Nadia Chawky

Risk factors for completed suicide in schizophrenia and other chronic psychotic disorders: A case–control study

OBJECTIVE Despite an increased risk for suicide among individuals diagnosed with psychotic disorders, risk factors for completed suicide remain largely unexamined in this population. Using a case-control design, this study aimed to investigate clinical and behavioural risk factors for suicide completion in schizophrenia and other chronic psychotic disorders. METHOD A total of 81 psychotic subjects were examined; of these, 45 died by suicide. Proxy-based interviews with, on average, 2 informants were conducted using the SCID I and II interviews and a series of personality trait assessments. RESULTS Psychotic individuals at risk for suicide are most readily identified by the presence of depressive disorders NOS, moderate to severe psychotic symptoms and a family history of suicidal behaviour. They also exhibited fewer negative symptoms, had more comorbid diagnoses and, contrary to findings in other populations, we found that cluster A and C personality trait symptoms seem to have protective effects against suicide in schizophrenics and other chronic psychotic suicides. CONCLUSIONS Our study suggests that behavioural mediators of suicide risk, such as impulsive-aggressive behaviours, do not play a role in schizophrenic and chronic psychotic suicide. This is contrary to findings in other diagnostic groups, thus implying heterogeneity in predisposing mechanisms involved in suicide.

Patterns of co-morbidity in male suicide completers

BACKGROUND Psychiatric co-morbidity is thought to be an important problem in suicide, but it has been little investigated. This study aims to investigate patterns of co-morbidity in a group of male suicide completers. METHOD One hundred and fifteen male suicide completers from the Greater Montreal Area and 82 matched community controls were assessed using proxy-based diagnostic interviews. Patterns of co-morbidity were investigated using latent class analysis. RESULTS Three subgroups of male suicide completers were identified (L2 = 171.62, df = 2012, P < 0.05). they differed significantly in the amount of co-morbidity (Kruskal-Wallis chi2 = 71.227, df = 2. P < 0.000) and exhibited different diagnostic profiles. Co-morbidity was particularly found in subjects with disorders characterized by impulsive and impulsive-aggressive traits, whereas subjects without those traits had levels of co-morbidity which were not significantly different from those of controls (chi2 = 8.17, df = 4, P = 0.086). CONCLUSIONS Suicide completers can be divided into at least three subgroups according to co-morbidity: a low co-morbidity group, a substance-dependent group and a group exhibiting childhood onset of psychopathology.

TPH and suicidal behavior: a study in suicide completers.

An association between the gene that codes for tryptophan hydroxylase (TPH)—the rate-limiting enzyme in the synthesis of serotonin—and suicidal behavior has been investigated with some detail in samples of living subjects who attempted suicide. In this study, we investigated TPH and suicide completion, the most severe form of suicidal behavior. A relatively large sample of suicide completers (n = 101) was genotyped at three TPH loci (two polymorphisms in the promoter region, A-6526G and G-5806T, and one in intron 7, A218C) and compared to psychiatrically normal living controls (n = 129). Although no significant differences were found between groups for genetic variation at single loci, haplotype analysis revealed that one haplotype (-6526G -5806T 218C) was significantly more frequent among suicide cases than in normal controls (χ2 = 11.30, df = 2, P = 0.0008; OR = 2.0 CI: 1.30–3.6). Further analyses suggested that this haplotype is particularly more frequent among subjects who committed suicide using violent methods. Similar results were observed in recent haplotype analyses in suicide attempters, which found that the equivalent of haplotype -6526G -5806T 218C was more frequent in impulsive attempters (Rotondo et al, Mol Psychiatry 1999; 4: 360–368). Our results replicate in suicide completers previous data observed in suicide attempters. These and other results continue to point to the substantial role that the gene that codes for TPH may play in the neurobiology of suicidal behavior

Life trajectories and burden of adversity: mapping the developmental profiles of suicide mortality.

BACKGROUND Little is known about differential suicide profiles across the life trajectory. This study introduces the life-course method in suicide research with the aim of refining the longitudinal and cumulative assessment of psychosocial factors by quantifying accumulation of burden over time in order to delineate distinctive pathways of completed suicide. METHOD The psychological autopsy method was used to obtain third-party information on consecutive suicides. Life-history calendar analysis served to arrive at an adversity score per 5-year segment that was then cluster-analysed and correlated to define victim profiles. RESULTS Two distinct life trajectories emerged: (1) individuals who experienced childhood traumas, developmental adversity and little protection were more likely to present concurrent psychiatric and Axis II disorders; and (2) individuals who experienced less adversity but seemed more reactive to later major difficulties. CONCLUSIONS The life calendar approach presented here in suicide research adds to the identification of life events, distal and recent, previously associated with suicide. It also quantifies the burden of adversity over the life course, defining two distinct profiles that could benefit from distinct targeted preventive intervention.

Suicide and serotonin: study of variation at seven serotonin receptor genes in suicide completers.

Suicide is an important public health problem, accounting for a significant proportion of total mortality among young people, particularly males. There is growing and consistent evidence suggesting that genetic factors play an important role in the predisposition to suicide. Based on several lines of evidence supporting a reduced serotonergic neurotransmission in subjects who committed suicide, we investigated variation at genes that code for serotonin receptor 1B (5‐HTR1B), 1Dα (5‐HTR1Dα), 1E (5‐HTR1E), 1F (5‐HTR1F), 2C (5‐HTR2C), 5A (5‐HTR5A), and 6 (5‐HTR6) in a total sample of 106 suicide completers and 120 normal controls. No differences were observed in allelic or genotypic distributions between groups for any of the loci investigated. Moreover, further analysis according to suicide method or psychopathology also failed to reveal differences between groups. Our results do not support a substantial role of these serotonergic receptors in suicide completion.

STin2 Variant and Family History of Suicide as Significant Predictors of Suicide Completion in Major Depression

BACKGROUND Suicide is the most serious outcome of major depression, yet not all depressed patients will commit suicide. Genes, along with other factors, might account for this difference. Serotonergic alterations have been observed in suicide and depression and impulsive-aggressive behaviors. Therefore, we aimed to identify predictors of suicide, considering genetic variation at the serotonin transporter (5-HTT) gene. METHODS We investigated the 5-HTT gene-linked polymorphic region (5-HTTLPR) and intron 2 (STin2) variants of this gene and their relationship to behavioral and clinical risk factors for suicide in a sample of depressed suicides (n =106) and depressed control subjects (n =152), diagnosed by means of proxy-based interviews. RESULTS We found a significant association of suicide completion with having at least one copy of the STin2 10 allele [chi(2)(1) = 10.833, p = .002]. No differences were found for the 5-HTTLPR variable number of tandem repeats. After controlling for behavioral and clinical risk factors for suicide, the STin2 variant remained a significant predictor of suicide in major depression when jointly considered with a family history of suicide (odds ratio 5.560, 95% confidence interval 1.057-29.247). CONCLUSIONS The STin2 locus might account, at least in part, for the observed familial aggregation of suicidal behavior. These results should be further explored in families where clustering of suicidal behavior is observed.

Alpha 2A adrenergic receptor gene and suicide

Suicide is a complex trait resulting from the interaction of several predisposing factors, among which genes seem to play an important role. Alterations in the noradrenergic system have been observed in postmortem brain studies of suicide victims when compared to controls. The purpose of this study was to test the hypothesis that genetic variants of the alpha(2A) adrenergic receptor gene are implicated in suicide and/or have a modulatory effect on personality traits that are believed to mediate suicidal behavior. We studied a sample of suicides (N=110) and control subjects (N=130) for genetic variation at four loci, including three in the promoter region (g-1800t, c-1291 g and the g-261a) of the alpha(2A) adrenergic receptor gene, and a potentially functional locus, N251K, which leads to an amino acid change (asparagine to lysine). No significant differences were observed at the promoter loci in terms of allelic or genotypic distribution between suicides and controls. However, analysis of the functional polymorphism N251K revealed that the 251 K allele was only present among suicides, though only three suicide cases had this allele, two of which were homozygous. These results are preliminary. If confirmed, they suggest that variation at the alpha(2A) adrenergic receptor gene may play a role in a small proportion of suicide cases.

Wolfram Syndrome and Suicide: Evidence for a Role of WFS1 in Suicidal and Impulsive Behavior

There is evidence suggesting that subjects affected with the Wolfram syndrome (WFS) and normal carriers present an increased risk of psychiatric disorders, particularly depression and suicidal behavior. We investigated a possible role of the gene involved in WFS (WFS1) in the neurobiology of suicide and the potential modulatory effect on traits associated to suicidal behavior. Genetic variation at WFS1 (H611R, R456H, and I333V) was investigated in 111 suicide victims and 129 normal controls. Possible effects on psychopathology and behavioral traits were investigated in a subsample of suicide cases (N = 31) for whom phenotyping was carried out by means of structured psychiatric interviews and questionnaires adapted for psychological autopsies. We found a significantly higher frequency of the 611R/611R genotype in suicide completers as compared to controls (χ2 = 19.21, df=2, P = 0.001). Suicide completers with this genotype had higher scores on measures of impulsivity (t = −3.15, df = 15.3, P = 0.006); novelty seeking (NS) (t = −3.35, df = 13.8, P = 0.005); and conversely, lower scores of persistence (t = 2.4, df = 16.6, P = 0.028). Scores of impulsivity and NS remained higher in subjects with the associated genotype after adjusting for age, gender, and psychopathology. These results suggest a role for WFS1 in the pathophysiology of impulsive suicide, and are consistent with previous clinical reports suggesting an increased risk of suicidal behavior in WFS homozygotes and heterozygotes. However, these findings are preliminary and should be confirmed in independent samples.

Suicide cases in New Brunswick from April 2002 to May 2003: the importance of better recognizing substance and mood disorder comorbidity.

Objective: To investigate all suicide cases that occurred in New Brunswick in the 14 months spanning April 1, 2002, to May 31, 2003, to determine 6-month and lifetime prevalence rates of psychopathology in the deceased. Method: We used 2 psychological autopsy methods: direct proxy-based interviews and medical chart reviews, together with telephone contacts with informants. Consensus DSM-IV diagnoses were formulated by clinical panels on the basis of the Structured Clinical Interviews I and II for DSM-IV complemented by medical charts. Results: Of the 109 suicide deaths identified by the coroner at the time of the study, we were able to investigate 102. At time of death, 65% of the suicide victims had a mood disorder, 59% had a substance-related disorder, and 42% had concurrent mood and substance-related disorders. The lifetime prevalence of substance-related disorders among these suicide victims was 66%. Finally, 52% of the suicide victims presented with a personality disorder; one-half of these were of the cluster B type. Conclusions: Although treatment of depression has frequently been recognized as the focal point of clinically based suicide-prevention efforts, our results underscore substance-related disorders as a key dimension of completed suicide. Suicide-prevention programs should be designed to address this problem more directly.

Systematic Services Audit of Consecutive Suicides in New Brunswick: The Case for Coordinating Specialist Mental Health and Addiction Services

Objective: To weight the potential of promotion, prevention, and treatment programs to help establish priorities in multipronged suicide prevention strategies. Methods: Psychological autopsy methods served to collect information on consecutive suicides over 14 months in New Brunswick (n = 102). A panel of researchers, clinicians, provincial planners, and consumers reviewed the cases and applied a systematic needs assessment procedure to establish interventions and services received, unmet needs at the individual level, and programmatic and systemic shortcomings. Results: More than two-thirds of the individuals suffered from a depressive disorder and a similar proportion from substance (essentially alcohol) abuse or dependence; one-half also presented a personality disorder. In the last year, more than one-half had been in contact with a mental health services specialist, but less than 5% had contact with addiction services, though one-third had previous contact in their lifetime. In one-third of the cases, service gaps called for greater coordination and integration of mental health specialists and addiction services within the health care system. In one-half of the cases, system needs were found to be unmet for public awareness efforts aimed at encouraging individuals to consult health and social services professionals, and in terms of training efforts geared to improving detection, treatment, and referral for mental illness, substance-related problems, and suicidal behaviour by primary medical, social, and specialist services. Conclusion: This study supports multipronged suicide prevention strategies that should include integrated public promotion, professional development campaigns, and better program coordination. Authorities in New Brunswick have opted to favour the latter strategy component, whose development and application must be evaluated to determine its impact on suicide rates.