Risk factors of suicide re-attempt: A two-year prospective study.

BACKGROUND: History of suicide attempt (SA) is the strongest predictor of a new SA and suicide. It is primordial to identify additional risk factors of suicide re-attempt. The aim of this study was to identify risk factors of suicide re-attempt in patients with recent SA followed for 2 years. METHODS: In this multicentric cohort of adult inpatients, the median of the index SA before inclusion was 10 days. Clinicians assessed a large panel of psychological dimensions using validated tools. Occurrence of a new SA or death by suicide during the follow-up was recorded. A cluster analysis was used to identify the dimensions that best characterized the population and a variable "number of personality traits" was created that included the three most representative traits: anxiety, anger, and anxious lability. Risk factors of re-attempt were assessed with adjusted Cox regression models. RESULTS: Among the 379 patients included, 100 (26.4 %) re-attempted suicide and 6 (1.6 %) died by suicide. The two major risk factors of suicide re-attempt were no history of violent SA and presenting two or three personality traits among trait anxiety, anger and anxious lability. LIMITATIONS: It was impossible to know if treatment change during follow-up occur before or after the re-attempt. DISCUSSION: One of the most important predictors of re-attempt in suicide attempters with mood disorders, was the presence of three personality traits (anger, anxiety, and anxious lability). Clinicians should provide close monitoring to patients presenting these traits and proposed treatments specifically targeting these dimensions, especially anxiety.

Polymorphisms of stress pathway genes and emergence of suicidal ideation at antidepressant treatment onset.

The prescription of antidepressant drugs is one of the most frequently used strategies to prevent suicide and suicidal behavior. However, some patients develop suicidal ideation at antidepressant treatment onset, a phenomenon known as treatment-emergent suicidal ideation (TESI). Few studies have explored TESI pharmacogenomics. As the Hypothalamic-Pituitary-Adrenal (HPA) axis might be implicated in suicidal behavior, we assessed the relationship between TESI and single nucleotide polymorphisms (SNPs) in the HPA axis-implicated NR3C1 (n = 7 SNPs), FKBP5 (n = 5 SNPs), AVPR1B (n = 1 SNPs), CRHR1 (n = 1 SNPs), and SKA2 (n = 1 SNPs) genes, in a sample of 3566 adult outpatients with depression for whom an antidepressant treatment was introduced. General practitioners and psychiatrists throughout France followed participants for 6 weeks after the initial prescription of tianeptine, an antidepressant molecule showing mu agonism. Suicidal ideation was assessed with item 10 of the Montgomery-Åsberg Depression Rating Scale (item dedicated to suicidal ideation) at baseline, and at week 2, 4, and 6 of treatment. Within the informative sample, 112 patients reported TESI and 384 did not. TESI was significantly associated with the TT genotype of the SNP rs6902321 in FKBP5 (OR = 1.76, 95% CI = [1.07; 2.90]; p-value = 0.03) and the GG/AG genotype of the SNP rs7208505 in SKA2 (OR = 1.85, 95% CI = [1.03;3.33]; p-value = 0.04). These associations were not significant after multiple test correction. Nevertheless, our results suggest a possible involvement of HPA axis elements in treatment-emergent suicidal ideation (TESI).

Effects of an individualized exercise training program on severity markers of obstructive sleep apnea syndrome: a randomised controlled trial.

OBJECTIVE: Obstructive sleep apnea (OSA) is a high prevalent disorder with severe consequences including sleepiness, metabolic, and cardiovascular disorders. The aim of this study was to assess the effect of an individualized exercise-training (IET) program with educational sessions vs educational sessions alone on severity markers of OSA over an eight-week duration. METHODS: This was a randomised, controlled, parallel-design study. In sum, 64 patients with moderate-to-severe OSA (apnea-hypopnea index AHI 15-45/hour), low physical activity level (Voorrips<9), body-mass index (BMI) <40 kg/m2 were included in intervention group (IG) or control group (CG), and 54 patients finished the study. All underwent polysomnography (PSG), multiple sleep latency test (MSLT), constant workload exercise test, blood samples and fulfilled questionnaires twice. The primary endpoint was the change in apnea-hypopnea (AHI) at eight weeks from baseline. Main secondary endpoints were daytime sleepiness assessed by questionnaire and objective tests. RESULTS: No significant between-group differences were found for changes in AHI. A reduction in AHI was found in IG only (p = 0.005). Compared to CG, exercise training leads to a greater decrease in AHI during REM sleep (p = 0.0004), with a significant increase in mean daytime sleep latency (p = 0.02). Between-group differences were significant for weight reduction, severity of fatigue, insomnia and depressive symptoms with trend for sleepiness symptoms. CONCLUSIONS: In adult patients with moderate-to-severe OSA, IET did not decrease AHI compared to the control group but improved markers of severity of OSA, in particular AHI in rapid eye movement (REM) sleep and objective daytime sleepiness. Adding personalized exercise training to the management of patients with OSA should be considered. CLINICALTRIALS. GOV IDENTIFIER: NCT01256307.

Natural history of excessive daytime sleepiness: a population-based 5-year longitudinal study.

STUDY OBJECTIVES: To document the rates of persistent, remitted, and intermittent excessive daytime sleepiness (EDS) in a longitudinal 5-year community study of adults and to assess how changes in risk factors over time can predict improvement of daytime sleepiness (DS). METHODS: Participants were recruited in 2007-2008 as part of a population-based epidemiological study implemented in Canada. They completed postal assessments at baseline and at each yearly follow-up. An Epworth Sleepiness Scale total score >10 indicated clinically significant EDS; a 4-point reduction between two consecutive evaluations defined DS improvement. Socio-demographic, lifestyle, health characteristics, and sleep-related measures (e.g. insomnia symptoms, sleep duration, sleep medication) were self-reported at each time point. Cox proportional-hazard models were used to predict EDS and DS remissions over 5 years. RESULTS: Among the 2167 participants, 33% (n = 714) met criteria for EDS at baseline, of whom 33% had persistent EDS, 44% intermittent EDS, and 23% remitted EDS over the follow-up. Furthermore, 61.4% of 2167 initial participants had stable DS, 27.1% sustained DS improvement and 8.5% transient improvement over the follow-up. The main predictors of EDS remission or DS improvement were normal weight, taking less hypnotics, having hypertension, increased nighttime sleep duration, and decreased insomnia, and depressive symptoms. CONCLUSIONS: EDS waxes and wanes over time with frequent periods of remission and is influenced by behavioral characteristics and changes in psychological, metabolic, and nighttime sleep patterns. Targeting these predictors in future interventions is crucial to reduce DS in the general adult population.

Association of symptoms of attention deficit-hyperactivity disorder and impulsive-aggression with severity of suicidal behavior in adult attempters.

Literature emphasizes the relationship between attention deficit-hyperactivity disorder (ADHD) and suicidal behavior (SB). However, the link between ADHD and the severity of SB is yet to be determined. We investigated the association between a probable diagnosis of ADHD and the severity of SB in 539 hospitalized suicide attempters, and determined the role of comorbid psychiatric diagnoses. The severity of SB was defined as the number of suicide attempts, age at first suicide attempt, seriousness and violence of suicide attempts. A diagnosis of probable adult ADHD (probable ADHD) was defined as the presence of both current ADHD symptoms and ADHD symptoms in childhood. We evaluated the combined effect of high impulsive-aggression levels and probable ADHD. Probable ADHD was not associated with early or frequent suicide attempts after adjustment for psychiatric disorders and treatment intake. High levels of impulsive-aggression increased the risk of an early suicide attempt, particularly in patients with ADHD symptoms, and independently of other clinical factors. The association between serious suicide attempts and probable ADHD remained significant after adjustment. Although ADHD is involved in suicidal vulnerability, psychiatric comorbidities and impulsive-aggression appear to largely explain the severity of SB in adult attempters with ADHD symptoms.

Impact of bipolar disorder on eating disorders severity in real-life settings.

BACKGROUND: Comorbidity of bipolar disorder (BD) and eating disorders (ED) is common and increases the course and severity of BD. However, the impact of comorbid BD on the clinical profile of ED patients remains unclear. Most studies have focused on patients primarily assessed for BD and data on patients with a primary diagnosis of ED are sparse. We investigated the association between a dual diagnosis and severity in terms of clinical, neuropsychological dimensions and daily functioning. METHOD: Two hundred and sixty-one patients with ED were consecutively recruited. BD was screened with the MINI and further confirmed in the French expert centre network. The severity of ED symptoms was assessed with the EDE-Q and EDI-2, daily functioning with the FAST. The neurocognitive assessment targeted attention, set-shifting and decision-making. RESULTS: Forty-nine patients screened positive for BD, but diagnosis was confirmed in only thirty patients (11.5% of the cohort). After multiple adjustments, comorbidity was associated with greater severity on the total score and three subscales of the EDE-Q and on four of the ten dimensions of the EDI-2. Comorbid BD was associated with lower daily functioning but not with lower neuropsychological performance. LIMITATIONS: Sample referred to specialist clinics not large enough to authorize an analysis by subtype and cross-sectional evaluation. CONCLUSION: The association between ED and BD increases ED severity for most of these core features. It negatively impacts daily functioning. The results also highlight issues about the validity of screening tools to detect BD in patients with ED.

Polymorphism A118G of opioid receptor mu 1 (OPRM1) is associated with emergence of suicidal ideation at antidepressant onset in a large naturalistic cohort of depressed outpatients.

Antidepressants have been the object of an international controversy for about thirty years. Some patients are inclined to develop suicidal ideation (SI) at antidepressant onset; this phenomenon is known as Treatment Emergent Suicidal Ideation (TESI), and it has conducted regulatory bodies to prompt warnings on antidepressants. Since, few studies have explored the pharmacogenomics of TESI. Given the growing body of evidence connecting the opioidergic system with suicidal behavior (particularly mu opioid receptor (MOR)), we decided to examine the relationship between two genetic polymorphisms (SNPs) in the opioidergic system and TESI in a sample of 3566 adult depressed outpatients. General practitioners and psychiatrists throughout France followed participants for 6 weeks after an initial prescription of tianeptine, an antidepressant treatment with mu agonism. Suicidal ideation was assessed with the item 10 of the Montgomery-Asberg Depression Rating Scale (item dedicated to SI) at baseline, and after 2 weeks, 4 weeks and 6 weeks. We analysed rs1799971 from the OPRM1 gene and rs105660 from the OPRK1 gene. Within the sample, 112 patients reported TESI while 384 did not. We found a significant association between AA genotype of rs1799971 and TESI even after adjustment for potential cofounders (OR = 1.93, 95% CI = [1.07; 3.49]; p-value = 0.03). On the other hand there were no significant association between rs1799971 and rs105560 with worsening of suicidal ideation or lifetime suicide attempts. Nevertheless, our results suggest a possible involvement of opioidergic system in TESI.

Association between baseline pro-inflammatory cytokines and brain activation during social exclusion in patients with vulnerability to suicide and depressive disorder.

BACKGROUND: Neuroimaging studies suggest that social distress and suicidal vulnerability share common cerebral bases. Moreover, increased peripheral inflammatory activity is involved in both social distress and suicidal behavior. OBJECTIVE: To evaluate, in suicidal and non-suicidal individuals, the association between the activation of specific cerebral regions (anterior cingulate, insula and orbitofrontal cortex) during experimental social exclusion and the baseline blood levels of the pro-inflammatory cytokines interleukin-6 (IL-6), interleukin-1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) and of the anti-inflammatory cytokine interleukin-2 (IL-2). METHODS: In total, 101 euthymic women were recruited: 42 suicide attempters (SA), 40 affective controls (AC), and 19 healthy controls (HC). During functional MRI (fMRI), they performed the Cyberball game, a validated social exclusion task. Blood levels of IL-1ß, IL-6, TNF-α and IL-2 were measured prior to fMRI. The activation of insula, orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC) during the explicit social exclusion (ESE) vs social inclusion (INC) conditions of the Cyberball game was analyzed in function of the baseline cytokine levels. RESULTS: IL-1ß was negatively associated with right OFC activation (p = 0.01) in ESE vs. INC, whereas IL-2 was positively associated with activation of the right ACC (p = 0.02), insula (p = 0.002) and OFC (p = 0.004) in ESE vs. INC. These associations remained significant after controlling for group, indicating that they were independent of the suicidal status. CONCLUSION: Baseline IL-1ß and IL-2 blood levels are differentially associated with cerebral activation involved in the perception of social exclusion, independently of suicidal behavior. Our results may help to better understand the role of basal inflammation in social distress and its link with mood disorder pathophysiology.

Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression.

The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations.

Tianeptine is associated with lower risk of suicidal ideation worsening during the first weeks of treatment onset compared with other antidepressants: A naturalistic study.

Worsening of suicidal ideation during the first weeks of antidepressant treatment is a poorly understood phenomenon that prompted regulatory bodies to issue specific warnings. To better understand the causes of this phenomenon, this study compared the risk of suicidal ideation worsening in patients taking different types of antidepressant medications. To this aim, 4017 depressed adult outpatients were followed by general practitioners and psychiatrists throughout France for 6 weeks after prescription of an antidepressant treatment. The main study outcomes were to monitor changes (worsening or improvement) in suicidal ideation between baseline (treatment onset) and the study end (week 6) and to determine the remission rates according to the treatment type. Depression severity was assessed with the patient-administered Hospital Anxiety and Depression Scale and suicidal ideation with the 9-item Montgomery-Asberg Depression Rating Scale and the Hopelessness Scale. Use of tianeptine, a mu-opioid receptor agonist was significantly associated with a lower risk of suicidal ideation worsening compared with other antidepressants in the first 6 weeks of treatment. Conversely, remission rates were not significantly affected by the treatment type. Our results highlight a potential interest of opioid agonists to reduce the risk of worsening of suicidal ideation at antidepressant initiation.

Incidence, worsening and risk factors of daytime sleepiness in a population-based 5-year longitudinal study.

Excessive daytime sleepiness (EDS) is highly prevalent in the general population; however little is known about its evolution and predictors. Our objectives were to document its natural history, provide estimates of its prevalence, incidence and persistence rates, and to identify predictors of increased daytime sleepiness (DS) in a longitudinal community study of 2157 adults over 5 years. Participants completed postal assessment at baseline and at each yearly follow-up. DS was evaluated by the Epworth Sleepiness scale (ESS). At baseline, 33% reported EDS (ESS > 10) with 33% of them reported persistent EDS. Of those without EDS at baseline, 28% developed incident EDS (15% were persistent) and 31% increased DS (augmentation ≥4-points between two consecutive evaluations). Younger age and depression were independent predictors of incident EDS and DS increase while lower coffee consumption, smoking, insomnia, tiredness and chronic pain were associated with incident EDS, and living alone with DS increase only. Persistent vs transient EDS or DS showed association with poor general health including metabolic diseases. Thus, sleepiness fluctuated over time and it was predicted by common lifestyle and psychological factors potentially modifiable. However, persistent sleepiness was associated with chronic medical diseases thus highlighting a homogeneous group at risk requiring a dedicated management.

Affect lability predicts occurrence of suicidal ideation in bipolar patients: a two-year prospective study.

OBJECTIVE: The aim of our study was to investigate, in bipolar patients, whether affect lability was associated with suicidal ideation incidence during 2-year follow-up, and which subtype of affect lability was associated with suicidal ideation. METHOD: A total of 319 euthymic or mildly depressed bipolar outpatients recruited in the French FondaMental Advanced Centres of Expertise for Bipolar Disorder were divided into two subgroups according to the occurrence of suicidal ideation during a 2-year follow-up. Affect lability was assessed by the French version of the Affect Lability Scale. RESULTS: Bipolar patients with high affect lability were more likely to report suicidal ideation during follow-up, even after adjustment for age, study level, rapid cycling, current depression level, anxiety disorder, and lifetime history SA (OR = 2.47; 95% CI [1.15-5.30], P = 0.01). The risk of suicidal ideation increased with the level of affect lability. More specifically, the propensity to switch from neutral to elation affect, from anxious to depressive affect (or inversely), and from neutral to anger affect predicted suicidal ideation. CONCLUSION: Reducing affective lability could become a new therapeutic target of suicidal prevention in bipolar disorder.

Associations between adverse childhood experiences and clinical characteristics of eating disorders.

Patients with eating disorders (EDs) frequently report a history of childhood trauma (CT). We investigated whether certain subtypes of CT are associated with more severe features of EDs, independently of psychiatric comorbidity, and whether they act additively. One hundred and ninety-two patients with DSM-V-defined EDs were consecutively recruited. Five clinical characteristics were assessed: restraint, eating, shape and weight concerns on the EDE-Q, and daily functioning. CT was assessed by the childhood traumatism questionnaire. The clinical features were associated with at least one CT subtype (emotional, sexual or physical abuse, emotional neglect). Multivariate analyses adjusted for lifetime comorbid psychiatric disorders revealed that emotional abuse independently predicted higher eating, shape and weight concerns and lower daily functioning, whereas sexual and physical abuse independently predicted higher eating concern. A dose-effect relationship characterised the number of CT subtypes and the severity of the clinical features, suggesting a consistent and partly independent association between CT and more severe clinical and functional characteristics in EDs. Emotional abuse seems to have the most specific impact on ED symptoms. Last, not all CT subtypes have the same impact but they do act additively.

Effect of early trauma on the sleep quality of euthymic bipolar patients.

OBJECTIVE: Poor quality of sleep is frequent in euthymic bipolar patients and conveys worse clinical outcomes. We investigated the features of euthymic bipolar patients associated with poor sleep quality, with a focus on the effect of childhood trauma. METHOD: 493 euthymic patients with DSM-IV-defined bipolar disorders were recruited in FondaMental Advanced Centers of Expertize for Bipolar Disorders (FACE-BD) between 2009 and 2014. Clinical variables were recorded. Subjective sleep quality and history of childhood trauma were respectively measured by the Pittsburgh Sleep Quality Index (PSQI) and the Childhood Trauma Questionnaire (CTQ). RESULTS: Poor sleepers were older, less professionally active, had significantly higher anxiety levels, took more anxiolytic drugs and did endorse more suicide attempts and suicidal ideas than good sleepers after adjusting for anxiety levels and age. Emotional abuse was associated with poor sleep quality after adjustment for BMI, age, professional activity, and bipolar disorders (BD) type (OR=1.83; 95% CI [1.30; 3.10]; p=0.02). However, this association was lost after adjustment for anxiety levels, anxiolytic treatment and suicide ideation/attempts. LIMITATIONS: The main limitation was the type of sleep assessment, which only measured the subjective part of sleep complaints. CONCLUSION: A history of emotional abuse might underlie sleep problems in many bipolar patients but anxiety seems to act as a confounding factor in this relationship. New studies are needed to elucidate the role of childhood maltreatment on poor sleep among bipolar patients.

Increased CRP levels may be a trait marker of suicidal attempt.

Suicide is a leading cause of death worldwide. Identifying biomarkers will help enhance our understanding of suicidal pathophysiology and improve its prevention. Therefore, we investigated CRP levels in 600 depressed inpatients: 520 patients had a lifetime history of suicide attempts and 80 patients did not have any history of suicide attempts. For all patients, we assessed socio-demographic features, lifetime Axis I DSM-IV diagnoses, depression intensity, suicidal ideation, characteristics of suicidal history, and history of childhood trauma. The day following admission, fasting blood tests yielded samples collected for the measurement of high sensitivity hs-CRP. CRP levels were associated with a history of suicide attempts. The risk of suicide attempts increased with higher levels of CRP in a dose-response way before and after adjustments for age, gender, chronic diseases, addiction and anxiety comorbidities, antidepressants use, smoking status and sexual abuse. Noteworthy, the association between CRP levels and history of suicide attempts remained significant after having excluded patients with chronic diseases. There was no significant difference in CRP levels between patients who attempted suicide more or less than a week before plasma sampling, and no significant difference in CRP levels was evidenced between high vs low suicidal ideation. In conclusion, this is the first study suggesting that CRP may be a trait marker for suicidal vulnerability by associating CRP levels and a lifetime history of suicide attempts in depressed inpatients. Therefore, determining the inflammatory marker profile of individuals exhibiting suicidal behaviors could be relevant for anticipating behaviors and refining new therapeutic opportunities.

Increased risk of suicide attempt in bipolar patients with severe tobacco dependence.

BACKGROUND: The aim of our study was to investigate, in bipolar patients, the association between tobacco status (use and dependence) and history of suicide attempt, and to assess the possible role of inflammation as a missing link in the association between smoking status and history of suicide attempt. METHODS: A total of 453 adult bipolar out-patients recruited in the French FondaMental Advanced Centres of Expertise for Bipolar Disorder were divided into two subgroups: 274 patients without past history of suicide attempt (non-SA), and 179 patients with a past history of suicide attempt (SA). Tobacco use and dependence, psychiatric and somatic comorbidities, history of childhood abuse, family history of suicide were assessed. Fasting blood tests yielded samples collected for the measurement of high sensitivity (hs-)CRP. RESULTS: The risk of suicide attempt increased with smoking dependence. Notably, bipolar patients with a history of suicide attempt were three times more likely to have severe tobacco dependence, independently of confounding factors. However, we failed to find arguments promoting the hypothesis of inflammatory markers (through hs-CRP measure) in the link between tobacco dependence and suicidal behavior. CONCLUSIONS: We found a significant association between severe tobacco dependence and history of suicide attempt, but not with level of CRP, independently of confusing factors. Longitudinal studies taken into account all these potential confusing factors are needed to confirm our results.

A further assessment of decision-making in anorexia nervosa.

OBJECTIVE: Anorexia nervosa (AN) may be associated with impaired decision-making. Cognitive processes underlying this impairment remain unclear, mainly because previous assessments of this complex cognitive function were completed with a single test. Furthermore, clinical features such as mood status may impact this association. We aim to further explore the hypothesis of altered decision-making in AN. METHOD: Sixty-three adult women with AN and 49 female controls completed a clinical assessment and were assessed by three tasks related to decision-making [Iowa Gambling Task (IGT), Balloon Analogue Risk Task (BART), Probabilistic Reversal Learning Task (PRLT)]. RESULTS: People with AN had poorer performance on the IGT and made less risky choices on the BART, whereas performances were not different on PRLT. Notably, AN patients with a current major depressive disorder showed similar performance to those with no current major depressive disorder. CONCLUSION: These results tend to confirm an impaired decision making-process in people with AN and suggest that various cognitive processes such as inhibition to risk-taking or intolerance of uncertainty may underlie this condition Furthermore, these impairments seem unrelated to the potential co-occurent major depressive disorders.

The additive effect on suicidality of family history of suicidal behavior and early traumatic experiences.

Family history of suicidal behavior and personal history of childhood abuse are reported risk factors for suicide attempts and suicide completion. We aim to quantify the additive effect of family history of suicidal behavior and different subtypes of childhood abuse on suicidal behavior. We examined a sample of 496 suicide attempters, comparing individuals with family history of suicidal behavior and personal history of childhood (physical or sexual) abuse, individuals with family history of suicidal behavior only, individuals with history of early traumatic experiences only, and individuals with none of these two risk factors with regards to suicidal features. An additive effect was found for the age at the first attempt in suicide attempters with both family history of suicidal behavior and either physical or sexual abuse. No significant interactions were found between family history of suicidal behavior and childhood trauma in relation to any characteristics of suicidal behavior. Subjects presenting family history of suicidal behavior and childhood abuse attempt suicide earlier in life than subjects with just one or none of them, particularly if they were sexually abused. Other suicidality indexes were only partially or not associated with this combination of risk factors. A careful assessment of patients with both family history of suicidal behavior and childhood abuse could help to prevent future suicide attempts, particularly in young people.

A combined high CYP2D6-CYP2C19 metabolic capacity is associated with the severity of suicide attempt as measured by objective circumstances.

This study examined, for the first time, whether a high CYP2D6-CYP2C19 metabolic capacity combination increases the likelihood of suicidal intent severity in a large study cohort. Survivors of a suicide attempt (n=587; 86.8% women) were genotyped for CYP2C19 (*2, *17) and CYP2D6 (*3, *4, *4xN, *5, *6, *10, wtxN) genetic variation and evaluated with the Beck Suicide Intent Scale (SIS). Patients with a high CYP2D6-CYP2C19 metabolic capacity showed an increased risk for a severe suicide attempt (P<0.01) as measured by the SIS-objective circumstance subscale (odds ratio (OR)=1.37; 95% confidence interval (CI)=1.05-1.78; P=0.02) after adjusting for confounders (gender, age, level of studies, marital status, mental disorders, tobacco use, family history of suicide, personal history of attempts and violence of the attempt). Importantly, the risk was greater in those without a family history of suicide (OR=1.82; CI=1.19-2.77; P=0.002). Further research is warranted to evaluate whether the observed relationship is mediated by the role of CYP2D6 and CYP2C19 involvement in the endogenous physiology or drug metabolism or both.