Therapygenetics: how is effectiveness of psychotherapy related to genotype?

Abstract

Effectiveness of psychotherapy and of clinico-psychological interventions depends on different factors: skills and characteristics of a specialist; diagnosis and extent of severity of symptoms; social and personal peculiarities of patient/client; parameters of psychotherapeutic contact. Therapygenetics is a trend of applied research at the interface of molecular genetics and psychotherapy, which considers molecular-genetic predictors of success/failure of psychotherapeutic interventions.

The aim of the article is analysis and summarization of the current research works in the field of therapygenetics, substantiation of their theoretical and practical significance for psychiatry, psychotherapy and clinical psychology, discussion of the existing limitations and requirements to the design of the respective applied research works. By the moment, contra-dictory, but at the same promising positions in therapygenetics can be outlined. In the given article the results of therapygenetic research performed mostly in accordance with methods of identification of candidate genes, are systematized. Gene-environment correlations in psycho-therapy of anxiety and depressive disorders in children and adults are described. Scarce studies of genetic predictors of effectiveness of psychotherapy in posttraumatic stress-related disorders are summarized. While planning a therapygenetic study, the following methodological, methodical and organizational aspects should be taken into consideration: sufficient representativeness of an experimental sample both from the point of view of socio-demographic characteristics and from the point of view of the diagnosis and used therapy; existence of the control group; use of assessment scales and semi-structured diagnostic interviews for assessment of functioning of respondents; universalization of protocols of assessment of the results of application of methods of psychotherapy; use of polygenomic search for associations; observance of confidentiality and provision of respondents with minimally effective ways of rendering psychological assistance.

Keywords

therapygenetics / genetic predisposition / genetic marker / gene-environment correlation / effectiveness of psychotherapy / anxiety disorders / depression

References

[1] Pugovkina OD, Nikitina IV, Holmogorova AB, et al. Academic research of therapy process and efficient: History and main topics. Moskovskiy Psikhoterapevticheskiy Zhurnal. 2009;(1):35-68. (In Russ).

[2] Пуговкина О.Д., Никитина И.В., Холмогорова А.Б., и др. Научные исследования процесса психотерапии и ее эффективности: история проблемы // Московский психотерапевтический журнал. 2009. №1. С. 35-68.

[3] Regier DA, Kuhl EA, Kupfer DJ. The DSM-5: Classification and criteria changes. World Psychiatry. 2013;12(2):92-8. doi:10.1002/wps.20050

[4] Regier D.A., Kuhl E.A., Kupfer D.J. The DSM-5: Classification and criteria changes // World Psychiatry. 2013. Vol. 12, №2. P. 92-98. doi:10.1002/wps.20050

[5] ICD-11 for Mortality and Morbidity Statistics (ICD-11 MMS). Available at: https://icd.who.int/browse11/l-m/en. Accessed: 2020 September 25.

[6] ICD-11 for Mortality and Morbidity Statistics (ICD-11 MMS). Доступно по: https://icd.who.int/browse 11/lm/en. Ссылка активна на 25 сентября 2020.

[7] Russell RL, Orlinsky DE. Psychotherapy research in historical perspective. Implications for mental health care policy. Archives of General Psychiatry. 1996;53(8):708-15. doi:10.1001/archpsyc.1996.01830080060010

[8] Russell R.L., Orlinsky D.E. Psychotherapy research in historical perspective. Implications for mental health care policy // Archives of General Psychiatry. 1996. Vol. 53, №8. P. 708-715. doi:10.1001/archpsyc.1996.01830080060010

[9] Eysenck HJ. The effects of psychotherapy: An evaluation. Journal of Consulting Psychology. 1952;16(5):319-24. doi:10.1037/h0063633

[10] Eysenck H.J. The effects of psychotherapy: An evaluation // Journal of Consulting Psychology. 1952. Vol. 16, №5. P. 319-324. doi:10.1037/h0063633

[11] Wallerstein RS. The psychotherapy research prоjet (PRP) of the Menninger Foundation: An overview. Journal of Consulting and Clinical Psychology. 1989;57(2):195-205.

[12] Wallerstein R.S. The psychotherapy research prоjet (PRP) of the Menninger Foundation: An overview // Journal of Consulting and Clinical Psychology. 1989. Vol. 57, №2. P. 195-205.

[13] Ayzenk GDzh. Sorok let spustya: novyy vzglyad na problemy effektivnosti v psikhoterapii. Psikhologicheskiy Zhurnal. 1994;14(4):3-19. (In Russ).

[14] Айзенк Г.Дж. Сорок лет спустя: новый взгляд на проблемы эффективности в психотерапии // Психологический журнал. 1994. Т. 14, №4. С. 3-19.

[15] Kholmogorova AB. Two conflicting methodologies in the studies of psychotherapy and its efficiency: looking for a third way A.B. Kholmogorova. Part I. Moskovskiy Psikhoterapevticheskiy Zhurnal. 2009; (4):5-25. (In Russ).

[16] Холмогорова А.Б. Две конфликтующие методологии в исследованиях психотерапии и её эффективности: поиск третьего пути. Часть I // Московский психотерапевтический журнал. 2009. №4. С. 5-25.

[17] Kholmogorova AB, Garanyan NG, Nikitina IV, et al. Research concerning the process of psychotherapy and its efficacy: current situation. Part 2. Sotsial’naya i Klinicheskaya Psikhiatriya. 2010;20 (1):70-9. (In Russ).

[18] Холмогорова А.Б., Гаранян Н.Г., Никитина И.В., и др. Научные исследования процесса психотерапии и её эффективности: современное состояние проблемы. Часть 2 // Социальная и клиническая психиатрия. 2010. Т. 20, №1. С. 70-79.

[19] Eley TC, Hudson JL, Creswell C, et al. Therapy-genetics: The 5HTTLPR and response to psychological therapy. Molecular Psychiatry. 2012;17(3): 236-7. doi:10.1038/mp.2011.132

[20] Eley T.C., Hudson J.L., Creswell C., et al. Therapygenetics: The 5HTTLPR and response to psychological therapy // Molecular Psychiatry. 2012. Vol. 17, №3. P. 236-237. doi:10.1038/mp.2011.132

[21] Karg K, Burmeister M, Shedden K, et al. The Serotonin Transporter Promoter Variant (5-HTTLPR), Stress, and Depression Meta-Analysis Revisited: Evidence of Genetic Moderation. Archives of Gene-ral Psychiatry. 2011;68(5):444-54. doi:10.1001/archgenpsychiatry.2010.189

[22] Karg K., Burmeister M., Shedden K., et al. The Serotonin Transporter Promoter Variant (5-HTTLPR), Stress, and Depression Meta-Analysis Revisited: Evidence of Genetic Moderation // Archives of General Psychiatry. 2011. Vol. 68, №5. P. 444-454. doi:10.1001/archgenpsychiatry.2010.189

[23] Steel Z, Marnane C, Iranpour C, et al. The global prevalence of common mental disorders: a systematic review and meta-analysis 1980-2013. International Journal of Epidemiology. 2014;43(2):476-93. doi:10.1093/ije/dyu038

[24] Steel Z., Marnane C., Iranpour C., et al. The global prevalence of common mental disorders: a systematic review and meta-analysis 1980-2013 // International Journal of Epidemiology. 2014. Vol. 43, №2. P. 476-493. doi:10.1093/ije/dyu038

[25] Neznanov NG, Martynikhin IA, Mosolov SN.

[26] Незнанов Н.Г., Мартынихин И.А., Мосолов С.Н. Диагностика и терапия тревожных расстройств в Российской Федерации: результаты опроса врачейпсихиатров // Современная терапия психических расстройств. 2017. №2. С. 2-13. doi:10.21265/PSYPH.2017.41.6437

[27] Diagnosis and treatment of Anxiety Disorders in Russia: The Results of a Web-based Survey of

[28] Gregory A.M., Eley T.C. The genetic basis of child and adolescent anxiety. In: Silverman W.K., Field A.P., editors. Anxiety Disorders in Children and Adolescents. Cambridge: Cambridge University Press; 2011. P. 161-178.

[29] Psychiatrists. Sovremennaya terapiya psikhicheskikh rasstroystv. 2017;(2):2-13. doi:10.21265/PSYPH.2017.41.6437

[30] Stein M.B., Schork N.J., Gelernter J. Gene-by-Environment (Serotonin Transporter and Childhood Maltreatment) Interaction for Anxiety Sensitivity, an Intermediate Phenotype for Anxiety Disorders // Neuropsychopharmacology. 2008. Vol. 33, №2. P. 312-319. doi:10.1038/sj.npp.1301422

[31] Gregory AM, Eley TC. The genetic basis of child and adolescent anxiety. In: Silverman W.K., Field A.P., editors. Anxiety Disorders in Children and Adolescents. Cambridge: Cambridge University Press; 2011. P. 161-78.

[32] Furmark T., Carlbring P., Hammer S., et al. Effects of Serotonin Transporter and Tryptophan Hydroxylase-2 Gene Variation on the Response to Cognitive-Behavior Therapy in Individuals with Social Anxiety Disorder // Biological Psychiatry. 2010. №67. P. 1S-271S.

[33] Stein MB, Schork NJ, Gelernter J. Gene-by-Environment (Serotonin Transporter and Childhood Maltreatment) Interaction for Anxiety Sensitivity, an Intermediate Phenotype for Anxiety Disorders. Neuropsychopharmacology. 2008;33(2):312-9. doi:10.1038/sj.npp.1301422

[34] Lonsdorf T.B., Ruck C., Bergstrom J., et al. The COMT val158met polymorphism is associated with symptom relief during exposure-based cognitive-behavioral treatment in panic disorder // BMC Psychiatry. 2010. №10. P. 99. doi:10.1186/1471-244X-10-99

[35] Furmark T, Carlbring P, Hammer S, et al. Effects of Serotonin Transporter and Tryptophan Hydroxylase-2 Gene Variation on the Response to Cognitive-Behavior Therapy in Individuals with Social Anxiety Disorder. Biological Psychiatry. 2010;67:1S-271S.

[36] Lester K.J., Hudson J.L., Tropeano M., et al. Neurotrophic gene polymorphisms and response to psychological therapy // Translational Psychiatry. 2012. Vol. 2, №5. P. e108. doi:10.1038/tp.2012.33

[37] Lonsdorf TB, Ruck C, Bergstrom J, et al. The COMT val158met polymorphism is associated with symptom relief during exposure-based cognitive-behavioral treatment in panic disorder. BMC Psychiatry. 2010;(10):99. doi:10.1186/1471-244X-10-99

[38] Hedman E., Andersson E., Ljótsson B., et al. Clinical and genetic outcome determinants of Internet and group-based cognitive behavior therapy for social anxiety disorder // Acta Psychiatrica Scandinavica. 2012. Vol. 126, №2. P. 126-136. doi:10.1111/j.1600-0447.2012.01834.x

[39] Lester KJ, Hudson J, Tropeano M, et al. Neurotrophic gene polymorphisms and response to psychological therapy. Translational Psychiatry. 2012; 2(5):e108. doi:10.1038/tp.2012.33

[40] Fullana M.A., Alonso P., Gratacos M., et al. Variation in the BDNF Val66Met polymorphism and response to cognitive-behavior therapy in obsessivecompulsive disorder // European Psychiatry. 2012. Vol. 27, №5. P. 386-390. doi:10.1016/j.eurpsy.2011.09.005

[41] Hedman E, Andersson E, Ljótsson B, et al. Clinical and genetic outcome determinants of Internet and group-based cognitive behavior therapy for social anxiety disorder. Acta Psychiatrica Scandinavica. 2012;126(2):126-36. doi:10.1111/j.1600-0447.2012.01834.x

[42] Депрессия в Российской Федерации (2017). Доступно по: https://www.euro.who.int/ru/countries/ russian-federation/data-and-statistics/infographic-depression-in-the-russian-federation-2017. Ссылка активна на 25 сентября 2020.

[43] Fullana MA, Alonso P, Gratacos M, et al. Variation in the BDNF Val66Met polymorphism and response to cognitive-behavior therapy in obsessive-compulsive disorder. European Psychiatry. 2012; 27(5):386-90. doi:10.1016/j.eurpsy.2011.09.005

[44] Depression. Доступно по: https://www.who.int/ news-room/fact-sheets/detail/depression. Ссылка активна на 25 сентября 2020.

[45] Depressiya v Rossiyskoy Federatsii (2017). Available at: https://www.euro.who.int/ru/countries/russian-federation/data-and-statistics/infographic-depression-in-the-russian-federation-2017. Accessed: 2020 September 25. (In Russ).

[46] Sullivan P.F., Neale M.C., Kendler K.S. Genetic epidemiology of major depression: review and meta-analysis // The American Journal of Psychiatry. 2000. Vol. 157, №10. P. 1552-1562. doi:10.1176/ appi.ajp.157.10.1552

[47] Depression. Available at: https://www.who.int/news-room/fact-sheets/detail/depression. Accessed: 2020 September 25.

[48] Anttila V., Bulik-Sullivan B., Finucane H.K., et al. Analysis of shared heritability in common disorders of the brain // Science. 2018. Vol. 360, №6395. P. eaap8757. doi:10.1126/science.aap8757

[49] Sullivan PF, Neale MC, Kendler K. Genetic epidemiology of major depression: review and meta-analysis. The American Journal of Psychiatry. 2000; 157(10):1552-62. doi:10.1176/appi.ajp.157.10.1552

[50] Lester K.J., Eley T.C. Therapygenetics: Using genetic markers to predict response to psychological treatment for mood and anxiety disorders // Biology of Mood & Anxiety Disorders. 2013. Vol. 3, №1. P. 4. doi:10.1186/2045-5380-3-4

[51] Anttila V, Bulik-Sullivan B, Finucane HK, et al. Analysis of shared heritability in common disorders of the brain. Science. 2018;360(6395):eaap8757. doi:10.1126/science.aap8757

[52] Kotte A., McQuaid J.R., Kelsoe J. HTR2A: Genotypic Predictor of Depression Psychotherapy Treatment Outcome. San Diego, California: 62nd Annual Scientific Convention and Meeting of the Society of Biological Psychiatry; 2007.

[53] Lester KJ, Eley TC. Therapygenetics: Using genetic markers to predict response to psychological treatment for mood and anxiety disorders. Biology of Mood & Anxiety Disorders. 2013;3(1):4. doi:10.1186/2045-5380-3-4

[54] Bakker J.M., Lieverse R., Menne-Lothmann C. Therapygenetics in mindfulness-based cognitive therapy: do genes have an impact on therapy-induced change in reallife positive affective experiences? // Translational Psychiatry. 2014. Vol. 4, №4. P. e384. doi:10.1038/tp.2014.23

[55] Kotte A, McQuaid JR, Kelsoe J. HTR2A: Genotypic Predictor of Depression Psychotherapy Treatment Outcome. San Diego, California: 62nd Annual Sci-entific Convention and Meeting of the Society of Biological Psychiatry; 2007.

[56] Andersson E., Crowley J.J., Lindefors N., et al. Genetics of response to cognitive behavior therapy in adults with major depression: a preliminary report // Molecular Psychiatry. 2019. Vol. 24, №4. P. 484-490. doi:10.1038/s41380-018-0289-9

[57] Bakker JM, Lieverse R, Menne-Lothmann C. Therapygenetics in mindfulness-based cognitive therapy: do genes have an impact on therapy-induced change in real-life positive affective experiences? Translational Psychiatry. 2014;4(4):e384. doi:10.1038/tp.2014.23

[58] Rayner C., Coleman J.R.I., Purves K.L. A genomewide association meta-analysis of prognostic out-comes following cognitive behavioural therapy in individuals with anxiety and depressive disorders // Translational Psychiatry. 2019. Vol. 9, №1. P. 150. doi:10.1038/s41398-019-0481-y

[59] Andersson E, Crowley JJ, Lindefors N, et al. Genetics of response to cognitive behavior therapy in adults with major depression: a preliminary report. Molecular Psychiatry. 2019;24(4):484-90. doi:10.1038/s41380-018-0289-9

[60] Keesler R., Aguilar-Gaxiola S., Alonso J., et al. Trauma and PTSD in the WHO World Mental Health Surveys // European Journal of Psychotraumatology. 2017. Vol. 8, Suppl. 5. P. 1353383. doi:10.1080/20008198.2017.1353383

[61] Rayner C, Coleman JRI., Purves KL. A genome-wide association meta-analysis of prognostic out-comes following cognitive behavioural therapy in individuals with anxiety and depressive disorders. Translational Psychiatry. 2019;9(1):150. doi:10.1038/s41398-019-0481-y

[62] Li L., Bao Y., He S., et al. The Association Between Genetic Variants in the Dopaminergic System and Posttraumatic Stress Disorder: A Meta-Analysis // Medicine. 2016. Vol. 95, №11. P. e3074. doi:10.1097/MD.0000000000003074

[63] Keesler R, Aguilar-Gaxiola S, Alonso J, et al. Trauma and PTSD in the WHO World Mental Health Surveys. European Journal of Psychotraumatology. 2017;8(suppl 5):1353383. doi:10.1080/20008198.2017.1353383

[64] Castro-Vale I., van Rossum E.F.C., Machado J.C., et al. Genetics of glucocorticoid regulation and posttraumatic stress disorder – What do we know? // Neuroscience and Biobehavioral Review. 2016. Vol. 63. P. 143-157. doi:10.1016/j.neubiorev.2016.02.005

[65] Li L, Bao Y, He S, et al. The Association Between Genetic Variants in the Dopaminergic System and Posttraumatic Stress Disorder: A Meta-Analysis.

[66] Gressier F., Calati R., Balestri M., et al. The 5-HTTLPR polymorphism and post-traumatic stress disorder: a meta-analysis // Journal of Traumatic Stress. 2013. Vol. 26, №6. P. 645-653. doi:10.1002/jts.21855

[67] Medicine. 2016;95(11):e3074. doi:10.1097/MD.0000000000003074

[68] Bryant R.A., Felmingham K.L., Falconer E.M., et al. Preliminary Evidence of the Short Allele of the Serotonin Transporter Gene Predicting Poor Response to Cognitive Behavior Therapy in Posttraumatic Stress Disorder // Biological Psychiatry. 2010. Vol. 67, №12. P. 1217-1219. doi:10.1016/j.biopsych.2010.03.016

[69] Castro-Vale I, van Rossum EF, Machado JC, et al. Genetics of glucocorticoid regulation and post-traumatic stress disorder – What do we know?. Neuroscience and Biobehavioral Review. 2016; 63:143-57. doi:10.1016/j.neubiorev.2016.02.005

[70] Wang Z., Harrer J., Tuerk P., et al. 5-HTTLPR Influence PTSD Treatment Outcome. Vancouver, Canada: 64th Annual Scientific Convention and Meeting of the Society of Biological Psychiatry; 2009.

[71] Gressier F, Calati R, Balestri M, et al. The 5-HTTLPR polymorphism and post-traumatic

[72] Lau J.Y.F., Eley T.C. Changes in genetic and environmental influences on depressive symptoms across adolescence and young adulthood // British Journal of Psychiatry. 2006. Vol. 189, №5. P. 422-427. doi:10.1192/bjp.bp.105.018721

[73] stress disorder: a meta-analysis. Journal of

[74] Eley T.C. The future of therapygenetics: where will studies predicting psychological treatment response from genomic markers lead? // Depression & Anxiety. 2014. Vol. 31, №8. P. 617-620. doi:10.1002/da.22292

[75] Traumatic Stress. 2013;26(6):645-53. doi:10.1002/jts.21855

[76] Федотов И.А., Доровская В.А., Назаров Д.А. К вопросу о коморбидности обсессивнокомпульсивного расстройства и шизофрении // Наука молодых (Eruditio Juvenium). 2016. №2. С. 49-55.

[77] Bryant RA, Felmingham KL, Falconer EM, et al. Preliminary Evidence of the Short Allele of the Serotonin Transporter Gene Predicting Poor Response to Cognitive Behavior Therapy in Posttraumatic Stress Disorder. Biological Psychiatry. 2010; 67(12):1217-9. doi:10.1016/j.biopsych.2010.03.016

[78] Wang Z., Harrer J., Tuerk P., et al. 5-HTTLPR Influence PTSD Treatment Outcome. Vancouver, Canada: 64th Annual Scientific Convention and Meeting of the Society of Biological Psychiatry; 2009.

[79] Lau JYF, Eley TC. Changes in genetic and environmental influences on depressive symptoms across adolescence and young adulthood. British Journal of Psychiatry. 2006;189(5):422-7. doi:10.1192/bjp.bp.105.018721

[80] Eley TC. The future of therapygenetics: where will studies predicting psychological treatment response from genomic markers lead? Depression & Anxiety. 2014;31(8):617-20. doi:10.1002/da.22292

[81] Fedotov IA, Dorovskaya VA, Nazarov DA. The issue of comorbidity of obsessive-compulsive disorder and schizophrenia. Nauka Molodykh (Eruditio Juvenium). 2016;(2):49-55. (In Russ).

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