Association of the serotonin transporter and 5HT1Dbeta receptor genes with extreme, persistent and pervasive aggressive behaviour in children.
There is an inverse correlation between central nervous system serotonergic activity and human aggression, and aggressive traits are at least partially heritable. The present study sought to investigate the relationship between childhood aggression and polymorphisms of two serotonin system genes: the 5HT1Dbeta receptor gene and the serotonin transporter (5HTT) gene. Fifty children with a minimum 2-year history of aggression and scores above the 90th percentile on the Aggression subscales of both the Child Behaviour Checklist and the Teacher's Report Form were included in the study. All probands and locally recruited ethnically matched controls were genotyped for the 5HT1Dbeta G861C, 5HTTLPR (promoter) and 5HTT variable number of tandem repeats (VNTR) polymorphisms. Chi-square tests revealed a significantly reduced frequency of the 5HTT VNTR 10R allele in children displaying the high-aggression phenotype compared with normal controls (P=0.039). After correction for multiple comparisons, this association reached the level of a trend but was no longer significant. Probands also demonstrated an increased 5HT1Dbeta 861C allele frequency, but this was not statistically significant (P=0.156). 5HTTLPR was not found to be significantly associated with aggression, but our data support previous findings of an association between this polymorphism and attention deficit hyperactivity disorder (P=0.025). While these preliminary findings should be interpreted cautiously, our data suggest that the 5HTT VNTR polymorphism is associated with measures of aggressive behaviour in a sample of children displaying extreme, persistent and pervasive aggression.
Centre for Addiction and Mental Health, Clarke Division, Toronto, Ontario, Canada.
Kristen M
KM
Davidge
Leslie
L
Atkinson
Lori
L
Douglas
Vivien
V
Lee
Solomon
S
Shapiro
James L
JL
Kennedy
Joseph H
JH
Beitchman
D000293:Adolescent; D000374:Aggression / Q000502:physiology*; D002648:Child; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D001523:Mental Disorders / Q000235:genetics*; D018598:Minisatellite Repeats; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins
D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D044302:Receptor, Serotonin, 5-HT1B; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins