Catherine Genty’s research while affiliated with French National Centre for Scientific Research and other places

Background As mHealth may contribute to suicide prevention, we developed emma, an application using Ecological Momentary Assessment and Intervention (EMA/EMI). Objective This study evaluated emma usage rate and acceptability during the first month and satisfaction after 1 and 6 months of use. Methods Ninety-nine patients at high risk of suicide used emma for 6 months. The acceptability and usage rate of the EMA and EMI modules were monitored during the first month. Satisfaction was assessed by questions in the monthly EMA (Likert scale from 0 to 10) and the Mobile App Rating Scale (MARS; score: 0–5) completed at month 6. After inclusion, three follow-up visits (months 1, 3, and 6) took place. Results Seventy-five patients completed at least one of the proposed EMAs. Completion rates were lower for the daily than weekly EMAs (60 and 82%, respectively). The daily completion rates varied according to the question position in the questionnaire (lower for the last questions, LRT = 604.26, df = 1, p-value < 0.0001). Completion rates for the daily EMA were higher in patients with suicidal ideation and/or depression than in those without. The most used EMI was the emergency call module (n = 12). Many users said that they would recommend this application (mean satisfaction score of 6.92 ± 2.78) and the MARS score at month 6 was relatively high (overall rating: 3.3 ± 0.87). Conclusion Emma can target and involve patients at high risk of suicide. Given the promising users’ satisfaction level, emma could rapidly evolve into a complementary tool for suicide prevention.

Mental health issues, including major depressive disorder, which can lead to suicidal behavior, are considered by the World Health Organization as a major threat to global health. Alterations in neurotransmitter signaling, e.g., serotonin and glutamate, or inflammatory response have been linked to both MDD and suicide. Phosphodiesterase 8A (PDE8A) gene expression is significantly decreased in the temporal cortex of major depressive disorder (MDD) patients. PDE8A specifically hydrolyzes adenosine 3′,5′-cyclic monophosphate (cAMP), which is a key second messenger involved in inflammation, cognition, and chronic antidepressant treatment. Moreover, alterations of RNA editing in PDE8A mRNA has been described in the brain of depressed suicide decedents. Here, we investigated PDE8A A-to-I RNA editing-related modifications in whole blood of depressed patients and suicide attempters compared to age-matched and sex-matched healthy controls. We report significant alterations of RNA editing of PDE8A in the blood of depressed patients and suicide attempters with major depression, for which the suicide attempt took place during the last month before sample collection. The reported RNA editing modifications in whole blood were similar to the changes observed in the brain of suicide decedents. Furthermore, analysis and combinations of different edited isoforms allowed us to discriminate between suicide attempters and control groups. Altogether, our results identify PDE8A as an immune response-related marker whose RNA editing modifications translate from brain to blood, suggesting that monitoring RNA editing in PDE8A in blood samples could help to evaluate depressive state and suicide risk.

Background: The ability to differentiate emotions in social contexts is important for dealing with challenging social situations. Suicide attempters show some difficulties in emotion recognition that may result in hypersensitivity to social stress. However, other studies on the recognition of social complex emotions found that suicide attempters have similar performances as depressed non-attempters. Objectives: To investigate differences in social emotion recognition in patients with current Major Depressive Episode (MDE) with and without history of suicide attempt. Methods: Two hundred and ten patients with MDE were recruited among whom 115 had lifetime history of suicide attempt (suicide attempters, SA) and 95 did not (affective controls, AC). Recognition of complex social emotions was assessed using the Reading the Mind in the Eyes Test (RMET). Emotions were separated in three valence categories: positive, negative, and neutral. Verbal intelligence quotient (IQ) and attention were measured with the National Adult Reading Task (NART) and the d2 test, respectively. Results: Mixed logistic regression models adjusted for sex, lifetime bipolar disorder, verbal IQ and attention showed that the RMET performance for neutral emotions was worse in the SA than AC group (OR = 0.87 [0.75, 0.99]). Furthermore, when violent/serious SA were compared to non-violent/non-serious SA and AC, the RMET neutral valence category showed a trend for group factor (p < 0.059) and RMET scores were lower in the violent/serious SA than AC group (OR = 0.79 [0.64, 0.96]). Conclusion: Recognition of neutral emotions is poor in SA and this may complicate their daily life. Interventions to improve the understanding of complex emotions may be helpful to prevent suicidal risk in patients with depression.

Background Medical students are exposed to an emotionally exhausting training/work environment and to stressful academic demands. Consequently, psychopathologies, burnout and suicidal ideation are frequent in this population. These factors can also affect their empathy and quality of care. Therefore, the development and implementation of programs to promote resilience to stress specifically in medical students and the evaluation of their efficiency are a priority. Here, we describe the protocol of the first French study to assess the long-term effectiveness and acceptability of a mindfulness-based intervention (MBI) compared with relaxation training (RT) to reduce emotional exhaustion in medical students. Methods This multicenter randomized controlled trial (“Must prevent”) plans to enroll 612 students in the fourth and fifth year of medical studies from nine French universities. After inclusion, they will be assigned randomly to the MBI or RT group. Both interventions are structured around an 8-week program that includes one group class per week and daily at-home exercises. The primary endpoint is the emotional exhaustion score assessed with the Maslach Burnout Inventory at month 12 of the follow-up. Secondary endpoints include anxiety-depressive symptomatology, suicidality, psychoactive substance use, depersonalization, psychological and physical pain, empathy, emotional regulation, self-compassion, mindfulness, quality of life, and program acceptability. Evaluations will be done before and immediately after the 8-week intervention, and at month 6 and 12 of the post-intervention follow-up. Discussion If the proposed interventions are well accepted and useful to decrease negative emotions and/or increase wellbeing among medical students, they should be disseminated among this population and even included as part of the training on emotional skills needed for the routine medical practice. Trial registration This trial is registered under the number NCT04026594 (July 18, 2019).

Background: Many suicide risk factors have been identified, but traditional clinical methods do not allow the accurate prediction of suicide behaviors. To face this challenge, we developed emma, an app for Ecological Momentary Assessment/Intervention (EMA/EMI) and prediction of suicide risk in high risk patients.Objective: We wanted to test the feasibility of implementing this mHealth-based suicide risk assessment and prevention tool and its impact in subjects at high risk of suicide in real world conditions.Methods: The EMMA Study is an ongoing longitudinal interventional multicenter trial in which patients at high-risk for suicide (n=100) use emma for 6 months. During this period, they complete four EMA types (daily, weekly, monthly, spontaneous) and may use EMI modules. Participants undergo clinical assessment at month 0, 1, 3 and 6 after inclusion.Results: Among the 43 patients already recruited in the EMMA Study, 14 participants had completed the follow-up. Their data were analyzed to evaluate emma implementation and impact on suicide risk management. EMA completion rates were extremely heterogeneous among the 14 participants with a sharp decrease over time. The completion rates of the weekly EMA (25% to 87.5%) were higher than for the daily EMA (0% to 53.3%). Most patients (n=10/14) answered the EMA questionnaires spontaneously. Similarly, the Safety Plan Modules use was very heterogeneous (2 to 75 times). Specifically, 11 patients used the Call Module (1 to 29 times), designed by our team to help them to get in touch with healthcare professionals and/or relatives during a crisis. All patients used the Breathing Space Module and 8 the Emotion Regulation Module (1 to 46 times). The diversity of patient profiles and use of the EMA and EMI modules proposed by emma was highlighted by three case reports.Conclusions: These preliminary results suggest that it is possible and acceptable to collect longitudinal fine-grained contextualized data (EMA) and to offer personalized intervention (EMI) in real time to people at high risk of suicide. Patients have different clinical and digital profiles and needs that require a highly scalable, interactive and customizable app. To become a complementary tool for suicide prevention, emma should be integrated in the existing emergency procedures.

Suicidal behavior (SB) has been associated with structural and functional impairments in neuroimaging studies and with an increase of peripheral inflammation. We assumed that the increased level of peripheral inflammation markers could be correlated with some abnormalities of brain metabolites in areas involved in suicidal vulnerability such as the anterior and posterior cingulate gyrus cortex (ACC and PCC), the orbito-frontal cortex (OFC) and parietal precuneus cortex (PPC). This hypothesis has been tested by studying the association between levels of 6 cerebral metabolites [i.e. Glutamate (Glu), glutamine (Gln), N-Acetyl aspartate (TNAA), Myo-inositol (Myo)…], 15 biomarkers of inflammation (i.e. C reactive protein (CRP), interleukin (IL) 2, IL1β, IL6, RANTES…) and 8 clinical variables known to be involved in suicidal vulnerability (i.e. depression, childhood trauma, impulsivity, suicidal ideation…). Sixty-six participants were recruited and divided into three groups: 21 depressed patients with a recent SA (< 8 days), 23 affective controls (depressed patients without lifetime history of SA) and 22 healthy controls. Following a clinical assessment, they performed a Proton magnetic resonance spectroscopy to measure the levels of 6 cerebral metabolites (Fig. 1). A blood sample was collected to measure peripheral inflammation. We found a higher level of C reactive protein (CRP) in suicide attempters than in both affective controls and healthy controls. CRP level was negatively correlated with concentrations of Glutamate (R = −0.30 P < 0.01) in the PPC. We found a decrease of TNAA concentration in the ACC and an increase of Myo concentration in the PCC in both suicide attempters and affective controls vs healthy controls. However, this difference remains significant only for affective controls vs healthy controls. In the ACC, Glu concentration was significantly positively correlated with peripheral inflammatory markers (CD40L, IL1b, IL2, IL4, IL6, IL10, IL1a and TNFα) (R > 40% P < 0.001). Finally, we found a negative correlation between Glu concentration and depression severity (R = −0.24562 P = 0.0486). In conclusion, our main result showed a decrease of glutamate level in PPC link to an increase of peripheral CRP level in SA. Those results suggest new tracks of comprehension of physiopathology of SB.

Contexte Bien que les programmes de psychoéducation soient une intervention de référence dans le trouble bipolaire [1], [2], des outils innovants sont nécessaires pour élargir et consolider leurs effets sur l’observance du traitement. Les serious game, dont le but est de délivrer des messages éducatifs lors d’un jeu, sont une option [3]. Méthodes Dans un essai randomisé contrôlé incluant des patients bipolaires euthymiques ayant suivi un programme de psychoéducation, nous avons évalué le pourcentage de patients observants (score à la Medication Adherence Rating Scale, MARS > 7) ayant joué à un serious game BIPOLIFE® pendant un mois (n = 20) versus traitement habituel (n = 21) à 3 mois de la fin de l’intervention. Nous avons aussi évalué les croyances sur les traitements pharmacologiques (selon la Drug Attitude Inventory, DAI), la consommation de soins et l’acceptabilité du jeu BIPOLIFE®. Résultats La variation absolue de la MARS et de la DAI était plus élevée dans le groupe BIPOLIFE® que dans le groupe contrôle immédiatement après l’intervention (p = 0,03 et p = 0,02, respectivement) mais pas 3 mois plus tard (p = 0,22 et p = 0,07, respectivement). Le recours aux soins était comparable entre les groupes. L’acceptabilité était bonne. Conclusion L’utilisation de serious game est une piste pour favoriser l’observance chez certains patients.

Background: Although psychoeducation programmes are the gold-standard intervention in bipolar disorder (BD), more innovative tools are needed to broaden and consolidate their effects, especially on treatment adherence. Serious games could be an option. Methods: We carried out a two-arm open randomized controlled trial to compare the add-on use of the serious game BIPOLIFE® for one month (n = 20) vs. treatment as usual (TAU; n = 21) following the completion of a psychoeducation programme in euthymic adults with BD. The primary outcome was the percentage of adherent patients (i.e., patients with a Medication Adherence Rating Scale, MARS, total score >7) at 4 months after the end of the psychoeducation programme. We also measured the changes in therapeutic adherence and beliefs on pharmacological treatments (Drug Attitude Inventory, DAI) between study inclusion and the 1-month (end of BIPOLIFE® use) and 4-month visits, healthcare use during the study period, and BIPOLIFE® acceptability. Results: The percentage of adherent patients was lower in the BIPOLIFE® group than in the TAU group at inclusion (p = 0.02). Conversely, the absolute variation of the MARS and DAI scores was higher in the BIPOLIFE® than in the TAU group at the 1-month visit (p = 0.03 and p = 0.002, respectively) but not at the 4-month visit (p = 0.22 and p = 0.07, respectively). Limitations: Small sample size, and low frequency of connexion to BIPOLIFE® declared by the patients. Conclusion: BIPOLIFE® may help patients with BD to increase their confidence in medications, if used regularly.

BACKGROUND Many suicide risk factors have been identified, but traditional clinical methods do not allow the accurate prediction of suicide behaviors. To face this challenge, we developed emma, an app for Ecological Momentary Assessment/Intervention (EMA/EMI) and prediction of suicide risk in high risk patients. OBJECTIVE We wanted to test the feasibility of implementing this mHealth-based suicide risk assessment and prevention tool and its impact in subjects at high risk of suicide in real world conditions. METHODS The EMMA Study is an ongoing longitudinal interventional multicenter trial in which patients at high-risk for suicide (n=100) use emma for 6 months. During this period, they complete four EMA types (daily, weekly, monthly, spontaneous) and may use EMI modules. Participants undergo clinical assessment at month 0, 1, 3 and 6 after inclusion. RESULTS Among the 43 patients already recruited in the EMMA Study, 14 participants had completed the follow-up. Their data were analyzed to evaluate emma implementation and impact on suicide risk management. EMA completion rates were extremely heterogeneous among the 14 participants with a sharp decrease over time. The completion rates of the weekly EMA (25% to 87.5%) were higher than for the daily EMA (0% to 53.3%). Most patients (n=10/14) answered the EMA questionnaires spontaneously. Similarly, the Safety Plan Modules use was very heterogeneous (2 to 75 times). Specifically, 11 patients used the Call Module (1 to 29 times), designed by our team to help them to get in touch with healthcare professionals and/or relatives during a crisis. All patients used the Breathing Space Module and 8 the Emotion Regulation Module (1 to 46 times). The diversity of patient profiles and use of the EMA and EMI modules proposed by emma was highlighted by three case reports. CONCLUSIONS These preliminary results suggest that it is possible and acceptable to collect longitudinal fine-grained contextualized data (EMA) and to offer personalized intervention (EMI) in real time to people at high risk of suicide. Patients have different clinical and digital profiles and needs that require a highly scalable, interactive and customizable app. To become a complementary tool for suicide prevention, emma should be integrated in the existing emergency procedures. CLINICALTRIAL ClinicalTrials.gov NCT03410381; https://clinicaltrials.gov/ct2/show/NCT03410381.