Serotonin transporter and GABAA alpha 6 receptor variants are associated with neuroticism.
BACKGROUND
A tendency to experience negative affect, as measured by the neuroticism component of the Neuroticism, Extraversion, and Openness Personality Inventory (NEO-PI), is a trait marker for major depression. Epidemiologic studies indicate a strong genetic component, but to date few specific genetic variants have been definitively implicated. A serotonin transporter promoter polymorphism (5-HTTLPR) has been extensively studied in neuroticism and several psychiatric disorders, with inconclusive results. A GABA(A) receptor alpha6 subunit variant (Pro385Ser) has been associated with alcohol-related traits but has not been studied in neuroticism or depression.


METHODS
A total of 384 subjects who completed the NEO-PI were genotyped at 5-HTTLPR and Pro385Ser. Associations between polymorphisms and both alcohol use and personality domains were tested.


RESULTS
The 5-HTTLPR short allele (p =.008) and Pro385Ser Pro allele (p =.003) are associated with higher neuroticism scores. The 5-HTTLPR long allele (p =.006), but not Pro385Ser, is also associated with an increased presence of alcohol use. In addition, there is a nonsignificant suggestion of an interaction: the effect of 5-HTTLPR on neuroticism might be dependent on the Pro385Ser genotype.


CONCLUSIONS
These findings support a role for the serotonin transporter and GABA(A) alpha6 subunit in depression-related traits.
Sen
Srijan
S
Neuroscience Program, University of Michigan, Ann Arbor, MI 48109-0720, USA.
Villafuerte
Sandra
S
Nesse
Randolph
R
Stoltenberg
Scott F
SF
Hopcian
Jeffrey
J
Gleiberman
Lillian
L
Weder
Alan
A
Burmeister
Margit
M
D000328:Adult; D000437:Alcoholism / Q000235:genetics; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009497:Neurotic Disorders / Q000235:genetics*; D011110:Polymorphism, Genetic; D011392:Proline / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D011963:Receptors, GABA-A / Q000235:genetics*; D012044:Regression Analysis; D012694:Serine / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins; D011795:Surveys and Questionnaires
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011963:Receptors, GABA-A; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012694:Serine; D011392:Proline