How possible is the development of an operational psychometric method to assess the presence of the 5-HTTLPR s allele? Equivocal preliminary findings

<p>Abstract</p> <p>Objective</p> <p>The s allele of the 5-hydroxytryptamine transporter-linked promoter region (5-HTTLPR) polymorphism of the serotonin transporter gene has been found to be associated with neuroticism-related traits, affective temperaments and response to selective serotonin reuptake inhibitor (SSRI) treatment. The aim of the current study was to develop a psychometric tool that could at least partially substitute for laboratory testing and could predict the presence of the s allele.</p> <p>Methods</p> <p>The study included 138 women of Caucasian origin, mean 32.20 ± 1.02 years old. All subjects completed the Hungarian standardised version of the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A) instrument and were genotyped for 5-HTTLPR using PCR. The statistical analysis included the calculation of the Index of Discrimination (D), Discriminant Function Analysis, creation of scales on the basis of the above and then item analysis and calculation of sensitivity and specificity.</p> <p>Results</p> <p>Four indices were eventually developed, but their psychometric properties were relatively poor and their joint application did not improve the outcome.</p> <p>Conclusions</p> <p>We could not create a scale that predicts the 5-HTTLPR genotype with sufficient sensitivity and specificity, therefore we could not substitute a psychometric scale for laboratory genetic testing in predicting genotype, and also possibly affective disorder characterisation and treatment.</p

Association analysis of 5-HTTLPR variants, 5-HT2A receptor gene 102T/C polymorphism and migraine

It is well known that migraine has a strong genetic component, although the type and number of genes involved is not yet clear. There is evidence to suggest that serotonin-related genes participate in the pathogenesis of migraine. Previous studies have shown that gender differences influence the serotonergic neurotransmission and, in addition, the migraine prevalence is higher in females than males. Therefore, we investigated the functional polymorphism in the upstream regulatory region of the serotonin transporter gene (5-HTTLPR) and the 102T/C polymorphism of the 5-HT2A receptor gene in the Hungarian female population. These genes were analysed in 126 migraine sufferers (with or without aura)and 101 unrelated healthy controls using case control design. A borderline association (chi2 = 3.84, df = 1, p = 0.049; OR = 1.45, 95% CI = 1.00-2.12) between 5-HTTLPR short (S) allele and migraine was found. No significant difference between migraine sufferers and controls was observed for the 102T/C polymorphism of 5-HT2A receptor gene. Furthermore, there was no significant interaction between5-HTTLPR and 102T/C polymorphisms in our study population. In conclusion, our results support that the genetic susceptibility of migraine may be associated with a locus at or near the 5-HT transporter gene

Star-crossed? The association of the 5-HTTLPR s allele with season of birth in a healthy female population, and possible consequences for temperament, depression and suicide

BACKGROUND: Birth season has well-known effects on neuropsychiatric disorders, and may also influence genotype distribution by possibly influencing chance of conception via parental idiosyncratic conception patterns or survival of foetuses or infants. The 5-HTTLPR is associated with phenomena including affective temperaments or suicide which are also associated with birth season. Our aim was to investigate the association of 5- HTTLPR genotype and birth season in a healthy female population. METHODS: Birth date and 5-HTTLPR genotype was determined for 327 psychiatrically healthy women. The association between presence of s allele and time of birth was analysed using generalized linear models. RESULTS: A significant association between s allele frequency and time of birth was detected. S allele carrier frequency was marginally significantly higher in July borns and significantly lower in autumn borns. LIMITATIONS: We investigated an adult sample so genotype frequency data do not reflect birth frequencies. Our sample consisted exclusively of females. CONCLUSIONS: There is no clear explanation for the observed association, although idiosyncratic parental conception patterns, the association of 5-HTTLPR with sudden infant/intrauterine death, or other s allele-mediated behaviours may play a role. Our results are strikingly parallel with earlier data reporting a higher risk of completed suicide in July borns, and higher scores of July borns and lower scores of autumn borns on certain affective temperament scales, both of which are also associated with the s allele of 5-HTTLPR. Thus our results may add to the growing body of evidence regarding the etiological background of affective disorders