Association of 5HTR1A gene variants with suicidal behavior: Case-control study and updated meta-analysis

Introduction

The gene encoding the serotonin 1A receptor (5HTR1A) has been a candidate gene associated with suicidal behavior in case-control and meta-analysis studies. We carried out a meta-analysis and a case-control study on the 5HTR1A gene to examine the association of this gene with suicidal behavior.

Methods

We performed a systematic search in electronic databases to study meta-analytically the association of 5HTR1A gene with suicidal behavior; we found 9 published genetic association studies concerning the rs6295 polymorphism. To get a comprehensive knowledge of this association we conducted a case-control study on the following polymorphisms: rs1423691, rs6295, and rs878567 in a Mexican population; the sample was composed of 152 suicide attempters and 264 healthy subjects.

Results

The meta-analysis revealed that the rs6295 polymorphism is not associated with suicidal behavior. Similarly, no significant association for polymorphisms rs6295 and rs878567 was found in the case-control study. The polymorphism rs1423691 was excluded of the association analysis because cases and control groups were in Hardy–Weinberg disequilibrium.

Conclusion

The meta-analysis of functional rs6295 polymorphisms produced no association. Likewise, the analysis in our case-control study in a Mexican population resulted in lack of association of polymorphisms rs6295 and rs878567 with suicidal behavior. However, further studies assessing different populations, as well as larger samples are necessary to obtain conclusive outcomes.     

A common polymorphism in the 3′-UTR of the NOS1 gene was associated with completed suicides in Japanese male population

Background

Suicidal behavior has been widely accepted as familial. Its transmission cannot be explained by the transmission of psychiatric disorder alone and seems to be partly explained by the transmission of impulsive–aggressive behavior. Studies in laboratory animal have shown that mice lacking NOS1 manifest significant aggressive behavior. Further, several polymorphisms of neuronal nitric oxide synthase (NOS1) gene have been reported to be associated with impulsivity, aggression and suicide attempts. To further clarify the possible involvement of NOS1 with suicide, we carried out an association study of NOS1 gene polymorphisms with completed suicide.

Methods

We examined 7 single nucleotide polymorphisms (SNPs) of the NOS1 gene which were previously studied in several neuropsychiatric disorders (rs2682826, rs6490121, rs3782206, rs561712, rs3782219, rs3782221, and rs41279104), in age and gender matched 287 healthy control subjects and 284 completed suicides using the TaqMan probe assays.

Results

We found that both the genotypic distribution and the allelic frequencies of rs2682826 SNP were significantly different between the completed suicide and control groups (P = 0.0007 and 0.0005, respectively). The odd ratio for the minor allele of the SNP was 0.653 (95% CI 0.513–0.832). The significance was remained even after correction for multiple testing. Gender-based analysis showed that the significances were appeared in males only.

Conclusion

Our study raises a possibility that a genetic variation of NOS1 may be implicated in the pathophysiology of suicide in Japanese population, especially in males. Further studies on more NOS1 genetic variants are needed to confirm our observations.     

Epistatic effects between variants of kappa-opioid receptor gene and A118G of mu-opioid receptor gene increase susceptibility to addiction in Indian population

Objective

Unequivocal evidence suggests contribution of κ-opioid receptor (KOR) in addiction to drugs of abuse. A study was undertaken to identify the single nucleotide polymorphisms (SNP) at selective areas of kappa opioid receptor 1 (OPRK1) gene in heroin as well as in alcohol addicts and to compare them with that in control population. The potential interaction of the identified KOR SNPs with A118G of μ opioid receptor was also investigated.

Methods

Two hundred control subjects, one hundred thirty heroin and one hundred ten alcohol addicts, all male and residing in Kolkata, a city in eastern India, volunteered for the study. Exons 3 and 4 of OPRK1 and the SNP, A118G of mu opioid receptor 1 (OPRM1) in the DNA samples were genotyped by sequencing and restriction fragment length polymorphism respectively. The SNPs identified in the population were analyzed by odds ratio and its corresponding 95% confidence interval was estimated using logistic regression models. SNP–SNP interactions were also investigated.

Results

Three SNPs of OPRK1, rs16918875, rs702764 and rs963549, were identified in the population, none of which showed significant association with addiction. On the other hand, significant association was observed for A118G with heroin addiction (χ² = 7.268, P = 0.0264) as well as with alcoholic addition (χ² = 6.626, P = 0.0364). A potential SNP–SNP interaction showed that the odds of being addicted was 2.51 fold in heroin subjects [CI (95%) = 1.1524 to 5.4947, P = 0.0206] and 2.31 fold in alcoholics [CI (95%) = 1.025 to 5.24, P = 0.0433] with the OPRK1 (rs16918875) and A118G risk alleles than without either. A significant interaction was also identified between GG/AG of A118G and GG of rs702764 [O.R (95%) = 2.04 (1.279 to 3.287), P = 0.0029] in case of opioid population.

Conclusion

Our study suggests that set associations of polymorphisms may be important in determining the risk profile for complex diseases such as addiction.     

Aggression–impulsivity,mental pain,and communication difficulties in medically serious and medically non-serious suicide attempters

Background

Unbearable mental pain, depression, and hopelessness have been associated with suicidal behavior in general, while difficulties with social communication and loneliness have been associated with highly lethal suicide attempts in particular. The literature also links aggression and impulsivity with suicidal behavior but raises questions about their influence on the lethality and outcome of the suicide attempt.

Objectives

To evaluate the relative effects of aggression and impulsivity on the lethality of suicide attempts we hypothesized that impulsivity and aggression differentiate between suicide attempters and non-attempters and between medically serious and medically non-serious suicide attempters.

Method

The study group included 196 participants divided into four groups: 43 medically serious suicide attempters; 49 medically non-serious suicide attempters, 47 psychiatric patients who had never attempted suicide; and 57 healthy control subjects. Data on sociodemographic parameters, clinical history, and details of the suicide attempts were collected. Participants completed a battery of instruments for assessment of aggression–impulsivity, mental pain, and communication difficulties.

Results

The medically serious and medically non-serious suicide attempters scored significantly higher than both control groups on mental pain, depression, and hopelessness (p < .001 for all) and on anger-in, anger-out, violence, and impulsivity (p < .05 for all), with no significant difference between the two suicide attempter groups. Medically serious suicide attempters had significantly lower self-disclosure (p < .05) and more schizoid tendencies (p < .001) than the other three groups and significantly more feelings of loneliness than the medically non-serious suicide attempters and nonsuicidal psychiatric patients (p < .05). Analysis of aggression–impulsivity, mental pain, and communication variables with suicide lethality yielded significant correlations for self-disclosure, schizoid tendency, and loneliness. The interaction between mental pain and schizoid traits explained some of the variance in suicide lethality, over and above the contribution of each component alone.

Conclusions

Aggression–impulsivity and mental pain are risk factors for suicide attempts. However, only difficulties in communication differentiate medically serious from medically non-serious suicide attempters. The combination of unbearable mental pain and difficulties in communication has a magnifying effect on the risk of lethal suicidal behavior.     

Association study of polymorphisms in leptin and leptin receptor genes with antipsychotic-induced body weight gain

Background

Antipsychotic-induced weight gain (AIWG) is a serious side-effect of antipsychotic medication leading to metabolic syndrome and increased cardiovascular morbidity. Unfortunately, there are still no valid predictors to assess an individual's risk to gain weight. Previous studies have indicated an impact of genetic variation in the genes encoding leptin, LEP, and leptin receptor, LEPR, on AIWG, but results have not been conclusive. Thus, we investigated polymorphisms in both genes for an association with AIWG.

Methods

A total of 181 schizophrenic and schizoaffective patients treated with various antipsychotics were included. In a small subset of patients, leptin plasma levels were additionally obtained. Five polymorphisms in LEP and LEPR (LEP: rs7799039 (-2548G/A polymorphism), rs10954173, rs3828942; LEPR: rs1327120, rs1137101 (Q223R polymorphism) were genotyped using TaqMan assays. Statistical association with % weight change from baseline weight was performed using ANCOVA with baseline weight as covariate.

Results

ANCOVA showed a non-significant trend for genotype association of the rs7799039 marker (p = .068). No significant association of the other LEP and LEPR SNPs with AIWG was detected. However, we found a significant association between a haplotype of LEP rs7799039G–rs10954173G–rs3828942G (p = .035) and AIWG. The rs7799039 G-allele (p = .042) and G-allele of rs3828942 (p = .032) were associated with higher weight gain.

Conclusion

Our study supports the hypothesis of an impact of LEP gene variation on AIWG. Limitations of our study include heterogeneous samples, short treatment duration and multiple comparisons. Our findings were compared to previous studies in detail in order to provide the readers with a more conclusive picture. However, further studies are warranted including more gene variants and interaction analyses with other genes of the leptin–melanocortin pathway.     

Association of FKBP5 gene haplotypes with completed suicide in the Japanese population

Background

The hypothalamus-pituitary-adrenal (HPA) axis is known to have a role in suicidal behaviors in patients with affective disorders. However, the incomplete overlapping of the genetic factors of suicidal behaviors and the genetic factors of affective disorders suggest that the genes associated with predisposition to suicidal behaviors and affective disorders are different. There is increasing evidence that genes regulating the HPA axis have effects on suicidal behaviors. To test this idea, we examined the association of three HPA axis-related genes (glucocorticoid receptor (NR3C1), mineralocorticoid receptors (NR3C2), and FK506 binding protein 5 (FKBP5)) with suicide.

Methods

We selected 3 SNPs of the FKBP5 (rs3800373, rs1360780, and rs2395635), 2 SNPs of the NR3C1 (rs6196 and rs10052957), and 3 SNPs of the NR3C2 genes (rs5525, rs5522, and rs2070951) based on their frequency in the Japanese population. Using TaqMan probe assays, we determined these SNPs in 219 completed suicide victims and 228 age- and gender-matched healthy control subjects.

Results

No significant differences in genotypic distribution or allelic frequency of any single SNPs between the completed suicide and control groups were observed. The distributions of TT, TC, and GT haplotypes of the FKBP5 gene (comprised of rs3800373 and rs1360780) between the completed suicide and control groups were significantly different (p < 0.05 for each haplotype). The TC haplotype withstood correction for multiple comparisons (corrected p = 0.034).

Conclusion

Our results suggest that haplotypes in FKBP5 gene are associated with completed suicide. This finding needs to be confirmed using rigorous SNPs selection in a larger sample.     

Serum lipids,metabolic syndrome and lifetime suicide attempts in patients with bipolar disorder

Objective

Bipolar disorder is associated with a high risk of suicide. Many clinical characteristics and, recently, biomarkers have been studied with the aim to find useful predictors of suicidality. The role of serum lipids has also been explored albeit with conflicting results; however, few studies have been focused on patients with bipolar disorder.Aim of our study is to investigate whether serum cholesterol, triglycerides, HDL-c and metabolic syndrome are associated with lifetime suicide attempts in a large naturalistic sample of patients with bipolar disorder.

Methods

220 patients with bipolar disorder were included. History of lifetime suicide attempts was systematically and retrospectively assessed for each patient. Blood exams testing total cholesterol, triglycerides, and HDL-c levels were performed, and metabolic syndrome was diagnosed according to NCEP ATP-III modified criteria. Serum lipid levels and metabolic syndrome were compared in patients with or without history of suicide attempt. According to a theory that links impulsivity and violence with low cholesterol, the association between lipid levels and violent suicidal behavior was also assessed.

Results

Lifetime suicide attempts rate was 32.3%. There were no statistically significant differences between patients with and without lifetime suicide attempts in cholesterol, triglycerides, HDL-c levels, and the prevalence of metabolic syndrome. No differences in the same variables were found in violent suicide attempters compared with nonviolent ones. Clinical characteristics such as gender, low education, higher number of manic and depressive episodes, and taking more medications for bipolar disorder were associated with lifetime suicide attempts.

Conclusions

Our results do not support the hypothesis of a strong association between serum lipid levels and suicide in patients with bipolar disorder.     

Association between the dopamine D2 receptor (DRD2) polymorphism and the personality traits of healthy Japanese participants

Background

Dopamine neurotransmitter systems have been associated with reward-related and novelty-seeking personality traits. We investigated the possible relationship between the personality traits measured by the Temperament and Character Inventory (TCI) and the TaqI A and − 141C Ins/Del polymorphisms in the dopamine D2 receptor gene (DRD2).

Methods

The sample consisted of 1084 healthy Japanese medical students and medical staff (age = 29.0 ± 9.7 years), each of whom completed the TCI. Their genomic DNA was isolated from whole blood and genotyped using the TaqMan allele-specific assay method. The associations between gene polymorphisms and the scores for TCI were statistically analyzed by one-way analysis of covariance (ANCOVA) adjusting age. Males and females were analyzed separately. Epstatis was assesses using two-way ANCOVA between the DRD2 and ANKK1 genes.

Results

Men with the Ins/Del genotype of the − 141C Ins/Del polymorphism had significantly higher self-directedness scores than those with the Ins/Ins genotype (p = 0.021). None of the TCI scores differed among women with regard to the three genotype groups of the − 141C Ins/Del polymorphism. The DRD2/ANKK1 Taq1 A polymorphism did not affect any TCI factor for either men or women. An epistatic analysis did not reveal main effects of the two genes with regard to TCI scores, but an ANKK1 × DRD2 interaction significantly predicted TCI scores.

Conclusion

These findings suggest the possibility that the − 141C Ins/Del polymorphism and the DRD2/ANKK1 Taq1 A polymorphism are not strongly linked to personality traits directly, but influences them under the interaction between the DRD2 and ANKK1 genes.     

The role of brain-derived neurotrophic factor (BDNF) gene variants in antipsychotic response and antipsychotic-induced weight gain

Background

Brain-derived neurotrophic factor (BDNF) has extensive effects on the nervous system including cell survival, differentiation, neuronal growth and maintenance, as well as cell death. Moreover, it promotes synaptic plasticity and interacts with dopaminergic and serotonergic neurons, suggesting an important role on the alteration of brain function with antipsychotic medications and induced weight gain in schizophrenia patients. The differential effects of BDNF gene variants could lead to changes in brain circuitry that would in turn cause variable response to antipsychotic medication. Therefore, we hypothesized that genetic variation in this candidate gene helps in explaining the inter-individual variation observed in antipsychotic drug treatment with respect to response and induced weight gain.

Method

We examined four single-nucleotide polymorphisms across the BDNF gene, including Val66Met (rs6265). Prospective BPRS change scores and weight change after six weeks were obtained from a total of 257 schizophrenia patients of European ancestry.

Results

The markers rs11030104 and Val66Met were associated with antipsychotic response (P = 0.04; 0.007, respectively). On the other hand, marker rs1519480 was associated with weight gain (P = 0.04). Moreover, a two-marker haplotype across rs6265 and rs1519480 was associated with weight change (P = 0.001). Results with Val66Met in response, and results with rs6265-rs1519480 haplotypes remained significant at the modified Bonferroni corrected alpha of 0.017.

Conclusion

BDNF genetic variants might play an important role in predicting antipsychotic response and antipsychotic-induced weight gain. However, replication in larger and independent samples is required.     

Inpatient medical–surgical suicidal behavior: a 12-year case–control study

Objective

To describe a medical center's 12-year experience with medically or surgically hospitalized suicide attempters, with the goal of extending the limited literature on this sentinel event.

Patients and Methods

Eight Mayo Clinic Rochester patients' self-inflicting injuries serious enough to trigger mandatory reporting while hospitalized on a medical/surgical unit from January 1, 1998 to December 31, 2010 were matched with four same-sex and same-age controls, admitted to the same unit within 2 months. Cases were identified from Sentinel Event Tracking System and Minnesota Adverse Events Statute records. Data were analyzed with conditional logistic regression.

Results

Eight of 777,404 medical/surgical inpatients admitted during 12 years attempted suicide, with significantly more non-Caucasian patients among cases than controls (P= .020). Of 8 attempts, 1 was fatal. More cases than controls had undergone inpatient psychiatric evaluation prior to attempt (P= .020), and elevated risk of attempt was significantly associated with increased number of prior attempts (0.049). Near their attempts, each attempter had an identifiable stressor including inadequately controlled pain in 3, agitation and anxiety in 2 each, and acute delirium, insomnia and psychosocial difficulties in 1 each.

Conclusion

First, this study's findings underscore the rarity of reported inpatient medical/surgical suicidal behavior. In this sample, suicide attempters were distinct from nonattempters by the increased likelihood of prior suicide attempts as well as inpatient psychiatric consultations before their attempts. When patients have these characteristics, medical teams should take particular notice and initiate heightened watchfulness for suicidal behavior.     

Association study of EP1 gene polymorphisms with suicide completers in the Japanese population

Background

Both environmental and genetic factors have been reported to be involved in suicidal behaviors. Considerable evidence indicates that impulsive aggression is one of the important risk factors that contribute to suicide. A recent study has shown that prostaglandin E2 type 1 receptor (EP1) signaling regulates impulsive-aggressive behaviors in mice under both social and environmental stresses. To test the possible involvement of the EP1 gene in suicide, we carried out an association study of EP1 gene polymorphisms with suicide completers in the Japanese population.

Methods

We studied 5 SNPs including one SNP in exon 2 (rs3745459) and four SNPs in the potential promoter region of the EP1 gene (rs3810255, rs3810254, rs3810253 and rs10416814) in 374 healthy control and 287 completed suicide victims using standard Taqman probe genotyping assays.

Results

No significant differences of the genotypic distribution, allelic frequency or haplotype distribution between controls and suicide completers were found. Gender based analysis revealed that genotypic, allelic and haplotypic distributions of rs3810255, rs3810254, rs3810253 and rs10416814 SNPs were significantly different between the female control and female suicide groups, although the differences did not withstand correction for multiple comparisons.

Conclusion

We could not find an association of EP1 gene with suicide in the Japanese population. Because several SNPs in the promoter region of the EP1 gene were nominally significantly associated with suicide in the female, further studies with a larger sample size and different population are needed to confirm this result.     

SRD5A2 is associated with increased cortisol metabolism in schizophrenia spectrum disorders

Objective

Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is documented in bipolar disorder and schizophrenia, but the mechanism is unclear; recently, increased activity of cortisol metabolizing enzymes was indicated in these disorders. We investigated whether five genes involved in cortisol metabolism were associated with altered activity of cortisol metabolizing enzymes in bipolar disorder (BD) and schizophrenia spectrum disorders (SCZ).

Methods

A case–control sample of subjects with BD (N = 213), SCZ (N = 274) and healthy controls (N = 370) from Oslo, Norway, were included and genotyped from 2003 to 2008. A sub-sample (healthy controls: N = 151; SCZ: N = 40; BD: N = 39) had estimated enzyme activities based on measurements of urinary free cortisol, urinary free cortisone and metabolites. A total of 102 single nucleotide polymorphisms (SNPs) in the SRD5A1, SRD5A2, AKR1D1, HSD11B1 and HSD11B2 genes were genotyped, and significant SNPs analyzed in the sub-sample.

Results

There was a significant association of rs6732223 in SRD5A2 (5α-reductase) with SCZ (p = 0.0043, Bonferroni corrected p = 0.030, T risk allele). There was a significantly increased 5α-reductase activity associated with rs6732223 (T allele) within the SCZ group (p = 0.011).

Conclusions

The present data suggest an interaction between SCZ and SRD5A2 variants coding for the enzyme 5α-reductase, giving rise to increased 5α-reductase activity in SCZ. The findings may have implications for cortisol metabolizing enzymes as possible drug targets.     

Association study of the SLC25A12 gene and autism in Han Chinese in Taiwan

Purpose

Autism is a childhood-onset neurodevelopmental disorder with a strong genetic component in its etiology. Several studies reported that the solute carrier family 25 member A12 (SLC25A12) gene was associated with autism. This study aimed to replicate this finding in a Han Chinese sample from Taiwan using a population-based case–control approach.

Methods

We genotyped two single nucleotide polymorphisms (SNPs, rs2056202 and rs2292813) of the SLC25A12 gene that were previously reported to be associated with autism in 465 patients (402 males and 63 females) and 450 control subjects (227 males and 223 females) from Taiwan. Differences in the genotype, allele, and haplotype frequencies between the two groups were compared.

Results

We found no differences in the allele, genotype, or haplotype frequencies of these two SNPs between patients and controls.

Conclusions

Our data do not support that the SLC25A12 gene is associated with autism in our population. The discrepant results of other studies may come from the clinical heterogeneity of patients recruited for studies, or the genetic heterogeneity of autism in different populations.     

Role of serotonergic-related systems in suicidal behavior: Data from a case-control association study

Objective

To investigate whether functional polymorphisms directly (HTR2A and SLC6A4 genes) or indirectly (IL-1 gene complex, APOE and ACE genes) related with serotonergic neurotransmission were associated with suicidal behavior.

Subjects and methods

227 suicide attempters, 686 non-suicidal psychiatric patients, and 420 healthy controls from a homogeneous Spanish Caucasian population were genotyped using standard methods.

Results

There were no differences in genotype frequencies between the three groups. The −1438A/G [χ² (df) = 9.80 (2), uncorrected p = 0.007] and IL-1α −889C/T [χ² (df) = 8.76 (2), uncorrected p = 0.013] genotype frequencies between impulsive and planned suicide attempts trended toward being different (not significant after Bonferroni correction). Suicide attempts were more often impulsive in the presence of −1438G/G or IL-1α −889C/T or C/C genotypes. There was interaction between the polymorphism 5-HTTLPR and age [LRT (df) = 6.84 (2), p = 0.033] and between the polymorphisms APOE and IL-1RA (86 bp)_n [LRT (df) = 12.21 (4), p = 0.016] in relation to suicide attempt lethality.

Conclusion

These findings further evidence the complexity of the association between genetics and suicidal behavior, the need to study homogenous forms of the behavior and the relevance of impulsive and aggressive traits as endophenotypes for suicidal behavior.     

SCN8A as a novel candidate gene associated with bipolar disorder in the Han Chinese population

Background

Bipolar disorder (BPD) is a common, severe and recurrent psychiatric disorder. It has been suggested that BPD patients have a higher risk of suicide than patients with any other psychiatric illnesses. A recent study found that suicide attempt was associated with the SCN8A gene, which has been mapped close to one of the BPD susceptibility loci. Thus, SCN8A is likely to be a candidate gene for BPD.

Methods

In this study, three SNPs (rs1601012, rs303810, rs60637) were analyzed in 506 bipolar patients and 507 controls of Han origin.

Results

We found that two individual SNPs showed statistically significant differences between cases and controls in both allele and genotype distribution, but only rs303810 was still significant in allele distribution (p = 0.0164) after correction. No obvious linkage disequilibrium or haplotypes were observed among these SNPs.

Conclusion

Our results indicate that SCN8A may be a potential susceptibility gene for bipolar disorder in the Han Chinese population.     

No genetic association between NCAM1 gene polymorphisms and schizophrenia in the Chinese population

Background

The neural cell adhesion molecule 1(NCAM1, aliases NCAM and CD56) is a cell-surface molecule which makes homophilic adhesion between neural cells involved in cell migration, axon outgrowth and synaptic plasticity. Recent studies reported that NCAM1 might act as a candidate schizophrenia susceptibility gene.

Method

We genotyped five SNPs (rs1943620, rs1836796, rs1821693, rs686050, rs584427) within the NCAM1 gene and conducted a case-control study in 288 schizophrenic patients and 288 healthy subjects in the Chinese Han population. We compared allele and genotype frequencies and haplotype distributions between cases and controls.

Result

No significant differences in allele and genotype frequencies were found for each single SNP between schizophrenic patients and healthy subjects. Moreover, there were no significant differences in haplotype distributions between cases and controls (global χ² = 1.318, P = 0.725, df = 3).

Conclusion

Our study suggests that the five SNPs within NCAM1 gene we studied may not play a major role in the schizophrenia susceptibility in the Chinese Han population.     

Suicide attempts before joining the military increase risk for suicide attempts and severity of suicidal ideation among military personnel and veterans

Objective

Past self-injurious thoughts and behaviors (SITB) are robust predictors of future suicide risk, but no studies have explored the prevalence of SITB occurring prior to military service among military personnel and veterans, or the association of premilitary SITB with suicidal ideation and suicide attempts during or after military service. The current study explores these issues in two separate samples.

Method

Self-report data were collected from 374 college student veterans via anonymous only survey (Study 1) and from 151 military personnel receiving outpatient mental health treatment (Study 2).

Results

Across both studies, premilitary suicide attempts were among the most prominent predictor of subsequent suicide attempts that occurred after joining the military, even when controlling for demographics and more recent emotional distress. Among military personnel who made a suicide attempt during or after military service, approximately 50% across both samples experienced suicidal ideation and up to 25% made a suicide attempt prior to joining the military. Military personnel and veterans who made suicide attempts prior to joining the military were over six times more likely to make a later suicide attempt after joining the military. In Study 2, significantly more severe current suicidal ideation was reported by participants with histories of premilitary suicide risk, even when controlling for SITB occurring while in the military.

Conclusions

Military personnel and veterans who experienced SITB, especially suicide attempts, prior to joining the military are more likely to attempt suicide while in the military and/or as a veteran, and experience more severe suicidal crises.     

Sheehan Suicidality Tracking Scale (S-STS): Reliability,convergent and discriminative validity in young Italian adults

Background and purpose

The Sheehan Suicidality Tracking Scale (S-STS) is a patient self-report or clinician-administered rating scale that tracks spontaneous and treatment-emergent suicidal ideation and behaviors. This study set out to evaluate the reliability, convergent and divergent validity of the S-STS in a sample of college students, a population with a high risk of completed and attempted suicide.

Methods

Cross-sectional, survey design. Participants (303 undergraduate students; males: 42%) completed several measures assessing psychological distress (General Health Questionnaire; GHQ); self-esteem (Rosenberg Self Esteem Scale; RSES); social support (Modified Social Support Survey; MOSSS); and suicidal behavior, including ideation and attempts (S-STS).

Results

Both internal consistency and test–retest stability were excellent for the S-STS-global score. The S-STS subscale on suicide ideation also showed good reliability, while the subscale on suicidal behavior showed some inconsistency at retest. Convergent and divergent validity of S-STS was confirmed. All S-STS items loaded on a single factor, which had an excellent fit for the unidimensional model, thus justifying the use of the S-STS as a screening tool. In a mediation model, self-esteem and social support explained 45% of the effects of psychological distress on suicide ideation and behavior as measured by the S-STS-global score.

Conclusions

This study provided promising evidence on the convergent, divergent, internal consistency and test–retest stability of the Sheehan Suicidality Tracking Scale. The cross-sectional design and lack of measures of hopelessness and helplessness prevent any conclusion about the links of suicidal behavior with self-esteem and social support.     

Interaction of serotonin-related genes affects short-term antidepressant response in major depressive disorder

Background

Four serotonin-related genes including guanine nucleotide binding protein beta polypeptide 3 (GNB3), 5-hydroxytryptamine receptor 1A (HTR1A; serotonin receptor 1A), 5-hydroxytryptamine receptor 2A (HTR2A; serotonin receptor 2A), and solute carrier family 6 member 4 (SLC6A4; serotonin neurotransmitter transporter) have been suggested to be candidate genes for influencing antidepressant treatment outcome. The aim of this study was to explore whether interaction among these genes could contribute to the pharmacogenomics of short-term antidepressant response in a Taiwanese population with major depressive disorder (MDD).

Methods

Included in this study were 101 MDD patients who were treated with antidepressants, 35 of whom were rapid responders and 66 non-responders after 2 weeks of treatment. We genotyped four single nucleotide polymorphisms (SNPs), including GNB3 rs5443 (C825T), HTR1A rs6295 (C-1019G), HTR2A rs6311 (T102C), and SLC6A4 rs25533, and employed the generalized multifactor dimensionality reduction (GMDR) method to investigate gene–gene interactions.

Results

Single-locus analyses showed the GNB3 rs5443 polymorphism to be associated with short-term antidepressant treatment outcome (P-value = 0.029). We did not correct for multiple testing in these multiple exploratory analyses. Finally, the GMDR approach identified a significant gene–gene interaction (P-value = 0.025) involving GNB3 and HTR2A, as well as a significant 3-locus model (P-value = 0.015) among GNB3, HTR2A, and SLC6A4.

Conclusions

These results support the hypothesis that GNB3, HTR2A, and SLC6A4 may play a role in the outcome of short-term antidepressant treatment for MDD in an interactive manner. Future research with independent replication using large sample sizes is needed to confirm the functions of the candidate genes identified in this study as being involved in short-term antidepressant treatment response.     

TPH2 is not a susceptibility gene for suicide in Japanese population

Background

Serotonergic systems mediate a control of aggression and/or impulsivity in human and are suggested to be involved in suicidal behavior. The newly identified neuronal tryptophan hydroxylase isoform 2 (TPH2), the rate-limiting enzyme in serotonin synthesis, represents a prime candidate in numerous genetic association analyses of suicidal behavior; however, the results are still inconclusive. The discrepancy may result from the heterogeneity of pathogenesis of suicidal behavior and/or methodological mismatches. We, therefore, attempted to replicate the association of TPH2 gene with suicide using a case-control study of 234 completed suicides and 260 control subjects in Japanese population.

Methods

We genotyped 15 tagging-single nucleotide polymorphisms (SNPs) including 4 SNPs, which were previously reported to be associated with suicidal behavior, using the TaqMan probe assays and the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method.

Results

We found no significant differences in genotypic distributions (uncorrected p = 0.06–0.98) or allelic frequencies (uncorrected p = 0.09–0.95) of the fifteen SNPs between the completed suicides and control groups. Haplotypes constructed with these SNPs were also not associated with suicide (uncorrected p = 0.03–0.96 and corrected p = 0.20–1.00). Even when we took sex and suicidal methods (violent or non-violent) into account for the analyses, no significant differences in genotypic distributions, allelic/haplotypic frequencies were found in the two groups.

Conclusion

Our results suggest that the common SNPs and haplotypes of the TPH2 gene are unlikely to contribute to the genetic susceptibility to suicidal behavior in Japanese population.