Genes, Religion, and Response to Religious vs Conventional Psychotherapy: A Randomized Clinical Trial in Medically Ill Patients with Major Depression

Objective: We examine associations between religiosity and polymorphisms of the serotonin and monoamine oxidase genes, and the effect of genotype on response to religious cognitive behavioral therapy (RCBT) vs. conventional CBT (CCBT). Methods: 132 persons with chronic illness and major depressive disorder were recruited into a clinical trial to evaluate the efficacy of RCBT vs. CCBT. Four functional polymorphisms were assessed: 5-HTTLPR and rs25531 at the serotonin transporter gene (SLC6A4), rs6295 at 5-HT1A receptor gene (HTR1A), and uMAOA-VNTR at the monoamine oxidase A gene (MAOA). Results: Few associations were found between these polymorphisms and religious involvement, although they were consistent. Religious attendance was less frequent in those with one or more high-risk genotype in the overall sample. In post-hoc analyses, Blacks with LG genotypes of the rs25531 polymorphism were less likely to attend religious services or have daily spiritual experiences, and Blacks with high risk alleles of any gene were also less likely to attend religious services. Among men, daily spiritual experiences and overall religiosity were also lower in the presence of any high risk alleles. Genotype had no effect on response to RCBT vs. CCBT in the overall sample, except in participants with the C/C genotype of HTR1A (group x time interaction B=3.33, SE=1.17, t=2.86, p=0.006, d=0.73) and those with no high risk genotype (group x time interaction B=3.40, SE=1.60, t=2.12, p=0.042, d=0.75) who were more likely to respond to RCBT. Conclusion: Little overall relationship was found between genotype and either religiosity or response to RCBT. Whether high risk genotypes in certain subgroups of depressed persons may be associated with religious involvement or affect treatment response remains unclear.