Possible Association between Serotonin Transporter Gene Polymorphism and Suicide Behavior in Major Depressive Disorder

OBJECTIVE: The serotonin transporter (5-HTT) genes are major candidate genes for modulating the suicidal behavior. We investigated the association between serotonin transporter polymorphisms and suicidal behavior in patients with major depressive disorder (MDD). METHODS: Serotonin transporter intron 2 VNTR polymorphism (5-HTTVNTR) and serotonin transporter linked polymorphic region polymorphism (5-HTTLPR) were analyzed in 132 depressed patients with suicidal attempt as well as in 122 normal controls. Hamilton's 17-item Depression Rating Scale (HDRS), the Risk-Rescue rating system (RRR) and the Lethality Suicide Attempt Rating Scale updated (LSARS-II) were assessed for the depressed patients. RESULTS: Although not statistically significant, a trend was found such that the 10/10 and 10/12 alleles of 5-HTTVNTR were more common in suicidal subjects than in control subjects. Comparing allele frequency, those with a 10 allele or 10 allele carriers were higher in suicidal subjects than in control subjects. No difference was noted in 5-HTTLPR genotypes and haplotype distribution between the suicidal subjects and control subjects. The RRR scores in subjects with the 10/10 5-HTTVNTR genotype or 10 5-HTTVNTR allele were significantly lower than those in subjects with other genotypes. CONCLUSION: These results show the possibility that 10 allele of 5-HTTVNTR is related to suicidal behavior in the suicidal subjects with MDD and suggest that 12 allele of 5-HTTVNTR might be related to more lethality in the suicidal subjects with MDD.

Association Study between Norepinephrine Transporter Gene Polymorphism and Schizophrenia in a Korean Population

OBJECTIVE: We aimed to investigate possible associations between three norepinephrine transporter gene (SLC6A2) single nucleotide polymorphisms (T182C, A3081T, and G1287A) and schizophrenia. Also, we investigated the relationships of those polymorphisms with clinical severity and characteristics of schizophrenia. METHODS: Participants were 220 schizophrenia patients in the acute phase and 167 healthy controls. The genotype, allele frequency, and haplotype of each group were analyzed for T182C, A3081T, and G1287A polymorphisms. Of the 220 schizophrenia patients, 163 patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) and the Korean version of the Calgary depression scale for schizophrenia (K-CDSS) at baseline. RESULTS: We found no significant differences between the schizophrenia patient group and the control group in genotype distribution or allele frequency of the three tested polymorphisms. Likewise, we could not find any significant differences in genotype or allele frequency by analyzing according to gender. In the haplotype study, no significant association emerged between specific haplotype combinations and schizophrenia. We also found no association between clinical scales (PANSS and K-CDSS) and the studied polymorphisms. CONCLUSION: Our results suggest that the investigated polymorphisms of the NET gene are not associated with susceptibility to schizophrenia or its clinical features in a Korean population. However, this study remains significant because it is the first haplotype study to investigate associations between NET gene (SLC6A2) single nucleotide polymorphisms and schizophrenia in a Korean population. Future research with a larger sample size and more genetic markers is needed to replicate our results.

Evidence for Association between the Brain-Derived Neurotrophic Factor Gene and Panic Disorder: A Novel Haplotype Analysis

OBJECTIVE: Panic disorder (PD) is a common psychiatric disorder with a complex etiology, and several studies have suggested that it has a genetic component. Brain-derived neurotrophic factor (BDNF) is the most abundant of the neurotrophins in the brain and is recognized for its important role in the survival, differentiation and growth of neurons. Several lines of research have suggested possible associations between the BDNF gene and PD. In this study, we investigated the BDNF 196G/A (rs6265), 11757G/C (rs16917204), and 270C/T (rs56164415) single nucleotide polymorphisms (SNPs) in order to determine an association with PD. We also identified the genetic sequence associations with PD via haplotype analysis. METHODS: Participants in this study included 136 PD patients and 263 healthy controls. Male and female subjects were analyzed separately. The genotype and allele frequencies of the PD patients and controls were analyzed using chi2 statistics. Frequencies and haplotype reconstructions were calculated using the SNP analyzer 2.0. RESULTS: We found no significant statistical differences in the genotype distributions or allele frequencies of the three tested polymorphisms between the PD and control groups. In addition, no differences were found between PD patients and the controls in either male or female subgroups. However, we found that, the frequency of the G-C haplotype for 196G/A and 11757G/C was significantly higher in PD patients than in the controls. CONCLUSION: Our result suggest that patients with the G-C haplotype for 196G/A and 11757G/C may be more susceptible to the development of PD. Further studies are needed to replicate the associations that we observed.

Plasma Levels of IL-23 and IL-17 before and after Antidepressant Treatment in Patients with Major Depressive Disorder

OBJECTIVE: Cytokines are believed to have a role in the pathophysiology of major depression. The alteration in levels of pro-inflammatory cytokines [interleukin 1beta (IL-1beta), IL-2, IL-6, IL-12, interferon gamma, and tumor necrosis factor alpha] in major depression supports the cytokine hypothesis of this illness. IL-23 and IL-17 are also pro-inflammatory cytokines, but few studies have focused on their role in major depression. This study investigated the potential role of the IL-23 and IL-17 axis in major depression. METHODS: Plasma IL-23 and IL-17 levels were measured in 26 major depressive disorder (MDD) patients before and after 6-week treatment with antidepressants; these levels were measured in 28 age- and sex-matched normal controls. Depression severity was assessed using the Hamilton Depression Rating Scale (HDRS). IL-23 and IL-17 plasma levels were estimated using quantitative enzyme-linked immunosorbent assay. RESULTS: Pre-treatment plasma levels of IL-23 and IL-17 in MDD patients were not significantly different from those of normal controls. In MDD patients, IL-23 and IL-17 levels after 6 weeks of antidepressant treatment were not different from the baseline levels. There was no significant correlation between changes in the cytokine levels and changes in the HDRS scores representing the severity of depression. CONCLUSION: The present study does not support a potential involvement of IL-23 and IL-17 axis in major depression. Replication and extension using a larger sample are required.