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Effect of the serotonin transporter gene and of environment on the continuity of anxiety and depression traits throughout adolescence

Published online by Cambridge University Press:  22 October 2013

M. Nobile*
Affiliation:
Department of Child Psychiatry, ‘Eugenio Medea’ Scientific Institute, Bosisio Parini, Italy Department of Clinical Neurosciences, Hermanas Hospitalarias, FoRiPsi, Albese con Cassano, Italy
A. Greco
Affiliation:
Department of Psychology, Università degli Studi di Milano Bicocca, Milan, Italy
G. Perna
Affiliation:
Department of Clinical Neurosciences, Hermanas Hospitalarias, FoRiPsi, Albese con Cassano, Italy
P. Colombo
Affiliation:
Department of Child Psychiatry, ‘Eugenio Medea’ Scientific Institute, Bosisio Parini, Italy
V. Bianchi
Affiliation:
Department of Child Psychiatry, ‘Eugenio Medea’ Scientific Institute, Bosisio Parini, Italy
M. Bellina
Affiliation:
Department of Child Psychiatry, ‘Eugenio Medea’ Scientific Institute, Bosisio Parini, Italy
R. Giorda
Affiliation:
Department of Child Psychiatry, ‘Eugenio Medea’ Scientific Institute, Bosisio Parini, Italy
D. Monzani
Affiliation:
Department of Psychology, Università degli Studi di Milano Bicocca, Milan, Italy
O. Carlet
Affiliation:
Department of Child Psychiatry, ‘Eugenio Medea’ Scientific Institute, Conegliano, Italy
E. Griez
Affiliation:
Department of Psychiatry and Neuropsychology, University of Maastricht, The Netherlands
M. Molteni
Affiliation:
Department of Child Psychiatry, ‘Eugenio Medea’ Scientific Institute, Bosisio Parini, Italy
*
*Address for correspondence: Dr M. Nobile, Child Psychiatry Department, ‘Eugenio Medea’ Scientific Institute, via Don Luigi Monza 20, 23842 Bosisio Parini, LC, Italy. (Email: [email protected])

Abstract

Aims.

Many studies of various stress reactive phenotypes suggest that 5-HTTLPR short allele carriers (S-carriers) are characterised by the stable trait of negative affectivity that is converted to psychopathology only under conditions of stress. In this study, we examined the moderating role of the 5-HTTLPR on the relationship between two objective chronic risk factors, i.e. socioeconomic status (SES) and family structure, and internalising symptoms across adolescence.

Methods.

A multigroup path analysis was employed in a general adolescent population sample of a 5-year follow-up study.

Results.

Internalising problems were significantly more stable in the S-carriers. The focus on the main dimensions of internalising problems, i.e. anxiety and depression, revealed two different developmental patterns. In the S-carriers Anxiety problems seemed to be more stable and to predict a possible evolution towards the development of Depressive problems. In the long allele homozygotes (LL-subjects) the anxiety trait was significantly less stable, and, in late-adolescence, seemed to be significantly predicted by SES, suggesting a possible gene–environment interaction (G × E). Family structure seemed to play a role in a G × E perspective only until early-adolescence, while during late-adolescence SES seemed to play a pivotal role in interaction with 5-HTTLPR, with the S-allele playing a protective role.

Conclusions.

Future models of the developmental link between environmental adversities and internalising behaviour therefore need to consider that the effect of G × E interaction, may be associated with internalising behaviour via different mechanisms during different time frames and that shifts in the strength of this effect should be expected across development.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2013 

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References

Achenbach, TM, Rescorla, LA (2001). Manual for the ASEBA School-age Forms and Profiles. University of Vermont: Burlington, VT.Google Scholar
Bellani, M, Nobile, M, Bianchi, V, van Os, J, Brambilla, P (2013). G × E interaction and neurodevelopment II. Focus on adversities in paediatric depression: the moderating role of serotonin transporter. Epidemiology and Psychiatric Sciences 22, 2128.CrossRefGoogle Scholar
Bramlett, MD, Blumberg, SJ (2007). Family structure and children's physical and mental health. Health Affairs 26, 549558.CrossRefGoogle ScholarPubMed
Costello, EJ, Copeland, W, Angold, A (2011). Trends in psychopathology across the adolescent years: what changes when children become adolescents, and when adolescents become adults? Journal of Child Psychology and Psychiatry 52, 10151025.CrossRefGoogle ScholarPubMed
Cuffe, SP, McKeown, RE, Addy, CL, Garrison, CZ (2005). Family and psychosocial risk factors in a longitudinal epidemiological study of adolescents. Journal of American Academy of Child and Adolescent Psychiatry 44, 121129.CrossRefGoogle Scholar
Dunn, EC, Uddin, M, Subramanian, SV, Smoller, JW, Galea, S, Koenen, KC (2011). Research review: gene–environment interaction research in youth depression – a systematic review with recommendations for future research. Journal of Child Psychology and Psychiatry 52, 12231238.CrossRefGoogle ScholarPubMed
Fanous, AH, Kendler, KS (2004). The genetic relationship of personality to major depression and schizophrenia. Neurotoxicity Research 6, 4350.CrossRefGoogle ScholarPubMed
Frigerio, A, Vanzin, L, Pastore, V, Nobile, M, Giorda, R, Marino, C, Molteni, M, Rucci, P, Ammaniti, M, Lucarelli, L, Lenti, C, Walder, M, Martinuzzi, A, Carlet, O, Muratori, F, Milone, A, Zuddas, A, Cavolina, P, Nardocci, F, Tullini, A, Morosini, P, Polidori, G, De Girolamo, G (2006). The italian preadolescent mental health project (PrISMA): rationale and methods. International Journal of Methods in Psychiatric Research 15, 2235.CrossRefGoogle ScholarPubMed
Hollingshead, AB (1975). Four factor index of social status. Unpublished Document.Google Scholar
Hu, XZ, 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. American Journal of Medical Genetics 78, 815826.Google ScholarPubMed
ISTAT (2005). Rapporto annuale 2005. Istituto Nazionale di Statistica. Roma. Retrieved 24 May 2006 from http://www.istat.it/dati/catalogo/20060524_00/.Google Scholar
Jacobs, N, Kenis, G, Peeters, F, Derom, C, Vlietinck, R, van Os, J (2006). Stress-related negative affectivity and genetically altered serotonin transporter function: evidence of synergism in shaping risk of depression. Archives of General Psychiatry 63, 989996.CrossRefGoogle ScholarPubMed
Karg, K, Burmeister, M, Shedden, K, Sen, S (2011). The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: evidence of genetic moderation. Archives of General Psychiatry 68, 444454.CrossRefGoogle ScholarPubMed
Kendler, KS, Gardner, CO, Lichtenstein, P (2008). A developmental twin study of symptoms of anxiety and depression: evidence for genetic innovation and attenuation. Psychological Medicine 38, 15671575.CrossRefGoogle ScholarPubMed
Kline, RB (1998). Principles and Practice of Structure Equation Modeling. Guilford Press: New York.Google Scholar
Lau, JY, Eley, TC (2008). Attributional style as a risk marker of genetic effects for adolescent depressive symptoms. Journal of Abnormal Psychology 117, 849859.CrossRefGoogle ScholarPubMed
Lesch, KP, Bengel, D, Heils, A, Sabol, SZ, Greenberg, BD, Petri, S, Benjamin, J, Muller, CR, Hamer, DH, Murphy, DL (1996). Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274, 15271531.CrossRefGoogle ScholarPubMed
Martin, J, Cleak, J, Willis-Owen, SA, Flint, J, Shifman, S (2007). Mapping regulatory variants for the serotonin transporter gene based on allelic expression imbalance. Molecular Psychiatry 12, 421422.CrossRefGoogle ScholarPubMed
Meltzer, H, Gatward, R, Corbin, T, Goodman, R, Ford, T (2003). Persistence, Onset, Risk Factors and Outcomes of Childhood Mental Disorders. TSO: London.Google Scholar
Munafo, MR, Durrant, C, Lewis, G, Flint, J (2009). Gene × environment interactions at the serotonin transporter locus. Biological Psychiatry 65, 211219.CrossRefGoogle ScholarPubMed
Muthén, LK, Muthén, BO (2011). Mplus User's Guide, 6th edn. Muthén & Muthén: Los Angeles, CA.Google Scholar
Nobile, M, Begni, B, Giorda, R, Frigerio, A, Marino, C, Molteni, M, Ferrarese, C, Battaglia, M (1999). Effects of serotonin transporter promoter genotype on platelet serotonin transporter functionality in depressed children and adolescents. Journal of American Academy of Child and Adolescent Psychiatry 38, 13961402.CrossRefGoogle ScholarPubMed
Nobile, M, Giorda, R, Marino, C, Carnet, O, Pastore, V, Vanzin, L, Bellina, M, Molteni, M, Battaglia, M (2007). Socioeconomic status mediates the genetic contribution of the DRD4 and 5-HTTLPR polymorphisms to externalization in pre-adolescence. Development and Psychopatholgy 19, 11451158.Google Scholar
Nobile, M, Rusconi, M, Bellina, M, Marino, C, Giorda, R, Carlet, O, Vanzin, L, Molteni, M, Battaglia, M (2009). The influence of family structure, the TPH2 G-703T and the 5-HTTLPR serotonergic genes upon affective problems in children aged 10–14 years. Journal of Child Psychology and Psychiatry 50, 317325.CrossRefGoogle ScholarPubMed
Nobile, M, Colombo, P, Bellina, M, Molteni, M, Simone, D, Nardocci, F, Carlet, O, Battaglia, M (2013). Psychopathology and adversities from early- to late-adolescence: a general population follow-up study with the CBCL DSM-Oriented Scales. Epidemiology and Psychiatric Sciences 22, 6373.CrossRefGoogle ScholarPubMed
O'Connor, TG, Dunn, J, Jenkins, JM, Pickering, K, Rasbash, J (2001). Family settings and children's adjustment: differential adjustment within and across families. British Journal of Psychiatry 179, 110115.CrossRefGoogle ScholarPubMed
Office for National Statistics (2003). Persistence of Mental Disorders . In Persistence, Onset, Risk Factors and Outcomes of Childhood Mental Disorders (ed. Meltzer, H), pp 22–56 TSO: London.Google Scholar
Olsson, CA, Byrnes, GB, Anney, RJ, Collins, V, Hemphill, SA, Williamson, R, Patton, GC (2007). COMT val(158)met and 5HTTLPR functional loci interact to predict persistence of anxiety across adolescence: results from the victorian adolescent health cohort study. Genes, Brain, and Behavior 6, 647652.CrossRefGoogle ScholarPubMed
Petersen, IT, Bates, JE, Goodnight, JA, Dodge, KA, Lansford, JE, Pettit, GS, Latendresse, SJ, Dick, DM (2012). Interaction between Serotonin Transporter Polymorphism (5-HTTLPR) and stressful life events in adolescents' trajectories of anxious/depressed symptoms. Developmental Psychology 48, 14631475.CrossRefGoogle ScholarPubMed
Rao, U, Chen, LA (2009). Characteristics, correlates, and outcomes of childhood and adolescent depressive disorders. Dialogues in Clinical Neuroscience 11, 4562.CrossRefGoogle ScholarPubMed
Rice, F (2009). The genetics of depression in childhood and adolescence. Current Psychiatry Reports 11, 167173.CrossRefGoogle ScholarPubMed
Risch, N, Herrell, R, Lehner, T, Liang, KY, Eaves, L, Hoh, J, Griem, A, Kovacs, M, Ott, J, Merikangas, KR (2009). Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis. Journal of the American Medical Association 301, 24622471.CrossRefGoogle ScholarPubMed
Schruers, K, Esquivel, G, van Duinen, M, Wichers, M, Kenis, G, Colasanti, A, Knuts, I, Goossens, L, Jacobs, N, van Rozendaal, J, Smeets, H, van Os, J, Griez, E (2011). Genetic moderation of CO2-induced fear by 5-HTTLPR genotype. Journal of Psychopharmacology 25, 3742.CrossRefGoogle ScholarPubMed
Uher, R, McGuffin, P (2008). The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis. Molecular Psychiatry 13, 131146.CrossRefGoogle ScholarPubMed
Uher, R, McGuffin, P (2010). The moderation by the serotonin transporter gene of environmental adversity in the etiology of depression: 2009 update. Molecular Psychiatry 15, 1822.CrossRefGoogle ScholarPubMed
van der Valk, JC, van den Oord, EJ, Verhulst, FC, Boomsma, DI (2003). Genetic and environmental contributions to stability and change in children's internalizing and externalizing problems. Journal of the American Academy of Child and Adolescent Psychiatry 42, 12121220.CrossRefGoogle ScholarPubMed
van Oort, FV, van der Ende, J, Wadsworth, ME, Verhulst, FC, Achenbach, TM (2011). Cross-national comparison of the link between socioeconomic status and emotional and behavioral problems in youths. Social Psychiatry and Psychiatric Epidemiology 46, 167172.CrossRefGoogle ScholarPubMed