Hopelessness, a potential endophenotpye for suicidal behavior, is influenced by TPH2 gene variants |
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Authors: | Lazary Judit Viczena Veronika Dome Peter Chase Diana Juhasz Gabriella Bagdy Gyorgy |
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Institution: | a Department of Clinical and Theoretical Mental Health, Kutvolgyi Clinical Centre, Semmelweis University, Budapest, Hungaryb Department of Pharmacodynamics, Semmelweis University, Budapest, Hungaryc Neuroscience and Psychiatry Unit, School of Community Based Medicine, Faculty of Medical and Human Sciences, The University of Manchester, UKd Group of Neuropsychopharmacology, Semmelweis University and Hungarian Academy of Science, Budapest, Hungarye Group of Neurochemistry, Semmelweis University and Hungarian Academy of Science, Budapest, Hungary |
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Abstract: | ObjectivesHopelessness is one of the strongest risk factors for suicidal behavior but relevant genetic studies are poorly available. Tryptophan hydroxylase (TPH) is widely considered to be a good candidate for genetic association studies on depression and suicide, however, investigations on these complex, multifactorial phenotypes have resulted in conflicting data. We hypothesized that hopelessness could be a mediating phenotype between TPH2 gene, depression and suicidal behavior.MethodsDepressive phenotype and suicidal risk were investigated of 760 individuals from general population by Zung Self Rating Depression Scale (ZDS), Beck's Hopelessness Scale (BHS) and a detailed background questionnaire. All participants' DNA samples were genotyped for 7 tag SNPs in TPH2 gene. Generalized linear models were performed for single marker association studies and p-values were corrected by Bonferroni criteria. In haplotype analyses score tests were used and permutated p-values were computed.ResultsFour SNPs of TPH2 gene showed association with hopelessness but only rs6582078 had a significant effect on the BHS scores after Bonferroni's correction; GG individuals had significantly higher BHS scores, while GT and TT had intermediate and lower BHS scores respectively (p = 0.0047). Compared with other genotypes, homozygous GG individuals also had almost three times greater estimated suicidal risk, as did carriers of the AA genotype of rs6582078 (OR = 2.87; p = 0.005) and also of rs1352250 (OR = 2.86; p = 0.006). A risk and a protective haplotype of TPH2 gene were also identified in association with hopelessness. ZDS scores have not shown any association with TPH2 gene.ConclusionsWe found that hopelessness, with its allied increased suicidal risk was strongly associated with TPH2 gene variants in multiple tests. These findings suggest that TPH2 gene confers risk for suicidal behavior while hopelessness can be a potential endophenotype for suicidal vulnerability. |
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Keywords: | 5-HTTLPR serotonin transporter-linked polymorphic region BHS Beck's Hopelessness Scale BPD bipolar depression DNA dezoxyribonucleic acid fMRI functional magnetic resonance imaging LD linkage disequilibrium MAF minimal allele frequency MDD major depressive disorder OR odds ratio RNA ribonucleic acid SD standard deviation S E M standard error of mean SNP single nucletoid polymorphism TPH tryptophan hydroxylase UPD unipolar depression ZDS Zung Self-Rating Depression Scale |
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