A gene-environment investigation on personality traits in two independent clinical sets of adult patients with personality disorder and attention deficit/hyperactive disorder.
While an interactive effect of genes with adverse life events is increasingly appreciated in current concepts of depression etiology, no data are presently available on interactions between genetic and environmental (G x E) factors with respect to personality and related disorders. The present study therefore aimed to detect main effects as well as interactions of serotonergic candidate genes (coding for the serotonin transporter, 5-HTT; the serotonin autoreceptor, HTR1A; and the enzyme which synthesizes serotonin in the brain, TPH2) with the burden of life events (#LE) in two independent samples consisting of 183 patients suffering from personality disorders and 123 patients suffering from adult attention deficit/hyperactivity disorder (aADHD). Simple analyses ignoring possible G x E interactions revealed no evidence for associations of either #LE or of the considered polymorphisms in 5-HTT and TPH2. Only the G allele of HTR1A rs6295 seemed to increase the risk of emotional-dramatic cluster B personality disorders (p = 0.019, in the personality disorder sample) and to decrease the risk of anxious-fearful cluster C personality disorders (p = 0.016, in the aADHD sample). We extended the initial simple model by taking a G x E interaction term into account, since this approach may better fit the data indicating that the effect of a gene is modified by stressful life events or, vice versa, that stressful life events only have an effect in the presence of a susceptibility genotype. By doing so, we observed nominal evidence for G x E effects as well as main effects of 5-HTT-LPR and the TPH2 SNP rs4570625 on the occurrence of personality disorders. Further replication studies, however, are necessary to validate the apparent complexity of G x E interactions in disorders of human personality.
Jacob
Christian P
CP
Department of Psychiatry and Psychotherapy, University of Würzburg, Füchsleinstrasse 15, 97080, Würzburg, Germany. jacob_C@klinik.uni-wuerzburg.de
Nguyen
Thuy Trang
TT
Dempfle
Astrid
A
Heine
Monika
M
Windemuth-Kieselbach
Christine
C
Baumann
Katarina
K
Jacob
Florian
F
Prechtl
Julian
J
Wittlich
Maike
M
Herrmann
Martin J
MJ
Gross-Lesch
Silke
S
Lesch
Klaus-Peter
KP
Reif
Andreas
A
D000328:Adult; D000367:Age Factors; D001289:Attention Deficit Disorder with Hyperactivity / Q000209:etiology / Q000235:genetics*; D004777:Environment; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008016:Life Change Events; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010554:Personality Disorders / Q000209:etiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics; D012701:Serotonin / Q000235:genetics* / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D012737:Sex Factors; D014365:Tryptophan Hydroxylase / Q000235:genetics; D055815:Young Adult
D050486:Serotonin Plasma Membrane Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase