Perception of social inclusion/exclusion and response inhibition in adolescents with past suicide attempt: a multidomain task-based fMRI study.

The occurrence of suicidal behaviors increases during adolescence. Hypersensitivity to negative social signals and deficits in cognitive control are putative mechanisms of suicidal behaviors, which necessitate confirmation in youths. Multidomain functional neuroimaging could enhance the identification of patients at suicidal risk beyond standard clinical measures. Three groups of adolescents (N = 96; 78% females, age = 11.6-18.1) were included: patients with depressive disorders and previous suicide attempts (SA, n = 29); patient controls with depressive disorders but without any suicide attempt history (PC, n = 35); and healthy controls (HC, n = 32). We scanned participants with 3T-MRI during social inclusion/exclusion (Cyberball Game) and response inhibition (Go-NoGo) tasks. Neural activation was indexed by the blood-oxygenation-level dependent (BOLD) of the hemodynamic response during three conditions in the Cyberball Game ("Control condition", "Social Inclusion", and "Social Exclusion"), and two conditions in Go-NoGo task ("Go" and "NoGo" blocks). ANCOVA-style analysis identified group effects across three whole-brain contrasts: 1) NoGo vs. Go, 2) Social inclusion vs. control condition, 3) Social exclusion vs. control condition. We found that SA had lower activation in the left insula during social inclusion vs. control condition compared to PC and HC. Moreover, SA compared to PC had higher activity in the right middle prefrontal gyrus during social exclusion vs. control condition, and in bilateral precentral gyri during NoGo vs. Go conditions. Task-related behavioral and self-report measures (Self-reported emotional reactivity in the Cyberball Game, response times and number of errors in the Go-NoGo Task) did not discriminate groups. In conclusion, adolescent suicidal behaviors are likely associated with neural alterations related to the processing of social perception and response inhibition. Further research, involving prospective designs and diverse cohorts of patients, is necessary to explore the potential of neuroimaging as a tool in understanding the emergence and progression of suicidal behaviors.

Short-term effects of a simulation-based training program on suicide risk assessment and intervention for first-year psychiatry residents.

OBJECTIVES: Adequate training of mental health professionals in suicide risk assessment and intervention is crucial. Simulation-based education is a relevant method to acquire competences for challenging health interventions. Here, we aimed to evaluate the effects of a simulation-based training program on first-year psychiatry residents' skills, knowledge, attitudes and satisfaction. METHODS: We conducted pre- and immediately post-training assessments in 153 psychiatry residents during their first or second postgraduate semester in Paris, France, in 2020 and 2021. The simulation-based training occurred a few weeks after a two-hour theoretical lecture on suicidal behaviors. It consisted of a full-day training of small groups (n=5 to 9) with six scenarios played by professional actors and facilitated by two trained psychiatrists, and a 45-60minute debriefing session after each simulation. Educational objectives focused on basic aspects of patient-psychiatrist relation, the investigation of suicidal ideation, and basic interventions in various contexts (outpatient consultation, emergency room, telephone) and patient profiles. Outcome measures included the Suicide Intervention Response Inventory (SIRI-2), a short questionnaire on basic knowledge, a self-confidence four-item scale, and a satisfaction questionnaire. RESULTS: There were significant improvements in skills, basic knowledge, and self-confidence from pre- to post-training. Trainees also expressed a high level of satisfaction, an appreciation for this innovative pedagogy and a wish for more similar training. CONCLUSIONS: This practical training program based on simulation improved self-confidence, knowledge and skills in suicide risk assessment and intervention in the short-term among first year psychiatry residents. Results from this study are therefore promising. Longitudinal studies are, however, needed to evaluate the persistence of changes over time, positive changes in care in real settings and health benefits for patients. In a time of easily accessible and rapidly growing factual medical knowledge, of necessary need for skilled professionals and of growing demand in mental health care, the development of simulation training in psychiatry should be a pedagogical and a public health priority.

[Ketamine and suicidal behavior: Contribution of animal models of aggression-impulsivity to understanding its mechanism of action]. / Kétamine et suicidalité : modèles animaux pour comprendre son mécanisme d'action.

More than two-thirds of suicides occur during a major depressive episode. Acting out prevention measures and therapeutic options to manage the suicidal crisis are limited. The impulsive-aggressive dimensions are vulnerability factors associated with suicide in patients suffering from a characterized depressive episode: this can be a dimension involved in animals. Impulsive and aggressive rodent models can help analyze, at least in part, the neurobiology of suicide and the beneficial effects of treatments. Ketamine, a glutamatergic antagonist, by rapidly improving the symptoms of depressive episodes, would help reduce suicidal thoughts in the short term. Animal models share with humans impulsive and aggressive endophenotypes modulated by the serotonergic system (5-HTB receptor, MAO-A enzyme), neuroinflammation or the hypothalamic-pituitary-adrenal axis and stress. Significant effects of ketamine on these endophenotypes remain to be demonstrated.

Structural brain alterations associated with suicidal thoughts and behaviors in young people: results from 21 international studies from the ENIGMA Suicidal Thoughts and Behaviours consortium.

Identifying brain alterations associated with suicidal thoughts and behaviors (STBs) in young people is critical to understanding their development and improving early intervention and prevention. The ENIGMA Suicidal Thoughts and Behaviours (ENIGMA-STB) consortium analyzed neuroimaging data harmonized across sites to examine brain morphology associated with STBs in youth. We performed analyses in three separate stages, in samples ranging from most to least homogeneous in terms of suicide assessment instrument and mental disorder. First, in a sample of 577 young people with mood disorders, in which STBs were assessed with the Columbia Suicide Severity Rating Scale (C-SSRS). Second, in a sample of young people with mood disorders, in which STB were assessed using different instruments, MRI metrics were compared among healthy controls without STBs (HC; N = 519), clinical controls with a mood disorder but without STBs (CC; N = 246) and young people with current suicidal ideation (N = 223). In separate analyses, MRI metrics were compared among HCs (N = 253), CCs (N = 217), and suicide attempters (N = 64). Third, in a larger transdiagnostic sample with various assessment instruments (HC = 606; CC = 419; Ideation = 289; HC = 253; CC = 432; Attempt=91). In the homogeneous C-SSRS sample, surface area of the frontal pole was lower in young people with mood disorders and a history of actual suicide attempts (N = 163) than those without a lifetime suicide attempt (N = 323; FDR-p = 0.035, Cohen's d = 0.34). No associations with suicidal ideation were found. When examining more heterogeneous samples, we did not observe significant associations. Lower frontal pole surface area may represent a vulnerability for a (non-interrupted and non-aborted) suicide attempt; however, more research is needed to understand the nature of its relationship to suicide risk.

Risk of suicide attempt and suicide associated with benzodiazepine: A nationwide case crossover study.

BACKGROUND: Previous studies that found an association between benzodiazepines and suicidal behaviours were confounded by indication bias. AIMS: To limit this bias, a case crossover study (CCO) was conducted to estimate the risk of suicide attempt and suicide associated with benzodiazepines. METHOD: Patients ≥16 years, with hospitalised suicide attempt or suicide between 2013 and 2016, and at least one benzodiazepine dispensing within the 120 days before their act were selected in the nationwide French reimbursement healthcare system databases (SNDS). For each patient, frequency of benzodiazepine dispensing was compared between a risk period (days -30 to -1 before the event) and two matched reference periods (days -120 to -91, and -90 to -61). RESULTS: A total of 111,550 individuals who attempted suicide and 12,312 suicide victims were included, of who, respectively, 77,474 and 7958 had recent psychiatric history. Benzodiazepine dispensing appeared higher in the 30-day risk period than in reference ones. The comparison yielded adjusted odds ratios of 1.74 for hospitalised suicide attempt (95% confidence interval 1.69-1.78) and 1.45 for suicide (1.34-1.57) in individuals with recent psychiatric history, and of 2.77 (2.69-2.86) and 1.80 (1.65-1.97) for individuals without. CONCLUSION: This nationwide study supports an association between recent benzodiazepine use and both suicide attempt and suicide. These results strengthen the need for screening for suicidal risk carefully before initiation and during treatment when prescribing benzodiazepines. REGISTRATION NO: EUPAS48070 (http://www.ENCEPP.eu).

Hospitalisation for non-lethal self-harm and premature mortality in the 3 years following adolescent pregnancy: Population-based nationwide cohort study.

OBJECTIVE: To evaluate the risk of non-lethal self-harm and mortality related to adolescent pregnancy. DESIGN: Nationwide population-based retrospective cohort. SETTING: Data were extracted from the French national health data system. POPULATION: We included all adolescents aged 12-18 years with an International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) code for pregnancy in 2013-2014. METHODS: Pregnant adolescents were compared with age-matched non-pregnant adolescents and with first-time pregnant women aged 19-25 years. MAIN OUTCOME MEASURES: Any hospitalisation for non-lethal self-harm and mortality during a 3-year follow-up period. Adjustment variables were age, a history of hospitalisation for physical diseases, psychiatric disorders, self-harm and reimbursed psychotropic drugs. Cox proportional hazards regression models were used. RESULTS: In 2013-2014, 35 449 adolescent pregnancies were recorded in France. After adjustment, pregnant adolescents had an increased risk of subsequent hospitalisation for non-lethal self-harm in comparison with both non-pregnant adolescents (n = 70 898) (1.3% vs 0.2%, HR 3.06, 95% CI 2.57-3.66) and pregnant young women (n = 233 406) (0.5%, HR 2.41, 95% CI 2.14-2.71). Rates of hospitalisation for non-lethal self-harm were lower during pregnancy and higher between 12 and 8 months pre-delivery, 3-7 months postpartum and in the month following abortion. Mortality was significantly higher in pregnant adolescents (0.7‰) versus pregnant young women (0.4‰, HR 1.74, 95% CI 1.12-2.72), but not versus non-pregnant adolescents (0.4‰, HR 1.61, 95% CI 0.92-2.83). CONCLUSIONS: Adolescent pregnancy is associated with an increased risk of hospitalisation for non-lethal self-harm and premature death. Careful psychological evaluation and support should be systematically implemented for adolescents who are pregnant.

Risk of non-fatal self-harm and premature mortality in the three years following hospitalization in adolescents and young adults with an eating disorder: A nationwide population-based study.

INTRODUCTION: Eating disorders (ED) are associated with high rates of suicide attempts and premature mortality. However, data in large samples of adolescents and young adults are limited. This study aims to assess the risk of self-harm and premature mortality in young people hospitalized with an ED. METHODS: Individuals aged 12 to 25 years old hospitalized in 2013-2014 in France with anorexia nervosa and/or bulimia nervosa as a primary or associated diagnosis were identified from French national health records. They were compared to two control groups with no mental disorders, and with any other mental disorder than ED. The main outcomes were any hospitalization for deliberate self-harm and mortality in the 3 years following hospitalization. Logistic regression models were used. RESULTS: This study included 5, 452 patients hospitalized with an ED, 14,967 controls with no mental disorder, and 14,242 controls with a mental disorder other than an ED. During the three-year follow-up, 13.0% were hospitalized for deliberate self-harm (vs. 0.2 and 22.0%, respectively) and 0.8% died (vs. 0.03 and 0.4%). After adjustment, hospitalization with an ED was associated with more self-harm hospitalizations (hazard ratio [HR] = 46.0, 95% confidence interval [32.3-65.3]) and higher all-cause mortality (HR = 12.6 [4.3-37.3]) relative to youths without any mental disorder; less self-harm hospitalizations (HR = 0.5 [0.5-0.6]) but higher mortality (HR = 1.6 [1.0-2.4]) when compared to youths with any other mental disorder. CONCLUSION: Young patients hospitalized with an ED are at high risk of self-harm and premature mortality. It is urgent to evaluate and implement the best strategies for post-discharge care and follow-up. PUBLIC SIGNIFICANCE: We found that the risk of being hospitalized for a suicide attempt is 46 times higher and mortality 13 times higher than the general population in adolescents and young adults during the 3 years following hospitalization with an eating disorder. Eating disorders are also associated with a 1.5 higher risk of premature mortality relative to other mental disorders. This risk is particularly high in the 6 months following hospitalization. It is therefore crucial to implement careful post-discharge follow-up in patients hospitalized for eating disorders.

Trends in psychotropic drug consumption among French military personnel during the COVID-19 epidemic.

BACKGROUND: The coronavirus disease (COVID-19) pandemic may have had significant mental health consequences for military personnel, which is a population already exposed to psychological stress. To assess the potential impact of the COVID-19 pandemic, we analyzed the dispensing of three classes of psychotropic drugs (anxiolytics, hypnotics, and antidepressants) among French military personnel. METHODS: A retrospective analysis was conducted using the individualized medico-administrative data of persons insured by the National Military Social Security Fund from the National Health Data System. All active French military personnel aged 18-64 who received outpatient care and to whom drugs were dispensed between January 1, 2019, and April 30, 2021, were included from the French national health database. Rate ratios of dispensed anxiolytics, hypnotics and antidepressants (based on drug reimbursement) were estimated from negative binomial regressions before and after the start of the COVID-19 pandemic. RESULTS: Three hundred eighty-one thousand seven hundred eleven individuals were included. Overall, 45,148 military personnel were reimbursed for anxiolytics, 10,637 for hypnotics, and 4328 for antidepressants. Drugs were dispensed at a higher rate in 2020 and 2021 than in 2019. There was a notable peak at the beginning of the first lockdown followed by a decrease limited to the duration of the first lockdown. During the first lockdown only, there were temporary phenomena including a brief increase in drug dispensing during the first week followed by a decrease during the rest of lockdown, possibly corresponding to a stocking-up effect. For the study period overall, while there was a significant downward trend in psychotropic drug dispensing before the occurrence of COVID-19 (p < 0.001), the pandemic period was associated with an increase in dispensed anxiolytics (rate ratio, 1.03; 95% CI, 1.02-1.04, p < 0.05), hypnotics (rate ratio, 1.13; 95% CI, 1.11-1.16, p < 0.001) and antidepressants (rate ratio, 1.12; 95% CI, 1.10-1.13, p < 0.001) in the military population. CONCLUSIONS: The COVID-19 pandemic has probably had a significant impact on the mental health of French military personnel, as suggested by the trends in dispensed psychotropic drugs. The implementation of mental health prevention measures should be investigated for this population.

Comorbidity of long COVID and psychiatric disorders after a hospitalisation for COVID-19: a cross-sectional study.

OBJECTIVES: Long COVID is a major public health issue. Whether long COVID is comorbid with psychiatric disorders remains unclear. Here, we investigate the association between long COVID, psychiatric symptoms and psychiatric disorders. DESIGN: Cross-sectional. SETTINGS: Bicêtre Hospital, France, secondary care. PARTICIPANTS: One hundred seventy-seven patients admitted in intensive care unit during acute phase and/or reporting long COVID complaints were assessed 4 months after hospitalisation for an acute COVID. MAIN OUTCOME MEASURES: Eight long COVID complaints were investigated: fatigue, respiratory and cognitive complaints, muscle weakness, pain, headache, paraesthesia and anosmia. The number of complaints, the presence/absence of each COVID-19 complaint as well as lung CT scan abnormalities and objective cognitive impairment) were considered. Self-reported psychiatric symptoms were assessed with questionnaires. Experienced psychiatrists assessed Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-based diagnoses of psychiatric disorders. RESULTS: One hundred and fifteen (65%) patients had at least one long COVID complaint. The number of long COVID complaints was associated with psychiatric symptoms. The number of long COVID complaints was higher in patients with psychiatric disorders (mean (m) (SD)=2.47 (1.30), p<0.05), new-onset psychiatric disorders (m (SD)=2.41 (1.32), p<0.05) and significant suicide risk (m (SD)=2.67 (1.32), p<0.05) than in patients without any psychiatric disorder (m (SD)=1.43 (1.48)). Respiratory complaints were associated with a higher risk of psychiatric disorder and new-onset psychiatric disorder, and cognitive complaints were associated with a higher risk of psychiatric disorder. CONCLUSIONS: Long COVID is associated with psychiatric disorders, new-onset psychiatric disorders and suicide risk. Psychiatric disorders and suicide risk should be systematically assessed in patients with long COVID.

Non-presentation at hospital following a suicide attempt: a national survey.

BACKGROUND: A few previous studies suggest that a large number of individuals do not present at hospital following a suicide attempt, complicating recurrence prevention and prevalence estimation. METHODS: Data were extracted from a regular phone survey in representative samples of the French population aged 18-75 years old. Five surveys between 2000 and 2017 collected data about the occurrence of a previous suicide attempt and subsequent care contacts. A total of 102,729 individuals were surveyed. Among them, 6,500 (6.4%) reported a lifetime history of suicide attempt. RESULTS: Following their last suicide attempt, 39.3% reported they did not present to hospital (53.4% in 18-24 year-olds), with limited changes in rates with time. Risk factors for non-presentation were being male [adjusted odds ratio = 1.3, 95% confidence interval (1.1-1.5)], living with someone [1.2 (1.0-1.4)], being a non-smoker [1.4 (1.2-1.6)], and being younger at time of attempt [0.97 (0.96-0.98) per year]. Of those who did not present to hospital, only 37.7% reported visiting a doctor or a psychiatrist/psychologist after their act v. 67.1% in those who presented to hospital (as a second health contact). In both cases, half disclosed their act to someone else. Prevalence rates of suicide attempts reported in community were 4.6 times higher than those in hospital administrative databases. CONCLUSIONS: This survey at a national level confirmed that a large proportion of individuals does not go to the hospital and does not meet any health care professionals following a suicidal act. Assessment of unmet needs is necessary.

Temporal trends in calls for suicide attempts to poison control centers in France during the COVID-19 pandemic: a nationwide study.

Concerns have been raised about early vs. later impacts of the COVID-19 pandemic on suicidal behavior. However, data remain sparse to date. We investigated all calls for intentional drug or other toxic ingestions to the eight Poison Control Centers in France between 1st January 2018 and 31st May 2022. Data were extracted from the French National Database of Poisonings. Calls during the study period were analyzed using time trends and time series analyses with SARIMA models (based on the first two years). Breakpoints were determined using Chow test. These analyses were performed together with examination of age groups (≤ 11, 12-24, 25-64, ≥ 65 years) and gender effects when possible. Over the studied period, 66,589 calls for suicide attempts were received. Overall, there was a downward trend from 2018, which slowed down in October 2019 and was followed by an increase from November 2020. Number of calls observed during the COVID period were above what was expected. However, important differences were found according to age and gender. The increase in calls from mid-2020 was particularly observed in young females, while middle-aged adults showed a persisting decrease. An increase in older-aged people was observed from mid-2019 and persisted during the pandemic. The pandemic may therefore have exacerbated a pre-existing fragile situation in adolescents and old-aged people. This study emphasizes the rapidly evolving situation regarding suicidal behaviour during the pandemic, the possibility of age and gender differences in impact, and the value of having access to real-time information to monitor suicidal acts.

Effectiveness of simulation in psychiatry for nursing students, nurses and nurse practitioners: A systematic review and meta-analysis.

AIMS: Mental disorders constitute one of the main causes of disease and disability worldwide. While nurses are often at the frontline of mental health care, they have limited access to dedicated psychiatric training opportunities. Simulation training may foster the development of the appropriate competencies required when supporting people with mental disorders. To evaluate the effectiveness of simulation training in psychiatry for nursing students, nurses and nurse practitioners. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Eight electronic databases, trial registries, key journals and reference lists of selected studies were searched from inception to August 20, 2020 without language restriction. REVIEW METHODS: We included randomized and non-randomized controlled studies and single group pre/post studies. Cochrane Risk of Bias tool 2.0 was used for randomized controlled study appraisal, and the Medical Education Research Study Quality instrument was completed for all other studies. Meta-analysis was restricted to randomized controlled studies. The other studies were synthesized narratively. The main outcomes were based on Kirkpatrick levels. RESULTS: A total of 118 studies (6738 participants) were found. Interventions included simulated patients (n = 55), role-plays (n = 40), virtual reality (n = 12), manikins (n = 9) and voice simulations (n = 9). Meta-analyses based on 11 randomized controlled studies found a significant large effect size on skills at immediate post-test for simulation compared with active control; and a small and medium effect size on learners' attitudes for simulation compared with inactive control, at immediate post-test and at three-month follow-up respectively. Three quarters of non-randomized controlled studies and pre/post-tests assessing attitudes and skills showed significant differences, and three quarters of participants in randomized controlled studies and pre/post-tests showed significant differences in behaviours. Among the few studies assessing people with mental health outcomes, almost all reported significant differences. CONCLUSION: These findings support the effectiveness of simulation training in psychiatric nursing throughout professional development grades, despite heterogeneity in methods and simulation interventions.

Brain cortical and subcortical morphology in adolescents with depression and a history of suicide attempt.

Background: Suicidal behaviours are a major source of mortality and morbidity among adolescents. Given the maturational changes that occur in cortical and subcortical structures during adolescence, we tested whether atypical brain structural measurements were associated with a history of suicide attempt. Methods: We assessed 3 groups of adolescents (n = 92; 79% female, mean age 15.9 years, range 11.6-18.1 years): patients with a depressive disorder and a history of suicide attempt (n = 28); patient controls, who had a depressive disorder but no history of suicide attempt (n = 34); and healthy controls (n = 30). We derived regional cortical thickness and surface area, and subcortical volumes, from T1-weighted anatomic MRI scans acquired at 3 T. Results: We found significant group differences in surface area in the prefrontal, temporal and parietal regions, as well as in the volume of several subcortical nuclei (pFDR ≤ 0.05), but not in cortical thickness. Post hoc analyses indicated that morphological alterations primarily differentiated patients with a history of suicide attempt from healthy controls, but not from patient controls. However, patients with a history of suicide attempt exhibited positive correlations between age and cortical thickness in the temporal cortices and right insula, and between age and right putamen volume (i.e., thicker regional cortex and larger subcortical volumes with age). These correlations were negative in both patient controls and healthy controls (i.e., thinner regional cortex and smaller subcortical volumes). Limitations: Sample sizes, cross-sectional findings and psychiatric heterogeneity were limitations of this study. Conclusion: Macroscopic structural differences in several brain regions differentiated adolescents with a history of suicide attempt from healthy controls, but not from patient controls. However, adolescents with a history of suicide attempt may present with atypical maturation of specific cortical and subcortical regions that might contribute to the risk of suicidal behaviour.

Decision-making and cognitive control in adolescent suicidal behaviors: a qualitative systematic review of the literature.

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.

[Clinic of suicidal crisis]. / Clinique de la crise suicidaire.

Nearly 5% of the general population experiences a suicidal crisis every year in France. It is essential for any caregiver to learn to recognize it and intervene appropriately. This crisis most often occurs in a context of stress combined with individual vulnerability factors that causes the individual to lose their balance. The clinical presentation for suicidal crisis vary from one subject to another. It is usually fluctuating and temporary. The subject does not want to die; he wants to stop suffering. The suicidal act is the dreaded but not systematic outcome of the suicidal crisis. Here we will set out the general principles of the assessment of the suicidal crisis.

Association between hospital admission for ketoacidosis and subsequent suicide attempt in young adults with type 1 diabetes.

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.

Simulation in psychiatry for medical doctors: A systematic review and meta-analysis.

CONTEXT: Most medical doctors are likely to work with patients experiencing mental health conditions. However, educational opportunities for medical doctors to achieve professional development in the field of psychiatry are often limited. Simulation training in psychiatry may be a useful tool to foster this development. OBJECTIVES: The purpose of this study was to assess the effectiveness of simulation training in psychiatry for medical students, postgraduate trainees and medical doctors. METHODS: For this systematic review and meta-analysis, we searched eight electronic databases and trial registries up to 31 August 2018. We manually searched key journals and the reference lists of selected studies. We included randomised and non-randomised controlled studies and single group pre- and post-test studies. Our main outcomes were based on Kirkpatrick levels. We included data only from randomised controlled trials (RCTs) using random-effects models. RESULTS: From 46 571 studies identified, we selected 163 studies and combined 27 RCTs. Interventions included simulation by role-play (n = 69), simulated patients (n = 72), virtual reality (n = 22), manikin (n = 5) and voice simulation (n = 2). Meta-analysis found significant differences at immediate post-tests for simulation compared with active and inactive control groups for attitudes (standardised mean difference [SMD] = 0.52, 95% confidence interval [CI] 0.31-0.73 [I2  = 0.0%] and SMD = 0.28, 95% CI 0.04-0.53 [I2  = 52.0%], respectively), skills (SMD = 1.37, 95% CI 0.56-2.18 [I2  = 93.0%] and SMD = 1.49, 95% CI 0.39-2.58 [I2  = 93.0%], respectively), knowledge (SMD = 1.22, 95% CI 0.57-1.88 [I2  = 0.0%] and SMD = 0.72, 95% CI 0.14-1.30 [I2  = 80.0%], respectively), and behaviours (SMD = 1.07, 95% CI 0.49-1.65 [I2  = 68.0%] and SMD = 0.45, 95% CI 0.11-0.79 [I2  = 41.0%], respectively). Significant differences in terms of patient benefit and doctors' behaviours and skills were found at the 3-month follow-up. CONCLUSIONS: Despite heterogeneity in methods and simulation interventions, our findings demonstrate the effectiveness of simulation training in psychiatry training.

Reward systems and cognitions in Major Depressive Disorder.

A lack of motivation and anhedonia represent frequent and pervasive symptoms in depression, although with poor specificity. Historically described as a response bias, reward-related impairments in depression may account for the important aspects of the cognitive impairments associated with diagnosis of major depressive disorder. Reward processing is a broad psychological construct that can be parsed into 3 distinct components known as "reinforcement learning" (learning), "reward responsiveness" (liking), and "motivation to obtain a reward" (wanting). Depressed patients respond hyposensitively to reward and maladaptively to punishment: this pattern is related to a dysfunction in the frontostriatal systems modulated by the monoamine systems; seems to be observed in medicated and unmedicated patients with depression and in healthy individuals with high levels of anhedonia; and could be observed in patients with a history of depression, even when in full remission. Considered to be cognitive impairments, reward-related-impairments may also constitute part of an underlying neurobiological vulnerability to major depressive disorder (MDD). For example, the reward-related impairment is state dependent and, more or less, correlated with symptom severity in some studies but has also been proposed as being trait like, with endophenotype characteristics, possibly contributing to the persistence of the disease or treatment resistance. The 3 core aspects of reward processing have specific neurobiological correlates that involve the ventral and dorsal striatum, lateral habenula, ventral tegmental area, orbitofrontal cortex, anterior cingulate cortex, and ventromedial and dorsolateral prefrontal cortex. These structures underline the important role of the dopaminergic mesolimbic pathway, but glutamate and serotonin could also have an important role, at least in some aspects of reward-related impairments.

Investigation of miR-1202, miR-135a, and miR-16 in Major Depressive Disorder and Antidepressant Response.

Background: Major depressive disorder is a debilitating illness, which is most commonly treated with antidepressant drugs. As the majority of patients do not respond on their first trial, there is great interest in identifying biological factors that indicate the most appropriate treatment for each patient. Studies suggest that microRNA represent excellent biomarkers to predict antidepressant response. Methods: We investigated the expression of miR-1202, miR-135a, and miR-16 in peripheral blood from 2 cohorts of depressed patients who received 8 weeks of antidepressant therapy. Expression was quantified at baseline and after treatment, and its relationship to treatment response and depressive symptoms was assessed. Results: In both cohorts, responders displayed lower baseline miR-1202 levels compared with nonresponders, which increased following treatment. Conclusions: Ultimately, our results support the involvement of microRNA in antidepressant response and suggest that quantification of their levels in peripheral samples represents a valid approach to informing treatment decisions.

Implication of LRRC4C and DPP6 in neurodevelopmental disorders.

We performed whole-genome sequencing on an individual from a family with variable psychiatric phenotypes that had a sensory processing disorder, apraxia, and autism. The proband harbored a maternally inherited balanced translocation (46,XY,t(11;14)(p12;p12)mat) that disrupted LRRC4C, a member of the highly specialized netrin G family of axon guidance molecules. The proband also inherited a paternally derived chromosomal inversion that disrupted DPP6, a potassium channel interacting protein. Copy Number (CN) analysis in 14,077 cases with neurodevelopmental disorders and 8,960 control subjects revealed that 60% of cases with exonic deletions in LRRC4C had a second clinically recognizable syndrome associated with variable clinical phenotypes, including 16p11.2, 1q44, and 2q33.1 CN syndromes, suggesting LRRC4C deletion variants may be modifiers of neurodevelopmental disorders. In vitro, functional assessments modeling patient deletions in LRRC4C suggest a negative regulatory role of these exons found in the untranslated region of LRRC4C, which has a single, terminal coding exon. These data suggest that the proband's autism may be due to the inheritance of disruptions in both DPP6 and LRRC4C, and may highlight the importance of the netrin G family and potassium channel interacting molecules in neurodevelopmental disorders. © 2016 Wiley Periodicals, Inc.