Religion and Spirituality in Psychiatry

Religion/Spirituality and Neuropsychiatry 554.3.1. Insertion-Deletion in the PromoterRegion of the Serotonin Transporter Gene(5-HTTLPR)One important target of antidepressants,namely selective serotonin reuptake inhibitors(SSRIs), is the 5-HT transporter (5-HTT). It hastherefore widely been studied in depressive disordersbut also more broadly in several psychiatricconditions. Like many other neurotransmitters,5-HT is removed from the synaptic cleft by neurotransmittertransporters in a process calledreuptake . During the reuptake process, 5-HT istaken back into the axon terminal that released itso it cannot bind to its receptors. This reuptake isperformed by the 5-HTT.A forty-four-base pair (bp) insertion-deletionin the promoter region (a regulatory region ofDNA located upstream from a gene, providing acontrol point for regulated gene transcription) ofthe 5-HTT gene (5-HTTLPR) has been describedand shown to be functional (the short allele isassociated with reduced expression of the 5-HTtransporter and lower 5-HT reuptake activity).Nilsson et al. recently found that homozygosityfor the long 5-HTTLPR allele was associatedwith high scores of spiritual acceptance. The associations,however, were only found in boys.(42 )Interestingly, the long allele has been negativelyassociated with depression, anger- and aggression-relatedtraits, suicidal behavior, and otherpsychiatric conditions. Furthermore, homozygosityfor the long 5-HTT allele has been associatedwith high CSF levels of the 5-HT metabolite5-HIAA in nonhuman primates.(43 ) This resultadds weight to the hypothesis of a higher activityof the 5-HT system in spirituality. Interestingly, ithas been recently shown that 5-HTTLPR modulatesthe effect of stressful life events in severalpsychiatric outcomes.(44 ) This polymorphism hasalso been found to modulate the neuronal activityof the amygdala in response to fearful stimuli inhumans.(45 ) Indeed, homozygosity for the longallele of the 5-HTTLPR has been associated with adecreased amygdala reactivity and high capabilityto process environmental threat and to adaptivelycope with persistent stress. The Nilsson et al. findings,therefore, suggest a better function of the5-HT system in individuals with high spirituality.Given the role of this polymorphism and moregenerally of 5-HT in religiosity and spirituality, itcould be interesting to further investigate genesinvolved in 5-HT systems and religious behaviors.Why this association was observed only inboys remains a question to be debated. It remindsus of the association between 5-HT1A bindingpotentials and spiritual acceptance that was carriedin male subjects only. Gender differences inreligious behavior have been reported in the literature.(46) Taken together, these results indicatethat other uninvestigated variables such as environmentalor hormonal factors could govern thephenotypic expression of spirituality differentlyamong men and women. For instance, it has beenrecently found that the estrogen receptor alphagene may influence various aspects of personalityin women.(47 )Interestingly, Bachner-Melman et al., (48 )in an intriguing study analyzing genetic backgroundof dancers, found that the 5-HTTLPRgene was associated with spiritual facets of creativedance. They found that dancers carryingthe short allele of 5-HTTLPR scored high on theTellegen Absortion Scale, a questionnaire thatcorrelates positively with spirituality and alteredstates of consciousness. They unfortunately donot discuss why the short allele was linked to thisscale. It is not unusual to see discrepant geneticassociations with any one given trait in geneticstudies. They mainly reflect some undetectedbias such as ethnicity or gender. Nevertheless,these results, as well as those from Nilsson et al.,suggest an involvement of the 5-HT system inmanifestation of spirituality.4.3.2. Single Nucleotide Polymorphisms inthe 5-HT Receptors and SpiritualityBorg et al.(20 ) identified, as mentioned above,a relationship between self-transcendence and5-HT1A receptor binding potential. Someinvestigators were therefore interested in singlenucleotide polymorphism (SNP) within thegene’s coding for 5-HT receptors. These authorsreported associations of genotypes of the 5-HT1Areceptor and the 5-HT2A and 5-HT6 receptors