title: Gene x environment interactions for ADHD: synergistic effect of 5HTTLPR genotype and youth appraisals of inter-parental conflict.
abstract: BACKGROUND
  Serotonin genes have been hypothesized to play a role in the etiology of attention-deficit hyperactivity disorder (ADHD); prior work suggests that serotonin may interact with psychosocial stressors in ADHD, perhaps via mechanisms involved in emotional dysregulation. Because the development of behavioral and emotional regulation depends heavily both on the child's experience within the family context and the child's construals of that experience, children's appraisals of inter-parental conflict are a compelling candidate potentiator of the effects of variation within the serotonin transporter gene promoter polymorphism (5HTTLPR) on liability for ADHD.
  
  
  METHODS
  304 youth from the local community underwent a multi-informant diagnostic assessment procedure to identify ADHD cases and non-ADHD controls. Youth also completed the Children's Perception of Inter-Parental Conflict (CPIC) scale to assess appraisals of self-blame in relation to their parents' marital disputes. The trialleic configuration of 5HTTLPR (long/short polymorphism with A> G substitution) was genotyped and participants were assigned as having high (La/La N = 78), intermediate (La/Lg, La/short, N = 137), or low (Lg/Lg, Lg/short, short/short, N = 89) serotonin transporter activity genotypes. Teacher reported behavior problems were examined as the target outcome to avoid informant overlap for moderator and outcome measures.
  
  
  RESULTS
  Hierarchical linear regression analyses indicated significant 5HTTLPR x self-blame interactions for ADHD symptoms. Examination of the interactions indicated positive relations between reports of self-blame and ADHD symptoms for those with the high and low serotonin activity genotypes. There was no relation between self-blame and ADHD for those with intermediate activity 5HTTLPR genotypes.
  
  
  CONCLUSIONS
  Both high and low serotonergic activity may exert risk for ADHD when coupled with psychosocial distress such as children's self-blame in relation to inter-parental conflict. Results are discussed in relation to the role of serotonin in the etiology of the ADHD and related externalizing behaviors.
authors.affiliation: Department of Psychology, Michigan State University, East Lansing, Michigan, USA. nikolasm@msu.edu
authors.forename: Molly
authors.initials: M
authors.lastname: Nikolas
authors.forename: Karen
authors.initials: K
authors.lastname: Friderici
authors.forename: Irwin
authors.initials: I
authors.lastname: Waldman
authors.forename: Katherine
authors.initials: K
authors.lastname: Jernigan
authors.forename: Joel T
authors.initials: JT
authors.lastname: Nigg
mesh_terms: D000293:Adolescent; D000342:Affective Symptoms / Q000453:epidemiology / Q000235:genetics / Q000523:psychology; D017677:Age Distribution; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology / Q000235:genetics / Q000523:psychology; D002648:Child; D003072:Cognition Disorders / Q000453:epidemiology / Q000235:genetics / Q000523:psychology; D015897:Comorbidity; D019955:Conduct Disorder / Q000453:epidemiology / Q000235:genetics / Q000523:psychology; D003220:Conflict, Psychological; D004777:Environment; D005006:Ethnicity / Q000706:statistics & numerical data; D005260:Female; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D010290:Parents / Q000523:psychology; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D011627:Puberty; D012307:Risk Factors; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin
references.citation: Mol Psychiatry. 2002;7(1):118-22
references.pmid: 11803458
references.citation: Behav Sci Law. 2004;22(3):415-25
references.pmid: 15211560
references.citation: Acta Paediatr. 2007 Sep;96(9):1269-74
references.pmid: 17718779
references.citation: Biol Psychiatry. 1998 Mar 15;43(6):446-57
references.pmid: 9532350
references.citation: Behav Brain Funct. 2008 Oct 20;4:48
references.pmid: 18937842
references.citation: Monogr Soc Res Child Dev. 2009;74(1):vii, 1-79
references.pmid: 19302676
references.citation: Child Dev. 2008 Nov-Dec;79(6):1693-706
references.pmid: 19037943
references.citation: Hum Genet. 2009 Jul;126(1):51-90
references.pmid: 19506906
references.citation: Dev Psychopathol. 2005 Summer;17(3):785-806
references.pmid: 16262992
references.citation: Biol Psychiatry. 2005 Jun 1;57(11):1313-23
references.pmid: 15950004
references.citation: Annu Rev Psychol. 2002;53:463-90
references.pmid: 11752493
references.citation: Child Dev. 2000 Nov-Dec;71(6):1648-61
references.pmid: 11194263
references.citation: Am J Hum Genet. 2006 May;78(5):815-826
references.pmid: 16642437
references.citation: Psychoneuroendocrinology. 2004 Jun;29(5):651-68
references.pmid: 15041087
references.citation: Mol Psychiatry. 2000 Jan;5(1):32-8
references.pmid: 10673766
references.citation: Psychiatry Res. 1992 Sep;43(3):263-76
references.pmid: 1438624
references.citation: Science. 1996 Nov 29;274(5292):1527-31
references.pmid: 8929413
references.citation: Biol Psychiatry. 2005 Jun 1;57(11):1231-8
references.pmid: 15949993
references.citation: Arch Gen Psychiatry. 1990 May;47(5):419-26
references.pmid: 1691910
references.citation: Neurosci Biobehav Rev. 2000 Jun;24(4):417-63
references.pmid: 10817843
references.citation: Biol Psychiatry. 2005 Sep 1;58(5):374-81
references.pmid: 15993855
references.citation: J Fam Psychol. 2005 Sep;19(3):376-84
references.pmid: 16221018
references.citation: J Child Psychol Psychiatry. 2006 Nov;47(11):1175-83
references.pmid: 17076757
references.citation: Child Dev. 2007 May-Jun;78(3):775-89
references.pmid: 17517004
references.citation: Br J Psychiatry. 2007 May;190:410-4
references.pmid: 17470955
references.citation: Dev Psychol. 2009 Jan;45(1):77-89
references.pmid: 19209992
references.citation: Arch Gen Psychiatry. 1992 Jun;49(6):429-35
references.pmid: 1376104
references.citation: Behav Brain Sci. 2006 Aug;29(4):385-404; discussion 405-52
references.pmid: 17094843
references.citation: Dev Psychol. 2007 Nov;43(6):1428-1446
references.pmid: 18020822
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2008 Dec 5;147B(8):1359-68
references.pmid: 18846501
references.citation: J Abnorm Child Psychol. 1980 Sep;8(3):287-95
references.pmid: 7410730
references.citation: Twin Res Hum Genet. 2006 Feb;9(1):1-8
references.pmid: 16611461
references.citation: J Am Acad Child Adolesc Psychiatry. 2005 Jul;44(7):690-8
references.pmid: 15968238
references.citation: Br J Psychiatry. 1992 May;160:643-6
references.pmid: 1591573
references.citation: J Fam Psychol. 2005 Jun;19(2):324-33
references.pmid: 15982110
references.citation: Mol Psychiatry. 2001 Mar;6(2):235-8
references.pmid: 11317229
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2006 Sep 5;141B(6):566-70
references.pmid: 16856124
references.citation: J Neural Transm (Vienna). 2009 Apr;116(4):503-12
references.pmid: 19137235
references.citation: Am J Psychiatry. 1994 Feb;151(2):243-8
references.pmid: 8296897
references.citation: Biol Psychiatry. 2006 May 1;59(9):836-43
references.pmid: 16412987
references.citation: Mol Psychiatry. 2002;7(8):908-12
references.pmid: 12232786
references.citation: Twin Res. 2002 Dec;5(6):554-71
references.pmid: 12573187
references.citation: Child Adolesc Psychiatr Clin N Am. 2000 Jan;9(1):77-97
references.pmid: 10674191
references.citation: Psychiatry Res. 1999 Apr 19;86(1):29-40
references.pmid: 10359480
references.citation: J Child Psychol Psychiatry. 2008 Dec;49(12):1313-20
references.pmid: 19120710
references.citation: Am J Med Genet. 2001 Jan 8;105(1):91-5
references.pmid: 11425009
references.citation: Psychiatry Res. 1994 Jun;52(3):305-16
references.pmid: 7527565
references.citation: Am J Psychiatry. 2006 Jun;163(6):1103-5
references.pmid: 16741214
references.citation: J Psychiatr Res. 2008 Jul;42(9):708-16
references.pmid: 18331741
references.citation: Child Dev. 2008 Nov-Dec;79(6):1942-56
references.pmid: 19037959
references.citation: Neuropsychopharmacology. 2007 Nov;32(11):2375-83
references.pmid: 17342170
references.citation: Psychol Med. 1999 Sep;29(5):1043-53
references.pmid: 10576297
references.citation: Am J Med Genet. 1999 Feb 5;88(1):83-7
references.pmid: 10050973
references.citation: Child Dev. 1992 Jun;63(3):558-72
references.pmid: 1600822
references.citation: J Abnorm Child Psychol. 2008 Feb;36(2):187-206
references.pmid: 17912624
references.citation: J Abnorm Psychol. 2010 Feb;119(1):1-17
references.pmid: 20141238
references.citation: Pediatrics. 2009 Jun;123(6):1472-6
references.pmid: 19482756
references.citation: J Nucl Med. 2004 Apr;45(4):682-94
references.pmid: 15073266
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2006 Dec 5;141B(8):825-32
references.pmid: 16972235
references.citation: Psychopharmacology (Berl). 2000 Apr;149(2):147-52
references.pmid: 10805609
references.citation: J Emot Behav Disord. 2008 Mar 1;16(1):29-41
references.pmid: 20016758
references.citation: Psychol Bull. 1990 Sep;108(2):267-90
references.pmid: 2236384
references.citation: Twin Res Hum Genet. 2007 Jun;10(3):423-33
references.pmid: 17564500
references.citation: Arch Gen Psychiatry. 1998 Apr;55(4):362-8
references.pmid: 9554432
references.citation: Psychiatry Res. 2008 Mar 15;158(2):123-31
references.pmid: 18155777
references.citation: Psychol Assess. 2009 Sep;21(3):450-6
references.pmid: 19719356
references.citation: Mol Psychiatry. 1999 Jul;4(4):385-8
references.pmid: 10483057
references.citation: Ann N Y Acad Sci. 1986;487:47-62
references.pmid: 2436540
references.citation: Arch Gen Psychiatry. 1989 Jul;46(7):587-99
references.pmid: 2735812
references.citation: Am J Hum Genet. 1995 Nov;57(5):1252-4
references.pmid: 7485180
references.citation: J Fam Psychol. 2006 Mar;20(1):88-99
references.pmid: 16569093
references.citation: Physiol Behav. 2002 Dec;77(4-5):705-9
references.pmid: 12527023