Risk and protective genetic variants in suicidal behaviour: association with SLC1A2, SLC1A3, 5-HTR1B &NTRK2 polymorphisms.

BACKGROUND: Suicidal behaviour is known to aggregate in families. Patients with psychiatric disorders are at higher risk for suicide attempts (SA), however protective and risk genetic variants for suicide appear to be independent of underlying psychiatric disorders. Here we investigate genetic variants in genes important for neurobiological pathways linked to suicidal behaviour and/or associated endophenotypes, for association with SA among patients with co-existing psychiatric illness. Selected gene-gene and gene-environment interactions were also tested. METHODS: DNA was obtained from bloods of 159 patients (76 suicide attempters and 83 non-attempters), who were profiled for DSM-IV Axis I psychiatric diagnosis. Twenty-eight single nucleotide polymorphisms (SNPs) from 18 candidate genes (COMT, 5-HT2A, 5-HT1A, 5-HTR1B, TPH1, MAO-A, TPH2, DBH, CNR1, BDNF, ABCG1, GABRA5, GABRG2, GABRB2, SLC1A2, SLC1A3, NTRK2, CRHR1) were genotyped. Genotyping was performed by KBioscience. Tests of association between genetic variants and SA were conducted using Chi squared and Armitage Trend tests. Binary logistical regression analyses were performed to evaluate the contribution of individual genetic variants to the prediction of SA, and to examine SNPs for potential gene-gene and gene-environment interactions. RESULTS: Our analysis identified 4 SNPs (rs4755404, rs2269272, rs6296 and rs1659400), which showed evidence of association with SA compared to a non-attempter control group. We provide evidence of a 3-locus gene-gene interaction, and a putative gene-environment interaction, whereby genetic variation at the NTRK2 locus may moderate the risk associated with history of childhood abuse. CONCLUSION: Preliminary findings suggest that allelic variability in SLC1A2/3, 5-HTR1B and NTRK2 may be relevant to the underlying diathesis for suicidal acts.

Adolescents with suicidal behaviour: attendance at A&E and six month follow-up.

OBJECTIVES: To review the clinical presentation, and Accident and Emergency Department clinical response to 14-20 year olds in suicidal crisis in inner city Dublin and to carry out a six month follow up of these young people. METHOD: A retrospective review of the case notes of all 14-20 year olds who had attended the Mater Hospital A&E department between June 2001 and May 2002 with suicidal behaviour or ideation was carried out in order to establish socio-demographic information, type of suicidal or self-harming behaviour, intervention in the A&E department, and discharge plan. Active outreach attempts were made to trace, contact and interview these young peoples at least six months after the initial presentation. Quantitative measures of psychological functioning at follow-up included the General Health Questionnaire, The Beck Depression Inventory and The Scale for Suicidal Ideation. A qualitative interview covered their recall of the reasons for their deliberate self harm, their view of their current psychological functioning and personal relationships, reported repetition of deliberate self harm, and their views of what type of services would be useful for young people with suicidal ideation or behaviour. RESULTS: A total of 89 young people aged 14-20 years (male: female ratio = 2:3) presented to the Mater A&E department between June 2001 and May 2002 with deliberate self-harm, deliberate self-poisoning and/or suicidal ideation, and accounted for 108 presentations. They showed high levels of psychosocial disadvantage. Almost half had a history of previous contact with mental health services, while the same proportion had a history of previous deliberate self-harm. Drug overdose using paracetamol was the most common method used. Psychiatric assessment was documented in 66% of cases, and documented follow up recommendations were made in 60% of cases. Two thirds of the 89 young people who formed the study population were traced. Half of those contacted agreed to be interviewed and half refused. The majority of those interviewed described themselves as functioning better psychologically than at the time of the index attendance at the A&E department The quantitative measures supported this. One third of those interviewed reported repeated deliberate self-harm since their index attendance, for which most did not seek medical intervention. Many of the young people had clear views about the importance of talking to someone when in crisis. They described a service, which was informal, accessible on a 24-hour basis, and staffed by people with experience of mental health, alcohol and drug related disorders. CONCLUSIONS: This is a particularly vulnerable group of patients from a socio-demographic and mental health perspective. Their attendance at the A&E department provides a unique opportunity for an in-depth psychosocial assessment, which should be recorded in a systematic way to assist clinical audit, facilitate strategic mental health planning and may confer some therapeutic clinical benefit to at risk young people. An easily accessible, active DSH team specifically tailored for young people in the A&E department could provide assessment and short-term follow-up. This is the approach recommended by young people in suicidal crisis, whose views need to be heard.