nach oben

European Child & Adolescent Psychiatry

Erschienen in:

01.01.2016 | Original Contribution

Mechanisms in the relation between GABRA2 and adolescent externalizing problems

verfasst von: Frances L. Wang, Laurie Chassin, Christian Geiser, Kathryn Lemery-Chalfant

Erschienen in: European Child & Adolescent Psychiatry | Ausgabe 1/2016

Einloggen, um Zugang zu erhalten

Abstract

Conduct problems, alcohol problems and hyperactive–inattentive symptoms co-occur at a high rate and are heritable in adolescence. The γ-aminobutyric acid A receptor, α2 gene (GABRA2) is associated with a broad spectrum of externalizing problems and disinhibitory-related traits. The current study tested whether two important forms of disinhibition in adolescence, impulsivity and sensation seeking, mediated the effects of GABRA2 on hyperactive–inattentive symptoms, conduct problems, and alcohol problems. Participants were assessed at two waves (11–17 and 12–18 years old; N = 292). Analyses used the GABRA2 SNP, rs279858, which tags the two complementary (yin–yang) GABRA2 haplotypes. Multiple informants reported on adolescents’ impulsivity and sensation seeking and adolescents self-reported their hyperactive–inattentive symptoms, conduct problems and lifetime alcohol problems. Impulsivity mediated the effect of GABRA2 on alcohol problems, hyperactive–inattentive symptoms, and conduct problems, whereas sensation seeking mediated the effect of GABRA2 on alcohol problems (AA/AG genotypes conferred risk). GABRA2 directly predicted adolescent alcohol problems, but the GG genotype conferred risk. Results suggest that there may be multiple pathways of risk from GABRA2 to adolescent externalizing problems, and suggest important avenues for future research.

Hicks BM, Foster KT, Iacono WG, McGue M (2013) Genetic and environmental influences on the familial transmission of externalizing disorders in adoptive and twin offspring. JAMA Psychiatr 70:1076–1083CrossRef

Young SE, Stallings MC, Corley RP, Krauter KS, Hewitt JK (2000) Genetic and environmental influences on behavioral disinhibition. Am J Med Genet B Neuropsychiatr Genet 96:684–695CrossRef

Barnard EA, Skolnick P, Olsen RW et al (1998) Subtypes of γ-aminobutyric acid_A receptors: classification on the basis of subunit structure and receptor function. Pharmacol Rev 50:291–313PubMed

Enoch MA (2008) The role of GABA_A receptors in the development of alcoholism. Pharmacol Biochem Be 90:95–104CrossRef

Johnson SW, North RA (1992) Opioids excite dopamine neurons by hyperpolarization of local interneurons. J Neurosci 12:483–488PubMed

Steffensen SC, Svingos AL, Pickel VM, Henriksen SJ (1998) Electrophysiological characterization of GABAergic neurons in the ventral tegmental area. J Neurosci 18:8003–8015PubMed

Comings DE, Blum K (2000) Reward deficiency syndrome: genetic aspects of behavioral disorders. Prog Brain Res 126:325–341PubMedCrossRef

Dick DM, Latendresse SJ, Lansford JE et al (2009) Role of GABRA2 in trajectories of externalizing behavior across development and evidence of moderation by parental monitoring. Arch Gen Psychiatr 66:649–657PubMedPubMedCentralCrossRef

Dick D, Aliev F, Latendresse S et al (2013) How phenotype and developmental stage affect the genes we find: GABRA2 and impulsivity. Twin Res Hum Genet 16:661–669PubMedPubMedCentralCrossRef

10.

Dick DM, Bierut L, Hinrichs A et al (2006) The role of GABRA2 in risk for conduct disorder and alcohol and drug dependence across developmental stages. Behav Genet 36:577–590PubMedCrossRef

11.

Sakai JT, Stallings MC, Crowley TJ et al (2010) Test of association between GABRA2 (SNP rs279871) and adolescent conduct/alcohol use disorders utilizing a sample of clinic referred youth with serious substance and conduct problems, controls and available first degree relatives. Drug Alcohol Depend 106:199–203PubMedPubMedCentralCrossRef

12.

Trucco EM, Villafuerte S, Heitzeg MM, Burmeister M, Zucker RA (2014) Rule breaking mediates the developmental association between GABRA2 and adolescent substance abuse. J Child Psychol Psyc. doi:10.1111/jcpp.12244

13.

Melroy WE, Stephens SH, Sakai JT et al (2014) Examination of genetic variation in GABRA2 with conduct disorder and alcohol abuse and dependence in a longitudinal study. Behav Genet 44:356–367PubMedPubMedCentralCrossRef

14.

Dick DM, Agrawal A, Schuckit M et al (2006) Marital status, alcohol dependence, and GABRA2: evidence for gene–environment correlation and interaction. J Stud Alcohol Drugs 67:185–194CrossRef

15.

Agrawal A, Edenberg HJ, Foroud T et al (2006) Association of GABRA2 with drug dependence in the collaborative study of the genetics of alcoholism sample. Behav Genet 36:640–650PubMedCrossRef

16.

Covault J, Gelernter J, Hesselbrock V, Nellissery M, Kranzler HR (2004) Allelic and haplotypic association of GABRA2 with alcohol dependence. Am J Med Genet B Neuropsychiatr Genet 129:104–109CrossRef

17.

Edenberg HJ, Dick DM, Xuei X et al (2004) Variations in GABRA2, encoding the alpha 2 subunit of the GABA(A) receptor, are associated with alcohol dependence and with brain oscillations. Am J Hum Genet 74:705–714PubMedPubMedCentralCrossRef

18.

Fehr C, Sander T, Tadic A, Lenzen KP, Anghelescu I, Klawe C (2006) Confirmation of association of the GABRA2 gene with alcohol dependence by subtype-specific analysis. Psychiatr Genet 16:9–17PubMedCrossRef

19.

Lappalainen J, Krupitsky E, Remizov M et al (2005) Association between alcoholism and gamma-amino butyric acid alpha2 receptor subtype in a Russian population. Alcohol Clin Exp Res 29:493–498PubMedCrossRef

20.

Lind P, MacGregor S, Agrawal A, Heath AC, Martin NG, Whitfield JB (2008) The role of GABRA2 in alcohol dependence, smoking and illicit drug use in an Australian population sample. Alcohol Clin Exp Res 32:1721–1731PubMedPubMedCentralCrossRef

21.

Philibert RA, Gunter TD, Beach SRH et al (2009) Role of GABRA2 on risk for alcohol, nicotine, and cannabis dependence in the Iowa adoption studies. Psychiatr Genet 19:91–98PubMedPubMedCentralCrossRef

22.

Soyka M, Preuss UW, Hesselbrock V, Zill P, Koller G, Bondy B (2008) GABA-A2 receptor subunit gene (GABRA2) polymorphisms and risk for alcohol dependence. J Psychiatr Res 42:184–191PubMedCrossRef

23.

Villafuerte S, Heitzeg MM, Foley S et al (2012) Impulsiveness and insula activation during reward anticipation are associated with genetic variants in GABRA2 in a family sample enriched for alcoholism. Mol Psychiatry 17:511–519PubMedPubMedCentralCrossRef

24.

Villafuerte S, Strumba V, Stoltenberg SF, Zucker RA Burmeister (2013) Impulsiveness mediates the association between GABRA2 SNPs and lifetime alcohol problems. Genes Brain Behav 12:525–531PubMedPubMedCentralCrossRef

25.

Li D, Sulovari A, Cheng C, Zhao H, Kranzler HR, Gelernter J (2014) Association of γ-aminobutyric acid A receptor α2 gene (GABRA2) with alcohol use disorder. Neuropsychopharmacology 39:907–918PubMedPubMedCentralCrossRef

26.

Kendler KS, Schmitt E, Aggen SH, Prescott CA (2008) Genetic and environmental influences on alcohol, caffeine, cannabis, and nicotine use from early adolescence to middle adulthood. Arch Gen Psychiatry 65:674–682PubMedPubMedCentralCrossRef

27.

Dick DM (2007) Identification of genes influencing a spectrum of externalizing psychopathology. Curr Dir Psychol Sci 16:331–335CrossRef

28.

Dick DM, Cho SB, Latendresse SJ et al (2013) Genetic influences on alcohol use across stages of development: GABRA2 and longitudinal trajectories of drunkenness from adolescence to young adulthood. Addict Biol. doi:10.1111/adb.12066

29.

Bauer LO, Covault J, Harel O et al (2007) Variation in GABRA2 predicts drinking behavior in project MATCH subjects. Alcohol Clin Exp Res 31:1780–1787PubMedPubMedCentralCrossRef

30.

Dick DM, Smith G, Olausson P et al (2010) Review: understanding the construct of impulsivity and its relationship to alcohol use disorders. Addict Biol 15:217–226PubMedPubMedCentralCrossRef

31.

Jonas KG, Markon KE (2014) A meta-analytic evaluation of the endophenotype hypothesis: effects of measurement paradigm in the psychiatric genetics of impulsivity. J Abnorm Psychol 123:660–675PubMedCrossRef

32.

Steinberg L (2010) A dual systems model of adolescent risk-taking. Dev Psychobiol 52:216–224PubMed

33.

Whiteside SP, Lynam DR (2001) The five factor model and impulsivity: using a structural model of personality to understand impulsivity. Pers Individ Dif 30:669–689CrossRef

34.

Handley ED, Chassin L, Haller MM, Bountress KE, Dandreaux D, Beltran I (2011) Do executive and reactive disinhibition mediate the effects of familial substance use disorders on adolescent externalizing outcomes? J Abnorm Psychol 120:528–542PubMedPubMedCentralCrossRef

35.

Miller J, Flory K, Lynam D, Leukefeld C (2003) A test of the four-factor model of impulsivity-related traits. Personal Individ Differ 34:1403–1418CrossRef

36.

Miller DJ, Derefinko KJ, Lynam DR, Milich R, Fillmore MT (2010) Impulsivity and attention deficit-hyperactivity disorder: subtype classification using the UPPS impulsive behavior scale. J Psychopathol Behav Assess 32:323–332PubMedPubMedCentralCrossRef

37.

Bates ME, Labouvie EW (1995) Personality environment constellations and alcohol use: a process-oriented study of intraindividual change during adolescence. Psychol Addict Behav 9:23–25CrossRef

38.

Derefinko K, DeWall CN, Metze AV, Walsh EC, Lynam DR (2011) Do different facets of impulsivity predict different types of aggression? Aggress Behav 37:223–233PubMedPubMedCentralCrossRef

39.

Lynam DR, Miller JD (2004) Personality pathways to impulsive behavior and their relations to deviance: results from three samples. J Quant Criminol 20:319–341CrossRef

40.

Castellanos-Ryan N, Rubia K, Conrod P (2011) Sensation seeking and common and unique variance in conduct disorder and substance misuse. Alcohol Clin Exp Res 35:1–15CrossRef

41.

Comeau N, Stewart SH, Loba P (2001) The relations of trait anxiety, anxiety sensitivity, and sensation seeking to adolescents’ motivations for alcohol, cigarette, and marijuana use. Addict Behav 26:803–825PubMedCrossRef

42.

Raine A (2002) Biosocial studies of antisocial and violent behavior in children and adults: a review. J Abnorm Child Psychol 30:311–326PubMedCrossRef

43.

Frick PJ, Morris AS (2004) Temperament and developmental pathways to conduct problems. J Clin Child Adolesc Psychol 33:54–68PubMedCrossRef

44.

O’Connor TG, Neiderhiser JM, Reiss D, Hetherington EM, Plomin R (1998) Genetic contributions to continuity, change, and co-occurrence of antisocial and depressive symptoms in adolescence. J Child Psychol Psyc 39:323–336CrossRef

45.

McGue M, Bacon S, Lykken DT (1993) Personality stability and change in early adulthood: a behavioral genetic analysis. Dev Psychol 29:96–109CrossRef

46.

Chassin L, Barrera M, Bech K, Kossak-Fuller J (1992) Recruiting a community sample of adolescent children of alcoholics: a comparison of three subject sources. J Stud Alcohol 53:316–319PubMedCrossRef

47.

Fendrich M, Yun Soo Kim J (2001) Multiwave analysis of retest artifact in the national longitudinal survey of youth drug use. Drug Alcohol Depend 62:239–253PubMedCrossRef

48.

Hodgkinson CA et al (2008) Addictions biology: haplotype-based analysis for 130 candidate genes on a single array. Alcohol Alcohol 43:505–515PubMedPubMedCentralCrossRef

49.

Ward LD, Kellis M (2012) HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants. Nucleic Acids Res 40:D930–D934PubMedPubMedCentralCrossRef

50.

Perry BL, Pescosolido BA, Bucholz K (2013) Gender-specific gene-environment interaction in alcohol dependence: the impact of daily life events and GABRA2. Behav Genet 43:402–414PubMedPubMedCentralCrossRef

51.

Tian C, Gregersen PK, Seldin MF (2008) Accounting for ancestry: population substructure and genome-wide association studies. Hum Mol Genet 17:R143–R150PubMedPubMedCentralCrossRef

52.

Zucker RA, Ellis DA, Fitzgerald HE (1994) Developmental evidence for at least two alcoholisms. I. biopsychosocial variation among pathways into symptomatic difficulty. Ann NY Acad Sci 708:134–146PubMedCrossRef

53.

Stoltenberg SF, Mudd SA, Blow FC, Hill EM (1998) Evaluating measures of family history of alcoholism: density versus dichotomy. Addiction 93:1511–1520PubMedCrossRef

54.

Robins LN, Cottler LB, Bucholz KK, Compton WM, North CS, Rourke KM (2000) Diagnostic interview schedule for the DSM-IV (DIS-IV). Washington University School of Medicine, MO

55.

Endicott J, Andreasen N, Spitzer RL (1975) Family history-research diagnostic criteria. Biometrics Research, New York State Psychiatric Institute, New York

56.

Eysenck SBG, Easting G, Pearson PR (1985) Age norms for impulsiveness, venturesomeness and empathy in children. Pers Indiv Differ 5:315–321CrossRef

57.

Zuckerman M (1979) Sensation seeking: beyond the optimal level of arousal. Lawrence Erlbaum Associates, Hillsdale

58.

Achenbach TM, Rescorla LA (2001) Manual for the ASEBA School-Age Forms & Profiles. Burlington, VT: University of Vermont, Research Center for Children, Youth, & Families

59.

Rhee SH, Hewitt JK, Young SE, Corley RP, Crowley TJ, Stallings MC (2003) Genetic and environmental influences on substance initiation, use, and problem use in adolescents. Arch Gen Psychiatry 60:1256–1264PubMedCrossRef

60.

Fisher SL, Bucholz KK, Reich W, Fox L, Kuperman S, Kramer J (2006) Teenagers are right—parents do not know much: an analysis of adolescent-parent agreement on reports of adolescent substance use, abuse, and dependence. Alcohol Clin Exp Res 30:1699–1710PubMedCrossRef

61.

Muthén LK, Muthén BO (1998–2012) Mplus User’s Guide. Seventh Edition. Los Angeles, CA

62.

MacKinnon DP, Lockwood CM, Williams J (2004) Confidence limits for the indirect effect: distribution of the product and resampling methods. Multivariate Behav Res 39:99–128PubMedPubMedCentralCrossRef

63.

Hur Y, Bouchard TJ (1997) The genetic correlation between impulsivity and sensation seeking traits. Behav Genet 27:455–463PubMedCrossRef

64.

Rothbart MK, Bates JE (2006) Temperament. In: Damon W, Eisenberg N (eds) Handbook of child psychology, vol 3., Social, emotional, personality developmentWiley, New York, pp 88–166

65.

Haughey HM, Ray LA, Finan P, Villanueva R, Niculescu M, Hutchison KE (2008) The human GABA(A) receptor alpha2 gene moderates the acute effects of alcohol and brain mRNA expression. Genes Brain Behav 7:447–454PubMedCrossRef

66.

Pierucci-Lagha A, Covault J, Feinn R et al (2005) GABRA2 alleles moderate the subjective effects of alcohol, which are attenuated by finasteride. Neuropsychopharmacology 30:1193–1203PubMedCrossRef

67.

Uhart M, Weerts EM, Mccaul ME et al (2013) GABRA2 markers moderate the subjective effects of alcohol. Addict Biol 18:357–369PubMedPubMedCentralCrossRef

68.

Cohen P, Cohen J, Kasen S et al (1993) An epidemiological study of disorders in late childhood and adolescence, 1: age- and gender-specific prevalence. J Child Psychol Psychiatr 34:851–867CrossRef

69.

Enoch MA, Schwartz L, Albaugh B, Virkkunen M, Goldman D (2006) Dimensional anxiety mediates linkage of GABRA2 haplotypes with alcoholism. Am J Med Genet B Neuropsychtr Genet 141:599–607CrossRef

70.

Vassos E, Collier DA, Fazel S (2014) Systematic meta-analyses and field synopsis of genetic association studies of violence and aggression. Mol Psychiatry 19:471–477PubMedPubMedCentralCrossRef

71.

Storey JD (2002) A direct approach to false discovery rates. J R Stat Soc Series B Stat Methodol 64:479–498CrossRef

72.

Gottesman II, Gould TD (2003) The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 160:636–645PubMedCrossRef

Titel: Mechanisms in the relation between GABRA2 and adolescent externalizing problems
verfasst von: Frances L. Wang
Laurie Chassin
Christian Geiser
Kathryn Lemery-Chalfant
Publikationsdatum: 01.01.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: European Child & Adolescent Psychiatry / Ausgabe 1/2016
Print ISSN: 1018-8827
Elektronische ISSN: 1435-165X
DOI: https://doi.org/10.1007/s00787-015-0703-7

Neu im Fachgebiet Psychiatrie

23.04.2024 | Demenz | Nachrichten

Update Psychiatrie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Mechanisms in the relation between GABRA2 and adolescent externalizing problems

Abstract

Neu im Fachgebiet Psychiatrie

Demenzkranke durch Antipsychotika vielfach gefährdet

Weniger postpartale Depressionen nach Esketamin-Einmalgabe

„Psychotherapie ist auch bei sehr alten Menschen hochwirksam!“

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Update Psychiatrie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2016

A first assessment of the needs of young refugees arriving in Europe: what mental health professionals need to know

Off-label prescribing of psychotropic drugs in a Danish child and adolescent psychiatric outpatient clinic

Erratum to: Mechanisms in the relation between GABRA2 and adolescent externalizing problems

The discriminative capacity of CBCL/1½-5-DSM5 scales to identify disruptive and internalizing disorders in preschool children

Attention-deficit/hyperactivity disorder dimensionality: the reliable ‘g’ and the elusive ‘s’ dimensions

Migration mental health issues in Europe: the case of Greece

Neu im Fachgebiet Psychiatrie

Demenzkranke durch Antipsychotika vielfach gefährdet

Weniger postpartale Depressionen nach Esketamin-Einmalgabe

„Psychotherapie ist auch bei sehr alten Menschen hochwirksam!“

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Update Psychiatrie