Genetic and Familial Environmental Effects on Suicide – An Adoption Study of Siblings

Petersen, Liselotte; Sørensen, Thorkild I. A.; Andersen, Per Kragh; Mortensen, Preben Bo; Hawton, Keith

doi:10.1371/journal.pone.0077973

Cited by 17 publications

(16 citation statements)

References 25 publications

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“…A high level of impulsivity in early childhood has been implicated in later adolescent self-harming (Goldston, Daniel, Mathias & Dougherty, 2008) and the effects of puberty are also thought to play a part in influencing selfharming behaviour (Patton, Hemphill, Byers et al, 2007). A genetic association with attempted suicide has recently been shown (Petersen , Sørensen, Andersen, Mortensen & Hawton, 2014).…”

Section: Discussionmentioning

confidence: 99%

Making Sense of an Unknown Terrain

et al. 2016

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Self-harm is common in young people, and can have profound effects on parents and other family members. We conducted narrative interviews with 41 parents and other family members of 38 young people, aged up to 25, who had self-harmed. Most of the participants were parents, but included one sibling and one spouse. This article reports experiences of the parent participants. A cross-case thematic analysis showed that most participants were bewildered by self-harm. The disruption to their world-view brought about by self-harm prompted many to undergo a process of 'sense-making' -by ruminative introspection, looking for information and building a new way of seeing -in order to understand and come to terms with self-harm. Most participants appeared to have been successful in making sense of self-harm, though not without considerable effort and emotional struggle. Our findings provide grounds for a deeper socio-cultural understanding of the impact of self-harm on parents.Keywords: Self-harm; adolescence; young adults; parents; families 3 Self-harm is defined as intentional self-injury or self-poisoning regardless of motive (Hawton, Saunders & O'Connor, 2012; Oldershaw, Richards, Simic & Scmidt, 2008). It is common in young people, with some studies reporting up to 38% of young adults engaging in self-harm (Andover, Primack, Gibb & Pepper, 2010). Between 10-17% of adolescents are said to selfharm (Hawton, Rodham, Evans & Weatherall, 2002;Klonsky, 2009). While some research suggests that rates of self-harm are comparable in men and women (Andover et al. 2010), international studies with large community samples show that self-harm occurs three to four times more often in female adolescents than in males (Hawton et al., 2002; Madge et al., 2008;O'Connor, Rasmussen, Miles & Hawton, 2009., Mars et al., 2014McMahon et al. 2014). While suicidal intent may or may not be involved, the most frequent motives for selfharm are intrapersonal -e.g. affect regulation, self-punishment (Klonsky, 2009) or interpersonal -e.g. appeal to others (Scoliers et al., 2009; Hjelmeland et al., 2002). Self-harm is frequently repeated (Hawton et al., 2002;Hawton, Bergen, Kapur, Cooper, Steeg et al., 2012) and often done in secret (Madge et al., 2008). While self-harm in young people often ceases by late adolescence or early adulthood (Moran et al., 2012) it can be a precursor of specific mental health problems (Mars et al., 2014). It also carries a significant risk of suicide .Previous qualitative research has explored the needs, perspectives and responses of parents to their children's self-harm (Byrne, Morgan, Fitzpatrick et al., 2008., Oldershaw et al., 2008Raphael, Clarke & Kumar, 2006). These studies found that parents were deeply distressed by self-harm and that they struggled to understand and cope with it. They often felt helpless and worried about future incidents of self-harm. Their anxieties were increased by feeling that they lacked the parenting skills to respond appropriately, in some cases, and that they did not always rece...

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Section: Discussionmentioning

confidence: 99%

Making Sense of an Unknown Terrain

et al. 2016

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“…However, multiple lines of research point to genetic influences. Twin and adoption studies have been consistent with a significant genetic component to suicide, with a higher risk present in monozygotic twins than in dizygotic twins, [13][14][15][16] and higher risk of suicide evident in biological relatives than a proband's adoptive family. [10][11][12] Analyses of family pedigree data have identified families possessing an increased risk of suicide, with visualization of effects conferred across generations.…”

Section: Introductionmentioning

confidence: 91%

Genome-wide association study of suicide death and polygenic prediction of clinical antecedents

Docherty

Shabalin

Anderson

et al. 2017

Preprint

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Background: Heritability of suicide risk is estimated at 43%, thus genetic risk likely plays an important role in completion of suicide. Previous genetic research has focused primarily on suicidal behavior or ideation rather than actual completed suicide. And previous genome-wide association studies of completion of suicide have been very small due to the difficulty in obtaining suicide sample data, and have been unable to identify genome-wide significant variants, likely due to power limitations. This study presents results from the first wave of a large Utah sample of completed suicides, and represent the most statistically powerful sample of completed suicide to date. Methods: Tissue samples from 1321 decedents were collected via partnership with the Utah Office of the Medical Examiner and genotyped using the Illumina Infinium PsychArray platform. Bioconductor package RaMWAS (A.S.) was used on post-QC hard call data (271,894 common variants) to conduct GWAS. Because the sample is from Utah, the authors were able to conduct a relatively direct comparison with 1000 Genomes controls also from Utah (CEU), as well as European controls (EUR). The first GWAS with Utah CEU controls (n of only 99) was followed by a second GWAS with EUR controls (n = 503) with and without CEU included in the control sample. Results: Analyses identified 8 SNPs in 6 genes associated with the completion of suicide. Six SNPs met genome-wide significance. Two of these variant hits were replicated using EUR controls not including the CEU sample, though the case sample was the same in both analyses. Subsequent QC steps (linkage disequilibrium analysis and EUR GWAS replication) further substantiated significant results implicating cytochrome P450 genes. Conclusions: This GWAS and partial replication of findings across control samples, using hard call genotype data, represents a significant step toward understanding the genetic architecture of suicide. These are late-breaking results, and in January this group will follow up with analyses using the full 2 waves (N = 4800 cases), a larger control group, and imputed data to ~11 million variants. Analyses to date implicate cytochrome P450 sites involved in metabolism of arachidonic acid and related inflammatory mediators. Results implicate inflammation in suicide risk, and add to a growing body of evidence that lung function may be tied to suicide.

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“…Genetic studies, as adoption (Petersen et al, 2013) or twin studies (Voracek and Loibl, 2007), have shown the role of genetics in suicidal behavior, independently from the environment and from mood disorders (Brent and Mann, 2006). Among the different pathways involved in depression and suicidal behavior, the neurotrophin pathway, also known as BDNF/NTRK2 pathway, is a major one to consider.…”

Section: Introductionmentioning

confidence: 99%

Neurotrophin Genes and Antidepressant-Worsening Suicidal Ideation: A Prospective Case-Control Study

Voegeli

Ramoz

Shekhtman

et al. 2016

IJNPPY

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Background:Antidepressant-worsening suicidal ideation is a rare but serious phenomenon. This study aimed to test for association between antidepressant-worsening suicidal ideation and polymorphisms of BDNF/NTRK2 neurotrophin pathway genes, known to be involved in depression and suicide.Methods:This was a case-control study comparing patients with antidepressant-worsening suicidal ideation to patients without. Patients were collected from the GENESE cohort (3771 depressed tianeptine-treated outpatients). Antidepressant-worsening suicidal ideation was defined by an increase of at least 2 points on the Montgomery-Åsberg Depression Rating Scale-item10 during treatment. Controls were matched for age, sex, and baseline Montgomery-Åsberg Depression Rating Scale-item10 score. Thirteen single nucleotide polymorphisms covering 5 BDNF/NTRK2 pathway genes were genotyped.Results:A total 78 cases and 312 controls were included. Two NTRK2 single nucleotide polymorphisms were associated to antidepressant-worsening suicidal ideation: rs1439050 (P=.01) and rs1867283 (P=.04). Association with rs1439050 remained significant after adjustment for potentially confounding factors, including previous suicide attempts (P<.01).Conclusions:This naturalistic prospective study is consistent with previous studies on highlighting the potential role of the neurotrophin pathway, and especially of NTRK2, in antidepressant-worsening suicidal ideation.

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Genetic and Familial Environmental Effects on Suicide – An Adoption Study of Siblings

Cited by 17 publications

References 25 publications

Making Sense of an Unknown Terrain

Making Sense of an Unknown Terrain

Genome-wide association study of suicide death and polygenic prediction of clinical antecedents

Neurotrophin Genes and Antidepressant-Worsening Suicidal Ideation: A Prospective Case-Control Study

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