No association between childhood-onset disorder and serotonin transporter using a haplotype relative risk approach

Objective: Clinical aspects in depressed infants, adolescent and adult patients are strikingly similar, suggest-ing that childhood-onset and later-onset depressions are variants of the same condition. Serotonin pathways seem to play an important role in the pathophysiology of depressive disorders. The human serotonin transporter (5-HTT) and its upstream promoter region (5-HTTLPR) are thus candidate loci which may be associated with susceptibility to depressive disorders. Previous linkage analyses produced conflicting results. We tested the hypothesis of whether these two loci were associated with childhood-onset depressive disorders. Method: Probands were administered the structured interview, DICA-R, and the psychometric scale CDI. Depressive disorders were diagnosed according to DSM IV criteria. Seven patients were recruited (five males and two females). According to the HRR strategy, blood samples were collected from both the probands and their parents for DNA analyses. Both were native Italian. The mean age of probands was 14.3 ± 3.3 years. DNA analyses were performed according to literature. Results: We tested the association of the disease locus and the VNTR polymorphism of the second intron of the 5-HTT gene. No significant association was found (genotype: chi-square = 2.0, df = 2, P = .37; allele: chi-square = 1.28, df = 1, P = 0.26). We also tested the hypothesis of association between the 5-HTTLPR region and childhood depressive disorders. We found no significant association (genotype: chi-square = 3.9, P = .14; allele: chi-square = 2.4, P = .12). Conclusions: It might be possible that, due to the high complexity of this system, association studies involving 5-HTT as a candidate gene require a larger sample size, in order to obtain more reliable results. In this light, further studies are needed.