Using the Strategy of Genome-Wide Association Studies to Identify Genetic Markers of Suicidal Behavior: A Narrative Review.

BACKGROUND: Several studies involving various suicidal phenotypes based on the strategy of the search of genome-wide associations with single nucleotide polymorphisms have been performed recently. These studies need to be generalized. AIM: To systematize the findings of a number of genome-wide association studies (GWAS) for suicidal phenotypes, annotate the identified markers, analyze their functionality, and possibly substantiate the hypothesis holding that these phenotypes reflect a nonspecific set of gene variants that are relevant as relates to stress-vulnerability as a key endophenotype of suicidal behavior (SB). METHODS: A search on the PubMed and related resources using the combinations "suicide AND GWAS" and "suicidal behavior AND GWAS" was performed. It yielded a total of 34 independent studies and meta-analyses. RESULTS: For the 10 years since such studies emerged, they have undergone significant progress. Estimates of the SNP heritability of SB in some cases are comparable with estimates of heritability based on the twin method. Many studies show a high genetic correlation with the genomic markers of the most common mental disorders (depression, bipolar disorder, schizophrenia, post-traumatic stress disorder). At the same time, a genomic architecture specific to SB is also encountered. Studies utilizing the GWAS strategy have not revealed any associations of SB with candidate genes that had been previously studied in detail (different neurotransmitters, stress response system, polyamines, etc.). Frequently reported findings from various studies belong in three main groups: 1) genes involved in cell interactions, neurogenesis, the development of brain structures, inflammation, and the immune responses; 2) genes encoding receptors for neurotrophins and various components of the intracellular signaling systems involved in synaptic plasticity, embryonic development, and carcinogenesis; and 3) genes encoding various neuro-specific proteins and regulators. CONCLUSION: In general, GWAS in the field of suicidology mainly serve the purpose of a deeper understanding of the pathophysiology of suicidal behavior. However, they also demonstrate growing capability in terms of predicting and preventing suicide, especially when calculating the polygenic risk score among certain populations (psychiatric patients) and in combination with tests of different modalities. From our point of view, there exists a set of markers revealed by the GWAS strategy that seems to point to a leading role played by stress vulnerability, an endophenotype that is formed during early development and which subsequently comes to play the role of key pathogenetic mechanism in SB.

Psychosocial and Psychiatric Factors Associated with Expected Fatality during Suicide Attempt in Men and Women.

BACKGROUND: Differential factors that influence intention and subjectively perceived fatality during non-fatal suicidal acts amongst men and women have rarely been explored in the extant literature. Exploring these factors may help to understand how they influence medical outcomes and may also be used in a post-crisis counselling. This study aims to assess factors influencing intent in relation to expected fatality during suicidal acts in men and women. METHOD: In the current study, 433 individuals who attempted suicide (age 24.89±0.98 years, male/female ratio=1.29) were surveyed using the WHO-5 Well-Being Index, Beck Depression Inventory, Beck Suicide Intent Scale, Plutchik Feelings and Acts of Violence Scale, and Spielberger State/Trait Anger Scale. Life stress was evaluated as an accumulation of negative life events, whilst psychiatric disorders were assessed using CIDI 2.1 inventory. RESULTS: It was found that the higher expected fatality was associated with higher suicide intention scores, whereas the medical severity of attempts and violent/non-violent attempts distribution did not differ between groups. Although there was no difference in suicide intent scores and medical severity between men and women, men demonstrated a 2.4-3.5 times higher proportion of violent attempts, depending on the group. Higher perceived fatality was associated with lower general well-being, higher depression and violence, hopelessness, and total life stress in men, whereas among women higher perceived fatality was only associated with total life stress. Moreover, in men and women, higher intent and expected fatality was associated with a differential set of negative life events that occurred during childhood. The prevalence of mental health disturbances in the entire sample was about 50% and equally distributed among men and women. However, addictions prevailed among men, while neurotic and stress-related disorders were more common among women. Among those who expected more fatality the number of people with diagnoses and comorbidity was higher, especially in men. CONCLUSION: There is a difference in risk factors for expected fatality and intent in men and women attempting suicide, which may not necessarily result in severe medical outcomes but may help during the post-crisis counseling of suicide attempters. Expected fatality deserves more attention as a component of general intent. An in-depth study of this phenomenon may help to understand motives of men and women attempting suicide and help prevent future suicidal attempts.

Personality patterns of suicide attempters: gender differences in Ukraine.

In the present study, an attempt has been made to investigate the complete 'pattern' of a suicide attempter (SA) within the set of Big Five traits. Two models were used: M1, which includes the five main dimensions of Big Five in the analysis; and M2, which includes facets of those dimensions which were identified as important in M1. The study consisted of a group of SA (men - 326, women - 299) and a group of healthy volunteers (HV) (men - 143, women - 190) with a similar age range. Discriminant analysis (DA) showed that the factors most significant in discriminating the personality pattern of a male SA are (in decreasing order): (E) Extraversion, (N) Neuroticism, (C) Conscientiousness and (O) Openness; and for a female SA these factors were (E) Extraversion, (C) Conscientiousness and (A) Agreeableness. In M2 for men, the largest contribution to pattern recognition is (N3) Depression. Moreover, in M2 for men significant characteristics were (in descending order): (E6) Positive Emotions, (O1) Fantasy, (E4) Activity, and also (N2) Angry Hostility, (C3) Dutifulness, (C4) Achievement Striving, (C2) Order and (O6) Values; and for women: (E4) Activity, (C6) Deliberation, (C2) Order, (A6) Tender-Mindedness, (E5) Excitement Seeking, (E6) Positive Emotions, (C4) Achievement Striving, (A2) Straightforwardness, (C5) Self-Discipline and (E1) Warmth. Analysis of the obtained data demonstrates that suicide attempts amongst males, can largely be associated with personality variables reflecting negative emotions; while female suicide attempts are primarily associated with variables regarding activity and self-regulation.

Suicides in the COVID-19 Pandemic - Are We Well Informed Regarding Current Risks and Future Prospects?

Background: Suicides are predicted to drop in the acute phase of any crisis that poses a threat to the entire population, though data on this are inconsistent. A pandemic is the most severe global crisis one can imagine. There is an urgent need to identify objective trends in suicide rates across countries and populations in a real-time manner in order to be better informed regarding prospects and adaptation of preventive strategies. Objectives: To evaluate suicidal behaviour in a metropolis immediately after the introduction of severe containment measures due to the pandemic. Methods: Cases of completed suicides in St. Petersburg were obtained from the local city Bureau of Forensic Medical Examinations for the period 1 January 2016 to 31 July 2020. Data were accurately collected and monthly frequencies per 100,000 of the population in April-May 2020 (introduction of the most severe stay at home measures) were compared with corresponding data from 2016-2019. Confidence intervals were calculated according to Wilson. Results: Suicide frequencies in the population of St. Petersburg in April 2020 did not go up, in contrast, they were 30.3% lower than the average for the previous four years. The decrease in April was more pronounced in males than in females (36.3% and12.4%, respectively). When looking at age groups it was found that the biggest drop in suicides was in older males ( 55 years). In this group, suicide indices were 58.5% lower than average for the previous four years. However, in females, there was a 50% rise in suicides in June, while in young males (15-34 years) there was an 87.9% rise in May. Total number of suicides for the first half of 2020 was very close to the average seen in previous years. None of the registered changes were statistically significant. Conclusions: The analysis is preliminary and does not account for possible seasonality, however, we consider that the reduction in completed suicides immediately after crisis exposure deserves attention. It supports views that in the acute phase of the crisis, suicidal behaviour may decline, which may be quickly replaced by a rise. Such a rise in females and younger males points on possible risk groups and requires a response from society. More studies are needed to have a clearer picture of suicide dynamics in Russia during the different waves of the pandemic, and prevention should be prioritized regardless of the tendencies.

Mental health problems and suicide in the younger generation - implications for prevention in the Navy and merchant fleet.

Psychologists and psychiatrists worldwide are expressing concerns regarding the growing prevalence of mental health problems and the incidence of suicide in young adults. The reasons are seen in the extremely high tempo of social changes, information pressure, and values evolution in the younger generations, which are exposed to growing inequalities, loneliness and lack of social support. Poverty, social isolation, consumerism, hedonism, and unrealistic expectations of the future generate in the vulnerable part of the young adults inevitable frustrations, which give way to depression, anxiety, addictions, and suicide. This creates additional risks for the situation on board ships, both military and merchant, and requires greater efforts during pre-admission selection and in the course of the service or voyages. Suicides in the Navy are better registered than in the cargo fleet and are lower than in the same age and gender groups from the general population, and usually lower than in other types of forces. Data on suicides in the civilian maritime sector are less conclusive, but suggest it as a growing problem, especially considering stress on board. Recent studies revealed quite a lot of mental health problems in the merchant fleet crews, including depression, anxiety, and suicidal thoughts. Among the reasons such factor as "flag of convenience" strategy that implies lower standards, recruiting of the less trained and lower-paid workforce, multinational and multilanguage rotating crews, higher workload and stress and insufficient level of the pre-employment medical examination are mentioned. Recent trends in the mental health of the youth demand higher awareness both in the military ships and in the merchant fleet. We consider that more education and training aimed at mental health problems identification and stress-resilience promotion are needed both for the military and civilian staff on board. Better education of the whole personnel and "healthy ship" approach (better recognition of the crew members' needs, attention to mental health problems, nutrition, physical activity, etc.) may be applied both for the Navy and merchant fleet.

Association of the serotonin transporter promotor polymorphism with suicide attempters with a high medical damage.

Serotonergic neurotransmission has been implicated in suicidal behavior, including inconsistent results concerning the serotonin transporter promoter polymorphism (5-HTTLPR). Here, we analyzed the 5-HTTLPR in suicide attempters (n=85). Comparing the presence of SS with SL+LL genotypes showed a significantly higher prevalence of the SS genotype in suicide attempters with high medical damage scores (chi2=9.054, df=1, p=0.0026). The results suggest that the S-allele may predispose for suicidal behavior characterized by high determination.

Nature and nurture in suicidal behavior, the role of genetics: some novel findings concerning personality traits and neural conduction.

Suicide affects about one million people each year, a phenomenon characterized by heterogeneous and complex causes. Often environmental factors such as negative life events may act as a significant contributor to suicidal behavior. However, in many cases the exposure to the same environmental stress does not result in increased suicidality. It is now well established that there is also a substantial genetic contribution to suicidal behavior. Here, functional and association studies which implicate specific genes in psychological traits and environmental factors are discussed, interactions which are related to completed suicide or suicide attempt, and our novel findings which need replication are presented. We found that genetic variation in the noradrenergic tyrosine hydroxylase gene was associated with the angry/hostility personality trait and vulnerability to stress. Similarly, we recently discovered that genetic variation in components of the stress-related hypothalamic pituitary adrenocortical axis, T-box 19 and corticotropin releasing hormone receptor 1, showed association and linkage to high anger/hostility in and male depression the suicidal offspring, respectively. Further results from our studies have revealed that genetic variation in genes with roles in basal mechanisms of neural conduction, voltage-gated sodium channel type VIII alpha and vesicle-associated membrane 4 protein, showed association and linkage among suicide attempters. Additionally, we have results which give support to the findings of others, implicating the serotonin transporter and serotonin receptor 1A in suicidal behavior. Our future studies aim at identifying and resolving complex patterns and mechanisms of neurobiological gene-environment interactions, which may contribute to suicide.

The serotonin 1A receptor C(-1019)G polymorphism in relation to suicide attempt.

BACKGROUND: Serotonergic neurotransmission has been implicated in suicidal behavior. Association between suicidal completers and a regulatory C(-1019)G polymorphism (rs6295) in the serotonin 1A receptor (HTR1A) gene was previously reported, whereas a following study showed no association in a sample of suicide attempters. METHODS: The involvement of the implicated G-allele of the 5-HTR1A C(-1019)G polymorphism (rs6295) was analyzed with the transmission disequilibrium test (TDT) in a sample of 272 suicide attempter families. RESULTS: No overtransmission of the G-allele was found in the entire sample of suicide attempters (p = 0.1460; n = 272 trios). However, a strong trend for overtransmission of the G-allele was observed in a sub-sample selected for a high level of previous traumatic and/or stressful life events prior to the suicide attempt (p = 0.0630, two-tail; n = 94 trios). CONCLUSION: The current results show that variation at the rs6295 polymorphism of the HTR1A gene is not associated with suicide attempts generally. However, the results indicate a possible role of the G-allele in suicidal behavior in connection with high exposure to traumatic and/or stressful life events, which is in need of future investigation.

Successful model of suicide prevention in the Ukraine military environment.

The article deals with the problem of suicidal behavior in the Ukraine military environment and gives an example of the successful prevention approach. The model of prevention is based on (1) education of the responsible officers, (2) training of the representatives of the most vulnerable risk groups, and (3) follow-up procedures based on distribution of pocket books for soldiers, educational booklets, and sets of helpful materials for officers. One of the main conclusions is that the prevention activity must be organized as a continuum of actions, seminars, consultations, and materials distribution.

Suicide among war veterans.

Studies aiming to identify if war veterans are at higher risk of suicide have often produced inconsistent results; this could be due to the complexity of comparisons and different methodological approaches. It should be noted that this contingent has many risk factors, such as stressful exposures, wounds, brain trauma and pain syndrome. Most recent observations confirm that veterans are really more likely to die of suicide as compared to the general population; they are also more likely to experience suicidal ideation and suffer from mental health problems. Suicides are more frequent in those who develop PTSD, depression and comorbid states due to war exposure. Combat stress and its' frequency may be an important factor leading to suicide within the frame of the stress-vulnerability model. According to this model, the effects of stress may interact with social factors, interpersonal relations and psychological variables producing suicidal tendencies. Modern understanding of stress-vulnerability mechanisms based on genetic predispositions, early life development, level of exposure to stress and stress-reactivity together with interpersonal aspects may help to build more effective suicide prevention programs based on universal/selective/indicated prevention principles.