| Summary: | 博士 === 國防醫學院 === 醫學科學研究所 === 87 === Since the 1980s, a strong body of evidence, derived from family, adoption, and twin studies, has been built for a hereditary component in antisocial personality disorder and alcoholism. Type II alcoholism, affecting mainly sons of male alcoholics, is influenced only weakly by environmental factors and is usually associated with criminal behavior (Cloninger et al, 1981). There was no overlap between the congenital antecedents of alcoholism and nonalcoholic criminality, although antisocial personality disorder and alcoholism co-occurred frequently (Lewis et al, 1982). Since the genetic background affected the heredity of alcoholism or antisocial personality independently (Cadoret et al, 1995), it is important to differentiate the categorical diagnoses to find the candidate causal gene. Recent studies on the genetics of alcoholism have examined the association between alcoholism and the dopamine D2 receptor locus (DRD2) as well as the association between novelty seeking behavior and the dopamine D4 receptor locus (DRD4) for the reinforcement and reward effect on the limbic system. The different genotypes at the genes encoding the enzymes involved in alcohol metabolism, class one alcohol dehydrogenase (ADH2 and ADH3) and mitochondrial aldehyde dehydrogenase (ALDH2), have previously been shown to confer different predispositions to the development of alcoholism in Chinese Han males. This study employs the molecular genetic study to evaluate the evidence for an association between dopamine gene (DRD2, DRD4) and the categorical diagnosis ("antisocial personality without alcoholism; ASPD-S-ALC", " antisocial personality with alcoholism; ASPD-C-ALC", and " alcoholism without antisocial personality; ALC-S-ASPD"). We also test the association between the dopamine gene and the dimensional groups (high novelty seeking; middle novelty seeking and low novelty seeking). Furthermore, we try to replicate the differences of ADH and ALDH2 variants between alcoholics and non-alcoholics in antisocial personality disorder. Methods: We studied 285 male Han subjects [46 ASPD-S-ALCs, 50 ASPD-C-ALC, 62 ALC-S-ASPD, 88 CONTROL, and 39 NON-ASPALC (non-antisocial and non-alcoholics from criminality)] with categorical diagnosis defined according to DSM-III-R criteria under the SADS-L structured interview. All the subjects from criminality completed the novelty seeking scale. Results: There were no significant difference observed between these genetic variants at the DRD2 locus and categorical diagnosis in male Han. In contrast, a significant difference was observed between DRD4 gene and antisocial personality diagnosis. When test the association between DRD2 gene and novelty seeking groups, the result is negative. We found that there existed a positive correlation between the novelty seeking scores and the total repeat numbers at DRD4 exon3. There is a significant difference of novelty seeking behavior in the different genotypes at DRD4 exon3. For the antisocial personality, there is significant low frequencies of ALDH2 *2 in ASPD-C-ALC when comparing with the ASPD-S-ALC. The ADH2 gene also can be viewed as a risk/protect gene for the ALC-S-ASPD but not for the ASPD-C-ALC. There is a borderline significant difference in ADH2 allele frequencies between the ASPD-C-ALC and ASPD-S-ALC. Conclusion: In summary, this result do not support that DRD2 is associated with antisocial personality, its comorbid alcoholism and novelty seeking behavior in Han male criminals. In contrast, the DRD4 gene may be associated with antisocial personality and novelty seeking. There existed a positive correlation between the novelty seeking and the total repeat numbers at DRD4 exon3. The ADH2 and ALDH2 gene can be viewed as an alcoholic risk/protect gene for the antisocial criminals.
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