Study On The Risk Factors Of Suicidal Behaviors And Its Association With Single Nucleotide Polymorphism (SNP) Of A Novel Tryptophan Hydroxylase Isoform (TPH2) Gene

Background and Objective: Suicide is a serious problem in public health. Over 90% of suicide attempters have diagnosable psychiatric illness. About 15% of all depression and 10% of all schizophrenia are suicide victims. Many researchers had proved the relationship between suicide and Serotonin function disorder. The serotonin-related genes such as tryptophan hydroxylase, serotonin transporter and serotonin receptor genes were regarded as important candidates for suicide attempter's study, but no unanimous conclusion was drawn. Recently, a second TPH isoform (TPH2) was identified in mice, which were exclusively present in the brain. It was also demonstrated that TPH2 was expressed in human but only in brain. Tryptophan hydroxylase2 (TPH2), the rate-limiting enzyme in the synthesis of the neurotransmitter serotonin (5-HT) is being widely discussed as a major candidate gene in many psychiatric disorders such as depression, schizophrenia, and suicidal behavior. We performed a case-control study on the association between suicidal behavior and the single nucleotide polymorphism (SNP) of the TPH2 gene in the high suicidal attempt colony of psychiatric disorders so as to find out the risk factors of suicidal behaviors in patients with major depression.Materials and Methods: Patients with suicide behaviors of psychiatric disorders in Ankang hospital in Shandong province were selected to be case group; patients with no suicide behaviors of psychiatric disorders in the same hospital acted as control group. Psychiatric disorder patients with Han nationality were selected with self-editing questionnaire according to Diagnostic Investigation Genet Scale (DIGS) provided by Harvard University. CCMD-3 and the Hamilton depression rating scale for depression (HRSD), brief psychiatric scale (BPRS), clinical information and venous blood were gathered. We isolated genomic DNA from the blood samples and analyzed the rs7305155 SNP locus sequence after polymerase chain reaction (PCR) to show the distributing frequency of genotypes. We used chi-square test, t- test or F- test and logistic regression to analyze all the data. The level of test was α=0.05.Results:1. We collected 420 patients of psychiatric disorders (depression and schizophrenia) in total. It included 108 depression patients, 56 schizophrenia patients, 2 hysteria patients (all feminine) and 3 alcohol dependence (all man). The suicide behaviors occurred frequently in female, family with suicide history, negative life (P<0.05), no association with occupation, education, age, illness age, course of diseases, personality, anamnesis or psychiatric history of family were found (P>0.05). The way of suicide were self-inflicted poisoning (dose), self-harm by hanging, intentional self-harm by sharp object and jumping from a high place. Most patients did suicide just once.2. Three genotypes (A/A, A/G and G/G) of TPH2 gene rs7305155SNP location were detected. The distributing frequency tallied with Hardy-Weinberg equipoise principle in both case and control groups.3. The holistic distributing frequency of three genotypes between case and control group had no significant difference (P>0.05). But the genotypes A/A was significantly different between two groups (P<0.05)Conclusions:1. Womenfolk, family history of suicide, and negative life events were the risk factors of suicidal behaviors in patients with psychiatric disorders. The ORs are 1.788, 2.424, and 2.146 separeately.2. There was an association between TPH2 gene rs7305155SNP location genotypes A/A and suicide behaviors in hospital psychoses patients (with Han nationality). TPH2 gene rs7305155SNP location genotypes A/A might be a protective factor in suicide behaviors.3. Suicide may be caused by psychic disorder or genetic factors. Our research suggested that there was an association between TPH2 gene rs7305155SNP location genotypes A/A and suicide behaviors in hospital psychoses patients. But there was no health control; the problem need further study.4. Suicide behaviors are suggested to be an impulse control disorder. So there may be some related genetic factors. In this study we did not focus on the impulse control. This problem is worth further study.5. The suicide is likely related to the psychological reactivity or personality characteristic (susceptibility). Some people may suicide easily in specifically condition. We proved that the negative life events were the risk factors of suicidal behaviors and our study agreed to this theory.