Dataset Information

Effect of tryptophan hydroxylase-2 rs7305115 SNP on suicide attempts risk in major depression.

ABSTRACT: BACKGROUND: Suicide and major depressive disorders (MDD) are strongly associated, and genetic factors are responsible for at least part of the variability in suicide risk. We investigated whether variation at the tryptophan hydroxylase-2 (TPH2) gene rs7305115 SNP may predispose to suicide attempts in MDD. METHODS: We genotyped TPH2 gene rs7305115 SNP in 215 MDD patients with suicide and matched MDD patients without suicide. Differences in behavioral and personality traits according to genotypic variation were investigated by logistic regression analysis. RESULTS: There were no significant differences between MDD patients with suicide and controls in genotypic (AG and GG) frequencies for rs7305115 SNP, but the distribution of AA genotype differed significantly (14.4% vs. 29.3%, p < 0.001). The G-allele frequency was significantly higher in cases than control group (58.1% vs.45.6%, p < 0.001), but the A-allele carrier indicated a decreased trend in MDD with suicide behaviors than control group (41.9% vs.54.4%, p < 0.001). The multivariate logistic regression analysis indicated that TPH2 rs7305115 AA (OR 0.33, 95% CI 0.22-0.99), family history of suicide (OR 2.98, 95% CI 1.17-5.04), negative life events half year ago (OR 6.64, 95% CI 2.48-11.04) and hopelessness (OR 7.68, 95% CI 5.79-13.74) were significantly associated with the suicide behaviors in MDD patients. CONCLUSIONS: The study suggested that hopelessness, negative life events and family history of suicide were risk factors of attempted suicide in MDD while the TPH2 rs7305115A remained a significant protective predictor of suicide attempts.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC2939585 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Effect of tryptophan hydroxylase-2 rs7305115 SNP on suicide attempts risk in major depression.

Zhang Yuqi Y Zhang Changsong C Yuan Guozhen G Yao Jianjun J Cheng Zaohuo Z Liu Chaojun C Liu Qinghai Q Wan Gairong G Shi Guizhi G Cheng Yiren Y Ling Yang Y Li Ke K

Behavioral and brain functions : BBF 20100825

<h4>Background</h4>Suicide and major depressive disorders (MDD) are strongly associated, and genetic factors are responsible for at least part of the variability in suicide risk. We investigated whether variation at the tryptophan hydroxylase-2 (TPH2) gene rs7305115 SNP may predispose to suicide attempts in MDD.<h4>Methods</h4>We genotyped TPH2 gene rs7305115 SNP in 215 MDD patients with suicide and matched MDD patients without suicide. Differences in behavioral and personality traits according ...[more]

PMID: 20738857

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Project description:ImportancePatients with attention-deficit/hyperactivity disorder (ADHD) are at an increased risk of attempting suicide. Stimulants, such as methylphenidate hydrochloride, are the most common treatment for ADHD, but the association between their therapeutic use and suicide is unclear.ObjectiveTo investigate the association between methylphenidate and the risk of suicide attempts.Design, setting, and participantsA population-based, electronic medical records database from the Hong Kong Clinical Data Analysis & Reporting System was used to identify 25 629 individuals aged 6 to 25 years who were treated with methylphenidate between January 1, 2001, and December 31, 2015. Those who had attempted suicide were included in the analysis. A self-controlled case series design was used to control for time-invariant characteristics of the patients.Main outcomes and measuresRelative incidence of suicide attempt during periods when patients were exposed to methylphenidate compared with nonexposed periods.ResultsAmong 25 629 patients with methylphenidate prescriptions, 154 had their first recorded suicide attempt within the study period; of these individuals, 111 (72.1%) were male; mean (SD) age at baseline was 7.15 (2.19) years. The overall incidence of suicide attempts during methylphenidate treatment was 9.27 per 10 000 patient-years. An increased risk of suicide attempts was detected during the 90-day period before methylphenidate was initiated, with an incidence rate ratio (IRR) of 6.55 (95% CI, 3.37-12.72). The IRR remained elevated during the first 90 days of treatment (IRR, 3.91; 95% CI, 1.62-9.42) before returning to baseline levels during ongoing treatment (IRR, 1.35; 95% CI, 0.77-2.38). When the risk during the first 90 days of treatment was compared with the 90 days preceding first treatment, the incidence of suicide attempts was not elevated (IRR, 0.78; 95% CI, 0.26-2.35).Conclusions and relevanceThe incidence of suicide attempts was higher in the period immediately before the start of methylphenidate treatment. The risk remained elevated immediately after the start of methylphenidate treatment and returned to baseline levels during continuation of methylphenidate treatment. The observed higher risk of suicide attempts before treatment may reflect emerging psychiatric symptoms that trigger medical consultations that result in a decision to begin ADHD treatment. Therefore, this study's results do not support a causal association between methylphenidate treatment and suicide attempts.

Project description:ImportancePeripartum suicide attempt is a major psychiatric complication associated with pregnancy, but the risk factors remain largely uncertain.ObjectiveTo identify the demographic characteristics and predisposing risks for peripartum suicide attempts and postpartum depression.Design, setting, and participantsThis cohort study used retrospective data on pregnant women who delivered children between April 1, 2016, and March 31, 2021, at 712 hospitals in Japan. The nationwide Diagnosis Procedure Combination database was used.ExposuresPsychiatric and nonpsychiatric medical history, age, alcohol and tobacco use, and obstetric complications and procedures.Main outcomes and measuresData on admissions for prepartum suicide attempt and delivery during the same hospital stay and readmissions for depression or suicide attempt within 1 year post partum were collected. Comparisons of prevalence of each study variable were performed, and multivariable logistic regression analyses were used to determine risk factors.ResultsFrom a total of 39 908 649 hospitalization episodes, 804 617 cumulative pregnant women (median [IQR] age at childbirth, 33 [29-36] years) who delivered at the enrolled hospitals were identified, including 1202 who were admitted for suicide attempt and delivery during the same hospital stay and 111 readmitted for suicide attempt within 1 year post partum. Risk factors associated with prepartum suicide attempts included younger age (adjusted odds ratio [aOR], 0.99; 95% CI, 0.98-1.00) and histories of personality disorder (aOR, 10.81; 95% CI, 5.70-20.49), depression (aOR, 3.97; 95% CI, 2.35-6.70), schizophrenia (aOR, 2.89; 95% CI, 1.52-5.50), and adjustment disorder (aOR, 2.66; 95% CI, 1.07-6.58). Risk factors associated with postpartum suicide attempts included younger age (aOR, 0.96; 95% CI, 0.93-1.00), heavy tobacco use (aOR, 23.09; 95% CI, 5.46-97.62), and histories of alcohol use disorder (aOR, 163.54; 95% CI, 28.30-944.95), personality disorder (aOR, 10.28; 95% CI, 3.29-32.10), anxiety disorders (aOR, 8.13; 95% CI, 2.88-22.98), depression (aOR, 7.27; 95% CI, 2.95-17.91), schizophrenia (aOR, 5.77; 95% CI, 2.17-15.38), bipolar disorder (aOR, 3.98; 95% CI, 1.36-11.67), and insomnia (aOR, 3.17; 95% CI, 1.30-7.78). On sensitivity analysis, risk factors associated with postpartum depression after excluding those with prenatal depression included histories of personality disorder, adjustment disorder, bipolar disorder, insomnia, and anxiety disorders.Conclusions and relevanceThe findings of this cohort study suggest that histories of smoking and prenatal psychiatric disorders are potential risk factors for peripartum suicide attempts and may require additional treatment and prevention interventions.

Project description:Brain gene expression profiling studies of suicide and depression using oligonucleotide microarrays have often failed to distinguish these two phenotypes. Moreover, next generation sequencing approaches are more accurate in quantifying gene expression and can detect alternative splicing. Using RNA-seq, we examined whole-exome gene and exon expression in non-psychiatric controls (CON, N=29), DSM-IV major depressive disorder suicides (MDD-S, N=21) and MDD non-suicides (MDD, N=9) in the dorsal lateral prefrontal cortex (Brodmann Area 9) of sudden death medication-free individuals post mortem. Using small RNA-seq, we also examined miRNA expression (nine samples per group). DeSeq2 identified 35 genes differentially expressed between groups and surviving adjustment for false discovery rate (adjusted P<0.1). In depression, altered genes include humanin-like-8 (MTRNRL8), interleukin-8 (IL8), and serpin peptidase inhibitor, clade H (SERPINH1) and chemokine ligand 4 (CCL4), while exploratory gene ontology (GO) analyses revealed lower expression of immune-related pathways such as chemokine receptor activity, chemotaxis and cytokine biosynthesis, and angiogenesis and vascular development in (adjusted P<0.1). Hypothesis-driven GO analysis suggests lower expression of genes involved in oligodendrocyte differentiation, regulation of glutamatergic neurotransmission, and oxytocin receptor expression in both suicide and depression, and provisional evidence for altered DNA-dependent ATPase expression in suicide only. DEXSEq analysis identified differential exon usage in ATPase, class II, type 9B (adjusted P<0.1) in depression. Differences in miRNA expression or structural gene variants were not detected. Results lend further support for models in which deficits in microglial, endothelial (blood-brain barrier), ATPase activity and astrocytic cell functions contribute to MDD and suicide, and identify putative pathways and mechanisms for further study in these disorder

Dataset Information

Effect of tryptophan hydroxylase-2 rs7305115 SNP on suicide attempts risk in major depression.

Publications

Effect of tryptophan hydroxylase-2 rs7305115 SNP on suicide attempts risk in major depression.

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