 636–647.

  29. Fox M.D., Raichle M.E. Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci. 2007. 8: 700–711.

  30. Fox M.D., Snyder A.Z., Vincent J.L., Corbetta M., Van Essen D.C., Raichle M.E. The human brain is intrinsically organized into dynamic anticorrelated functional networks. Proc Natl Acad Sci USA. 2005. 102: 9673–9678.

  31. Fuchs M., Wagner M., Kastner J. Boundary element method volume conductor models for EEG source reconstruction. Clin Neurophysiol. 2001. 112: 1400–1407.

  32. Gale A. Electroencephalographic studies of extraversion–introversion: a case study in the psychophysiology of individual differences. Personality and Individual Differences. 1983. 4: 371–380.

  33. Gillihan S.J., Rao H., Wang J., Detre J.A., Breland J., Sankoorikal G.M.V., Brodkin E.S., Farah M.J. Serotonin transporter genotype modulates amygdala activity during mood regulation. Soc Cogn Affect Neurosci. 2010. 5: 1–10.

  34. Gilman T.L., Latsko M., Matt L., Flynn J., de la Cruz Cabrera O., Douglas D., Jasnow A.M., Coifman K.G. Variation of 5-HTTLPR and deficits in emotion regulation: a pathway to risk? Psychol Neurosci. 2015. 8: 397–413.

  35. Giuliani N., Gross J.J. Reappraisal. In D. Sander & K. Scherer (Eds.), Oxford companion to the affective sciences, NewYork, NY: Oxford University Press. 2009. 329–330.

  36. Greicius M.D., Supekar K., Menon V., Dougherty R.F. Resting-state functional connectivity reflects structural connectivity in the default mode network. Cereb Cortex. 2009. 19: 72–78.

  37. Gross J.J., John O.P. Individual differences in two emotion regulation processes: Implications for affect, relationships, and well–being. Journal of Personality and Social Psychology. 2003. 85: 348–362.

  38. Hamilton J.P., Chen M.C., Gotlib I.H. Neural systems approaches to understanding major depressive disorder: an intrinsic functional organization perspective. Neurobiol Dis. 2013. 52: 4–11.

  39. Hamilton J.P., Furman D.J., Chang C., Thomason M.E., Dennis E., Gotlib I.H. Default-mode and task-positive network activity in major depressive disorder: implications for adaptive and maladaptive rumination. Biological Psychiatry. 2011. 70: 327–333.

  40. Hariri A.R., Mattay V.S., Tessitore A., Kolachana B., Fera F., Goldman D., Egan M.F., Weinberger D.R. Serotonin transporter genetic variation and the response of the human amygdala. Science. 2002. 297: 400–403.

  41. Hayes A. An introduction to mediation moderation and conditional process analysis: A regression-based approach New York: Guilford. 2013.

  42. Heinz A., Braus D.F., Smolka M.N., Wrase J., Puls I., Hermann D., Klein S., Grusser S.M., Flor H., Schumann G., Mann K., Buchel C. Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter. Nat Neurosci. 2005. 8: 20–21.

  43. Hipp J.F., Hawellek D.J., Corbetta M., Siegel M., Engel A.K. Large-scale cortical correlation structure of spontaneous oscillatory activity. Nat Neurosci. 2012. 15: 884–890.

  44. Holmes A. Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease. Neurosci Biobehav Rev. 2008. 32: 1293–1314.

  45. Holmes T.H., Rahe R.H. The social readjustment rating scale. J Psychosom Res. 1967. 11: 213–218.

  46. Hu X., Oroszi G., Chun J., Smith T.L., Goldman D., Schuckit M.A. An expanded evaluation of the relationship of four alleles to the level of response to alcohol and the alcoholism risk. Alcohol Clin Exp Res. 2005. 29: 8–16.

  47. Joormann J., Gotlib I.H. Emotion regulation in depression: Relation to cognitive inhibition. Cognition and Emotion. 2010. 24: 281–298.

  48. Knyazev G.G., Bazovkina D.V., Savostyanov A.N., Naumenko V.S., Kuznetsova V.B., Proshina E.A. Suppression mediates the effect of 5-HTTLPR by stress interaction on depression. Scandinavian journal of psychology. 2017. 58(5): 373–378.

  49. Knyazev G.G., Savostyanov A.N., Bocharov A.V., Bazovkina D.V., Proshina E.A. Resting State Networks Mediate the Effect of Genotype by Environment Interaction on Mental Health. Neuroscience. 2018. 369: 139–151.

  50. Knyazev G.G., Savostyanov A.N., Bocharov A.V., Tamozhnikov S.S., Saprigyn A.E. Task-positive and task-negative networks and their relation to depression: EEG beamformer analysis. Behavioral Brain Research. 2016. 306: 160–169.

  51. Knyazev G.G., Savostyanov A.N., Bocharov A.V., Brak I.V., Osipov E.A., Filimonova E.A., Saprigyn A.E., Aftanas L.I. Task-positive and task-negative networks in major depressive disorder: A combined fMRI and EEG study. Journal of Affective Disorders. 2018. 235: 211–219.

  52. Lansbergen M.M., Arns M., van Dongen-Boomsma M., Spronk D., Buitelaar J.K. The increase in theta/beta ratio on resting state EEG in boys with attention-deficit/hyperactivity disorder is mediated by slow alpha peak frequency. Prog Neuropsychopharmacol Biol Psychiatry. 2011. 35: 47–52.

  53. Lemogne C., Gorwood P., Boni C., Pessiglione M., Lehericy S., Fossati P. Cognitive appraisal and life stress moderate the effects of the 5-httlpr polymorphism on amygdala reactivity. Hum Brain Mapp. 2011. 32: 1856–1867.

  54. Lesch K.P., Meyer J., Glatz K., Flügge G., Hinney A., Hebebrand J., Klauck S.M., Poustka A., Poustka F., Bengel D., Mössner R., Riederer P., Heils A. The 5-HT transporter gene-linked polymorphic region (5-HTTLPR) in evolutionary perspective: alternative biallelic variation in rhesus monkeys. J Neural Transm. 1997. 104(11-12): 1259–1266.

  55. Lesch K.P., Bengel D., Heils A., Sabol S.Z., Greenberg B.D., Petri S., Benjamin J., Muller C.R., Hamer D.H., Murphy D.L. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science. 1996. 274: 1527–1531.

  56. Litvak V., Eusebio A., Jha A, Oostenveld R., Barnes G.R., Penny W.D., Zrinzo L., Hariz M.I., Limousin P., Friston K.J., Brown P. Optimized beamforming for simultaneous MEG and intracranial local field potential recordings in deep brain stimulation patients. NeuroImage. 2010. 50: 1578–1588.

  57. Luckhoo H., Hale J.R., Stokes M.G., Nobre A.C., Morris P.G., Brookes M.J., Woolrich M.W. Inferring task-related networks using independent component analysis in magnetoencephalography. NeuroImage. 2012. 62: 530–541.

  58. Ma Y., Li B., Wang C., Shi Z., Sun Y., Sheng F., Zhang Y., Zhang W., Rao Y., Han S. 5-HTTLPR polymorphism modulates neural mechanisms of negative self-reflection. Cereb Cortex. 2014. 24: 2421–2429.

  59. MacKinnon D., Krull J., Lockwood C. Equivalence of the mediation confounding and suppression effect. Prev Sci. 2000. 1: 173–181.

  60. Mellings M.B., Alden L.E. Cognitive processes in social anxiety: the effects of self-focus, rumination, and anticipatory processing. Behaviour Research and Therapy. 2000. 38: 243–257.

  61. Menon V. Large-scale brain networks and psychopathology: a unifying triple network model. Trends Cogn Sci. 2011. 15: 483–506.

  62. Meyer-Lindenberg A. Neural connectivity as an intermediate phenotype: brain networks under genetic control. Hum Brain Mapp. 2009. 30: 1938–1946.

  63. Meyer-Lindenberg A. The future of fMRI and genetics research. NeuroImage. 2012.62: 1286–1292.

  64. Mitchell J.P. Mentalizing and Marr: an information processing approach to the study of social cognition. Brain Res. 2006. 1079: 66–75.

  65. Miu A.C., Vulturar R., Chiş A., Ungureanu L., Gross, J.J. Reappraisal as a mediator in the link between 5-HTTLPR and social anxiety symptoms. Emotion. 2013. 13(6): 1012.

  66. Moore S.A., Zoellner L.A., Mollenholt N. Are expressive suppression and cognitive reappraisal associated with stress–related symptoms? Behavior Research and Therapy. 2008. 46: 993–1000.

  67. Munafò M.R., Durrant C., Lewis G., Flint J. Gene X environment interactions at the serotonin transporter locus. Biol Psychiatry. 2009. 65: 211–219.

  68. Northoff G. Gene brains and environment—genetic neuroimaging of depression. Curr Opin Neurobiol. 2013. 23: 133–142.

  69. Nugent A.C., Robinson S.E., Coppola R., Furey M.L., Zarate C.A. Group differences in MEG-ICA derived resting state networks: application to major depressive disorder. NeuroImage. 2015. 118: 1–12.

  70. Papousek I., Reiser E.M., Schulter G., Fink A., Holmes E.A., Niederstatter H., Nagl S., Parson W., Weiss E.M. Serotonin transporter genotype (5-HTTLPR) and electrocortical responses indicating the sensitivity to negative emotional cues. Emotion. 2013. 13: 1173–1181.

  71. Pezawas L., Meyer-Lindenberg A., Drabant E.M., Verchinski B.A., Munoz K.E., Kolachana B.S., Egan M.F., Mattay V.S., Hariri A.R., Weinberger D.R. 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nat Neurosci. 2005. 8: 828–834.

  72. Puig M.V., Gulledge A.T. Serotonin and prefrontal cortex function: neurons networks and circuits. Mol Neurobiol. 2011. 44: 449–464.

  73. Rachmann S., Gruter-Andrew J., Shafran R. Post-event processing in social anxiety. Behaviour Research and Therapy. 2000. 38: 611–617.

  74. Raichle M.E., MacLeod A.M., Snyder A.Z., Powers W.J., Gusnard D.A., Shulman G.L. A default mode of brain function. Proc Natl Acad Sci USA. 2001. 98: 676–682.

  75. Risch N., Herrell R., Lehner T., Liang K.Y., Eaves L., Hoh J., Griem A., Kovacs M., Ott J., Merikangas K.R. Interaction between the serotonin transporter gene (5-HTTLPR) stressful life events and risk of depression: a meta-analysis. JAMA. 2009. 301: 2462–2471.

  76. Sadaghiani S., Scheeringa R., Lehongre K., Morillon B., Giraud A.L., D’Esposito M., Kleinschmidt A. Alpha-band phase synchrony is related to activity in the fronto-parietal adaptive control network. J Neurosci. 2012. 32: 14305–14310.

  77. Sadaghiani S., Scheeringa R., Lehongre K., Morillon B., Giraud A.L., Kleinschmidt A. Intrinsic connectivity networks alpha oscillations and tonic alertness: a simultaneous electroencephalography/functional magnetic resonance imaging study. J Neurosci. 2010. 30: 10243–10250.

  78. Schinka J.A., Busch R.M., Robichaux-Keene N. A meta-analysis of the association between the serotonin transporter gene polymorphism (5-HTTLPR) and trait anxiety. Mol Psychiatry. 2004. 9: 197–202.

  79. Schloss P., Williams D.C. The serotonin transporter: a primary target for antidepressant drugs. J Psychopharmacol. 1998. 12: 115–121.

  80. Schoffelen J.M., Gross J. Source connectivity analysis with MEG and EEG. Hum Brain Mapp. 2009. Jun; 30(6): 1857–65.

  81. Seeley W.W., Menon V., Schatzberg A.F., Keller J., Glover G.H., Kenna H., Greicius M.D. Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci. 2007. 27: 2349–2356.

  82. Selvaraj S., Godlewska B.R., Norbury R., Bose S., Turkheimer F., Stokes P. Decreased regional gray matter volume in S0 allele carriers of the 5-HTTLPR triallelic polymorphism. Mol Psychiatry. 2011. 16(471): 472. 471–473.

  83. Sen S., Burmeister M., Ghosh D. Meta-analysis of the association between a serotonin transporter promoter polymorphism (5-HTTLPR) and anxiety-related personality traits. Am J Med Genet B Neuropsychiatr Genet. 2004. 127B: 85–89.

  84. Sharpley C.F., Palanisamy S.K.A., Glyde N.S., Dillingham P.W., Agnew L.L. An update on the interaction between the serotonin transporter promoter variant (5-HTTLPR) stress and depression plus an exploration of non-confirming findings. Behav Brain Res. 2014. 273: 89–105.

  85. Sheppes G., Gross J.J. Is timing everything? Temporal considerations in emotion regulation. Personality and Social Psychology Review. 2011. 15: 319–331.

  86. Soper D.S. Interaction [Computer software]. Fullerton: California State University. 2013. Retrieved 25 August 2017 from http://www.danielsoper.com/Interaction/

  87. Szasz P.L., Szentagotai A., Hofmann S.G. The effect of emotion-regulation strategies on anger. Behaviour Research and Therapy. 2011. 49: 114–119.

  88. Thomason M.E., Henry M.L., Hamilton J.P., Joormann J., Pine D.S., Ernst M., Goldman D., Mogg K., Bradley B.P., Britton J.C., Lindstrom K.M., Monk C.S., Sankin L.S., Louro H.M., Gotlib I.H. Neural and behavioral responses to threatening emotion faces in children as a function of the short allele of the serotonin transporter gene. Biol Psychol. 2010. 85: 38–44.

  89. Treynor W., Gonzalez R., Nolen-Hoeksema S. Rumination reconsidered: A psychometric analysis. Cognitive Therapy and Research. 2003. 27: 247–259.

  90. Van Dijk K.R., Hedden T., Venkataraman A., Evans K.C., Lazar S.W., Buckner R.L. Intrinsic functional connectivity as a tool for human connectomics: theory properties and optimization. J Neurophysiol. 2009. 103: 297–321.

  91. Van Veen B.D., van Drongelen W., Yuchtman M., Suzuki A. Localization of brain electrical activity via linearly constrained minimum variance spatial filtering. IEEE Trans Biomed Eng. 1997. 44: 867–880.

  92. Vann S.D., Aggleton J.P., Maguire E.A. What does the retrosplenial cortex do? Nat Rev Neurosci. 2009. 10: 792–802.

  93. Von Wolff A., Holzel L.P., Westphal A., Harter M., Kriston L. Selective serotonin reuptake inhibitors and tricyclic antidepressants in the acute treatment of chronic depression and dysthymia: a systematic review and meta-analysis. J Affect Disord. 2013. 144: 7–15.

  94. Wager T.D., Davidson M.L., Hughes B.L., Lindquist M.A., Ochsner K.N. Prefrontal-subcortical pathways mediating successful emotion regulation. Neuron. 2008. 59: 1037–1050.

  95. Wegner D.M., Zanakos S. Chronic thought suppression.Journal of Personality. 1994. 62: 615–640.

  96. Wells A., Clark D.M., Salkovskis P., Ludgate J., Hackmann A., Gelder M. Social phobia: the role of in situation safety behaviors in maintaining anxiety and negative beliefs. Behavior Therapy. 1995. 26: 153–161.

  97. Wens V., Mary A., Bourguignon M., Goldman S., Marty B., Op de Beeck M., Van Bogaerta P., Peigneuxb P., De Tiege X. About the electrophysiological basis of resting state networks. Clin Neurophysiol. 2014. 125: 1711–1713.

Дополнительные материалы отсутствуют.

Инструменты

следующая статья выпуска предыдущая статья выпуска содержание выпуска

Журнал высшей нервной деятельности им. И.П. Павлова

Архивы выпусков Информация о журнале Отправить рукопись в журнал