Abstract
Suicidal behavior has been associated with a deficient serotonin neurotransmission which is likely a consequence of individual genetic architecture, exposure to environmental factors and interactions of those factors. We examined whether the interaction of child abuse, TPH2 (tryptophan hydroxylase 2) variant rs4290270, affecting alternative splicing and editing of TPH2 pre-mRNAs, and ADARB1 (adenosine deaminase acting on RNA B1) variants rs4819035 and rs9983925 may influence the risk for suicide attempt in psychiatric patients. TPH2 rs4290270 was genotyped in 165 suicide attempters and 188 suicide non-attempters diagnosed with major depressive disorder, bipolar disorder and schizophrenia. Genotyping data for ADARB1 variants were taken over from our previous study. Child abuse before the age of 18 years was assessed using the Early Trauma Inventory-Self Report. Generalized linear models and backward selection were applied to identify the main and interacting effects of environmental and genetic factors, including psychiatric diagnoses, patients’ gender and age as covariates. Childhood general traumas were independently associated with suicide attempt. Two-way interaction between TPH2 rs4290270 and general traumas revealed that TT homozygotes with a history of general traumas had an increased risk for suicide attempt. Three-way interaction of general traumas, TPH2 rs4290270 and ADARB1 rs4819035 indicated that the highest predisposition to suicide attempt was observed in individuals who experienced general traumas and were TT homozygote for rs4290270 and TT homozygote for rs4819035. Our findings suggest that the risk for suicide attempt in psychiatric patients exposed to an adverse childhood environment may depend on TPH2 and ADARB1 variants.
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Acknowledgements
This study was supported by a grant from the Ministry of Education, Science and Technological Development, Republic of Serbia (Grant No. 173016). The Ministry of Education, Science and Technological Development had no further role in the study design, in the collection, analyses, and interpretation of data, in the writing of the manuscript or in the decision to submit the manuscript for publication.
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All procedures performed in this study were in accordance with the ethical standards of the Ethics Committee of the Clinical Centre of Serbia (3672/10) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
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Karanović, J., Ivković, M., Jovanović, V.M. et al. Effect of childhood general traumas on suicide attempt depends on TPH2 and ADARB1 variants in psychiatric patients. J Neural Transm 124, 621–629 (2017). https://doi.org/10.1007/s00702-017-1677-z
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DOI: https://doi.org/10.1007/s00702-017-1677-z