Axel Schnabel

Elevated cytokine expression in the orbitofrontal cortex of victims of suicide.

Objective:  Based on the reported association between cytokines with depression and suicide, and evidence of increased markers of inflammation in the brain of suicide victims, the present study examined the expression of cytokines in the orbitofrontal cortex of suicide victims.

HTR2C and HTR1A gene variants in German and Italian suicide attempters and completers.

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.

Impact of employment status and work-related factors on risk of completed suicide A case-control psychological autopsy study

The objective of this study was to determine the impact of work-related factors on risk for completed suicide. Psychiatric disorders and socio-demographic factors including work-related factors were assessed by a semi-structured interview using the psychological autopsy method in 163 completed suicide cases and by personal interview in 396 living population-based control persons. Unemployment (in particular, for more than six months), (early) retirement, or homemaker status were associated with highly significantly increased suicide risk, independently of categorized psychiatric diagnosis. In addition, adverse psychosocial working conditions, such as monotonous work, increased responsibility and pronounced mental strain due to contact with work clients, significantly increased suicide risk as well, again independently of categorized psychiatric diagnosis. These findings demonstrate that negative consequences of unemployment, homemaker status with no outside occupation, or (early) retirement, as well as adverse psychosocial working conditions, present relevant risk factors contributing to suicidal behavior, independently of diagnosed psychiatric disorders. Employment and a positive modification of working conditions, may possibly be preventive to important adverse mental health outcomes, including suicidality.

NOS-I and -III Gene Variants are Differentially Associated With Facets of Suicidal Behavior and Aggression-Related Traits

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.

Substance use disorders as risk factors for suicide in an Eastern and a Central European city (Tallinn and Frankfurt/Main).

Cultural and regional differences on the well-known elevated suicide risk in substance use disorders have not been clarified yet. Therefore, the suicide risk associated with substance use disorders in a society of transition and in a socially and economically stable society should be identified and compared. Data from two population-based matched case-control studies were used to analyse the association between alcohol and other substance consumption and the risk of suicide. Data in Frankfurt were obtained by a semi-structured interview including the Structured Clinical Interview for DSM-IV Axis I (SCID-I) in 163 suicides that occurred in 1999 and 2000, and data from Tallinn were collected according to DSM-IV criteria on 156 deceased persons who committed suicide in 1999 by using the psychological autopsy method and in each city in matched population-based control persons by personal interview. In both cities, substance use disorders were significantly associated with suicide. Odds ratios for suicide were higher in Tallinn than in Frankfurt. The highest risk was observed in Tallinn among men with alcohol use disorders, aged 35 to 59 years. Although substance use and, in particular, alcohol use disorders were confirmed as risk factors for suicide in Tallinn and in Frankfurt, the much higher suicide risk associated with alcoholism in Tallinn than in Frankfurt indicates the importance of cultural, socio-political, and regional impact of suicide risk in alcoholism.

How do personality disorders modify suicide risk

There is a lack of psychological autopsy studies assessing the influence of axis II disorders on other risk factors for suicide. Therefore, we investigated if the estimated suicide risk for axis I disorders and socio-demographic factors was modified by personality disorders. 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) by psychological autopsy method in 163 completed suicides and by personal interview in 396 population-based control persons. Personality disorders modify suicide risk, differently for affective disorders, substance use disorders, smoking, life events during the last three months, and socio-demographic factors such as being single. Estimated suicide risk for socio-demographic factors and life events is not substantially altered following adjustment for affective disorders or substance use disorders. These findings suggest that treatment of personality disorders is essential for suicide prevention.

Tachykinin receptor 1 variants associated with aggression in suicidal behavior

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.

Dopa decarboxylase and tyrosine hydroxylase gene variants in suicidal behavior.

The dopaminergic system has been previously associated to behavioral facilitation and aggression, hence making the pathway a good candidate for suicidal behavior. We studied gene variants in the tyrosine hydroxylase (rs3842727, rs6356) and DOPA decarboxylase (rs1451371, rs1470750, rs998850) genes in a sample of 571 individuals consisting of 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 control subjects. TH variants were not associated with suicide (uncorrected P = 0.023) and related traits. Some marginal associations could be observed for DDC with suicide, violence, anger, and aggression. In conclusion, our study does not support the involvement of TH gene variants as major contributors to suicide, whereas DDC variants could mediate some features related to suicide and be involved in violent suicidal behavior.

Estrogen receptor gene 1 variants are not associated with suicidal behavior.

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.

Detection of alcohol consumption in suicides

AbstractScreening 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.