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.

Biomarkers of Bipolar Disorder in Late Life: An Evidence-Based Systematic Review.

PURPOSE OF REVIEW: Review the current evidence on biomarkers for bipolar disorder in the older adults. We conducted a systematic search of PubMed MEDLINE, PsycINFO, and Web of Science databases using the MeSH search terms "Biomarkers", "Bipolar Disorder", "Aged" and and "Aged, 80 and over". Studies were included if they met the following criteria: (1) the mean age of the study population was 50 years old or older, (2) the study included patients with bipolar disorder, and (3) the study examined one type of biomarkers or more including genetic, neuroimaging, and biochemical biomarkers. Reviews, case reports, studies not in English and studies for which no full text was available were excluded. A total of 26 papers were included in the final analysis. RECENT FINDINGS: Genomic markers of bipolar disorder in older adults highlighted the implication of serotonin metabolism, while the expression of genes involved in angiogenesis was dysregulated. Peripheral blood markers were mainly related with low grade inflammation, axonal damage, endothelial dysfunction, and the dysregulation of the HPA axis. Neuroanatomical markers reflected a dysfunction of the frontal cortex, a loss of neurones in the anterior cingulate cortex and a reduction of the hippocampal volume (in patients older than 50 years old). While not necessarily limited to older adults, some of them may be useful for differential diagnosis (neurofilaments), disease staging (homocysteine, BDNF) and the monitoring of treatment outcomes (matrix metalloproteinases). Our review provides a comprehensive overview of the current evidence on biomarkers for bipolar disorder in the older adults. The identification of biomarkers may aid in the diagnosis, treatment selection, and monitoring of bipolar disorder in older adults, ultimately leading to improved outcomes for this population. Further research is needed to validate and further explore the potential clinical utility of biomarkers in this population.

The impulsiveness level influences the salivary cortisol response and social stress sensitivity in suicidal patients.

INTRODUCTION: Suicide attempters (SA) are more vulnerable to social stress and show disturbed cortisol response in stressful conditions compared with psychiatric and healthy controls. Recent data suggest that this dysregulation might be related to impulsivity traits. However, little is known about the emotional consequences of social stress in SA exposed to stress. OBJECTIVES: The aim of our study was to evaluate the cortisol and emotional responses to social stress in patients with depression with and without suicide attempt, by taking into account impulsivity traits and depression severity. METHODS: 67 adult women (41 SA and 26 affective controls (AC,i.e. without suicide attempt history)) with lifetime history of major depressive episode were included. Patients performed the Trier Social Stress Test (TSST), a well-validated social stress task. Patients provided seven saliva samples, to measure the cortisol response, and filled in questionnaires to assess psychological pain, positive and negative mood, and anxiety at different time points (from 10 min before to 120 min after the TSST). Moderated regression models were used including suicide attempt history, depression severity, and impulsivity as independent variables and their interactions. RESULTS: In patients with low depression and high impulsivity, salivary cortisol response during the TSST was higher in SA than in AC (p < .001). Psychological pain, negative mood, and anxiety were increased in all patients just after the TSST, followed by a decrease at 120 min. Positive mood recovery was slower in SA, and in patients with high impulsivity and low depression level (p < .001). CONCLUSIONS: Impulsivity traits have an important role in suicidal vulnerability in stress conditions. Impulsivity traits might help to differentiate patients at risk of suicide who are highly sensitive to stress when depression level is low. Higher impulsiveness may increase the sensitivity to emotional distress that translates into inadequate physiological responses.

How Does COVID-19 Affect the Neurobiology of Suicide?

PURPOSE OF REVIEW: The aim of this review was to analyze COVID-19 effect on the biological features of suicidal vulnerability and its interaction with suicide-related biological pathways. We carried out a narrative review of international publications on the interactions of COVID-19 with the biological bases of suicide. RECENT FINDINGS: We hypothesize that SARS-CoV-2 interacts with multiple biological processes that underlie suicidal behavior, such as the renin-angiotensin system, nicotinic receptors, and central and systemic inflammation. Social distancing measures may also worsen subjective or objective social disconnection, thus increasing the risk of suicide. Interestingly, the drugs used to prevent suicide could be promising options to counteract brain damage caused by this coronavirus. SARS-CoV-2 interacts with multiple biological pathways involved in suicide and opens a new window for understanding the suicidal process. The development of suicide prevention treatments in the context of a pandemic may benefit from knowledge on these interactions.

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).

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.

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.

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.

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.