Joint effect of ADARB1 gene, HTR2C gene and stressful life events on suicide attempt risk in patients with major psychiatric disorders.
OBJECTIVE
Adenosine to inosine RNA editing, serotonin 2C receptor (HTR2C), and stressful life events (SLEs) have all been implicated in suicidal behaviour. We examined the main and moderating effects of RNA editing (ADAR, ADARB1) and HTR2C genes, childhood trauma (CT), recent SLEs and psychiatric disorders as contributors to suicide attempt (SA) vulnerability.


METHODS
Study included 165 suicide attempters and 188 suicide non-attempters, all diagnosed with one of major psychiatric disorders. CT and recent SLEs were assessed using Early Trauma Inventory-Self Report and List of Threatening Experiences Questionnaire, respectively. Selected ADAR and ADARB1 tag-variants, and HTR2C rs6318 were pre-screened for association with SA, while generalized linear models and backward selection were applied to identify individual and interacting SA risk factors.


RESULTS
ADARB1 rs9983925 and rs4819035 and HTR2C rs6318 were associated with SA. The best minimal model found emotional abuse, recent SLEs, rs9983925 and rs6318 as independent SA risk factors, and general traumas as a factor moderating the effect of psychiatric disorders and emotional abuse.


CONCLUSIONS
SA vulnerability in psychiatric patients is related to the joint effect of ADARB1 and HTR2C variants, the existing mood disorder and the cumulative exposures to a various childhood and recent stressful experiences.
Center for Human Molecular Genetics, Faculty of Biology, University of Belgrade , Belgrade , Serbia.
Jelena
J
Karanović
Saša
S
Šviković
Maja
M
Pantović
Svetlana
S
Durica
Goran
G
Brajušković
Aleksandar
A
Damjanović
Vladimir
V
Jovanović
Maja
M
Ivković
Stanka
S
Romac
Dušanka
D
Savić Pavićević
D000243:Adenosine Deaminase / Q000235:genetics*; D000328:Adult; D001714:Bipolar Disorder / Q000150:complications; D003865:Major Depressive Disorder / Q000150:complications*; D005260:Female; D005838:Genotype; D006801:Humans; D008016:Life Change Events; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017393:RNA Editing; D016601:RNA-Binding Proteins / Q000235:genetics*; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics*; D012307:Risk Factors; D012559:Schizophrenia / Q000150:complications; D013406:Suicide, Attempted / Q000523:psychology*; D014057:Tomography, X-Ray Computed
D016601:RNA-Binding Proteins; D044405:Receptor, Serotonin, 5-HT2C; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase
RNA editing; risk factors; serotonin 2C receptor; stressful events; suicide attempted