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Emotional Distress in Parents of Psychotic Patients is Modified by Serotonin Transporter Gene (5-HTTLPR) - Brain-Derived Neurotrophic Factor Gene Interactions

Published online by Cambridge University Press:  10 January 2013


Vera Golimbet
Affiliation:
Russian Academy of Medical Sciences (Russia)
Margarita Alfimova
Affiliation:
Russian Academy of Medical Sciences (Russia)
Galina Korovaitseva
Affiliation:
Russian Academy of Medical Sciences (Russia)
Lilia I. Abramova
Affiliation:
Russian Academy of Medical Sciences (Russia)
Vasily G. Kaled
Affiliation:
Russian Academy of Medical Sciences (Russia)
Corresponding
E-mail address:

Abstract

Caregiving of a family member with psychotic disorder is considered among the most significant stressors and relatives of a sufferer experienced psychological and physical burden that may be the cause of neurotic states. There is growing evidence that sensitivity of individuals to depressogenic effects of stressful factor is moderated by genetic variants of serotonin transporter (SERT) and brain-derived neurotrophic factors (BDNF). We examined the association of the 5-HTTLPR SERT and Val66Met BDNF polymorphisms with signs of depression and anxiety measured with the Minnesota Multiphasic Personality Inventory (MMPI) in 235 unaffected parents of patients with major psychosis and 102 agematched controls. A significant effect of the SERT-BDNF interaction on Depression and Psychasthenia scales was found in the group of parents, but not in the control group. Carriers of the Val/Val x SS variant scored higher as compared to other allelic combinations. The results obtained revealed that the SERT-BDNF interactions might moderate the level of anxiety and depression caused by caregiving status in parents of psychotic patients.


Cuidar a un miembro de la familia con un trastorno psicótico es considerado como uno de los estresores más significativos y los familiares de una persona que sufre dicho trastorno experimentan una carga psicológica y física que puede ser la causa de estados neuróticos. Hay cada vez más evidencia de que la sensibilidad de los individuos hacia los efectos depresógenos de los factores estresantes es moderada por variantes genéticos del transportador de la serotonina (SERT) y de factores neurotróficos derivados del cerebro (BDNF). Examinamos la asociación de los polimorfismos 5-HTTLPR SERT y Val66Met BDNF con los signos de la depresión y la ansiedad medidos con el Minnesota Multiphasic Personality Inventory (MMPI) en 235 familiares sanos de pacientes con psicosis mayor y 102 controles apareados en edad. Se encontró un efecto significativo de la interacción SERT-BDNF en las escalas de Depresión y Psicastenia en el grupo de familiares pero no en el grupo control. Los portadores de la variante Val/Val x SS puntuaban más alto en comparación con otras combinaciones alélicas. Los resultados obtenidos pusieron de manifiesto que las interacciones SERT-BDNF podrían moderar el nivel de ansiedad y depresión causado por el estatus de cuidador de los padres de pacientes psicóticos.


Type
Research Article
Copyright
Copyright © Cambridge University Press 2009

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References

Aguilera, M., Arias, B., Wichers, M., Barrantes-Vidal, N., Moya, J., Villa, H., van Os, J., Ibáñez, M.I., Ruipérez, M.A., Ortet, G.& Fañanás, L. (2009). Early adversity and 5-HTT/BDNF genes: new evidence of gene-environment interactions on depressive symptoms in a general population. Psychological Medicine. 12, 18.Google Scholar
Alessi, M.W., White, R.J., Ray, G.E.& Stewart, S.J.. (2001). Personality and psychopathology profiles of veterans' wives: measuring distress using the MMPI-2. Journal of Clinical Psychoogyl, 57, 15351542.CrossRefGoogle ScholarPubMed
Alfimova, M.V., Golimbet, V.E., Korovaitseva, G.I., Lezheiko, T.V., Abramova, L.I., Kaleda &, V.G., Barkhatova, A.N. (2008). The modulatory influence of polymorphism of the serotonin transporter gene on characteristics of mental maladaptation in relatives of patients with endogenous psychoses. Neuroscience and Behavioral Physiology. 38, 253258.CrossRefGoogle ScholarPubMed
Angermeyer, M.C., Liebelt, P.& Matschinger, H. (2001). Distress in parents of patients suffering from schizophrenia of affective disorders. Psychotherapie Psychosomartik Medicinische Psychologie, 51, 255260.CrossRefGoogle ScholarPubMed
Beresin, F.B., Miroshnikov, M.P.& Rojanez, R.V. (1976). The Multiple personality inventory. Moscow, Medicine. 176 p.Google Scholar
Brown, S.& Wistle, J. (1998). People with schizophrenia and their families. British Journal of Psychiatry, 173, 139144.CrossRefGoogle ScholarPubMed
Brummett, B.H., Boyle, S.H., Siegler, I.C., Kuhn, C.M., Ashley-Koch, A., Jonassaint, C.R., Züchner, S., Collins, A.& Williams, R.B. (2008). Effects of environmental stress and gender on associations among symptoms of depression and the serotonin transporter gene linked polymorphic region (5-HTTLPR). Behavioral Genetics. 38. 3443CrossRefGoogle Scholar
Caspi, A., Sugden, K., Moffitt, T.E., Taylor, A., Craig, I.W., Harrington, H., McClay, J, Mill, J, Martin, J, Braithwaite, A.& Poulton, R. (2003). Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science, 301, 386389.CrossRefGoogle ScholarPubMed
Cervilla, J.A., Molina, E., Rivera, M., Torres-González, F., Bellón, J.A., Moreno, B., Luna, J.D., Lorente, J.A., Mayoral, F., King, M.& Nazareth, I; PREDICT Study Core Group, Gutiérrez, B. (2007). The risk for depression conferred by stressful life events is modified by variation at the serotonin transporter 5HTTLPR genotype: evidence from the Spanish PREDICT-Gene cohort. Molecular Psychiatry, 12, 748755.CrossRefGoogle ScholarPubMed
Chen, Z.Y., Patel, P.D., Sant, G., Meng, C.X., Teng, K.K., Hempstead, B.L.& Lee, F.S. (2004) 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. Journal of Neuroscience, 24, 44014411.CrossRefGoogle ScholarPubMed
Duncan, LE, Hutchison, KE, Carey, G.& Craighead, W.E. (2009). Variation in brain-derived neurotrophic factor (BDNF) gene is associated with symptoms of depression. Journal of Affective Disorders, 115, 215219.CrossRefGoogle ScholarPubMed
Ferriter, M.& Huband, N. (2003). Experiences of parents with a son or daughter suffering from schizophrenia. Journal of Psychiatric and Mental Health Nursing, 10, 552560.CrossRefGoogle ScholarPubMed
Franklin, C.L., Repasky, S.A., Thompson, K.E., Shelton, S.A.& Uddo, M. (2002). Differentiating overreporting and extreme distress: MMPI-2 use with compensation-seeking veterans with PTSD. Journal of Personality Assessment, 79, 274285.CrossRefGoogle ScholarPubMed
Gillespie, N.A., Whitfield, J.B., Williams, B., Heath, A.C.& Martin, N.G. (2005). The relationship between stressful life events, the serotonin transporter (5-HTTLPR) genotype and major depression. Psychological Medicine, 35, 101111.CrossRefGoogle Scholar
Golimbet, V.E., Alfimova, M.V., Shcherbatykh, T.V. & Rogaev, EI. (2002). Allele polymorphism of the serotonin transporter gene and clinical heterogeneity of depressive disorders. Genetika, 38, 671677.Google Scholar
Grabe, H.J., Lange, M., Wolff, B., Volzke, H., Lucht, M., Freyberger, H.J., John, U.& Cascorbi, I. (2005). Mental and physical distress is modulated by a polymorphism in the 5-HT transporter gene interacting with social stressors and chronic disease burden. Molecular Psychiatry, 10, 220224.CrossRefGoogle Scholar
Gratacos, M., Gonzales, J.R., Mercader, J.M., de Cid, R., Urretavizcaya, M.& Estivill, X. (2007). Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case-control studies confirm association to substance-erelated disorders, eating disorders and schizophrenia. Biological Psychiatry. 61, 911922.CrossRefGoogle Scholar
Greenberg, B.D., Li, Q., Lucas, F.R., Hu, S., Sirota, L.A., Benjamin, J., Lesch, K.P., Hamer, D.& Murphy, D.L. (2000). Association between the serotonin transporter promoter polymorphism and personality traits in a primarily female population sample. American Journal of Medical Genetics (Neuropsychiatric Genetics), 96, 202216.3.0.CO;2-J>CrossRefGoogle Scholar
Hwang, J.P., Tsai, S.J., Hong, C.J., Yang, C.H., Lirng, J.F.& Yang, Y.M. (2006). The Val66Met polymorphism of the brain-derived neurotrophic-factor gene is associated with geriatric depression., 27, 18341837.Google Scholar
Kaufman, J., Yang, B.Z., Douglas-Palumberi, H., Houshyar, S., Lipschitz, D., Krystal, J.H.& Gelernter, J. (2004). Social supports and serotonin transporter gene moderate depression in maltreated children. Proceedings of the National Academy of Sciences of the United States of Fmerica, 101, 1731617321.CrossRefGoogle Scholar
Kaufman, J., Yang, B.Z., Douglas-Palumberi, H., Grasso, D., Lipschitz, D., Houshyar, S., Krystal, J.H.& Gelernter, J. (2006). Brain-derived neurotrophic factor-5-HTTLPR gene interactions and environmental modifiers of depression in children. Biological Psychiatry, 59, 673680.CrossRefGoogle ScholarPubMed
Kendler, K.S., Kuhn, J.W., Vittum, J., Prescott, C.A.& Riley, B. (2005). The interaction of stressful life events and a serotonin transporter polymorphism in the prediction of episodes of major depression: a replication. Archives of General Psychiatry, 62, 529535.CrossRefGoogle Scholar
Kim, J.M., Stewart, R., Kim, S.W., Yang, S.J., Shin, I.S., Kim, Y.H.& Yoon, J.S. (2007). Interactions between life stressors and susceptibility genes (5-HTTLPR and BDNF) on depression in Korean elders. Biological Psychiatry. 62, 423428.CrossRefGoogle Scholar
Kim, J.M., Stewart, R., Kim, S.W., Yang, S.J., Shin, I.S., Kim, Y.H.& Yoon, J.S.. (2008). BDNF genotype potentially modifying the association between incident stroke and depression. Neurobiology of Aging 29,789792CrossRefGoogle Scholar
Kohen, R., Cain, K.C., Mitchell, P.H., Becker, K., Buzaitis, A., Millard, S.P., Navaja, G.P., Teri, L., Tirschwell, D.& Veith, R. (2008). Association of serotonin transporter gene polymorphisms with poststroke depression. Archives of General Psychiatry, 65, 12961302.CrossRefGoogle ScholarPubMed
Lang, U.E., Hellweg, R., Kalus, P., Bajbouj, M., Lenzen, K.P., Sander, T., Kunz, D.& Gallinat, J. (2005). Association of a functional BDNF polymorphism and anxiety-related personality traits. Psychopharmacology, 180,: 9599.CrossRefGoogle ScholarPubMed
Lee, H.J., Lee, M.S., Kang, R.H., Kim, H., Kim, S.D., Kee, B.S., Kim, Y.H., Kim, Y.K., Kim, J.B., Yeon, B.K., Oh, K.S., Oh, B.H., Yoon, J.S., Lee, C., Jung, H.Y., Chee, I.S.& Paik, I.H. (2005). Influence of the serotonin transporter promoter gene polymorphism on susceptibility to posttraumatic stress disorder. Depression and Anxiety; 21, 135139.CrossRefGoogle ScholarPubMed
Lesch, K.P., Bengel, D., Heils, A., Sabol, S.Z, Greenberg, B.D., Petri, S., Benjamin, J., Müller, C.R., Hamer, D.H.& Murphy, D.L. (1996). Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science; 274, 15271531.CrossRefGoogle ScholarPubMed
Lesch, K.P.& Mossner, R. (1998). Genetically driven variation in serotonin uptake: is there a link to affective spectrum, neurodevelopmental, and neurodenegerative disorders? Biological Psychiatry; 44, 179192.CrossRefGoogle Scholar
Lesch, K.P. (2001). Serotonergic gene expression and depression: implications for developing novel antidepressants. Journal of Affective Disorders; 62, 5776.CrossRefGoogle ScholarPubMed
Li, D.& He, L. (2007). Meta-analysis supports association between serotonin transporter (5-HTT) and suicidal behavior. Molecular Psychiatry, 12, 4754.CrossRefGoogle ScholarPubMed
Lohoff, F.W., Sander, T., Ferraro, T.N., Dahl, J.P., Gallinat, J.& Berrettini, W.H. (2005). Confirmation of association between the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene and bipolar I disorder. American Journal of Medical Genetics B Neuropsychiatric Genetics; 139, 5153.CrossRefGoogle Scholar
Lotrich, F.E.& Pollock, B.G. (2004). Meta-analysis of serotonin transporter polymorphisms and affective disorders. Psychiatric Genetics, 14, 121129.CrossRefGoogle ScholarPubMed
Magliano, L., Fiorillo, A., De Rosa, C., Malangone, C., Maj, M. & the National Mental Health Project Working Group. (2005). Family burden in long-term diseases: a comparative study in schizophrenia vs. physical disorders. Social Science and Medicine; 61, 313322.CrossRefGoogle ScholarPubMed
Mendlewicz, J., Massat, I., Souery, D., Del-Favero, J., Oruc, L., Nöthen, M.M., Blackwood, D., Muir, W., Battersby, S., Lerer, B., Segman, R.H., Kaneva, R., Serretti, A., Lilli, R., Lorenzi, C., Jakovljevic, M., Ivezic, S., Rietschel, M., Milanova, V.& Van Broeckhoven, C. (2004). Serotonin transporter 5HTTLPR polymorphism and affective disorders: no evidence of association in a large European multicenter study. European Journal of Human Genetics, 12, 377382.CrossRefGoogle Scholar
Moldin, S.O., Gottesman, I.I.& Erlenmeyer-Kimling, L. (1987). Psychometric validation of psychiatric diagnoses in the New York High-Risk Study. Psychiatry Research; 22, 159177.CrossRefGoogle ScholarPubMed
Mossner, R., Daniel, S., Albert, D., Heils, A., Okladnova, O., Schmitt, A.& Lesch, K.P. (2000). Serotonin transporter function is modulated by brain-derived neurotrophic factor (BDNF) but not nerve growth factor (NGF). Neurochemistry International; 6, 197202.CrossRefGoogle Scholar
Munafo, M.R., Clark, T.G., Moore, L.R., Payne, E., Walton, R.& Flint, J. (2003). Genetic polymorphisms and personality in healthy adults: a systematic review and meta-analysis. Molecular Psychiatry; 8: 471484.CrossRefGoogle ScholarPubMed
Neves-Pereira, M., Mundo, E., Muglia, P., King, N., Macciardi, F.& Kennedy, J.L. (2002). The brain-derived neurotrophic factor gene confers susceptibility to bipolar disorder: evidence from a family-based association study. American Journal of Human Genetics; 71, 651655.CrossRefGoogle ScholarPubMed
Pezawas, L., Meyer-Lindenberg, A., Goldman, A.L., Verchinski, B.A., Chen, G., Kolachana, B.S., Egan, M.F., Mattay, V.S., Hariri, A.R.& Weinberger, D.R. (2008). Evidence of biologic epistasis between BDNF and SLC6A4 and implications for depression. Molecular Psychiatry. 13, 709–16CrossRefGoogle Scholar
Reine, G., Lancon, C., Simeoni, M.C., Duplan, S.& Auquier, P. (2003). Caregiver burden in relatives of persons with schizophrenia: an overview of measure instruments. Encephale; 29, 137147.Google ScholarPubMed
Ren-Patterson, R.F., Cochran, L.W., Holmes, A., Sherrill, S., Huang, S.J.& Tolliver, T. (2005). Loss of brain-derived neurotrophic factor gene allele exacerbates brain monoamine deficiencies and increases stress abnormalities of serotonin transporter knockout mice. Journal of Neuroscience Research; 79, 756771.CrossRefGoogle ScholarPubMed
Ribeiro, L., Busnello, J.V., Cantor, R.M., Whelan, F., Whittaker, P., Deloukas, P., Wong, M.L.& Licinio, J. (2007). The brain-derived neurotrophic factor rs6265 (Val66Met) polymorphism and depression in Mexican-Americans. Neuroreport, 18, 12911293.CrossRefGoogle ScholarPubMed
Salleh, M.R. (1994). The burden of care of schizophrenia in Malay families. Acta Psychiatrica Scandinavica; 89. 180185.CrossRefGoogle ScholarPubMed
Scheibe, S., Bagby, R.M., Miller, L.S.& Dorian, B.J. (2001). Assessing posttraumatic stress disorder with the MMPI-2 in a sample of workplace accident victims. Psychological Assessment; 13, 369374.CrossRefGoogle Scholar
Scheid, J.M., Holzman, C.B., Jones, N., Friderici, K.H., Nummy, K.A., Symonds, L.L., Sikorskii, A., Regier, M.K.& Fisher, R. (2007). Depressive symptoms in mid-pregnancy, lifetime stressors and the 5-HTTLPR genotype. Genes, Brain and Behavior. 6, 453464.CrossRefGoogle ScholarPubMed
Sen, S., Nesse, R.M., Stoltenberg, S.F., Li, S., Gleiberman, L., Chakravarti, A., Weder, AB& Burmeister, M. (2003). A BDNF coding variant is associated with the NEO personality inventory domain neuroticism, a risk factor for depression. Neuropsychopharmacology; 28, 397401.CrossRefGoogle Scholar
Sjoberg, R.L., Nilsson, K.W., Nordquist, N., Ohrvik, J., Leppert, J., Lindstrom, L.& Oreland, L. (2005). Development of depression: sex and the interaction between environment and a promoter polymorphism of the serotonin transporter gene. International Journal of Neuropsychopharmacology; 15, 17.Google Scholar
Sklar, P., Gabriel, S.B., McInnis, M.G., Bennett, P., Lim, Y.M., Tsan, G., Schaffner, S., Kirov, G., Jones, I., Owen, M., Craddock, N., Paulo, J.R.& Lander, E.S. (2002). Family-based association study of 76 candidate genes in bipolar disorder: BDNF is a potential risk locus. Molecular Psychiatry, 7, 579593.CrossRefGoogle ScholarPubMed
Stilley, C.S., Miller, D.J.& Tarter, R.E. (1997). Measuring psychological distress in candidates for liver transplantation: a pilot study. Journal of Clinical Psychology; 53, 459464.3.0.CO;2-I>CrossRefGoogle ScholarPubMed
Strauss, J., Barr, C.L., George, C.J., Devlin, B., Vetro, A., Kiss, E., Baji, I, King, N, Shaikh, S, Lanktree, M., Kovacs, M.& Kennedy, J.L. (2005). Brain-derived neurotrophic factor variants are associated with childhood-onset mood disorder: confirmation in a Hungarian sample. Molecular Psychiatry, 10, 861867.CrossRefGoogle Scholar
Subotnik, K.L., Asarnow, R.F., Nuechterlein, K.H., Fogelson, D.L., Thorpe, T.I., Payne, D.L., Giannini, C.A., Kuppinger, H.E., Torquato, R.D., Mintz, J., Hwang, S.S.& Gottesman, I.I. (2005). MMPI vulnerability indicators for schizophrenia and attention deficit disorder: UCLA family study of biological parents of offspring with childhood-onset schizophrenia or ADHD. Behavioral Genetics, 35, 159175.CrossRefGoogle ScholarPubMed
Surtees, P.G., Wainwright, N.W., Willis-Owen, S.A., Sandhu, M.S., Luben, R., Day, N.E.& Flint, J. (2007). No association between the BDNF Val66Met polymorphism and mood status in a non-clinical community sample of 7389 older adults. Journal of PsychiatricResearch, 41, 404409.Google Scholar
Taylor, S.E., Way, B.M., Welch, W.T., Hilmert, C.J., Lehman, B.J.& Eisenberger, N.I. (2006). Early family environment, current adversity, the serotonin transporter promoter polymorphism, and depressive symptomatology. Biological Psychiatry, 60, 671676.CrossRefGoogle ScholarPubMed
Wichers, M., Kenis, G., Jacobs, N., Mengelers, R., Derom, C., Vlietinck, R.& van Os, J. (2008). The BDNF Val(66)Met x 5-HTTLPR x child adversity interaction and depressive symptoms: An attempt at replication. American Journal of Medical Genetics B Neuropsychiatric Genetics, 147, 120123.CrossRefGoogle Scholar
Wilhelm, K., Mitchell, P.B., Niven, H., Finch, A., Wedgwood, L., Scimone, A., Blair, I.P., Parker, G.& Schofield, P.R. (2006). Life events, first depression onset and the serotonin transporter gene. British Journal of Psychiatry, 188, 210215.CrossRefGoogle ScholarPubMed

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