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Suicide is a public health problem all around the world. Family studies showed a strong heritability but, to date, few genetic data are available. Thus, in the present study we investigated whether a panel of single nucleotide polymorphisms (SNPs) in neuronal cell adhesion molecule 1 (NCAM) 1 was associated with suicidal behaviour as well as specific traits related to suicide. A total of two hundred and fifty-nine individuals with a positive history of suicidal behaviour and 312 healthy subjects were enrolled in the study. Rs2301228, rs1884, rs1245113, rs1369816, rs2196456 and rs584427 in NCAM1 were genotyped. No marker was significantly associated with suicidal behaviour vs. controls or with sub-types of attempted vs. completed, violent vs. non-violent, impulsive vs. non-impulsive suicide. Nonetheless rs1884 and rs2196456 SNPs were both marginally associated with the trait "inhibition of aggressiveness" in suicide attempters. Even though the investigated SNPs in NCAM1 do not seem to be directly associated with suicidal behaviour, our results could suggest that SNP variants in NCAM1 may impact on related traits, particularly by mediating inhibition of aggressiveness. However, independent studies are needed to validate these results., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Estrogen is thought to be involved in the pathophysiology of depression and suicidal behaviors. We studied gene variants of estrogen receptor alpha (rs827421, rs1913474, rs1801132, rs722207, rs974276 and rs910416) in 167 German suicide attempters (affective spectrum n=107, schizophrenia spectrum n=35, borderline personality disorder n=25), 92 German individuals who committed suicide and 312 German healthy subjects. Single markers and haplotype analysis in relation to suicidal behaviors (suicide attempters/completers) did not reveal any significant association. These were also not associated with related features, such as violence or impulsivity of suicide attempt, State-Trait Anger Expression Inventory (STAXI) and Questionnaire for Measuring Factors of Aggression (FAF) scores. In conclusion, our study does not support the hypothesis that estrogen receptor alpha gene variants are major contributors to suicide or to anger- or aggression-related behaviors.

The neurobiological basis of suicidal behaviour is multifactorial and complex. Several lines of evidence indicate that environmental factors as well as multiple genes and interactions of both are implicated in its aetiology. The aim of this study was to establish the transcriptomic expression profile of post-mortem brain tissue of suicide victims in order to identify new candidate genes and biological patterns for suicidal behaviour. Post-mortem orbitofrontal cortex tissue was derived from 11 suicide victims and 10 non-psychiatric controls carefully selected from a brain bank of over 150 brains, and the expression of more than 23000 messenger RNAs was assessed in this case-control study. Validation experiments were carried out using quantitative RT-PCR as an independent method. A classification of the differentially expressed genes according to their biological function and statistical analyses of the data were performed in order to identify biological pathways that are over-represented in the suicide group. In total, 124 transcripts demonstrated significant changes (fold changes > or = 1.3, p value < or = 0.01), with 59 showing under-, and 65 over-expression in the suicide group. The results could be validated for nine particularly interesting transcripts (CDCA7L, CDH12, EFEMP1, MLC1, PCDHB5, PTPRR, S100A13, SCN2B, and ZFP36). The pathway analysis showed that the Gene Ontology categories 'central nervous system development', 'homophilic cell adhesion', 'regulation of cell proliferation' and 'transmission of nerve impulse' were significantly enriched. The differentially expressed genes and significant biological processes might be involved in the pathophysiology of suicide and warrant further attention.

Nitric oxide (NO) is a neurotransmitter which modulates depressive and aggressive behaviors. We studied gene variants of NOS-I (rs2682826;rs1353939;rs2293049;rs693534) and NOS-III (rs2070744;rs1799983;rs891512) in a total of 571 cases (167 German suicide attempters, 92 Caucasian suicide completers and 312 German healthy subjects). A NOS-I risk haplotype C-G-G (rs2682826-rs1353939-rs693534) was associated with suicidal behavior (P = 0.01), and more specifically with suicide attempts (P = 0.01). Sliding windows analysis showed similar results for the haplotype G-G (rs1353939-rs693534) being a risk factor for suicidal behavior (P = 0.01) again especially in suicide attempters (P = 0.004). Additionally, the G-allele of rs693534 was associated with suicidal behavior (P = 0.005) and more specifically with suicide attempts (P = 0.003). Interestingly, the same haplotype (G-G) as well as the rs693534 G-allele were also associated with increased aggression. Regarding NOS-III, a protective haplotype C-T-A (rs2070744-rs1799983-rs891512) was observed (P = 0.01) with a pronounced effect against suicide completion (P = 0.005). Sliding window analysis showed the same effect of haplotype T-A (rs1799983-rs891512) (P = 0.01) which was again protective against suicide completion (P = 0.006). Single marker analysis showed the same protective effect of the rs891512 A-allele (P = 0.009) again especially against suicide completion (P = 0.007). Additionally, a second haplotype (T-T-G) was associated with increased aggression (P = 0.0002; sliding haplotype T-G, P = 0.002). In conclusion, our study suggests a possible involvement of NOS-I and NOS-III gene variants in suicidal behavior and related intermediate phenotypes., ((c) 2007 Wiley-Liss, Inc.)

Substance P is involved in the modulation of depression, anxiety, and suicidal-related behaviors. We studied gene variants of Tachykinin Receptor 1 (TACR1-rs3771810, rs3771825, rs726506, rs1477157) in 167 German suicide attempters (affective spectrum n = 107, schizophrenia spectrum n = 35, borderline personality disorder n = 25), 92 Caucasian individuals who committed suicide and 312 German healthy subjects. Single markers and haplotype analysis in relation to suicidal behaviors (suicide attempters/completers) did not reveal any significant association. The rarest rs3771825 T allele however showed a marginal association with higher Reactive Aggression scores on the Questionnaire for Measuring Factors of Aggression (FAF) (F = 9.86, df = 1; P = 0.0017). Haplotype analyses confirmed the finding. Violence or impulsivity of suicide attempt and State-Trait Anger Expression Inventory (STAXI) scores were not associated with gene variants. In conclusion, our study suggests that TACR1 gene variants have no major influence on suicidal behavior but may modulate aggression features., (Copyright 2007 Wiley-Liss, Inc.)

The ABCG1 transporter seems to be involved in human cholesterol and sterol homeostasis. As alterations in cholesterol homeostasis have been widely linked to aggression, violence and suicidal behavior, we considered ABCG1 as a candidate gene for these traits. We studied 5 gene variants of ABCG1 in a sample of 571 suicide attempters, healthy controls and suicide completers. We also analyzed the relation to aggression-related traits, assessed by STAXI and FAF. Regarding the genotypes, there was no association with completed or attempted suicide with the tested SNPs. Regarding alleles, only one SNP (rs1044317) showed a slight association with suicide attempters in comparison to the controls. Interestingly, rs225374 G allele carriers had higher scores on the STAXI subscales "State Anger" and "Anger Out", as well as on the FAF subscales "Spontaneous Aggression", "Irritability" and "Aggression". Carriers of the rs914189 G allele scored higher on the FAF subscales "Spontaneous Aggression", "Reactive Aggression" and "Aggression". Carriers of the rs1044317 G allele had lower scores for STAXI "Trait Anger" and "Trait Temperament", and higher scores for STAXI "Anger Control". Our results provide evidence that the ABCG1 may influence aggression-related traits. Given that these represent intermediate phenotypes of suicidal behavior, ABCG1 might also act on suicidal behavior through these traits. The observed associations warrant further replications.

The serotonin 2C (HTR2C) and 1A (HTR1A) receptors have been involved in suicide-related behaviors. We studied gene variants of both receptors in suicide attempters and completers. The sample was composed of 167 German suicide attempters (affective spectrum n = 107, schizophrenia spectrum n = 35, borderline personality disorder n = 25), 92 Caucasian individuals who committed suicide, 312 German healthy subjects, 152 Italian suicide attempters (major depression n = 68 and bipolar disorder n = 84), and 131 Italian healthy volunteers. HTR2C (SNP: rs547536, rs2192372, rs6318, rs2428707, rs4272555, rs1801412) and HTR1A (SNP: rs1423691, rs878567, and rs6295) variants were analyzed in the German sample. HTR2C rs6318 and HTR1A rs6295 were analyzed in the Italian sample. Haplotype analysis in relation to suicidal behaviors did not reveal any significant association. Single markers and haplotypes were not or only marginally associated with other related features, such as violence of suicide attempt, family history for suicide attempt or State-Trait Anger Expression Inventory (STAXI) and Questionnaire for Measuring Factors of Aggression (FAF) scores. In conclusion, our study does not support the notion that HTR2C and HTR1A gene variants are major contributors to suicide-, anger-, or aggression-related behaviors in our sample., ((c) 2006 Wiley-Liss, Inc.)

There is a lack of psychological autopsy studies assessing the influence of axis I disorders on axis II disorders as risk factors for suicide. Therefore, we investigated the association between personality disorders, axis I disorders, and suicide. Psychiatric disorders were evaluated by a semi-structured interview including the Structured Clinical Interview for DSM-IV Axis I (SCID-I) and Personality Disorders (SCID-II) in 163 completed suicides (mean age 49.6 +/- 19.3 years; 64.4% men) and by personal interview in 396 population-based control persons (mean age 51.6 +/- 17.0 years; 55.8% men). In both genders, suicides significantly more often had personality disorders of all clusters than controls, also after adjustment for axis I disorders (p < 0.001, each). In addition, alcohol-related disorders, major depression, and co-occurrence of personality disorders of more than one cluster (men: OR = 16.13; women: OR = 20.43) remained independent predictors for suicide in both genders, "pure" cluster B personality disorders only in women and "pure" cluster C personality disorders only in men. In both genders, co-occurrence of personality disorders of more than one cluster contributed to risk of completed suicide after control for axis I psychiatric disorders and has to be considered as an independent risk factor for suicide.

Screening instruments for detection of alcohol consumption, abuse, and dependence for use in psychological autopsy studies with case control design are not validated. Therefore, interrater and test-retest reliability of the Luebeck Alcohol Dependence and Abuse Screening Test (LAST) and the usability of this test for the psychological autopsy method were investigated. Alcohol consumption was evaluated by a semi-structured interview including the Structured Clinical Interview for DSM-IV Axis I (SCID-I) and the LAST in 163 completed suicides (mean age 49.6 +/- 19.3 years; 64.4% men) and by personal interview in 396 population-based controls (mean age 51.6 +/- 17.0 years; 55.8% men). Of the controls, 35 were additionally assessed by interviewing informants; these results were compared with those generated by personal interview. Comparison of LAST scores by personal and informant's interview of controls generated a Spearman correlation coefficient of 0.74 (P < 0.0001). The LAST (7 item-version, cut-off of 2) revealed high sensitivity and specificity for alcohol abuse and dependence, in both controls and suicides. LAST scores were significantly associated with high, frequent, and hazardous alcohol consumption (P < 0.001) in suicides. Our findings provide support for reliability and validity of identifying individuals with alcohol dependence and abuse obtained through the best-estimate method using the LAST. This 7-item questionnaire can be recommended as a useful tool for the psychological autopsy procedure in postmortem research.

Purpose. – Despite of higher rates of substance-related disorders in psychiatric patients and suicides than in the general population, there is no clear specificity to the relationship between nicotine use and other psychiatric disorders for suicide risk.Methods. – One hundred and sixty-three suicides (mean age 49.8 ± 19.3 years; 64.4% males; using psychological autopsy method) and 396 control persons (mean age 51.6 ± 17.0 years; 55.8% males) were assessed with a standardised semi-structured interview including SCID-I and SCID-II (for DSM-IV). Suicides and controls were compared in terms of nicotine consumption and psychiatric disorders. Logistic regression was used to evaluate the interactions of tobacco consumption with psychiatric disorders.Results. – Suicides were significantly more often current smokers and heavy users of cigarettes (>20 cigarettes per day; P < 0.001, each). Alcohol dependence, other axis I disorders than substance-related disorders, and cluster B personality disorder(s) remained independent predictors for suicide in both genders, current nicotine consumption only in men (OR = 2.6, 95% CI 1.3–5.2).Discussion and conclusions. – In males, but not in females, nicotine consumption contributed to risk of completed suicide after control for psychiatric disorders and has to be considered as independent risk factor for suicide. [Copyright &y& Elsevier]