Effect of childhood general traumas on suicide attempt depends on TPH2 and ADARB1 variants in psychiatric patients

• Published in: Journal of Neural Transmission Vol. 124; no. 5; pp. 621 - 629
• Main Authors: Karanovic, Jelena, Ivkovic, Maja, Jovanovic, Vladimir M, Svikovic, Sasa, Pantovic-Stefanovic, Maja, Brkusanin, Milos, Damjanovic, Aleksandar, Brajuskovic, Goran, Savic-Pavicevic, Dusanka
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01-05-2017
• Subjects: Adenosine Deaminase - genetics; Adenosine Deaminase - metabolism; Adult; Adult Survivors of Child Abuse; Female; Gene-Environment Interaction; Genetic Variation; Genotyping Techniques; Humans; Linear Models; Male; Medicine; Medicine & Public Health; Mental Disorders - genetics; Mental Disorders - psychology; Neurology; Neurosciences; Protein Isoforms; Psychiatry; Psychiatry and Preclinical Psychiatric Studies - Original Article; Risk Factors; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Schizophrenic Psychology; Suicide, Attempted; Tryptophan Hydroxylase - genetics; Tryptophan Hydroxylase - metabolism; Tryptophan hydroxylase; Suicide attempted; RNA editing; Child abuse; Gene–environment interaction; rs4290270
• ISSN: 0300-9564; 1435-1463
• DOI: 10.1007/s00702-017-1677-z

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.