Religion and Spirituality in Psychiatry

58 Nader Perroudspiritual acceptance. However, in girls and not inboys, they found an interactive effect of the genotypesfor 5-HTTLPR and AP-2β. Indeed the presenceof the LL genotype of 5-HTTLPR and theshort allele of the AP-2β polymorphism resultedin low scores in self-transcendence whereas highscores were associated with a short allele of 5-HT-TLPR and a short AP-2β allele. The inverse patternwas observed for the homozygous of the longallele of the AP-2β.AP-2 and other transcription factors regulatethe expression of a number of monoamineneurons during development and also a varietyof candidate genes involved in psychiatric disorders.These transcription factors are thereforegood candidates for explaining interindividualdifferences in temperament and psychiatric vulnerability.For instance, it has been proposed thathomozygosity for the long AP-2β allele couldbe associated with low central 5-HT activity. Inother words, the results of Nilsson et al. suggestedthat low self-transcendence/spiritual acceptanceare linked to low central 5-HT activity throughthe AP-2β genotype. This hypothesis is concordantwith the above results showing not only aninvolvement of 5-HT in spirituality but also thehigher activity of 5-HT system during meditationsand related experiences.4.3.3.1.3. The cytochrome P450 2C19(CYP2C19) polymorphismThe gene coding for the CYP2C19 enzymemainly involved in the metabolism of sex hormonesis also highly polymorphic. Of interest inour subject, this enzyme has been implicated inmultiple brain functions and also catalyzes themetabolism of 5-HT.(64 ) One study in a Japanesesample (65 ) found that in females, scores of selftranscendencewere lower in those consideredas poor metabolizers (given their genotype)than those considered as extensive metabolizers.Because these results were based on womenonly, we may assume an involvement of sexhormones, and especially, a higher testosteroneconcentration.Considering the progress in gene-environmentinteraction studies and its effect on complex traitssuch as spirituality, it would be of interest to takeinto account environmental factors in furthergenetic studies on spiritual traits. The importanceof gene-environment interactions in research andespecially in psychiatric research will be discussedb elow.5. GENE-ENVIRONMENTINTERACTION AND CORRELATION5.1. Gene-Environment InteractionRecently, research has paid attention to the geneenvironmentinteraction as a new and differentcomprehensive model of psychiatric disorders.(66 ) Classical approaches in genetic psychiatricresearch assume a direct path between genesand behavior. The goal of this approach is toassociate psychiatric disorders or intermediatephenotypes (or endophenotypes such as spiritualtranscendence) with individual differencesin DNA sequences. However, many studieshave failed to replicate previous findings, andbecause of inconsistent findings, many scientistshave abandoned this approach. A recentand promising approach is the understanding ofcomplex disease and personality traits throughthe gene-environment interaction approach, orGxE. GxE typically occurs when the effects ofone given environmental factor on one individualis dependant on his or her genotypebackground. For example, exposure to cannabisis a well-known environmental pathogenthat elicits the development of schizophrenia.However, not all individuals smoking cannabiswill develop schizophrenia, only those whohave a genetic vulnerability will. Another classicalillustration of GxE is the phenylketonuria.Children with two abnormal copies of the genethat codes for phenylanaline hydroxylase, a keyenzyme that converts the amino acid phenylanalineto another amino acid thyrosine, express thedisease. Accumulation of phenylanaline in theblood of children who lack both functional copiesof the gene leads to abnormal developmentof the brain and mental retardation. However,a simple reduction of phenylanaline intake by