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Abstract Background Obsessive-compulsive disorder (OCD) and eating disorders (ED) share common features, including the presence of obsessions and compulsions, and they often co-occur. Additionally, there is a significant comorbidity between ED and childhood traumatic experiences (CTE), as well as between CTE and OCD. Various biological and environmental factors have been proposed to explain the connection between ED, OCD, and CTE. This study explores the link between CTE and the comorbidity of ED and OCD, with the hypothesis that specific types of CTE may increase the risk of developing OCD in individuals with ED. Methods Participants (N = 562) were enrolled at an eating disorder unit in Montpellier, France, between March 2013 and January 2020. The Childhood Trauma Questionnaire (CTQ), Eating Disorder Examination Questionnaire (EDE-Q), and Mini International Neuropsychiatric Interview (MINI) were used to evaluate childhood maltreatment, assess clinical characteristics associated with ED, and categorize participants into two groups: patients with and without OCD. Results Bivariate analysis revealed that patients with comorbid ED and OCD had higher EDE-Q scores (p

Abstract Over 700,000 people die by suicide annually. Collecting longitudinal fine-grained data about at-risk individuals, as they occur in the real world, can enhance our understanding of the temporal dynamics of suicide risk, leading to better identification of those in need of immediate intervention. Self-assessment questionnaires were collected over time from 89 at-risk individuals using the EMMA smartphone application. An artificial intelligence (AI) model was trained to assess current level of suicidal ideation (SI), an early indicator of the suicide risk, and to predict its progression in the following days. A key challenge was the unevenly spaced and incomplete nature of the time series data. To address this, the AI was built on a missing value imputation algorithm. The AI successfully distinguished high SI levels from low SI levels both on the current day (AUC = 0.804, F1 = 0.625, MCC = 0.459) and three days in advance (AUC = 0.769, F1 = 0.576, MCC = 0.386). Besides past SI levels, the most significant questions were related to psychological pain, well-being, agitation, emotional tension, and protective factors such as contacts with relatives and leisure activities. This represents a promising step towards early AI-based suicide risk prediction using a smartphone application.

Abstract Objectives Electroconvulsive therapy (ECT) is one of the most effective treatments in mood disorders, mainly in major depressive episode (MDE) in the context of either unipolar (MDD) or bipolar disorder (BD). However, ECT remains a neglected and underused treatment. Older people are at high risk patients for the development of adverse drug reactions. In this context, we sought to determine the duration of MDEs and the number of lines of treatment before the initiation of ECT in patients aged 65 years or over according to the presence or absence of first-line indications for using ECT from international guidelines. Methods In this multicenter, retrospective study including patients aged 65 years or over with MDEs in MDD or BD who have been treated with ECT for MDEs, data on the duration of MDEs and the number of lines of treatment received before ECT were collected. The reasons for using ECT, specifically first-line indications (suicidality, urgency, presence of catatonic and psychotic features, previous ECT response, patient preference) were recorded. Statistical comparisons between groups used standard statistical tests. Results We identified 335 patients. The mean duration of MDEs before ECT was about 9 months. It was significantly shorter in BD than in MDD- about 7 and 10 months, respectively. The co-occurrence of chronic medical disease increased the duration before ECT in the MDD group. The presence of first-line indications for using ECT from guidelines did not reduce the duration of MDEs before ECT, except where there was a previous response to ECT. The first-line indications reduced the number of lines of treatment before starting ECT. Conclusion Even if ECT seems to be a key treatment in the elderly population due to its efficacity and safety for MDEs, the delay before this treatment is still too long.

Abstract Background With 11,558 deaths and 200,000 suicide attempts in 2019, France is among the European countries most affected. The aim of this study was to determine the costs and burden of suicides and suicide attempts in France (population 67 million). Methods We estimated direct costs, comprising healthcare, as well as post-mortem costs including autopsy, body removal, funeral expenses, police intervention and support groups; indirect costs comprised lost productivity, daily allowances; the burden of disease calculations used a monetary value for death and disability based on incidence data. Data was obtained from the national statistics, health and social care database, registries, global burden of disease, supplemented by expert opinion. We combined top down and bottom up approaches. Results The total costs and burden of suicides and suicide attempts was estimated at €18.5 billion and €5.4 billion, respectively. Direct costs were €566 million and €75 million; indirect costs were €3.8 billion and €3.5 billion; monetary value for death and disability was €14.6 billion and €1.3. The monetary value for death and disability represented 79.1% and 24.8% of total costs for suicide and suicide attempt respectively. Some costs were based upon expert opinion, caregivers’ burden was not counted and pre COVID data only is reported. Conclusions In France, the total cost and burden of suicides and suicide attempts was several billion €, suggesting major potential savings from public health interventions.

Abstract Bipolar disorder (BD) has been associated with premature cellular aging with shortened telomere length (TL) as compared to the general population. We recently identified a subgroup of young individuals with prematurely shortened TL. The aims of the present study were to replicate this observation in a larger sample and analyze the expression levels of genes associated with age or TL in a subsample of these individuals. TL was measured on peripheral blood DNA using quantitative polymerase chain reaction in a sample of 542 individuals with BD and clustering analyses were performed. Gene expression level of 29 genes, associated with aging or with telomere maintenance, was analyzed in RNA samples from a subsample of 129 individuals. Clustering analyses identified a group of young individuals (mean age 29.64 years), with shorter TL. None of the tested clinical variables were significantly associated with this subgroup. Gene expression level analyses showed significant downregulation of MYC, POT1, and CD27 in the prematurely aged young individuals compared to the young individuals with longer TL. After adjustment only POT1 remained significantly differentially expressed between the two groups of young individuals. This study confirms the existence of a subgroup of young individuals with BD with shortened TL. The observed decrease of POT1 expression level suggests a newly described cellular mechanism in individuals with BD, that may contribute to telomere shortening.

BackgroundMajor depressive disorder is one of the leading causes of disability worldwide. Although most international guidelines recommend psychological and psychosocial interventions as first-line treatment for mild to moderate depression, access remains limited in France due to the limited availability of trained clinicians, high costs for patients in the context of nonreimbursement, and the fear of stigmatization. Therefore, online blended psychological treatment such as Deprexis could improve access to care for people with depression. It has several advantages, such as easy accessibility and scalability, and it is supported by evidence. ObjectiveThis study aims to evaluate the real-life acceptability of Deprexis for people with depression in France outside of a reimbursement pathway. MethodsDeprexis Acceptability Study Measure in Real Life (DARE) was designed as a multicenter cross-sectional study in which Deprexis was offered to any patient meeting the inclusion criteria during the fixed inclusion period (June 2022-March 2023). Inclusion criteria were (1) depression, (2) age between 18 and 65 years, (3) sufficient French language skills, and (4) access to the internet with a device to connect to the Deprexis platform. Exclusion criteria were previous or current diagnoses of bipolar disorder, psychotic symptoms, and suicidal thoughts during the current episode. The primary objective was to measure the prospective acceptability of Deprexis, a new digital therapy. Secondary objectives were to examine differences in acceptability according to patient and clinician characteristics and to identify reasons for refusal. All investigators received video-based training on Deprexis before enrollment to ensure that they all had the same level of information and understanding of the program. ResultsA total of 245 patients were eligible (n=159, 64.9% were women and n=138, 56.3% were single). The mean age was 40.7 (SD 14.1) years. A total of 78% (n=191) of the patients had moderate to severe depression (according to the Patient Health Questionnaire-9 [PHQ-9]). More than half of the population had another psychiatric comorbidity (excluding bipolar disorder, psychotic disorders, and suicidal ideation). A total of 33.9% (n=83) of patients accepted the idea of using Deprexis; the main reason for refusal was financial at 83.3% (n=135). Multivariate logistic regression identified factors that might favor the acceptability of Deprexis. Among these, being a couple, being treated with an antidepressant, or having a low severity level favored the acceptance of Deprexis. ConclusionsDARE is the first French study aiming at evaluating the prospective acceptability of digital therapy in the treatment of depression. The main reason for the refusal of Deprexis was financial. DARE will allow better identification of factors influencing acceptability in a natural setting. This study highlights the importance of investigating factors that may be associated with the acceptability of digital interventions, such as marital status, medication use, and severity of depression.

Suicidal behavior and Non-Suicidal Self-Injuries (NSSIs) are a major health problem in the adolescent population. New technologies can contribute to the development of innovative interventions in suicide prevention. Here, we present the SmartCrisis-Teen study protocol. The study consists of a randomized clinical trial which aims to evaluate the effectiveness of a digital safety plan to prevent suicidal behavior and NSSIs in adolescents. This is a multicentric study which will be conducted among the adolescent population, both in clinical and student settings, with a target sample of 1080 participants. The intervention group will receive an Ecological Momentary Intervention (EMI) consisting of a digital safety plan on their mobile phone. All participants will receive their Treatment As Usual (TAU). Participants will be followed for six months, with weekly and monthly telephone visits and face-to-face visits at three and six months. Participants will be assessed using traditional questionnaires as well as Ecological Momentary Assessment (EMA) and Implicit Association Tests (IATs). With this intervention, we expect a reduction in NSSIs through the acquisition of coping strategies and a decrease in suicidal behavior over the course of follow-up. This study provides a novel, scalable digital intervention for preventing suicidal behavior and NSSIs in adolescents, which could contribute to improving adolescent mental health outcomes globally.

Abstract Background Many patients with depression refuse treatment. Moreover, suicide attempters often display low perceived need of treatment and impaired decision-making. These observations raise questions about the capacity to treatment consent in depressed suicide attempters (SA). Methods In patients with current depressive episode (N = 33 SAs and N = 27 non-SAs), consent capacity was evaluated with the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), insight with the Beck Cognitive Insight Scale, and depression severity with the Beck Depression Inventory (BDI). Results The median BDI score in the whole sample (N = 60) was 21 [10;36], and was higher in SAs than non-SAs (27 [11;36] vs. 15 [10:33], p

Abstract Background Considering the recently growing number of potentially traumatic events in Europe, the European Psychiatric Association undertook a study to investigate clinicians’ treatment choices for post-traumatic stress disorder (PTSD). Methods The case-based analysis included 611 participants, who correctly classified the vignette as a case of PTSD, from Central/ Eastern Europe (CEE) (n = 279), Southern Europe (SE) (n = 92), Northern Europe (NE) (n = 92), and Western Europe (WE) (N = 148). Results About 82% woulduse antidepressants (sertraline being the most preferred one). Benzodiazepines and antipsychotics were significantly more frequently recommended by participants from CEE (33 and 4%, respectively), compared to participants from NE (11 and 0%) and SE (9% and 3%). About 52% of clinicians recommended trauma-focused cognitive behavior therapy and 35% psychoeducation, irrespective of their origin. In the latent class analysis, we identified four distinct “profiles” of clinicians. In Class 1 (N = 367), psychiatrists would less often recommend any antidepressants. In Class 2 (N = 51), clinicians would recommend trazodone and prolonged exposure therapy. In Class 3 (N = 65), they propose mirtazapine and eye movement desensitization reprocessing therapy. In Class 4 (N = 128), clinicians propose different types of medications and cognitive processing therapy. About 50.1% of participants in each region stated they do not adhere to recognized treatment guidelines. Conclusions Clinicians’ decisions for PTSD are broadly similar among European psychiatrists, but regional differences suggest the need for more dialogue and education to harmonize practice across Europe and promote the use of guidelines.

Abstract Background Physical pain is a common issue in people with bipolar disorder (BD). It worsens mental health and quality of life, negatively impacts treatment response, and increases the risk of suicide. Lithium, which is prescribed in BD as a mood stabilizer, has shown promising effects on pain. Methods This naturalistic study included 760 subjects with BD ( FACE-BD cohort) divided in two groups: with and without self-reported pain (evaluated with the EQ-5D-5L questionnaire). In this sample, 176 subjects were treated with lithium salts. The objectives of the study were to determine whether patients receiving lithium reported less pain, and whether this effect was associated with the recommended mood-stabilizing blood concentration of lithium. Results Subjects with lithium intake were less likely to report pain (odds ratio [OR] = 0.59, 95% confidence interval [CI], 0.35–0.95; p = 0.036) after controlling for sociodemographic variables, BD type, lifetime history of psychiatric disorders, suicide attempt, personality traits, current depression and anxiety levels, sleep quality, and psychomotor activity. Subjects taking lithium were even less likely to report pain when lithium concentration in blood was ≥0.5 mmol/l (OR = 0.45, 95% CI, 0.24–0.79; p = 0.008). Conclusions This is the first naturalistic study to show lithium’s promising effect on pain in subjects suffering from BD after controlling for many confounding variables. This analgesic effect seems independent of BD severity and comorbid conditions. Randomized controlled trials are needed to confirm the analgesic effect of lithium salts and to determine whether lithium decreases pain in other vulnerable populations.

Abstract The high mortality rate in nursing homes during the COVID-19 pandemic may be linked to psychological disorders in staff. Hence, we assessed the prevalence and associated factors of probable post-traumatic stress disorder (PTSD), anxiety, depression, and burnout of nursing home staff during the COVID-19 pandemic in a cross-sectional study including 66 randomly selected nursing homes in southern France. 537 of the contacted 3 821 nursing home workers (14.0%) responded between April and October 2021. We collected information on center organization, severity of COVID-19 exposure, and socio-demographic information in an online survey. The prevalence of probable PTSD (PCL-5), anxiety and depressive disorders (Hospital Anxiety Depression Scale) and the sub-scores of burnout syndrome (Maslach Burnout Inventory Human Services Survey for Medical Personnel) were assessed. Probable PTSD was reported in 115/537 responders (21.4% (95% CI [18.0%–24.9%])). After adjustment, low-level exposure to COVID-19 in nursing home residents (AOR, 0.5; 95% CI [0.3–0.9]), fear of managing COVID-19 residents (AOR, 3.5; 95% CI [1.9–6.4]), conflicts with residents (AOR, 2.3; 95% CI, [1.2–4.4]), conflicts with colleagues (AOR, 3.6; 95% CI [1.7–8.6]), cancellation of leave (AOR, 4.8; 95% CI [2.0–11.7]) and temporary worker employment (AOR, 3.4; 95% CI [1.7–6.9]) were associated with higher prevalence of probable PTSD. The prevalence of probable anxiety and depression were 28.8% (95% CI [24.9%–32.7%]) and 10.4% (95% CI [7.8%–13.1%]), respectively. Psychological disorders were observed in nearly one third of nursing home workers during the COVID-19 pandemic. Hence, continuous surveys and preventive measures are needed in this particularly at-risk population.

Decision-making styles are a habit-based propensity that drive behavior and affect daily life. Rational and intuitive decision-making styles have been associated with good mental health. However, the underlying mechanisms are not clear. In the last decade, high basal levels of heart rate variability (HRV) have been proposed as an index of health and emotional control, and this could be one of the variables involved in the effects of decision making on health. Therefore, the aim of this study is to analyze the capability of decision-making styles to predict resting HRV. A cross-sectional study was conducted in a sample of 199 (119 women) young university students, and a resting ECG was recorded to extract frequency domain HRV variables. Subsequently, participants completed sociodemographic data and the General Decision-Making Style questionnaire (GDMS). Results showed that the intuitive style predicted high-frequency HRV, while the avoidant style predicted less low-frequency HRV. This study presents new data on the relationship between decision-making style and HRV, suggesting that the intuitive style has a cardioprotective effect, while the avoidant style is related to lower HRV, which has been associated with health vulnerability. In conclusion, this study contributes to the understanding of HRV and its potential as a biomarker for cognitive styles that may improve health.

Background: Patients with major mood disorders are at high risk of suicidal behavior compared to the general population. Suicide is a public health concern, accounting for around 1.2% of deaths worldwide. Understanding its underlying mechanisms may help identify predictive biomarkers and design novel targeted treatments. Immune dysfunctions, in particular affecting the gut-brain axis, are of interest given their dual involvement in mood disorders and suicidal behavior. We thus explored the possible relationships between suicide attempt (SA) and circulating biomarkers of intestinal permeability and systemic inflammation in patients with major depressive disorder (MDD) or bipolar disorder (BD) with and without a history of SA. Method: 137 patients with BD and 168 with MDD were included, and among them, 133 had a history of SA and 172 did not. Among them, 104 were males (34%) and 201 females (66%). Depressive symptoms were evaluated using the Inventory of Depressive Symptomatology clinical scale (IDS-C30). Circulating levels of intestinal fatty acid binding protein (IFABP), calprotectin, apolipoprotein E (ApoE), lipopolysaccharides binding protein (LBP), lipopolysaccharides (LPS), soluble beta-2-microglobulin (B2m), and C-reactive protein (CRP), were determined. Multivariate linear regressions were performed according to the gender status given the proportion of the herein studied male and female individuals and the higher propensity of females to experience SA as compared to males. Results: After adjusting for confounding variables, patients in the SA group had significantly higher CRP, and lower IFABP levels in comparison to the NSA group. Limitations: The unavailability of confounding variables such as dietary habits, should be noted. In addition, the cross-sectional nature of the study hampers the identification of causative effects. Conclusion: Although preliminary, our observations revealed associations between markers of inflammation and intestinal permeability in patients with suicidal behavior warranting further confirmation in larger cohorts.

Since the middle of the 20th century, synthetic sex hormones (estrogens and progestins) have been administered to millions of pregnant or not women worldwide, mainly to avoid miscarriage or for comfort, although their mode of action and their effects on the mother and fetus were ignored. Despite the alerts and the description of somatic and psychiatric disorders in children exposed in utero, synthetic estrogens were prohibited for pregnant women only in the 1970s and 1980s, but some progestins are still authorized. In this review, we summarize the psychiatric disorders described in children exposed in utero to such hormones, focusing particularly on schizophrenia, bipolar disorders, severe depression, eating disorders, suicide and suicide attempts. Moreover, only in 2017 the mechanism of action of these xenohormones has started to be deciphered. Some studies showed that in the fetus exposed in utero, they alter the DNA methylation profile (mainly hypermethylation), and consequently the expression of genes implicated in neurodevelopment and in regulating the sexual organ morphogenesis and also of the promoter of estrogen receptors, located in the amygdala. These deleterious effects may be transmitted also to the next generations, thus affecting the children directly exposed and also the following generations.

Abstract The variability of suicidal thoughts and other clinical factors during follow-up has emerged as a promising phenotype to identify vulnerable patients through Ecological Momentary Assessment (EMA). In this study, we aimed to (1) identify clusters of clinical variability, and (2) examine the features associated with high variability. We studied a set of 275 adult patients treated for a suicidal crisis in the outpatient and emergency psychiatric departments of five clinical centers across Spain and France. Data included a total of 48,489 answers to 32 EMA questions, as well as baseline and follow-up validated data from clinical assessments. A Gaussian Mixture Model (GMM) was used to cluster the patients according to EMA variability during follow-up along six clinical domains. We then used a random forest algorithm to identify the clinical features that can be used to predict the level of variability. The GMM confirmed that suicidal patients are best clustered in two groups with EMA data: low- and high-variability. The high-variability group showed more instability in all dimensions, particularly in social withdrawal, sleep measures, wish to live, and social support. Both clusters were separated by ten clinical features (AUC = 0.74), including depressive symptoms, cognitive instability, the intensity and frequency of passive suicidal ideation, and the occurrence of clinical events, such as suicide attempts or emergency visits during follow-up. Initiatives to follow up suicidal patients with ecological measures should take into account the existence of a high variability cluster, which could be identified before the follow-up begins.

Abstract This study of a cohort of 1-year treatment-compliant survivors of a suicide attempt examined for the first time whether a high CYP2D6-CYP2C19 metabolic capacity (pharmacogenes related to psychopathology, suicide, and attempt severity) and/or polypharmacy treatments predicted repeat suicide attempts, adjusting for sociodemographic and clinical factors as confounders. Of the 461 (63% women) consecutively hospitalized patients who attempted suicide and were evaluated and treated after an index attempt, 191 (67.5% women) attended their 6- and 12-month follow-up sessions. Clinicians were blinded to the activity scores (AS) of their genotypes, which were calculated as the sum of the values assigned to each allele (CYP2C19 *2, *17; CYP2D6 *3, *4, *4xN, *5, *6, *10, wtxN). No differences were found in polypharmacy prescription patterns and the variability of CYP2D6 and CYP2C19 genotypes between adherents and dropouts, but the formers were older, with a higher frequency of anxiety and bipolar disorders and fewer alcohol and substance use disorders. The risk of reattempts was higher for CYP2D6 ultrarapid (AS > 2) metabolizers (β = 0.561, p = 0.005) and violent suicide survivors (β = −0.219, p = 0.042) if the attempt occurred during the first 6-month period, individuals with an increased number of MINI DSM-IV Axis I mental disorders (β = 0.092, p = 0.032) during the second 6-month period and individuals with a combined high CYP2D6-CYP2C19 metabolic capacity (AS > 4) (β = 0.345, p = 0.024) and an increased use of drugs other than antidepressants, anxiolytics-depressants and antipsychotics-lithium (β = 0.088, p = 0.005) in multiple repeaters during both periods. CYP2D6 and CYP2C19 rapid metabolism and polypharmacy treatment for somatic comorbidities must be considered to prevent the severe side effects of short-term multiple suicide reattempts after a previous attempt.

BackgroundSuicide is a major global public health issue that is becoming increasingly common despite preventive efforts. Though current methods for predicting suicide risk are not sufficiently accurate, technological advances provide invaluable tools with which we may evolve toward a personalized, predictive approach. ObjectiveWe aim to predict the short-term (1-week) risk of suicide by identifying changes in behavioral patterns characterized through real-time smartphone monitoring in a cohort of patients with suicidal ideation. MethodsWe recruited 225 patients between February 2018 and March 2020 with a history of suicidal thoughts and behavior as part of the multicenter SmartCrisis study. Throughout 6 months of follow-up, we collected information on the risk of suicide or mental health crises. All participants underwent voluntary passive monitoring using data generated by their own smartphones, including distance walked and steps taken, time spent at home, and app usage. The algorithm constructs daily activity profiles for each patient according to these data and detects changes in the distribution of these profiles over time. Such changes are considered critical periods, and their relationship with suicide-risk events was tested. ResultsDuring follow-up, 18 (8%) participants attempted suicide, and 14 (6.2%) presented to the emergency department for psychiatric care. The behavioral changes identified by the algorithm predicted suicide risk in a time frame of 1 week with an area under the curve of 0.78, indicating good accuracy. ConclusionsWe describe an innovative method to identify mental health crises based on passively collected information from patients’ smartphones. This technology could be applied to homogeneous groups of patients to identify different types of crises.

Abstract Cell-free biosensors are promising tools for medical diagnostics, yet their performance can be affected by matrix effects arising from the sample itself or from external components. Here we systematically evaluate the performance and robustness of cell-free systems in serum, plasma, urine, and saliva using two reporter systems, sfGFP and luciferase. In all cases, clinical samples have a strong inhibitory effect. Of the different inhibitors, only RNase inhibitor mitigated matrix effects. However, we found that the recovery potential of RNase inhibitor was partially muted by interference from glycerol contained in the commercial buffer. We solved this issue by designing a strain producing an RNase inhibitor protein requiring no additional step in extract preparation. Furthermore, our new extract yielded higher reporter levels than previous conditions and tempered interpatient variability associated with matrix effects. This systematic evaluation and improvements of cell-free system robustness unified across many types of clinical samples is a significant step towards developing cell-free diagnostics for a wide range of conditions.

Abstract Background The opioid tramadol is used as analgesic drug, and more recently was also proposed for the management of major depressive disorder. However, growing evidence suggests a link between opioid system dysfunction and suicidal behaviors, raising the question of tramadol use in view of the high addictive and suicidal risk. Here, we present the case of a young adult woman with multiple suicide attempts related to tramadol addiction. Case presentation A 25-year-old woman was admitted for suicide attempt by phlebotomy in the Department of Psychiatric Emergency and Acute Care, Montpellier (France), in March 2020. The suicide attempt occurred 3 days after an abrupt tramadol withdrawal. In 2018, due to spinal disc herniation, she had a first prescription of tramadol to which she became addicted. The patient described an effect on psychological pain and suicidal ideation. However, she had to increase tramadol dose to obtain the desired effects, and for several months her intake was 2 000 mg per day. When she could not obtain tramadol any longer, suicidal ideation and psychological pain increased, leading to the suicide attempt. At the time of a worldwide opioid crisis that contributes to increasing suicidal behaviors, this case raises questions about tramadol prescription (often considered to be less addictive and with lower abuse potential) to individuals at risk of suicide.

Abstract In clinical practice, differentiating Bipolar Disorder (BD) from unipolar depression is a challenge due to the depressive symptoms, which are the core presentations of both disorders. This misdiagnosis during depressive episodes results in a delay in proper treatment and a poor management of their condition. In a first step, using A-to-I RNA editome analysis, we discovered 646 variants (366 genes) differentially edited between depressed patients and healthy volunteers in a discovery cohort of 57 participants. After using stringent criteria and biological pathway analysis, candidate biomarkers from 8 genes were singled out and tested in a validation cohort of 410 participants. Combining the selected biomarkers with a machine learning approach achieved to discriminate depressed patients (n = 267) versus controls (n = 143) with an AUC of 0.930 (CI 95% [0.879–0.982]), a sensitivity of 84.0% and a specificity of 87.1%. In a second step by selecting among the depressed patients those with unipolar depression (n = 160) or BD (n = 95), we identified a combination of 6 biomarkers which allowed a differential diagnosis of bipolar disorder with an AUC of 0.935 and high specificity (Sp = 84.6%) and sensitivity (Se = 90.9%). The association of RNA editing variants modifications with depression subtypes and the use of artificial intelligence allowed developing a new tool to identify, among depressed patients, those suffering from BD. This test will help to reduce the misdiagnosis delay of bipolar patients, leading to an earlier implementation of a proper treatment.

Objectives: The two-fold aim of this study was: (i) to determine the effect s of undernutrition on the myokines in patients with restrictive anorexia nervosa (AN) and (ii) to examine the potential link between myokines and bone parameters. Methods: In this study, 42 young women with restrictive AN and 42 age-matched controls (CON) (mean age, 18.5 ± 4.2 years and 18.6 ± 4.2 years, respectively) were enrolled. aBMD and body composition were determined with DXA. Resting energy expenditure (REEm), a marker of energy status, was indirectly assessed by calorimetry. Bone turnover markers and myokines (follistatin, myostatin and irisin) were concomitantly evaluated. Results: AN patients presented low aBMD at all bone sites. REEm, bone formation markers, myostatin and IGF-1 were significantly lower, whereas t he bone resorption marker and follistatin were higher in AN compared with controls . No difference was observed between groups for irisin levels. When the whole population was studied, among myokines, only myostatin was positively correlated with aBMD at all bone sites. However, multiple regression analyses showed that in the AN group, the independent variables for aBMD were principally amenorrhoea duration, lean tissue mass (LTM) and procollagen type I N-terminal propeptide (PINP). For CON, the independent variables for aBMD were principally LTM, age and PINP. Whatever the group analysed, none of the myokines appeared as explicative independent variables of aBMD. Conclusion: This study demonstrated that despite the altered myokine levels in patients with AN, their direct effect on aBMD loss and bone turnover alte ration seems limited in comparison with other well-known disease-related factors such as oestrogen deprivation.

Depressive disorders represent the largest proportion of mental illnesses, and by 2030, they are expected to be the first cause of disability-adjusted life years [1]. The COVID-19 pandemic exacerbated prevalence and burden of depression and increased the occurrence of depressive symptoms in general population [2]. The urgency of implementing mental health services to address new barriers to care persuaded clinicians to use telemedicine to follow patients and stay in touch with them, and to explore digital therapeutics (DTx) as potential tools for clinical intervention [2]. The combination of antidepressants and psychotherapy is widely recommended for depression by international guidelines [3] but is less frequently applied in real-world practice. Commonly used treatments are pharmacological, but while being effective, some aspects such as adherence to the drug regimen, residual symptoms, resistance, lack of information, and stigma may hinder successful treatment. In case of less severe depression, standalone psychological therapies should be the first-line treatment option [3], but access to trained psychotherapists remains inequitable. DTx are evidence-based therapies driven by software programs to treat or complement treatment of a specific disease. DTx are classified as Medical Devices, and given their therapeutic purpose, they need to be validated through randomized controlled clinical trials, as for drug-based therapies. In the last 10 years, studies of digital interventions have proliferated; these studies demonstrate that digital interventions increase remission rates and lower the severity of depressive symptoms compared with waitlist, treatment as usual, and attention control conditions [4]. Despite the efficacy demonstrated in clinical trials, many of these tools never reach real-life patients; thus, it might be necessary to implement DTx in the public health system to expand access to valid treatment options. In this framework, DTx represent a good opportunity to help people with depression receive optimal psychotherapeutic care [5].

Abstract Background Childhood trauma (CT), depression, and psychological pain are known predictors of suicidal ideation. Recent literature additionally highlights the importance of the attachment system. Methods We aimed to predict suicidal ideation through CT, attachment, and psychological and social pain by using mediation models aiming to predict suicidal ideation through CT (predictor) and attachment (mediator). In the same models, we introduced psychological or social pain as a moderator of the relationship between attachment, CT, and suicidal ideation. We included 161 depressed patients and assessed depression, attachment, CT, suicidal ideation, psychological pain, and social pain. Results We found (1) a complete mediating effect of anxious attachment (a2b2 = 0.0035, CI95% = [0.0010; 0.0069]) on the relationship between CT on suicidal ideation, and (2) a significant complete conditional mediating effect of anxious attachment and psychological pain (index of moderated mediation VAS: 0.0014; CI95% = [0.0002; 0.0032]) but not social pain on the relationship between CT and suicidal ideation. Both models were controlled for history of suicidal attempt, depression severity, and sex. Conclusions Our results suggest a developmental profile of suicidal ideation in mood disorder that is characterized by the presence of CT and insecure attachment, especially anxious attachment, that is sensitive to experiences of psychological pain. Nevertheless, we cannot conclude that avoidantly attached individuals do not present the same mechanism, as they may not disclose those ideas.

Abstract Since the beginning of the COVID-19 pandemic, evidence shows the negative psychological impact of lockdown measures in the general population. It is also important to identify predictors of psychological distress in vulnerable people, particularly patients with history of depressive episodes (the most prevalent psychiatric disorder), in order to adapt mental health strategies for future lockdown measures. This study aim was to (1) compare in 69 healthy controls (HC) and 346 patients with a major depressive episode in the two previous years (PP) self-reported psychological symptoms (depression, anxiety, insomnia, suicidal ideation, traumatic stress, anger) and living conditions during the first national French lockdown, and (2) identify predictors of significant psychological distress in PP. The levels of psychological symptoms were very low in HC compared with PP, independently of the living conditions. Half of PP had no psychiatric contact during the lockdown. Loneliness and boredom were independent predictors of depression, anxiety and insomnia, whereas daily physical activity was a protective factor. Virtual contacts protected against suicidal ideation. Our results highlight the need of specific strategies to target loneliness and boredom and to improve care access, including telepsychiatry. Longitudinal studies must investigate the COVID-19 pandemic psychological impact in clinical samples.

It is acknowledged that diethylstilbestrol (DES), a synthetic diphenol with powerful estrogenic properties, causes structural anomalies of the reproductive tract and increases the risk of cancer and genital malformations in children and grandchildren of mothers treated during pregnancy. Conversely, data on DES effects on neurodevelopment and psychiatric disorders in in-utero exposed children and their descendants are rare, especially concerning Autism Spectrum Disorders (ASD). Recent studies presented in this review strengthen the hypothesis that in-utero exposure to DES and also other synthetic estrogens and progestogens, which all are endocrine disruptors, contributes to the pathogenesis of psychiatric disorders, especially ASD. A large epidemiological study in the USA in 2010 reported severe depression in in-utero exposed children (n=1,612), and a French cohort study (n=1,002 in-utero DES exposed children) in 2016 found mainly bipolar disorders, schizophrenia, major depression, suicide attempts, and suicide. Few publications described ASD in in-utero exposed children, mainly a Danish cohort study and a large Chinese epidemiological study. Molecular studies on endocrine disruptors demonstrated the transgenerational induction of diseases and DES epigenetic impact (DNA methylation changes) at two genes implicated in neurodevelopment (ZFP57 and ADAM TS9). We recently described in an informative family, somatic and psychiatric disorders in four generations, particularly ASD in boys of the third and fourth generation. These data show that the principle of precaution must be retained for the protection of future generations: women (pregnant or not) should be extremely vigilant about synthetic hormones.

Previous studies set out profound cognitive impairments in subjects with treatment-resistant depression (TRD). However, little is known about the course of such alterations depending on levels of improvement in those patients followed longitudinally. The main objective of this study was to describe the course of cognitive impairments in responder versus non-responder TRD patients at one-year follow-up. The second aim was to evaluate the predictive aspect of cognitive impairments to treatment resistance in patients suffering from TRD. We included 131 patients from a longitudinal cohort (FACE-DR) of the French Network of Expert TRD Centers. They undertook comprehensive sociodemographic, clinical, global functioning, and neuropsychological testing (TMT, Baddeley task, verbal fluencies, WAIS-4 subtests, D2 and RLRI-16) at baseline (V0) and one-year follow-up (V1). Most patients (n = 83; 63.36%) did not respond (47 women, 49.47 ± 12.64 years old), while one-third of patients responded (n = 48, 30 women, 54.06 ± 12.03 years old). We compared the cognitive performances of participants to average theoretical performances in the general population. In addition, we compared the cognitive performances of patients between V1 and V0 and responder versus non-responder patients at V1. We observed cognitive impairments during the episode and after a therapeutic response. Overall, each of them tended to show an increase in their cognitive scores. Improvement was more prominent in responders at V1 compared to their non-responder counterparts. They experienced a more marked improvement in code, digit span, arithmetic, similarities, and D2 tasks. Patients suffering from TRD have significant cognitive impairments that persist but alleviate after therapeutic response. Cognitive remediation should be proposed after therapeutic response to improve efficiency and increase the daily functioning.

Introduction Suicide is one of the leading public health issues worldwide. Mobile health can help us to combat suicide through monitoring and treatment. The SmartCrisis V.2.0 randomised clinical trial aims to evaluate the effectiveness of a smartphone-based Ecological Momentary Intervention to prevent suicidal thoughts and behaviour.Methods and analysis The SmartCrisis V.2.0 study is a randomised clinical trial with two parallel groups, conducted among patients with a history of suicidal behaviour treated at five sites in France and Spain. The intervention group will be monitored using Ecological Momentary Assessment (EMA) and will receive an Ecological Momentary Intervention called ‘SmartSafe’ in addition to their treatment as usual (TAU). TAU will consist of mental health follow-up of the patient (scheduled appointments with a psychiatrist) in an outpatient Suicide Prevention programme, with predetermined clinical appointments according to the Brief Intervention Contact recommendations (1, 2, 4, 7 and 11 weeks and 4, 6, 9 and 12 months). The control group would receive TAU and be monitored using EMA.Ethics and dissemination This study has been approved by the Ethics Committee of the University Hospital Fundación Jiménez Díaz. It is expected that, in the near future, our mobile health intervention and monitoring system can be implemented in routine clinical practice. Results will be disseminated through peer-reviewed journals and psychiatric congresses. Reference number EC005-21_FJD. Participants gave informed consent to participate in the study before taking part.Trial registration number NCT04775160.

BackgroundAs mHealth may contribute to suicide prevention, we developed emma, an application using Ecological Momentary Assessment and Intervention (EMA/EMI).ObjectiveThis study evaluated emma usage rate and acceptability during the first month and satisfaction after 1 and 6 months of use.MethodsNinety-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.ResultsSeventy-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).ConclusionEmma 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.

Introduction Impulsivity is present in a range of mental disorders and has been associated with suicide. Traditional measures of impulsivity have certain limitations, such as the lack of ecological validity. Virtual reality (VR) may overcome these issues. This study aims to validate the VR assessment tool ‘Spheres & Shield Maze Task’ and speech analysis by comparing them with traditional measures. We hypothesise that these innovative tools will be reliable and acceptable by patients, potentially improving the simultaneous assessment of impulsivity and decision-making.Methods and analysis This study will be carried out at the University Hospital Fundación Jiménez Díaz (Madrid, Spain). Our sample will consist of adults divided into three groups: psychiatric outpatients with a history of suicidal thoughts and/or behaviours, psychiatric outpatients without such a history and healthy volunteers. The target sample size was established at 300 participants (100 per group). Participants will complete the Barratt Impulsiveness Scale 11; the Urgency, Premeditation, Perseverance, Sensation Seeking, Positive Urgency, Impulsive Behaviour Scale; Iowa Gambling Task; Continuous Performance Test; Stop signal Task, and Go/no-go task, three questions of emotional affect, the Spheres & Shield Maze Task and two satisfaction surveys. During these tasks, participant speech will be recorded. Construct validity of the VR environment will be calculated. We will also explore the association between VR-assessed impulsivity and history of suicidal thoughts and/or behaviour, and the association between speech and impulsivity and decision-making.Ethics and dissemination This study was approved by the Ethics Committee of the University Hospital Fundación Jiménez Díaz (PIC128-21_FJD). Participants will be required to provide written informed consent. The findings will be presented in a series of manuscripts that will be submitted to peer-reviewed journals for publication.Trial registration number NCT05109845; Pre-results.

Abstract 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.

Introduction Prevalence of suicidal thoughts and behaviours is higher among patients with borderline personality disorder than the general population. However, evidence concerning the role of specific borderline symptoms for predicting suicide-related outcomes is lacking and no systematic review/meta-analysis (SR/MA) investigated this topic. Our aim will be to investigate the relationship between any borderline symptom (except criterion 5) and suicide-related outcomes both through an SR/MA and an individual patient data meta-analysis (IPD-MA).Methods We will search PubMed/MEDLINE, Scopus, Web of Science, Embase, PsycINFO, CINAHL and Cochrane Library databases from 1974 until September 2021. Both published and unpublished studies showing the association between any borderline symptom (except criterion 5) and suicide-related outcomes (death wish, suicidal ideation, suicidal plan, non-suicidal self-injury, deliberate self-harm, suicide attempt, suicidal behaviour disorder, suicide) will be included. Two team members will independently perform the selection of the studies and data extraction, with the supervision of two other members in case of discrepancies; and assess each study with study quality assessment tools by National Institutes of Health and Grading of Recommendations Assessment, Development and Evaluation. Each author will be contacted. If possible, we will perform both random-effect meta-analyses on the collected data (odds, risk, rate ratios or correlations) and an IPD-MA on collected databases.Ethics and dissemination This study does not require an ethical approval. Results will be publicly disseminated, included in research presentations and published in peer-review journals.PROSPERO registration number CRD42018078696.

Abstract Background Suicide constitutes a cause of death which could be prevented by e-health programs accessible to the general population. Effective promotion has the potential to maximize the uptake of such programs. However, few e-health programs have been combined with promotion campaigns. The primary objective of this trial is to assess the effectiveness of a tailored promotion, at a local level, of a mobile application and website offering evidence-based content for suicide prevention (the StopBlues program), and to compare the effectiveness of two types of local promotion in terms of their impact on suicidal acts. Secondary objectives focus on the effectiveness of the promotion in terms of the intensity of utilization of the StopBlues program, help-seeking behaviors and the level of psychological impairment of program users. Methods/design This is a three-arm, parallel-group, cluster-randomized controlled trial, with before-and-after observation. Thirty-four clusters, corresponding to geographical areas sharing a common local authority in France, will be included. They will be randomly assigned to one of the following arms with a ratio of 1:1:1: a control group; a basic promotion group in which promotion of the StopBlues program will be done by local authorities; and an intensified promotion group in which basic promotion will be supplemented by an additional one in a general practitioner’s waiting room. The primary outcome measure will be the number of suicidal acts within each cluster over a 12-month period following the launch of the intervention. Baseline data will be collected for each cluster over the 12-month period prior to the trial. Secondary outcomes will include length of use of the StopBlues program, measures of help-seeking behaviors and level of psychological distress among users of the program, as well as the cost-effectiveness and budgetary impact of its promotion. A more sustained promotion by local authorities will also be implemented after 12 months in the control group and assessed using the same outcome measures. Discussion This research should contribute to the sparse evidence base regarding the promotion of e-health programs and will support the wider delivery of the intervention evaluated if proven effective. Trial registration ClinicalTrials.gov , ID: NCT03565562 . Registered on 11 June 2018

It is not fully understood why some patients respond or do not respond to antidepressant treatment. Here the authors show that in the blood of individuals with depression, GPR56 expression increases in responders to antidepressant treatment, but not in non-responders.

Abstract 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).

BackgroundNoncommunicable disease (NCD)–related deaths account for 71% of deaths worldwide. The World Health Organization recently developed a global action plan to address the impact of NCDs, with the goal of reducing the number of premature NCD-related deaths to 25% by the year 2025. Appropriate therapeutic adherence is critical for effective disease management; however, approximately 30%-50% of patients with an NCD do not comply with disease management activities as prescribed. Web-based patient communities can represent platforms from which specific information on patients’ perception of treatment adherence can be gathered outside of a clinical trial setting. ObjectiveThis study aims to better understand patients’ perspectives regarding therapeutic adherence and iatrogenic risk in 2 major groups of NCDs for which poor disease management can have fatal consequences: cardiovascular diseases and mental disorders. Therapeutic adherence, motivational factors, patients’ awareness and perception of iatrogenesis, and treatment tools used by patients were assessed. MethodsA web-based survey was performed among patients with cardiovascular diseases or mental disorders or both conditions who were registered on the French Carenity platform, a web-based community in which patients with an NCD can share experiences and receive support and information. The study inclusion criteria were defined as follows: diagnosis of cardiovascular disease or mental disorder or both conditions (self-declared), age ≥18 years, residence in France, registration on the French Carenity platform, and ongoing pharmaceutical treatment for the condition. Patients who met the inclusion criteria were then invited to complete a self-administered web-based questionnaire that included questions addressing therapeutic adherence and iatrogenic risk. ResultsA total of 820 patients were enrolled in the study, including patients with cardiovascular diseases (403/820, 49.2%), patients with mental disorders (292/820, 35.6%), and patients with both cardiovascular diseases and mental disorders (125/820, 15.2%). The mean age of the participants was 55.2 (SD 12.7) years. We found that 82.8% (679/820) of patients experienced adverse effects of medication. Patients tended to perceive themselves to be more adherent than they actually were; a significant number of patients disregarded their prescription and stopped or interrupted medication without consulting with a doctor. Patients with cardiovascular diseases were nearly twice as adherent as patients with a mental disorder (P≤.001). Adherence was significantly associated with gender (P≤.001), age (P≤.001), and treatment complexity (P≤.001). Finally, for each disease type, 3 patient profiles were identified, which provide interesting insight for improving therapeutic adherence and adjustment strategies specifically according to patient behavior. ConclusionsThis study provides insight into the perspectives of patients receiving therapy for cardiovascular diseases or mental disorders or both conditions, which could help improve the management of NCDs and prevent premature death. Our study also shows that web-based patient platforms provide new opportunities to improve disease management by understanding patients’ experiences.

AbstractBackgroundWhile shared clinical decision-making (SDM) is the preferred approach to decision-making in mental health care, its implementation in everyday clinical practice is still insufficient. The European Psychiatric Association undertook a study aiming to gather data on the clinical decision-making style preferences of psychiatrists working in Europe.MethodsWe conducted a cross-sectional online survey involving a sample of 751 psychiatrists and psychiatry specialist trainees from 38 European countries in 2021, using the Clinical Decision-Making Style – Staff questionnaire and a set of questions regarding clinicians’ expertise, training, and practice.ResultsSDM was the preferred decision-making style across all European regions ([central and eastern Europe, CEE], northern and western Europe [NWE], and southern Europe [SE]), with an average of 73% of clinical decisions being rated as SDM. However, we found significant differences in non-SDM decision-making styles: participants working in NWE countries more often prefer shared and active decision-making styles rather than passive styles when compared to other European regions, especially to the CEE. Additionally, psychiatry specialist trainees (compared to psychiatrists), those working mainly with outpatients (compared to those working mainly with inpatients) and those working in community mental health services/public services (compared to mixed and private settings) have a significantly lower preference for passive decision-making style.ConclusionsThe preferences for SDM styles among European psychiatrists are generally similar. However, the identified differences in the preferences for non-SDM styles across the regions call for more dialogue and educational efforts to harmonize practice across Europe.

Abstract Background Suicidal ideation (SI) is an important risk factor of death by suicide. Recent data suggest that suicidal depression (i.e., moderate to severe depression with SI) could be a specific depression subtype with worse clinical outcomes than nonsuicidal depression (i.e., without SI). Methods Among 898 French adult inpatients (67% women, mean age: 41.23 [SD: 14.33]) with unipolar depression, 71.94% had moderate to severe depression (defined using the cut-offs of validated scales: beck depression inventory, clinician-rated 30-item inventory depression symptomatology, and quick inventory of depressive symptomatology) and among them, 63.6% had SI according to the suicidal item (score ≥ 2) of the depression scale they filled in. Clinical features (anxiety, psychological pain, and hopelessness) were assessed at baseline. The occurrence of a suicide attempt (SA) or a suicide event (SE) (i.e., actual, aborted or interrupted SA, or hospitalization for SI) was recorded during the 1-year follow-up. The risk of actual SA and SE was compared between groups with adjusted Cox regression models. Results The risk of actual SA and SE during the follow-up was 2- and 1.8-fold higher, respectively, in patients with suicidal depression, independently of potential cofounders such as history of lifetime SA, age, sex, and baseline depression severity. Conclusions Suicidal depression is associated with poorer prognosis in terms of actual SA/SE, despite optimal care (i.e., care in a hospital department specialized in the management of suicidal crisis). Specific therapeutic strategies might be needed for these patients.

Background: Electrodermal hyporeactivity has been proposed as a marker of suicidal risk. The EUDOR-A study investigated the prevalence of electrodermal hyporeactivity among patients with depression and its association with attempted and completed suicide.Methods: Between August 2014 and March 2016, 1,573 in- and outpatients with a primary diagnosis of depression (active or remission phase) were recruited at 15 European psychiatric centers. Each patient was followed-up for 1 year. Electrodermal activity was assessed at baseline with the ElectroDermal Orienting Reactivity Test. Data on the sociodemographic characteristics, clinical diagnoses, and treatment of the subjects were also collected. The severity of the depressive symptoms was assessed through the Montgomery–Asberg Depression Rating Scale. Information regarding number, time, and method of suicide attempts was gathered at baseline and at the end of the 1-year follow-up. The same data were collected in case of completed suicide.Results: Hyporeactive patients were shown to be significantly more at risk of suicide attempt compared to reactive patients, both at baseline and follow-up. A sensitivity of 29.86% and a positive predictive value (PPV) of 46.77% were found for attempted suicide at baseline, while a sensitivity of 35.36% and a PPV of 8.92% were found for attempted suicide at follow-up. The sensitivity and PPV for completed suicide were 25.00 and 0.61%, respectively. However, when controlled for suicide attempt at baseline, the association between hyporeactivity and follow-up suicide attempt was no longer significant. The low number of completed suicides did not allow any analysis.

Background: The ability to move joints beyond the normal range of motion is called Joint Hypermobility (JHM). JHM has been associated with a plethora of physical problems and is a frequent sign of hereditary disorders of connective tissue. Neuropsychiatric conditions such as eating disorders (ED) have also been related to JHM. However, little is known about the clinical profile of people with ED and JHM. The aim of this study was to explore JHM in patients with ED and to compare the clinical characteristics of hypermobile ED patients with non-hypermobile ED patients.Method: Fifty-three outpatients diagnosed with ED were assessed using the Beighton score for JHM, the Eating Disorders Inventory 2, the Eating Disorder Examination, and the Detail and Flexibility Questionnaire. Information relating to patients' psychiatric and somatic comorbidities/symptoms was also collected.Results: Using the traditional Beighton score's cutoff of ≥4, 41.5% of the sample presented with JHM. Our results indicate that compared with non-hypermobile ED patients, those with JHM are significantly younger, suffer at a greater extent from joint pain and easy bruising, have a shorter duration of the ED, and have lower scores for cognitive rigidity. In addition, for those with anorexia nervosa, the restricting subtype represents a significantly lower proportion of hypermobile ED patients compared to non-hypermobile ED patients. Multivariate analyses showed that cognitive rigidity, age, and duration of the ED could predict the JHM status in this sample.Conclusion: These results suggest that JHM is frequent in patients with ED and is accompanied by signs of tissue fragility. Patients with ED and JHM seem to present a specific profile characterized by less cognitive rigidity and restricting behavior in the case of anorexia nervosa. Further research is needed in order to confirm these results.

Introduction: Treatment-resistant depression (TRD) is a disabling psychiatric condition characterized by the failure of two antidepressants (ADs). Since the occurrence of side effects (SEs) appears to be one of the main determinants of early discontinuation of pharmacological treatments contributing to a pseudo-resistance, the purpose of this study was to determine the parameters associated with the occurrence of SEs under ADs in a cohort of patients with TRD.Methods: An observational, cross-sectional, multicentre study was carried out using data from the French network of Expert Centers for TRD. For the 108 patients enrolled in the study, the statistical analyses focused on the overall occurrence and on the profile of the SEs (9 categories, 32 items).Results: SEs were influenced by age and sex and were positively associated with the intensity of anxious, depressive and suicidal symptoms, a history of childhood trauma (sexual abuse, emotional abuse and neglect), and negatively associated with self-esteem, and assessment of overall functioning.Conclusion: Using variables accessible in common practice, these results fall within the dynamic of a more tailored approach to medicine that could allow, through integrated pharmacological management, the continuation of antidepressant treatments, and therefore limit the risk of therapeutic failure.

Abstract Background The screening of digital footprint for clinical purposes relies on the capacity of wearable technologies to collect data and extract relevant information’s for patient management. Artificial intelligence (AI) techniques allow processing of real-time observational information and continuously learning from data to build understanding. We designed a system able to get clinical sense from digital footprints based on the smartphone’s native sensors and advanced machine learning and signal processing techniques in order to identify suicide risk. Method/design The Smartcrisis study is a cross-national comparative study. The study goal is to determine the relationship between suicide risk and changes in sleep quality and disturbed appetite. Outpatients from the Hospital Fundación Jiménez Díaz Psychiatry Department (Madrid, Spain) and the University Hospital of Nimes (France) will be proposed to participate to the study. Two smartphone applications and a wearable armband will be used to capture the data. In the intervention group, a smartphone application (MEmind) will allow for the ecological momentary assessment (EMA) data capture related with sleep, appetite and suicide ideations. Discussion Some concerns regarding data security might be raised. Our system complies with the highest level of security regarding patients’ data. Several important ethical considerations related to EMA method must also be considered. EMA methods entails a non-negligible time commitment on behalf of the participants. EMA rely on daily, or sometimes more frequent, Smartphone notifications. Furthermore, recording participants’ daily experiences in a continuous manner is an integral part of EMA. This approach may be significantly more than asking a participant to complete a retrospective questionnaire but also more accurate in terms of symptoms monitoring. Overall, we believe that Smartcrises could participate to a paradigm shift from the traditional identification of risks factors to personalized prevention strategies tailored to characteristics for each patient. Trial registration number NCT03720730. Retrospectively registered.

The range of chemicals detectable by cell-free systems is still limited. Here the authors combine metabolic cascades with transcription factor networks to detect small molecules in complex environments.

In the current study, we provide the list of pharmacological interventions applied during the one-year follow-up period of the Pharmacological treatment profiles in the FACE-BD cohort study. These data show the treatments used in the new clusters formed in this previous study and also in usual bipolarity subtypes. The proportion of each treatment used during the follow-up was calculated. Days on each treatment were also included in this dataset. The complete clinical and paraclinical data analyzed for clusters and bipolar subtypes were included in this dataset. Socio-demographic self-administered and clinician-administered scales, clinical evaluation during the follow-up, psychiatric and somatic comorbidities, and blood tests are shown in this material.

The coronavirus disease 2019 (COVID-19) outbreak may have affected the mental health of patients at high risk of suicide. In this study we explored the wish to die and other suicide risk factors using smartphone-based ecological momentary assessment (EMA) in patients with a history of suicidal thoughts and behaviour. Contrary to our expectations we found a decrease in the wish to die during lockdown. This is consistent with previous studies showing that suicide rates decrease during periods of social emergency. Smartphone-based EMA can allow us to remotely assess patients and overcome the physical barriers imposed by lockdown.