84 Gene-environment interaction studies using identified suscepti

84 Gene-environment interaction studies using identified susceptibility genes rather than unmeasured latent genetic factors can provide more secure estimates.84 Based on results from quantitative genetic studies showing gene-environment interaction for antisocial behavior, Caspi et al123 studied the association between childhood maltreatment, and a Inhibitors,research,lifescience,medical functional polymorphism in the promoter region of the MAOA gene on antisocial behavior

assessed through a range of categorical and dimensional measures using questionnaire and interview data plus official records. The results showed no main effect of the gene, a main effect for maltreatment and a substantial and significant interaction between the gene and adversity.

The maltreated children whose genotype conferred low levels of MAOA expression more often developed Galunisertib conduct disorder and antisocial Inhibitors,research,lifescience,medical personality than children with a high activity MAOA genotype. Foley et al124 replicated this finding and extended the initial analysis by showing that the gene-environment interaction could not be accounted for by gene-environment correlation. Other studies have failed to replicate the gene-environment interaction effect (eg, ref 125). In a recent meta-analysis, however, Inhibitors,research,lifescience,medical the original finding was replicated. In addition the findings was extended to include childhood (closer in time to the maltreatment), and the possibility of a spurious finding was ruled out by accounting Inhibitors,research,lifescience,medical for gene-environment correlation.126 The interaction between MAOA and childhood maltreatment in the etiology of antisocial PD appear to be one of the few

replicated findings in the molecular genetics of PDs. Future directions Information from genetic Inhibitors,research,lifescience,medical epidemiologic studies can contribute to improvement in the validity of diagnoses of mental disorders, and thereby a more empirically based classification system.49,56,127 Several lines of evidence, including multivariate twin studies, have shown that common axis I disorders can be divided into two main groups (internalizing and externalizing) based on shared etiological factors.49,68 Currently an alternative classification system are being considered for DSM-V based on the hypothesis that, in addition to phenotypic similarity, spectra or clusters of disorder can be identified based TCL on shared liability or risk factors.56 Such clusters transcend the axis I-axis II division. Multivariate twin studies, including a comprehensive number of axis I and axis II disorders, could provide new important insights relevant to this proposal and further clarify the etiology of mental disorders by identifying genetic and environmental risk factors shared in common between groups of disorders.

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