The transition from suicidal ideas to a suicide act is an important topic of research for the identification of those patients at risk of acting out. We investigated here whether specific brain ...activity and connectivity measures at rest may be differently associated with suicidal thoughts and behaviors. A large sample of acutely depressed patients with major depressive disorder was recruited in three different centers (Montreal/Canada, Stanford/USA, and Jena/Germany), covering four different phenotypes: patients with a past history of suicide attempt (n = 53), patients with current suicidal ideas but no past history of suicide attempt (n = 40), patients without current suicidal ideation nor past suicide attempts (n = 42), and healthy comparison subjects (n = 107). 3-T resting-state functional magnetic resonance imaging (fMRI) measures of the amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) were obtained and examined in a whole-brain data-driven analysis. Past suicide attempt was associated with a double cortico-subcortical dissociation in ALFF values. Decreased ALFF and DC values mainly in a frontoparietal network and increased ALFF values in some subcortical regions (hippocampus and thalamus) distinguished suicide attempters from suicide ideators, patient controls, and healthy controls. No clear neural differences were identified in relation to suicidal ideas. Suicide attempters appear to be a distinct subgroup of patients with widespread brain alterations in functional activity and connectivity that could represent factors of vulnerability. Our results also indirectly support at the neurobiological level the relevance of the transition model described at the psychological and clinical levels. The brain bases of suicidal ideas occurrence in depressed individuals needs further investigations.
Finasteride, a 5α-reductase inhibitor used in benign prostatic hyperplasia and androgenetic alopecia, has been associated with an increased suicidal risk, whereas it is unclear whether such risk is ...similar to that for another 5α-reductase inhibitor, dutasteride. We aimed to assess the risk of suicidal behaviours with finasteride relative to dutasteride. A nationwide cohort study was conducted using the French National Health Data System (SNDS). Men aged 50 years or older initiating finasteride 5 mg or dutasteride 0.5 mg in France between 01-01-2012 and 30-06-2016 were included and followed until outcome (suicide death identified from death certificate or self-harm hospitalisation), treatment discontinuation or switch, death, or 31-12-2016. Self-harm by violent means or resulting in admission to an intensive care unit were also examined. Cox proportional hazards models controlled for age and psychiatric and non-psychiatric conditions by inverse probability of treatment weighting (IPTW). Analyses were stratified according to psychiatric history. The study compared 69,786 finasteride new users to 217,577 dutasteride new users (median age: 72.0 years Q1-Q3 = 64.5-80.2 vs. 71.1 Q1-Q3 = 65.0-79.2). During follow-up, 18 suicide deaths (0.57/1000 person-years) and 34 self-harm hospitalisations (1.08/1000) occurred among finasteride users versus 47 deaths (0.43/1000) and 87 hospitalisations (0.79/1000) among dutasteride users. Overall, finasteride was not associated with an increased risk of any suicidal outcome (IPTW-adjusted Hazard Ratio = 1.21 95% Confidence Interval .87-1.67), suicide death or self-harm hospitalisation. However, among individuals with a history of mood disorders, finasteride was associated with an increased risk of any suicidal outcome (25 versus 46 events; HR = 1.64 95% CI 1.00-2.68), suicide death (8 versus 10 events; HR = 2.71 95% CI 1.07-6.91), self-harm by violent means (6 versus 6 events; HR = 3.11 95% CI 1.01-9.61), and self-harm with admission to an intensive care unit (7 versus 5 events; HR = 3.97 95% CI 1.26-12.5). None of these risks was significantly increased among individuals without a psychiatric history. These findings do not support an increased risk of suicide with finasteride used in the treatment of benign prostatic hyperplasia. However, an increased risk cannot be excluded among men with a history of mood disorder, but this result based on a limited number of events should be interpreted with caution.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Suicide and suicidal behaviors represent a leading cause of morbidity and mortality during adolescence. While several lines of evidence suggest that suicidal behaviors are associated with risky ...decisions and deficient cognitive control in laboratory tasks in adults, comparatively less is known about adolescents. Here, we systematically reviewed the literature on the association between these neurocognitive variables and adolescent suicidal behaviors. The online search strategy identified 17 neurocognitive studies examining either cognitive control or decision-making processes in adolescents with past suicidal behaviors. Several studies have reported that adolescents with a history of suicidal behaviors present neuropsychological differences in the cognitive control (using Go/NoGo, suicide Stroop Test, continuous performance test, suicide/death Implicit Association Test), and decision-making (Iowa Gambling Task, Cambridge Gambling Task, cost computation, delay discounting, loss aversion tasks) domains. Due to a lack of replication or conflicting findings, our systematic review suggests that no firm conclusion can be drawn as to whether altered decision-making or poor cognitive control contribute to adolescent suicidal behaviors. However, these results collectively suggest that further research is warranted. Limitations included scarcity of longitudinal studies and a lack of homogeneity in study designs, which precluded quantitative analysis. We propose remediating ways to continue neuropsychological investigations of suicide risk in adolescence, which could lead to the identification of novel therapeutic targets and predictive markers, enabling early intervention in suicidal youth.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
The mu opioid receptor (MOR) is a G protein-coupled receptor that plays an essential role in reward and hedonic processes, and that has been implicated in disorders such as depression and addiction. ...Over the last decade, several brain imaging studies in depressed patients have consistently found that dysregulation of MOR function occurs in particular in the anterior insular cortex, an important brain site for the perception of internal states and emotional regulation. To investigate molecular mechanisms that may underlie these effects, here we assessed genetic polymorphisms, expression, and functional G-protein coupling of MOR in a large post-mortem cohort (N = 95) composed of depressed individuals who died by suicide, and healthy controls. Results indicated that depression, but not comorbid substance use disorder or acute opiate consumption, was associated with increased MOR activity. This effect was partly explained by a specific increase in expression of the inhibitory alpha G-protein subunit GNAI2. Consistent with previous neuroimaging studies, our findings support the notion that enhanced endogenous opioidergic tone in the anterior insula may buffer negative affective states in depressed individuals, a mechanism that could potentially contribute to the antidepressant efficacy of emerging opioid-based medications.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Objectives. We aimed at reviewing studies exploring dysfunctional cognitive processes, and their neuroanatomical basis, in suicidal behaviour, and to develop a neurocognitive working model. ...Methods. A literature search was conducted. Results. Several limitations were found. The main reported neuropsychological findings are a higher attention to specific negative emotional stimuli, impaired decision-making, lower problem-solving abilities, reduced verbal fluency, and possible reduced non-specific attention and reversal learning in suicide attempters. Neuroimaging studies mainly showed the involvement of ventrolateral orbital, dorsomedial and dorsolateral prefrontal cortices, the anterior cingulate gyrus, and, to a lesser extent, the amygdala. In addition, alterations in white matter connections are suggested. Conclusions. These studies support the concept of alterations in suicidal behaviour distinct from those of comorbid disorders. We propose that a series of neurocognitive dysfunctions, some with trait-like characteristics, may facilitate the development of a suicidal crisis during stressful circumstances: (1) an altered modulation of value attribution, (2) an inadequate regulation of emotional and cognitive responses, and (3) a facilitation of acts in an emotional context. This preliminary model may represent a framework for the design of future studies on the pathophysiology, prediction and prevention of these complex human behaviours.
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IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Suicidal behaviors result from a complex interaction between social stressors and individual vulnerability. However, little is known of the specific neural network supporting the sensitivity to ...social stressors in patients at risk of suicidal acts. Using functional Magnetic Resonance Imaging, we investigated brain processing of social rejection in suicide attempters. Thirty-six euthymic women with a history of depression and suicidal behavior were compared to 41 euthymic women with a history of depression but no suicidal attempt, and 28 healthy controls. The Cyberball Game was used as a validated social exclusion paradigm. Relative to healthy controls, both patient groups reported higher levels of social distress related to the task, without significant differences according to suicidal status. Compared to patients without any history of suicide attempt and healthy controls, suicide attempters showed decreased contrast in the left insula and supramarginal gyrus during the exclusion vs. inclusion condition, after controlling for number of depressive episodes, medication, mood disorder type or social phobia. Our study highlights impaired brain response to social exclusion in euthymic female suicide attempters in regions previously implicated in pain tolerance and social cognition. These findings suggest sustained brain dysfunctions related to social perception in suicide attempters.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background:
More than 2% of the general population experience suicidal ideas each year and a large number of them will attempt suicide. Evidence-based therapeutic options to manage suicidal crisis ...are currently limited.
Objectives:
The aim of this study was to overview the findings on the use of ketamine and esketamine for the treatment of suicidal ideas and acts.
Design:
Systematic review.
Data Sources and methods:
PubMed, article references, and Clinicaltrials.gov up to June 30, 2022. Meta-analyses published within the last 2 years were also reviewed.
Results:
We identified 12 randomized controlled trials with reduction of suicidal ideation as the primary objective and 14 trials as secondary objectives. Intravenous racemic ketamine was superior to control drugs (placebo or midazolam) within the first 72 h, in spite of large placebo effects. Adverse events were minor and transient. In contrast, intranasal esketamine did not differ from placebo in large-scale studies. Limitations, clinical considerations, and opportunities for future research include the following points: large placebo effects when studying suicidal ideation reduction; small concerns about blinding quality due to dissociative effects; no studies on the risk/prevention of suicidal acts and mortality; lack of studies beyond affective disorders; no studies in adolescents and older people; lack of knowledge of long-term side effects, notably liability for abuse; no robust predictive markers; limited understanding of the mechanisms of ketamine on suicidal ideas; need for improved assessment of suicidal ideation in clinical trials; need for studies in outpatient settings, emergency room, and liaison consultation; need for research on ketamine administration; limited knowledge on the positive and negative effects of concomitant treatments.
Conclusion:
Overall, there is compelling evidence for a favorable short-term benefit-risk balance with intravenous racemic ketamine but not intranasal esketamine. The place of ketamine will have to be defined within a multimodal care strategy for suicidal patients. Caution remains necessary for clinical use, and pharmacovigilance will be essential.
Suicidal behavior has been associated with structural and functional impairments in neuroimaging studies, mainly localized in the prefrontal cortex. However, little is known of the in vivo ...biochemical alterations that could be markers of suicidal risk.
Proton magnetic resonance spectroscopy was used to measure at-rest levels of 9 metabolites (glutamate, glutamine, glutathione, GABA, N-acetylaspartate (NAA), N-acetylaspartylglutamate, myo-inositol, aspartate, total choline), in the right dorsal prefrontal cortex of 25 unmedicated depressed patients, including 15 with a history of suicidal behavior, and 33 healthy controls. We compared metabolite levels between groups, and run correlations with 9 clinical variables relevant for suicide risk.
We found very significant associations between NAA levels and psychological pain measured by a simple analog scale (r=−0.47, p<10−3), and between choline levels and current suicidal ideas (r=0.53, p<10−3). These associations were independent from group, gender, age or depression level. While psychological pain and suicidal ideas were highly inter-correlated (r=0.61, p<10−3), the above-mentioned associations with compounds were independent. Mental pain was also correlated with Stroop interference, verbal fluency and (indirectly) decision-making, all cognitive measures previously associated with suicidal risk. Lower NAA levels, and higher glutamine levels were found in suicide attempters and in all patients relative to healthy controls, but these differences did not survive co-variation with age or Bonferroni's correction.
This preliminary study suggests that markers of impaired neuronal and glial functioning in right dorsal prefrontal cortex underlie cardinal symptoms of the suicidal crisis. Targeting this region may be relevant for the short-term suicidal prevention. This study also supports a dimensional perspective in research on suicidal behavior.
•Nine metabolites were measured with spectroscopy in right dorsal prefrontal cortex.•Suicide attempters did not differ from controls after correction.•NAA levels were negatively correlated with psychological pain.•Choline levels were positively correlated with suicidal ideas.•Glial and neuronal impairments may underlie cardinal signs of the suicidal crisis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Aims/hypothesis
The aim of this study was to examine the associations between hospitalisation for diabetic ketoacidosis and subsequent hospitalisation for suicide attempt in young adults with type 1 ...diabetes.
Methods
This nationwide historical cohort study included hospital data on all young people hospitalised in France for type 1 diabetes in 2008. Epidemiological follow-up focused on hospitalisations (medical and psychiatric hospital data) from the index hospitalisation to 2017. Survival analyses were done using a Cox proportional hazards regression model to explore the association between hospitalisation for ketoacidosis and subsequent hospitalisation for a suicide attempt.
Results
In 2008, 16,431 people aged 18–35 years had a hospitalisation mentioning type 1 diabetes. Among them, 1539 (9.4%) had at least one hospitalisation for ketoacidosis between 2008 and 2010. At 9 years, 7.2% of the group hospitalised for ketoacidosis had been hospitalised for a suicide attempt vs only 2.5% in the group not hospitalised for ketoacidosis. The association between hospitalisation for ketoacidosis and suicide attempt decreased over time and was no longer significant after 5 years.
Conclusions/interpretation
We found that young adults admitted to hospital for diabetic ketoacidosis have an increased risk of being admitted to hospital for a subsequent suicide attempt. The risk of a suicide attempt was the highest in the 12 months following the ketoacidosis episode. Our findings support the recommendation that screening for depression and suicide risk should be part of the routine clinical assessment of individuals with type 1 diabetes and ketoacidosis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Impaired Decision Making in Suicide Attempters Jollant, Fabrice; Bellivier, Frank; Leboyer, Marion ...
The American journal of psychiatry,
02/2005, Volume:
162, Issue:
2
Journal Article
Peer reviewed
OBJECTIVE: The understanding of suicidal behavior is incomplete. The stress-diathesis model suggests that a deficit in serotonergic projections to the orbitofrontal cortex is involved in ...susceptibility to suicidal behavior. The orbitofrontal cortex has been implicated in decision making, a cognitive function dealing with complex choices that may be under serotonergic modulation. In this preliminary study, the authors assessed decision making in suicide attempters. METHOD: The authors used the Iowa Gambling Task to investigate patients with a history of violent (N=32) or nonviolent (N=37) suicidal behavior, patients suffering from affective disorders with no history of suicidal behavior (N=25), and healthy comparison subjects (N=82). Patients were assessed when they were not suffering from a current axis I disorder. The authors also assessed the correlation of Iowa Gambling Task performance with psychometric measures of impulsivity, hostility, anger, aggression, and emotional instability. RESULTS: Both groups of suicide attempters scored significantly lower than healthy comparison subjects, and violent suicide attempters performed significantly worse than affective comparison subjects. No significant differences were observed between the groups of suicide attempters or between the two comparison groups. The differences in performance could not be accounted for by age, intellectual ability, educational level, number of suicide attempts, age at first suicide attempt, history of axis I disorder, or medication use. Iowa Gambling Task performances were correlated positively with affective lability and with anger expression but not with impulsivity. CONCLUSIONS: Impaired decision making, possibly due to emotional dysfunction, may be a neuropsychological risk factor for suicidal behavior.
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