We measured suicidal ideation (SI) and suicide attempt (SA) history and the association of six gene polymorphisms with SB: COMT (rs4680), HTR1A (rs6295), TPH1 (rs1800532), BDNF (rs6265), SLC1A3 (rs2269272), and SLC1A2 (rs4755404).
We focused on the catechol-O-methyltransferase gene (COMT) and we performed: a review of studies investigating the association between COMT and both suicidal behavior and personality; a meta-analysis of studies investigating the association between suicidal behavior and COMT rs4680 polymorphism; an association study investigating the link between seven COMT polymorphisms (rs737865, rs5844402, rs5993883, rs4680, rs4633, rs165599 and rs9332377) and both personality traits and suicidal behavior.
The findings support an association between the COMT gene and suicidal behaviour phenotypes with and without childhood maltreatment as environmental factor.
The results for COMT support past literature that has found a relationship between suicidal behavior and COMT, and has also found that the relationship differs for males and females.
In addition, we found an increased frequency of the COMT Met/Met genotype among suicidal (P=0.002) and patients who attempted suicide (P<0.001) and an increased frequency of COMT Val/Val genotype in patients with an early onset of alcohol dependence (P=0.004).
The interaction analysis showed a significant interaction between CRH receptor type 1 (CRHR1) and CRH binding protein (CRHBP) in influencing suicide attempt and the severity of suicidal behaviour.
Similarly, we recently discovered that genetic variation in components of the stress-related hypothalamic pituitary adrenocortical axis, T-box 19 and corticotropin releasing hormone receptor 1, showed association and linkage to high anger/hostility in and male depression the suicidal offspring, respectively.
The interaction analysis showed a significant interaction between CRH receptor type 1 (CRHR1) and CRH binding protein (CRHBP) in influencing suicide attempt and the severity of suicidal behaviour.
Patients with at least one earlier suicide attempt (repeaters) showed a trend for higher CSF ApoE levels compared to suicide attempters debuting with suicidal behavior at inclusion in the study.
It is now well established that induction of delta-aminolevulinic acid synthase, the rate controlling enzyme of the heme biosynthetic pathway, is fundamental to porphyrogenicity, and that drug-induced hepatic heme depletion via induction or suicidal inactivation of cytochrome P450 is central to this process.
No significant associations between the CYP2D6 and CYP2C19 genotypes and suicidal behavior or substance abuse disorder were noted, and we conclude that cytochrome P450 genotyping in its present form is clinically irrelevant with respect to these phenomena.
No significant associations between the CYP2D6 and CYP2C19 genotypes and suicidal behavior or substance abuse disorder were noted, and we conclude that cytochrome P450 genotyping in its present form is clinically irrelevant with respect to these phenomena.
DBH, located on chromosome 9q34.2 has variants with potential functional consequences which may be related to alterations of neurotransmitter function and several psychiatric phenotypes, including alcohol dependence (AD), depression (MD) and suicidal behavior (SA).
Parental psychopathology was assessed using items from the Familial History of Psychiatric Disorders section of the NSC-R in conjunction with items designed to capture dimensions of attachment and suicidal behaviours.
In conclusion, our study does not support the involvement of TH gene variants as major contributors to suicide, whereas DDC variants could mediate some features related to suicide and be involved in violent suicidal behavior.