HT2A studies. Studies of suicidal behavior and the HTR2A receptor have examined three polymorphisms—T102C, His 452Tyr, and A1438G. Comparisons of suicide victims to controls (Du et al., 1999; Turecki et al., 1999) revealed no relationship between HTR2A polymorphisms (His452Tyr for Du et al., 1999; T102C in both studies, A1438G for Turecki et al., 1999). Turecki et al. (1999) found some functional significance of the 102T/1438A haplotype, which was associated with increased 5HT2A receptor binding. Most studies comparing suicide attempters to controls also demonstrated no effect (Geijer et al., 2000; Kunugi et al., 1999; Tsai et al., 1999). One study did report an association between suicide attempt and the 102C form of the allele (Zhang et al., 1997).

MAOA studies. In a study of community volunteers, Manuck et al. (2000) identified 4 haplotypes of monoamine oxidase-A (MAOA) and found an association between the 2-3 haplotype4 and impulsive aggression in men. This haplotype was also associated with an altered response to the fenfluramine challenge test. The relationship of these genetic variants to suicide attempt has not yet been studied.

Methodological issues. To date, while some trends are evident in the results for candidate genes, inconsistencies in the literature exist. Differences in diagnostic makeup may have accounted for differences in results. For example, many of the TPH studies that examined attempts in non-affectively-disordered samples found associations with the 779C or 218C allele, where studies in mood disordered samples tended to find associations with the A218 allele. In this linked set of polymorphisms, some studies find an association with the A and some with the C allele. The inconsistency is hard to explain—it could be due to sex differences, diagnostic differences, or design differences, or it could be that both polarities of the allele, under different circumstances, predispose to a suicide attempt. The association of the S allele in the serotonin transporter promoter region to suicide attempt in alcoholics was strongly influenced by the presence or absence of a history of major depression (Gorwood et al., 2000). Some studies used “healthy” controls, although screening for “healthy” ranged from an extensive psychiatric interview to asking subjects whether they had ever had any psychiatric difficulties. Other studies used diagnostically matched controls. By controlling for diagnosis, one can detect genes above and beyond those related to disorder that may account for suicidal behavior.

4  

A haplotype is a combination of alleles that tend to be inherited together.



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