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Published in: European Archives of Psychiatry and Clinical Neuroscience 5/2014

01-08-2014 | Original Paper

High social support buffers the effects of 5-HTTLPR genotypes within social anxiety disorder

Authors: Eva Reinelt, Maren Aldinger, Malte Stopsack, Christian Schwahn, Ulrich John, Sebastian E. Baumeister, Hans Jörgen Grabe, Sven Barnow

Published in: European Archives of Psychiatry and Clinical Neuroscience | Issue 5/2014

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Abstract

An interaction between genetic aspects and environmental stressors has been suggested with regard to the etiology of social anxiety disorder (SAD). However, potential protective interplays which might decrease the risk of SAD have not been considered so far. Thus, we analyzed the interaction between 5-HTTLPR and differing levels of social support regarding SAD. The sample was based on participants of the Study of Health in Pomerania, Germany. We used the triallelic genotype of 5-HTTLPR and longitudinal data of social support. Final analyses were conducted in 79 individuals with SAD and 1,708 without. The diagnosis of SAD was derived from diagnostic interviews in accordance with DSM-IV. Considering the risk of SAD, a general protective effect of high social support was shown independent of variation in 5-HTTLPR genotype. In contrast, the risk of SAD was increased for both genotypes within those individuals with low social support. Additionally, the odds ratio for suffering from SAD was about two times higher for carriers of the l/l genotype compared to those with at least one short allele in those perceiving less-supportive social environments. The findings suggest that SAD is influenced by a protective and a contributing gene × environment interaction. High social support might act in a protective and low social support in an increasing manner on the risk of SAD especially within carriers of the l/l genotype. Therefore, effects of 5-HTTLPR might be buffered by high social support with respect to the risk of SAD.
Literature
1.
go back to reference APA (2000) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Association, Washington, DC APA (2000) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Association, Washington, DC
2.
go back to reference Arbelle S, Benjamin J, Golin M, Kremer I, Belmaker RH, Ebstein RP (2003) Relation of shyness in grade school children to the genotype for the long form of the serotonin transporter promoter region polymorphism. Am J Psychiatry 160:671–676PubMedCrossRef Arbelle S, Benjamin J, Golin M, Kremer I, Belmaker RH, Ebstein RP (2003) Relation of shyness in grade school children to the genotype for the long form of the serotonin transporter promoter region polymorphism. Am J Psychiatry 160:671–676PubMedCrossRef
3.
go back to reference Benjamin LS (2003) Interpersonal diagnosis and treatment of personality Disorders. Guilford Press, New York Benjamin LS (2003) Interpersonal diagnosis and treatment of personality Disorders. Guilford Press, New York
4.
go back to reference Blom RM, Samuels JF, Riddle MA, Joseph Bienvenu O, Grados MA, Reti IM, Eaton WW, Liang K-Y, Nestadt G (2011) Association between a serotonin transporter promoter polymorphism (5HTTLPR) and personality disorder traits in a community sample. J Psychiatr Res 45:1153–1159PubMedCentralPubMedCrossRef Blom RM, Samuels JF, Riddle MA, Joseph Bienvenu O, Grados MA, Reti IM, Eaton WW, Liang K-Y, Nestadt G (2011) Association between a serotonin transporter promoter polymorphism (5HTTLPR) and personality disorder traits in a community sample. J Psychiatr Res 45:1153–1159PubMedCentralPubMedCrossRef
5.
go back to reference Canli T, Lesch K-P (2007) Long story short: the serotonin transporter in emotion regulation and social cognition. Nat Neurosci 10:1103–1109PubMedCrossRef Canli T, Lesch K-P (2007) Long story short: the serotonin transporter in emotion regulation and social cognition. Nat Neurosci 10:1103–1109PubMedCrossRef
6.
go back to reference Domschke K, Stevens S, Beck B, Baffa A, Hohoff C, Deckert J, Gerlach AL (2009) Blushing propensity in social anxiety disorder: influence of serotonin transporter gene variation. J Neural Transm 116:663–666PubMedCrossRef Domschke K, Stevens S, Beck B, Baffa A, Hohoff C, Deckert J, Gerlach AL (2009) Blushing propensity in social anxiety disorder: influence of serotonin transporter gene variation. J Neural Transm 116:663–666PubMedCrossRef
8.
go back to reference Furmark T, Tillfors M, Garpenstrand H, Marteinsdottir I, Långström B, Oreland L, Fredrikson M (2004) Serotonin transporter polymorphism related to amygdala excitability and symptom severity in patients with social phobia. Neurosci Lett 362:189–192PubMedCrossRef Furmark T, Tillfors M, Garpenstrand H, Marteinsdottir I, Långström B, Oreland L, Fredrikson M (2004) Serotonin transporter polymorphism related to amygdala excitability and symptom severity in patients with social phobia. Neurosci Lett 362:189–192PubMedCrossRef
9.
go back to reference Fydrich T, Renneberg B, Schmitz B, Wittchen HU (1997) Strukturiertes klinisches interview für DSM-IV Achse II: Persönlichkeitsstörungen, interviewheft. Hogrefe, Göttingen Fydrich T, Renneberg B, Schmitz B, Wittchen HU (1997) Strukturiertes klinisches interview für DSM-IV Achse II: Persönlichkeitsstörungen, interviewheft. Hogrefe, Göttingen
10.
go back to reference Fydrich T, Sommer G, Tydecks S, Brähler E (2009) Fragebogen zur sozialen unterstützung (F-SozU): normierung der Kurzform (K-14). Zeitschrift Med Psychol 18:43–48 Fydrich T, Sommer G, Tydecks S, Brähler E (2009) Fragebogen zur sozialen unterstützung (F-SozU): normierung der Kurzform (K-14). Zeitschrift Med Psychol 18:43–48
11.
go back to reference Gingrich JA (2002) Mutational Analysis of the Serotonergic System: recent findings using knockout mice. Curr Drug Targets-CNS Neurol Disord 1:449–465PubMedCrossRef Gingrich JA (2002) Mutational Analysis of the Serotonergic System: recent findings using knockout mice. Curr Drug Targets-CNS Neurol Disord 1:449–465PubMedCrossRef
12.
go back to reference Grabe HJ, Schwahn C, Mahler J, Schulz A, Spitzer C, Fenske K, Appel K, Barnow S, Nauck M, Schomerus G, Biffar R, Rosskopf D, John U, Völzke H, Freyberger HJ (2012) Moderation of adult depression by the serotonin transporter promoter variant (5-HTTLPR), childhood abuse and adult traumatic events in a general population sample. Am J Med Genet B Neuropsychiatr Genet 159B:298–309PubMedCrossRef Grabe HJ, Schwahn C, Mahler J, Schulz A, Spitzer C, Fenske K, Appel K, Barnow S, Nauck M, Schomerus G, Biffar R, Rosskopf D, John U, Völzke H, Freyberger HJ (2012) Moderation of adult depression by the serotonin transporter promoter variant (5-HTTLPR), childhood abuse and adult traumatic events in a general population sample. Am J Med Genet B Neuropsychiatr Genet 159B:298–309PubMedCrossRef
13.
go back to reference Heils A, Teufel A, Petri S, Stöber G, Riederer P, Bengel D, Lesch KP (1996) Allelic variation of human serotonin transporter gene expression. J Neurochem 66:2621–2624PubMedCrossRef Heils A, Teufel A, Petri S, Stöber G, Riederer P, Bengel D, Lesch KP (1996) Allelic variation of human serotonin transporter gene expression. J Neurochem 66:2621–2624PubMedCrossRef
14.
go back to reference Homberg JR, Lesch K-P (2011) Looking on the bright side of serotonin transporter gene variation. Biol Psychiatry 69:513–519PubMedCrossRef Homberg JR, Lesch K-P (2011) Looking on the bright side of serotonin transporter gene variation. Biol Psychiatry 69:513–519PubMedCrossRef
15.
go back to reference Hu X, Lipsky RH, Zhu G, Akhtar LA, Taubman J, Greenberg BD, Xu K, Arnold PD, Richter MA, Kennedy JL, Murphy DL, Goldman D (2006) Serotonin transporter promoter gain-of-function genotypes are linked to obsessive–compulsive disorder. Am J Hum Genet 78:815–826PubMedCentralPubMedCrossRef Hu X, Lipsky RH, Zhu G, Akhtar LA, Taubman J, Greenberg BD, Xu K, Arnold PD, Richter MA, Kennedy JL, Murphy DL, Goldman D (2006) Serotonin transporter promoter gain-of-function genotypes are linked to obsessive–compulsive disorder. Am J Hum Genet 78:815–826PubMedCentralPubMedCrossRef
16.
go back to reference John U, Hensel E, Lüdemann J, Piek M, Sauer S, Adam C, Born G, Alte D, Greiser E, Haertel U, Hense H-W, Haerting J, Willich S, Kessler C (2001) Study of Health in Pomerania (SHIP): a health examination survey in an east German region: objectives and design. Soc Prev Med 46:186–194CrossRef John U, Hensel E, Lüdemann J, Piek M, Sauer S, Adam C, Born G, Alte D, Greiser E, Haertel U, Hense H-W, Haerting J, Willich S, Kessler C (2001) Study of Health in Pomerania (SHIP): a health examination survey in an east German region: objectives and design. Soc Prev Med 46:186–194CrossRef
17.
go back to reference Kaufman J, Yang BZ, Douglas-Palumberi H, Houshyar S, Lipschitz D, Krystal JH, Gelernter J (2004) Social supports and serotonin transporter gene moderate depression in maltreated children. Proc Natl Acad Sci USA 101:17316–17321PubMedCentralPubMedCrossRef Kaufman J, Yang BZ, Douglas-Palumberi H, Houshyar S, Lipschitz D, Krystal JH, Gelernter J (2004) Social supports and serotonin transporter gene moderate depression in maltreated children. Proc Natl Acad Sci USA 101:17316–17321PubMedCentralPubMedCrossRef
18.
go back to reference Knappe S, Beesdo K, Fehm L, Lieb R, Wittchen H-U (2009) Associations of familial risk factors with social fears and social phobia: evidence for the continuum hypothesis in social anxiety disorder? J Neural Transm 116:639–648PubMedCentralPubMedCrossRef Knappe S, Beesdo K, Fehm L, Lieb R, Wittchen H-U (2009) Associations of familial risk factors with social fears and social phobia: evidence for the continuum hypothesis in social anxiety disorder? J Neural Transm 116:639–648PubMedCentralPubMedCrossRef
19.
go back to reference Kuo JR, Goldin PR, Werner K, Heimberg RG, Gross JJ (2011) Childhood trauma and current psychological functioning in adults with social anxiety disorder. J Anxiety Disord 25:467–473PubMedCentralPubMedCrossRef Kuo JR, Goldin PR, Werner K, Heimberg RG, Gross JJ (2011) Childhood trauma and current psychological functioning in adults with social anxiety disorder. J Anxiety Disord 25:467–473PubMedCentralPubMedCrossRef
20.
go back to reference La Greca AM, Harrison HM (2005) Adolescent peer relations, friendships, and romantic relationships: do they predict social anxiety and depression? J Clin Child Adolesc Psychol 34:49–61PubMedCrossRef La Greca AM, Harrison HM (2005) Adolescent peer relations, friendships, and romantic relationships: do they predict social anxiety and depression? J Clin Child Adolesc Psychol 34:49–61PubMedCrossRef
21.
go back to reference La Greca AM, Lopez N (1998) Social anxiety among adolescents: linkages with peer relations and friendships. J Abnorm Child Psychol 26:83–94PubMedCrossRef La Greca AM, Lopez N (1998) Social anxiety among adolescents: linkages with peer relations and friendships. J Abnorm Child Psychol 26:83–94PubMedCrossRef
22.
go back to reference Lesch K-P, Zeng Y, Reif A, Gutknecht L (2003) Anxiety-related traits in mice with modified genes of the serotonergic pathway. Eur J Pharmacol 480:185–204PubMedCrossRef Lesch K-P, Zeng Y, Reif A, Gutknecht L (2003) Anxiety-related traits in mice with modified genes of the serotonergic pathway. Eur J Pharmacol 480:185–204PubMedCrossRef
23.
go back to reference Maffei C, Fossati A, Agostoni I, Barraco A, Bagnato M, Deborah D, Namia C, Novella L, Petrachi M (1997) Interrater reliability and internal consistency of the structured clinical interview for DSM-IV axis II personality disorders (SCID-II), version 2.0. J Pers Disord 11:279–284PubMedCrossRef Maffei C, Fossati A, Agostoni I, Barraco A, Bagnato M, Deborah D, Namia C, Novella L, Petrachi M (1997) Interrater reliability and internal consistency of the structured clinical interview for DSM-IV axis II personality disorders (SCID-II), version 2.0. J Pers Disord 11:279–284PubMedCrossRef
24.
go back to reference Mathew SJ, Ho S (2006) Etiology and neurobiology of social anxiety disorder. J Clin Psychiatry 67(Suppl 12):9–13PubMed Mathew SJ, Ho S (2006) Etiology and neurobiology of social anxiety disorder. J Clin Psychiatry 67(Suppl 12):9–13PubMed
25.
go back to reference Nakamura M, Ueno S, Sano A, Tanabe H (2000) The human serotonin transporter gene linked polymorphism (5-HTTLPR) shows ten novel allelic variants. Mol Psychiatry 5:32–38PubMedCrossRef Nakamura M, Ueno S, Sano A, Tanabe H (2000) The human serotonin transporter gene linked polymorphism (5-HTTLPR) shows ten novel allelic variants. Mol Psychiatry 5:32–38PubMedCrossRef
26.
go back to reference Rapee RM, Heimberg RG (1997) A cognitive-behavioral model of anxiety in social phobia. Behav Res Ther 35:741–756PubMedCrossRef Rapee RM, Heimberg RG (1997) A cognitive-behavioral model of anxiety in social phobia. Behav Res Ther 35:741–756PubMedCrossRef
27.
go back to reference Reinelt E, Stopsack M, Aldinger M, John U, Grabe HJ, Barnow S (2013) Testing the diathesis-stress model: 5-HTTLPR, childhood emotional maltreatment, and vulnerability to social anxiety disorder. Am J Med Genet B Neuropsychiatr Genet 162:253–261CrossRef Reinelt E, Stopsack M, Aldinger M, John U, Grabe HJ, Barnow S (2013) Testing the diathesis-stress model: 5-HTTLPR, childhood emotional maltreatment, and vulnerability to social anxiety disorder. Am J Med Genet B Neuropsychiatr Genet 162:253–261CrossRef
28.
go back to reference Rothman K (2002) Epidemiology: an introduction. University Press, New York Rothman K (2002) Epidemiology: an introduction. University Press, New York
29.
go back to reference Schmidt L, Polak C, Spooner A (2005) Biological and environmental contributions to childhood shyness: a diathesis-stress model. In: Crozier W, Alden L (eds) The essential handbook of social anxiety for clinicians. Wiley, Chichester, pp 33–55 Schmidt L, Polak C, Spooner A (2005) Biological and environmental contributions to childhood shyness: a diathesis-stress model. In: Crozier W, Alden L (eds) The essential handbook of social anxiety for clinicians. Wiley, Chichester, pp 33–55
30.
31.
go back to reference Uher R (2009) The role of genetic variation in the causation of mental illness: an evolution-informed framework. Mol Psychiatry 14:1072–1082PubMedCrossRef Uher R (2009) The role of genetic variation in the causation of mental illness: an evolution-informed framework. Mol Psychiatry 14:1072–1082PubMedCrossRef
32.
go back to reference Völzke H, Alte D, Schmidt CO, Radke D, Lorbeer R, Friedrich N, Aumann N, Lau K, Piontek M, Born G, Havemann C, Ittermann T, Schipf S, Haring R, Baumeister SE, Wallaschofski H, Nauck M, Frick S, Arnold A, Jünger M, Mayerle J, Kraft M, Lerch MM, Dörr M, Reffelmann T, Empen K, Felix SB, Obst A, Koch B, Gläser S, Ewert R, Fietze I, Penzel T, Dören M, Rathmann W, Haerting J, Hannemann M, Röpcke J, Schminke U, Jürgens C, Tost F, Rettig R, Kors JA, Ungerer S, Hegenscheid K, Kühn J-P, Kühn J, Hosten N, Puls R, Henke J, Gloger O, Teumer A, Homuth G, Völker U, Schwahn C, Holtfreter B, Polzer I, Kohlmann T, Grabe HJ, Rosskopf D, Kroemer HK, Kocher T, Biffar R, John U, Hoffmann W (2011) Cohort profile: the Study of Health in Pomerania. Int J Epidemiol 40:294–307PubMedCrossRef Völzke H, Alte D, Schmidt CO, Radke D, Lorbeer R, Friedrich N, Aumann N, Lau K, Piontek M, Born G, Havemann C, Ittermann T, Schipf S, Haring R, Baumeister SE, Wallaschofski H, Nauck M, Frick S, Arnold A, Jünger M, Mayerle J, Kraft M, Lerch MM, Dörr M, Reffelmann T, Empen K, Felix SB, Obst A, Koch B, Gläser S, Ewert R, Fietze I, Penzel T, Dören M, Rathmann W, Haerting J, Hannemann M, Röpcke J, Schminke U, Jürgens C, Tost F, Rettig R, Kors JA, Ungerer S, Hegenscheid K, Kühn J-P, Kühn J, Hosten N, Puls R, Henke J, Gloger O, Teumer A, Homuth G, Völker U, Schwahn C, Holtfreter B, Polzer I, Kohlmann T, Grabe HJ, Rosskopf D, Kroemer HK, Kocher T, Biffar R, John U, Hoffmann W (2011) Cohort profile: the Study of Health in Pomerania. Int J Epidemiol 40:294–307PubMedCrossRef
33.
go back to reference Widiger TA (1992) Generalized social phobia versus avoidant personality disorder: a commentary on three studies. J Abnorm Psychol 101:340–343 PubMedCrossRef Widiger TA (1992) Generalized social phobia versus avoidant personality disorder: a commentary on three studies. J Abnorm Psychol 101:340–343 PubMedCrossRef
34.
go back to reference Wittchen HU, Lachner G, Wunderlich U, Pfister H (1998) Test–retest reliability of the computerized DSM-IV version of the Munich-Composite International Diagnostic Interview (M-CIDI). Soc Psychiatry Psychiatr Epidemiol 33:568–578PubMedCrossRef Wittchen HU, Lachner G, Wunderlich U, Pfister H (1998) Test–retest reliability of the computerized DSM-IV version of the Munich-Composite International Diagnostic Interview (M-CIDI). Soc Psychiatry Psychiatr Epidemiol 33:568–578PubMedCrossRef
Metadata
Title
High social support buffers the effects of 5-HTTLPR genotypes within social anxiety disorder
Authors
Eva Reinelt
Maren Aldinger
Malte Stopsack
Christian Schwahn
Ulrich John
Sebastian E. Baumeister
Hans Jörgen Grabe
Sven Barnow
Publication date
01-08-2014
Publisher
Springer Berlin Heidelberg
Published in
European Archives of Psychiatry and Clinical Neuroscience / Issue 5/2014
Print ISSN: 0940-1334
Electronic ISSN: 1433-8491
DOI
https://doi.org/10.1007/s00406-013-0481-5

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