Religion and Spirituality in Psychiatry

Religion/Spirituality and Neuropsychiatry 574.3.3.1.1. Polymorphisms in the DopamineReceptor 4 gene (DRD4)The gene coding for the Dopamine Receptor4 (DRD4 ) is highly polymorphic, although mostof the research in psychiatry and personalityfocused largely on a variable number of tandem(VNTR) polymorphisms in exon 3. These polymorphismshave been shown to be functional.(53 ) Following the Cloninger hypothesis, whichsuggested an involvement of dopaminergic systemsin some dimensions of personality, (36 , 37 ,54 ) Commings et al.(55 , 56 ) were intrigued bythe considerable role of dopamine genes, and theDRD4 gene in particular, in spiritual transcendence.As already said, dopamine receptors, andespecially DRD4, play an important role in thefunction of the prefrontal cortex. The DRD4 geneis indeed expressed in a high level in the frontalarea and the nucleus acumbens, (57–59) regionsassociated with affective and emotional behaviors.(57) Because spirituality may especially usethe prefrontal cortex, it should use dopaminergicsystems. From this perspective, Coming etal., (55 , 56 ) in two consecutive studies investigatingseveral polymorphisms (including theVNTR) in the DRD4 gene, found a significantrelationship between spiritual transcendence andDRD4 receptor polymorphisms. At a lesser level,Comings et al. also found other dopamine receptorsto be associated with spiritual transcendence.Their results suggest an involvement of DRD4in the personality trait of spiritual acceptance.Their authors concluded that this may be a functionof the high concentration of the dopamineD4 receptor in the cortical areas, especially thefrontal cortex. Dopamine is thought to increasecreative drive of idea generation. This involvementin creativity could be linked to spirituality.Indeed, as previously mentioned, creative dancecorrelated positively with spirituality and alteredstates of consciousness. So better dopaminergictone in people carrying particular genotypes ofthe DRD4 gene could lead people to seek spiritualityand religious practices to give them pleasureor euphoria through higher effectiveness ofDRD4 receptors and also because these practiceshave been shown to enhance dopamine levels(see upstream). It has effectively been argued thatthe activation of the dopaminergic system duringmeditation and other religious activities may berelated to the seeking of these activities.(4 )However, the link with spirituality is far morecomplex than this single association would tell us,because it has been shown that the dopaminergicsystem is under the control of 5-HT1. Indeed,stimulation of 5-HT2A and 5-HT1A receptors –half of the dopaminergic neurons in the medialprefrontal cortex (mPFC) express 5-HT2A receptors– can elicit dopamine release.(60 , 61 )4.3.3.1.2. Activating protein-2 (AP-2)Transcription factor AP-2 (activating protein-2[AP-2]) is a specific DNA-binding transcriptionfactor family. In one sense, it participates in andregulates specific neural gene expression and hasbeen shown to be involved in neural survival,death, and development.(62 , 63 ) In particular,gene coding for dopamine transporter and5-HTT displays multiple AP-2 binding sites intheir regulatory regions. It has been proposedthat AP-2, by its regulation of monoaminergicgenes (dopamine and 5-HT), could affect therelease and metabolism of 5-HT and dopaminein the frontal cortex. Because dopamine receptorsand 5-HTT have been implicated in personalitytraits and spirituality, one might speculateAP-2 could interactively influence these traits.Different isoforms of the AP-2 family have beenidentified, including the AP-2β. One polymorphismof interest for spirituality in the gene codingfor the transcription factor AP-2β is a four basepairrepeat polymorphism in the second intron(CAAA,) which has been associated with anxiety,binge-eating disorder, and levels of homovanillicacid. Homovanillic acid is a metabolite of majorcatecholamines like dopamine. Nilsson et al., (42 )in the same paper investigating 5-HTTLPR, founda significant association between this repeat polymorphismand Self-Transcendence. Again andas observed for 5-HTTLPR, this association wasobserved only in boys and showed that carriersof the short allele (less repeat) had higher selftranscendencescores. Interestingly, this observationwas also completely explained by the subscale