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P.2.a.023 Effect of polymorphisms in the tryptophan hydroxylase 2 gene on suicide risk in Korean with major depressive disorder
P.2.a Affective disorders and antidepressants – Affective disorders (clinical) most frequent encountered diagnostic category in infertile women (19.6%) namely generalized anxiety disorder (GAD), social phobia and agoraphobia; followed by mood disorders (17.8%) namely dysthymia and major depressive disorder (MDD). Comorbidity between mood and anxiety disorders was high, 17 patient (15.9%) of infertility patients group had comorbid diagnoses (P= 0.025) together with high anxiety and depressive states even in subsyndromal categories. Low socioeconomic status (P= 0.005), premenstrual dysphoric disorder (PMDD) (P= 0.001) and treatment method (undergoing Assisted Reproductive Techniques (ART)) (P= 0.036) indicate certain vulnerability while other variables showed insignificant statistical difference. Infertile women with Axis-I diagnosis are at risk for poor response to fertility treatment, as 77.4% of all infertile patients with psychiatric morbidity failed to achieve pregnancy – in one year interval – in comparison to 35.6% of infertile ladies without psychiatric morbidity (P = 0.000). Moreover, the infertile patients with comorbid psychiatric diagnoses has the most poor outcome (pregnancy rate = 11.8%), followed by mood disorders (15.8%) and then anxiety disorders (28.6%) while it reached 64.4% among infertile women without psychiatric morbidity (P = 0.000). Conclusion: Infertility problem for Egyptian women is not merely a physical problem but it has a deep psychological impact that infertile women in Egypt are at risk for developing mood and anxiety disorders and comorbidities between both, especially dysthymia, GAD and MDD. Such morbidity is higher in unprivileged socioeconomic classes, prior history of PMDD or undergoing ARTs as treatment method. Psychiatric morbidity (Axis I diagnoses namely dysthymia, GAD, MDD and comorbid diagnoses) is negatively correlated with infertility treatment outcome. References [1] Inhorn, M.C., 1994 Quest for Conception: Gender, Infertility, and Egyptian Medical Traditions. University of Pennsylvania Press. Philadelphia, 3−18. [2] First, M.B., Spitzer, R.L., Williams, W., Gibbon, M., 1995 Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) in Handbook of Psychiatric Measures. Washington, American Psychiatric Association. [3] Beck, A.T., Ward, C.H., Mendelson, M., Mock, J., Eurbaugh G., 1961 An inventory for measuring depression. Archives of General Psychiatry 4, 561–571.
P.2.a.023 Effect of polymorphisms in the tryptophan hydroxylase 2 gene on suicide risk in Korean with major depressive disorder 1 Seoul Y.Y. Nam1 ° , C.H. Kim2 , D.Y. Cho3 , H.S. Lee4 . National Hospital, Dept. of Planning & Public Relations, Seoul, South-Korea; 2 Yonsei University College of Medicine, Dept. of Psychiatry, Seoul, South-Korea; 3 LabGenomics, Clinical Research Institute, Seoul, South-Korea; 4 Yonsei University College of Medicine, Dept. of psychiatry, Seoul, South-Korea
Introduction: The tryptophan hydroxylase gene (TPH2) encodes the rate-limiting enzyme in the serotonin biosynthesis in brain. Despite suicide attempt is strongly associated with major depressive disorder (MDD), not all patients with MDD attempt suicide. We hypothesized variation at the TPH2 gene and its 5 upstream region may predispose to attempt suicide in depressed patients. We also investigated associations between haplotypes in the TPH2 gene and suicide attempts. Methods: One hundred ninety five unrelated patients with MDD (74 males, 38%) participated in the present study. All
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subjects were between 18 and 55 years old who were treated at out-patients clinic. Those who had a past history of other psychiatric illnesses and neurological illnesses before diagnosis of MDD were excluded. Diagnosing current and past Axis I mental illnesses was made by using the Korean version of Structured Clinical Interview for DSM-IV Axis I disorder (SCID-I). The clinical severity and personality traits was measured with Hamilton Depression Rating Scale (HDRS), Beck’s Depression Inventory (BDI), Beck Hopelessness Scale (BHS), Beck’s Scale for Suicidal Ideation (SSI), Spielberger State Trait Anger Expression Inventory (STAXI) and Barratt’s impulsivity scale (BIS). To investigate characteristics of suicide attempt, we used Beck Suicide Intent Scale (SIS) and Medical lethality of suicide attempt of DIGS (Diagnostic Interview for Genetic Studies). We analyzed three single nucleotide polymorphisms (SNPs) in the 5 upstream region (rs11178997, rs4570625) and rs7305115 in the exon 7 of the gene. Reconstruction of haplotypes on rs11178997-rs4570625rs7305115 were made by the PHASE (v.2.1.1. Stephens et al., 2003) and six haplotypes were selected (TGA, TGG, TTA, TTG, ATA, ATG). We examined the association between three SNPs of the TPH2 and its haplotypes and suicide attempt and whether the TPH2 genetic variants would predict the likelihood of suicide attempt in patients with MDD. Results: For one hundred ninety five patients with MDD, 82 suicide attempters (SA) and 113 patients who did not attempt suicide (non-SA) were compared for genotypes of the polymorphisms in the TPH2. We also analyzed associations between haplotypes and suicide attempt. All SNPs were in Hardy-Weinberg equilibrium in both the SA group as well as the non-SA group. There were significant differences in the distribution of the three genotypes (GG, GA, and AA) of rs7305115 in exon 7 between suicide attempters and non-attempters (X2 = 10.4, p = 0.006). There was an excess of GG genotypes in the suicide attempter group compared with the non-attempter group. We found a significant association between the distribution of haplotypes and suicide attempts (X2 = 12.1, p = 0.029). Controlling for suicide risk factors, multiple logistic regression analysis showed GG genotype significantly predicted suicide attempts in patients with MDD (OR = 2.32, 95% CI=1.13−4.73, p = 0.021). Conclusions: The TPH2 gene variants may be associated with the biological susceptibility for suicide attempts in MDD. If replicated, these findings may shed light on the biological basis of this potentially dangerous adverse event and help identify patients at increased risk. If replicated, these findings may help us to identify depressed patients at increased risk of suicide.
P.2.a.024 Vagus nerve stimulation for treatmentresistant depression: open-label European study – 24-month outcomes J. Allen1 ° . 1 Cyberonics, Biostatistics & Clinical Informatics, Houston, USA Background: Selecting appropriate therapy for patients with treatment-resistant depression (TRD) poses a challenge for clinicians. Long-term studies evaluating the efficacy of vagus nerve stimulation (VNS) have shown improvement in depressive symptoms of patients for whom multiple trials of antidepressant therapies have proven ineffective [1,2]. This post-market, open-label study of VNS for TRD was designed to confirm the safety and efficacy of VNS in treating patients with unipolar or bipolar depression.
P.2.a.023 Effect of polymorphisms in the tryptophan hydroxylase 2 gene on suicide risk in Korean with major depressive disorder 1 Seoul Y.Y. Nam1 ° , C.H. Kim2 , D.Y. Cho3 , H.S. Lee4 . National Hospital, Dept. of Planning & Public Relations, Seoul, South-Korea; 2 Yonsei University College of Medicine, Dept. of Psychiatry, Seoul, South-Korea; 3 LabGenomics, Clinical Research Institute, Seoul, South-Korea; 4 Yonsei University College of Medicine, Dept. of psychiatry, Seoul, South-Korea
Introduction: The tryptophan hydroxylase gene (TPH2) encodes the rate-limiting enzyme in the serotonin biosynthesis in brain. Despite suicide attempt is strongly associated with major depressive disorder (MDD), not all patients with MDD attempt suicide. We hypothesized variation at the TPH2 gene and its 5 upstream region may predispose to attempt suicide in depressed patients. We also investigated associations between haplotypes in the TPH2 gene and suicide attempts. Methods: One hundred ninety five unrelated patients with MDD (74 males, 38%) participated in the present study. All
S305
subjects were between 18 and 55 years old who were treated at out-patients clinic. Those who had a past history of other psychiatric illnesses and neurological illnesses before diagnosis of MDD were excluded. Diagnosing current and past Axis I mental illnesses was made by using the Korean version of Structured Clinical Interview for DSM-IV Axis I disorder (SCID-I). The clinical severity and personality traits was measured with Hamilton Depression Rating Scale (HDRS), Beck’s Depression Inventory (BDI), Beck Hopelessness Scale (BHS), Beck’s Scale for Suicidal Ideation (SSI), Spielberger State Trait Anger Expression Inventory (STAXI) and Barratt’s impulsivity scale (BIS). To investigate characteristics of suicide attempt, we used Beck Suicide Intent Scale (SIS) and Medical lethality of suicide attempt of DIGS (Diagnostic Interview for Genetic Studies). We analyzed three single nucleotide polymorphisms (SNPs) in the 5 upstream region (rs11178997, rs4570625) and rs7305115 in the exon 7 of the gene. Reconstruction of haplotypes on rs11178997-rs4570625rs7305115 were made by the PHASE (v.2.1.1. Stephens et al., 2003) and six haplotypes were selected (TGA, TGG, TTA, TTG, ATA, ATG). We examined the association between three SNPs of the TPH2 and its haplotypes and suicide attempt and whether the TPH2 genetic variants would predict the likelihood of suicide attempt in patients with MDD. Results: For one hundred ninety five patients with MDD, 82 suicide attempters (SA) and 113 patients who did not attempt suicide (non-SA) were compared for genotypes of the polymorphisms in the TPH2. We also analyzed associations between haplotypes and suicide attempt. All SNPs were in Hardy-Weinberg equilibrium in both the SA group as well as the non-SA group. There were significant differences in the distribution of the three genotypes (GG, GA, and AA) of rs7305115 in exon 7 between suicide attempters and non-attempters (X2 = 10.4, p = 0.006). There was an excess of GG genotypes in the suicide attempter group compared with the non-attempter group. We found a significant association between the distribution of haplotypes and suicide attempts (X2 = 12.1, p = 0.029). Controlling for suicide risk factors, multiple logistic regression analysis showed GG genotype significantly predicted suicide attempts in patients with MDD (OR = 2.32, 95% CI=1.13−4.73, p = 0.021). Conclusions: The TPH2 gene variants may be associated with the biological susceptibility for suicide attempts in MDD. If replicated, these findings may shed light on the biological basis of this potentially dangerous adverse event and help identify patients at increased risk. If replicated, these findings may help us to identify depressed patients at increased risk of suicide.
P.2.a.024 Vagus nerve stimulation for treatmentresistant depression: open-label European study – 24-month outcomes J. Allen1 ° . 1 Cyberonics, Biostatistics & Clinical Informatics, Houston, USA Background: Selecting appropriate therapy for patients with treatment-resistant depression (TRD) poses a challenge for clinicians. Long-term studies evaluating the efficacy of vagus nerve stimulation (VNS) have shown improvement in depressive symptoms of patients for whom multiple trials of antidepressant therapies have proven ineffective [1,2]. This post-market, open-label study of VNS for TRD was designed to confirm the safety and efficacy of VNS in treating patients with unipolar or bipolar depression.