The present study re-examined the potential association of a functional 5-HT1A-receptor polymorphism, a history of suicide attempts, and personality traits of harm avoidance and neuroticism. Our results do not support an association between the C(-1019)G 5-HT1A-promoter polymorphism with these personality and temperament traits, and also failed to detect an association between this functional polymorphism and a history of suicide attempts in 185 alcohol-dependent individuals. Significant associations were found between Babor's Type B and increased number of suicide attempts in history as well as higher neuroticism and harm avoidance scores.
The only previous study reporting an association between personality traits and this polymorphism in individuals of Caucasian background described the C(-1019)G 5-HT1A promoter polymorphism to be associated with the personality traits harm avoidance and neuroticism [15
]. In accord with our assessments, in this prior study personality traits were assessed by NEO-PIR and TPQ.
The NEO FFI has five dimensions; their mean and standard deviation reference values in German population were described by authors of the German version [21
]. The scale Harm avoidance is in line with a low score in self-directedness reflecting low responsibility, low purposefulness, low resourcefulness, low self-acceptance and low congruent second nature [30
Thus, the divergent results deserve comments. The conceptual frame of anxiety-and depression-related personality traits and its assessment in alcoholics shortly after alcohol detoxification may be a relevant factor influencing the results.
The association of the G allele with certain personality traits may be different in subjects affected by other psychiatric disorders. For an association between suicide attempts and C(-1019)G 5-HT1A-promoter polymorphism the power of our sample might be too low (41 individuals reported a history of suicide attempts). Suicidal behaviour in general may be too heterogeneous to be a suitable phenotype to demonstrate genetic influence of single polymorphisms. Another limitation of the study is that participants were drug free only for 1,5 ± 0,6 weeks before the study but the 5-HT1A autoreceptor take 2–3 weeks to desensitise [31
]. Reinvestigation of the participants after a longer drug free interval could be helpful.
Furthermore, it is not unusual that results of association studies significantly depend on the assessment method, i.e. the type of questionnaires and tests used. In a recent meta-analysis contrasts between groups were shown to be significant for TCI/TPQ Harm avoidance but not for NEO Neuroticism [32
]. This may indicate more heterogeneity for the phenotype
Another meta-analysis reported significant effects on 5-HTTLPR. For studies using the Neuroticism scale of Costa and McCrae [33
]. Findings do indicate that the effect, if present, is small.
There are also effects from other parts of the serotonergic system on the 5-HT1A receptor. In a very recent study it was demonstrated for the first time that a functional polymorphism in the 5-HTT gene, but not the 5-HT1A-receptor gene itself, affects 5-HT1A receptor availability in man. The 5-HT1A-receptor genotype did not show any significant effects on [11C]WAY 100635 binding [34
]. These results may explain our results as far as functional significance is not as predicted.
Patients with panic disorder and depression exhibit an attenuation of 5-HT1A receptor-mediated neuroendocrine response, reflecting dysfunction of pre and postsynaptic 5-HT1A receptors [35
]. Subsequent studies suggested the same mechanism to be associated with agoraphobia in a group of patients with panic disorders [36
Decreased ligand binding of 5-HT1A receptors has been shown in depressed patients [37
Not much data are available about association of personality traits and C(-1019)G 5-HT1A-promoter polymorphism. Regarding an association between the C(-1019)G 5-HT1A-promoter polymorphism and suicidal behavior, a recent study detected a significant association between this polymorphism and completed suicide [12
]. However, the Pro16Leu and Gly272Asp polymorphisms of the 5-HT1A receptor gene failed to show an association with completed suicide in another study [38
Since not much data are available in this field additional data may provide additional support or fail to support the hypothesis. Use of haplotypes for a particular gene or a broader assessment of serotonergic genes is mentioned as a stronger methodology.