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Background: A RCT of a novel intervention to detect antidepressant medication response (the PReDicT Test) took place in five European countries, accompanied by a nested study of its acceptability and implementation presented here. The RCT results indicated no effect of the intervention on depression at 8 weeks (primary outcome), although effects on anxiety at 8 weeks and functioning at 24 weeks were found. Methods: The nested study used mixed methods. The aim was to explore patient experiences of the Test including acceptability and implementation, to inform its use within care. A bespoke survey was completed by trial participants in five countries (n = 778) at week 8. Semi-structured interviews were carried out in two countries soon after week 8 (UK n = 22, Germany n = 20). Quantitative data was analysed descriptively; for qualitative data, thematic analysis was carried out using a framework approach. Results of the two datasets were interrogated together. Outcomes: Survey results showed the intervention was well received, with a majority of participants indicating they would use it again, and it gave them helpful extra information; a small minority indicated the Test made them feel worse. Qualitative data showed the Test had unexpected properties, including: instigating a process of reflection, giving participants feedback on progress and new understanding about their illness, and making participants feel supported and more engaged in treatment. Interpretation: The qualitative and quantitative results are generally consistent. The Test's unexpected properties may explain why the RCT showed little effect, as properties were experienced across both trial arms. Beyond the RCT, the qualitative data sheds light on measurement reactivity, i.e., how measurements of depression can impact patients.

Background Anorexia nervosa (AN) is a severe psychiatric disorder associated with frequent relapses and variability in treatment responses. Previous literature suggested that such variability is influenced by premorbid vulnerabilities such as abnormalities of the reward system. Several factors may indicate these vulnerabilities, such as neurocognitive markers (tendency to favour delayed reward, poor cognitive flexibility, abnormal decision process), genetic and epigenetic markers, biological and hormonal markers, and physiological markers.The present study will aim to identify markers that can predict body mass index (BMI) stability 6 months after discharge. The secondary aim of this study will be focused on characterising the biological, genetic, epigenetic and neurocognitive markers of remission in AN.Methods and analysis One hundred and twenty-five (n=125) female adult inpatients diagnosed with AN will be recruited and evaluated at three different times: at the beginning of hospitalisation, when discharged and 6 months later. Depending on the BMI at the third visit, patients will be split into two groups: stable remission (BMI≥18.5 kg/m²) or unstable remission (BMI

Abstract Objective The Videos of Physical Exercise and Sedentary Behaviours (VPESB) database is a novel database designed to experimentally investigate neural reactivity to physical exercise. The aim of this database is to provide a variety of dynamic images with a minimum of confounding factors. Methods A total of 196 healthy participants were recruited to evaluate 10 clips of sedentary activities and 10 clips of physical exercise. Each activity was performed by a male and female performer, resulting in a total of 40 video clips of 10 s each. Results The validation procedure confirmed the ability of these videoclips to accurately represent both sedentary and physical activity. In addition, video clips of physical activity were associated with higher effort ratings than sedentary activities (p

Neurotrophic factors play pivotal roles in shaping brain development and function, with brain-derived neurotrophic factor (BDNF) emerging as a key regulator in various physiological processes. This review explores the intricate relationship between BDNF and anorexia nervosa (AN), a complex psychiatric disorder characterized by disordered eating behaviors and severe medical consequences. Beginning with an overview of BDNF’s fundamental functions in neurodevelopment and synaptic plasticity, the review delves into recent clinical and preclinical evidence implicating BDNF in the pathophysiology of AN. Specifically, it examines the impact of BDNF polymorphisms, such as the Val66Met variant, on AN susceptibility, prognosis, and treatment response. Furthermore, the review discusses the interplay between BDNF and stress-related mood disorders, shedding light on the mechanisms underlying AN vulnerability to stress events. Additionally, it explores the involvement of BDNF in metabolic regulation, highlighting its potential implications for understanding the metabolic disturbances observed in AN. Through a comprehensive analysis of clinical data and animal studies, the review elucidates the nuanced role of BDNF in AN etiology and prognosis, emphasizing its potential as a diagnostic and prognostic biomarker. Finally, the review discusses limitations and future directions in BDNF research, underscoring the need for further investigations to elucidate the complex interplay between BDNF signaling and AN pathology.

Background: Clinical remission is a step towards functional remission for subjects with schizophrenia. While recovery is both a subjective personal journey and a clinical outcome to be targeted, data on patient self-rated outcomes are scarce. Objectives: (i) To determine the extent to which the association between clinical and functional remission is mediated by the subjective experience of recovery as reported by patients versus their relatives or their psychiatrist and (ii) to assess differences according to treatment, specifically with oral antipsychotics only versus long-acting injectable antipsychotics (LAIs). Design: Clinical observational study. Methods: Community-dwelling participants with schizophrenia enrolled in the EGOFORS cohort ( N = 198) were included. Clinical symptoms and remission were assessed using the Positive and Negative Syndrome Scale. Functional remission was assessed with the Functional Remission of General Schizophrenia Scale. Awareness of recovery was assessed with one question ‘What percentage of recovery do you think you have now (from 0% – no recovery – to 100% – full recovery)?’, asked of the patient, also of the patient’s close relative, and the psychiatrist. We used mediation analyses, taking into account the type of pharmacological treatment. Results: Remission criteria and perceived remission measures were significantly correlated, both within and between groups ( r > 0.330). The patient’s awareness of recovery mediated the relationship between clinical remission and level of functional remission, while the level of recovery according to psychiatrists or close relatives did not. The direct effect of clinical remission on the level of functional remission became non-significant when taking into account the mediator (patients’ awareness of recovery) in the group of patients with LAI ( t = 1.5, p = 0.150) but not in the group of patients with other treatments ( t = 3.1, p = 0.003). Conclusion: Patients with LAIs may be more efficient in reporting their level of functional remission. Higher patient awareness could be an interesting candidate to explain this. However, as the study was cross-sectional, such a proposal should be tested with a more specifically designed protocol, such as a long-term cohort.

Abstract Background Anorexia nervosa (AN) is a serious mental illness. One-third of people develop severe, enduring, illness, adversely impacting quality of life with high health system costs. This study assessed the economic case for enhanced care for adults newly diagnosed with AN. Methods A five-state 312-month-cycle Markov model assessed the economic impact of four enhanced care pathways for adults newly diagnosed with AN in England, Germany, and Spain. Enhancements were halving wait times for any outpatient care, receiving specialist outpatient treatment post-referral, additional transitional support post-referral, and all enhancements combined. Care pathways, estimates of impact, resource use, and costs were drawn from literature. Net monetary benefits (NMBs), impacts on health system costs, and disability-adjusted life years (DALYs) averted were estimated. Parameter uncertainty was addressed in multi-way sensitivity analyses. Costs are presented in 2020 purchasing power parity adjusted Euros. Results All four enhanced care pathways were superior to usual care, with the combined intervention scenario having the greatest NMBs of €248,575, €259,909, and €258,167 per adult in England, Germany, and Spain, respectively. This represented maximum NMB gains of 9.38% (€21,316), 4.3% (€10,722), and 4.66% (€11,491) in England, Germany and Spain compared to current care. Healthcare costs would reduce by more than 50%. Conclusions Early and effective treatment can change the trajectory of AN. Reducing the untreated duration of the disorder is crucial. There is a good economic case in different country contexts for measures to reduce waiting times between diagnosis and treatment and increase access to enhanced outpatient treatment.

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.

ContextThe use of vagus nerve stimulation (VNS) to reduce or stop electroconvulsive therapy (ECT) in treatment-resistant depression seems promising. The aim of this study was to investigate the efficacy of VNS on the reduction of ECT sessions and mood stabilization.MethodsWe conducted a monocentric retrospective case series of patients who suffered from treatment-resistant depression, treated with ECT and referred to our center for VNS. We investigated the number and the frequency of ECT sessions before and after VNS implantation. Secondary criteria consisted in the Montgomery Åsberg Depression Rating Scale (MADRS) score, number of medical treatments, dosage of the main treatment and length of hospital stays before and after VNS. Additionally, we sent an anonymous survey to psychiatrists and other physicians in our institution to investigate their knowledge and perception of VNS therapy to treat treatment-resistant depression.ResultsSeven patients benefited from VNS: six (86%) were female (mean age of 51.7 +/− 16.0 years at surgery), and five (71%) suffered from bipolar depression (three type I and two type II). All patients were followed up at least 2 years post-implantation (range: 27–68 months). Prior to VNS, six patients were treated by maintenance ECT. After VNS, three (43%) patients did not require maintenance ECT anymore, and three (43%) patients required less frequent ECT session with a mean 14.7 +/− 9.8 weeks between sessions after VNS vs. 2.9 +/− 0.8 weeks before VNS. At last follow-up, 4 (57%) patients had stopped ECT. Five (71%) patients implanted with VNS were good responders (50% decrease relative to baseline MADRS). According to the survey, psychiatrists had a significantly better perception and knowledge of ECT, but a worse perception and knowledge of VNS compared to other physicians.ConclusionVNS is a good option for treatment-resistant depression requiring maintenance ECT dependence. Larger on-going studies will help broaden the implanted patients while strengthening psychiatrists’ knowledge on this therapy.

BackgroundBorderline personality disorder is often associated with self-injurious behaviors that cause personal suffering, family distress, and substantial medical costs. Mental health hotlines exist in many countries and have been shown to be effective in some contexts, but none have been specifically designed for borderline patients. The aim of the present study is to evaluate the impact of a 24/7 hotline dedicated to patients with borderline personality disorder on suicide attempts and self-injurious behaviors.MethodsWe conducted a single-blind, multicenter (9 French centers) clinical trial with stratified randomization (by age, sex and center). Patients (N = 315) with a diagnosis of borderline personality disorder (according to the SIDP-IV) were randomized into two groups with or without access to the hotline in addition to treatment as usual. The number of suicide attempts and self-injurious behaviors in each group within 12 month were analyzed in the “per protocol” population (Student’s t-tests, 5% significance threshold), adjusting for possible confounders in a multivariate analysis (using Poisson regression). The percentage of patients with suicide attempts and with self-injurious behaviors (and other percentages) were analyzed in the per protocol population (χ2-tests or exact Fischer tests, 5% significance threshold).ResultsThe mean number of suicide attempts was 3 times lower in the hotline group (0.41 vs. 1.18, p = 0.005) and the mean number of self-injurious behaviors was 9 times lower (0.90 vs. 9.5, p = 0.006). Multivariate analysis confirmed the effectiveness of the hotline in reducing suicide attempts and self-harm.ConclusionThis study supports the effectiveness of hotlines in reducing self-aggressive behavior in patients with borderline personality disorder. Such support is easy to use, cheap and flexible, and therefore easy to implement on a large scale.

Abstract Background Schizophrenia is mostly a chronic disorder whose symptoms include psychosis, negative symptoms and cognitive dysfunction. Poor adherence is common and related relapse can impair outcomes. Long-acting injectable antipsychotics (LAIs) may promote treatment adherence and decrease the likelihood of relapse and rehospitalization. Using LAIs in first-episode psychosis (FEP) and early-phase (EP) schizophrenia patients could benefit them, yet LAIs have traditionally been reserved for chronic patients. Methods A three-step modified Delphi panel process was used to obtain expert consensus on using LAIs with FEP and EP schizophrenia patients. A literature review and input from a steering committee of five experts in psychiatry were used to develop statements about patient population, adverse event management, and functional recovery. Recruited Delphi process psychiatrists rated the extent of their agreement with the statements over three rounds (Round 1: paper survey, 1:1 interview; Rounds 2–3: email survey). Analysis rules determined whether a statement progressed to the next round and the level of agreement deemed consensus. Measures of central tendency (mode, mean) and variability (interquartile range) were reported back to help panelists assess their previous responses in the context of those of the overall group. Results The Delphi panelists were 17 psychiatrists experienced in treating schizophrenia with LAIs, practicing in seven countries (France, Italy, US, Germany, Spain, Denmark, UK). Panelists were presented with 73 statements spanning three categories: patient population; medication dosage, management, and adverse events; and functional recovery domains and assessment. Fifty-five statements achieved ≥ 80% agreement (considered consensus). Statements with low agreement (40-79%) or very low agreement (

Summary: LEAP-2 is a ghrelin antagonist with an anorexigenic drive. This study investigates the evolution of plasma ghrelin and LEAP-2 concentrations in 29 patients with anorexia nervosa (AN) before and after refeeding and compares it to physiological adaptations during fasting in healthy controls or to mouse model of chronic food restriction and refeeding. Acute and chronic food restriction decrease LEAP-2 and increase ghrelin concentrations in both humans and mice, while patients with AN displayed higher ghrelin and LEAP-2 concentrations before than after refeeding (p = 0.043). After 6 months follow-up, patients with unstable weight gain (n = 17) had significantly decreased LEAP-2 concentrations after refeeding (p = 0.044), in contrast to patients with stable weight gain (n = 12). We provide evidence that the ghrelin/LEAP-2 system is not regulated according to the nutritional status in AN, in contrast to what is physiologically expected when coping with food restriction.

Schizophrenia (SZ) is a heterogeneous and debilitating psychiatric disorder with a strong genetic component. To elucidate functional networks perturbed in schizophrenia, we analysed a large dataset of whole-genome studies that identified SNVs, CNVs, and a multi-stage schizophrenia genome-wide association study. Our analysis identified three subclusters that are interrelated and with small overlaps: GO:0007017~Microtubule-Based Process, GO:00015629~Actin Cytoskeleton, and GO:0007268~SynapticTransmission. We next analysed three distinct trio cohorts of 75 SZ Algerian, 45 SZ French, and 61 SZ Japanese patients. We performed Illumina HiSeq whole-exome sequencing and identified de novo mutations using a Bayesian approach. We validated 88 de novo mutations by Sanger sequencing: 35 in French, 21 in Algerian, and 32 in Japanese SZ patients. These 88 de novo mutations exhibited an enrichment in genes encoding proteins related to GO:0051015~actin filament binding (p = 0.0011) using David, and enrichments in GO: 0003774~transport (p = 0.019) and GO:0003729~mRNA binding (p = 0.010) using Amigo. One of these de novo variant was found in CORO1C coding sequence. We studied Coro1c haploinsufficiency in a Coro1c+/− mouse and found defects in the corpus callosum. These results could motivate future studies of the mechanisms surrounding genes encoding proteins involved in transport and the cytoskeleton, with the goal of developing therapeutic intervention strategies for a subset of SZ cases.

Abstract Evidence about the involvement of genetic factors in the development of gambling disorder (GD) has been assessed. Among studies assessing heritability and biological vulnerability for GD, neurotrophin (NTF) genes have emerged as promising targets, since a growing literature showed a possible link between NTF and addiction-related disorders. Thus, we aimed to explore the role of NTF genes and GD with the hypothesis that some NTF gene polymorphisms could constitute biological risk factors. The sample included 166 patients with GD and 191 healthy controls. 36 single nucleotide polymorphisms (SNPs) from NTFs (NGF, NGFR, NTRK1, BDNF, NTRK2, NTF3, NTRK3, NTF4, CNTF and CNTFR) were selected and genotyped. Linkage disequilibrium (LD) and haplotype constructions were analyzed, in relationship with the presence of GD. Finally, regulatory elements overlapping the identified SNPs variants associated with GD were searched. The between groups comparisons of allele frequencies indicated that 6 SNPs were potentially associated with GD. Single and multiple-marker analyses showed a strong association between both NTF3 and NTRK2 genes, and GD. The present study supports the involvement of the NTF family in the aetiopathogenesis of GD. An altered cross-regulation of different NTF members signalling pathways might be considered as a biological vulnerability factor for GD.

Abstract Background Despite efforts toward greater gender equality in clinical and academic psychiatry in recent years, more information is needed about the challenges in professional development within psychiatry, and how these may vary with gender. Methods A cross-sectional 27-item online survey was conducted with psychiatrists and psychiatric trainee members of the European Psychiatric Association. Results A total of 561 psychiatrists and psychiatric trainees from 35 European countries participated representing a response rate of 52.8% for women and 17.7% for men from a total sample of 1,580. The specific challenges that women face in their professional development fall into two categories. One comprised women’s negative attitudes concerning their abilities in self-promotion and networking. The other identified environmental barriers related to lack of opportunity and support and gender discrimination. Compared to men, women reported higher rates of gender discrimination in terms of professional advancement. Women were less likely to agree that their institutions had regular activities promoting inclusion, diversity, and training to address implicit gender bias. Working in high-income countries compared to middle-income countries relates to reporting institutional support for career progression. Conclusions These findings are an open call to hospital leaders, deans of medical schools, and department chairs to increase efforts to eradicate bias against women and create safer, inclusive, and respectful environments for all psychiatrists, a special call to women psychiatrists to be aware of inner tendencies to avoid self-promotion and networking and to think positively and confidently about themselves and their abilities.

One in eight individuals worldwide lives with a mental health disorder. For many European countries, the prevalence is even higher, with one in four people reporting mental health problems [1]. Three-quarters of all mental health disorders develop before age 25, with many presenting initially in undiagnosed forms already in the mid-teens and eventually manifesting as severe disorders and lasting into old age [2]. There is also growing evidence that mental health disorder symptoms cross diagnoses and people frequently have more than one mental health disorder [3].

Depressive disorders have one of the highest disability-adjusted life years (DALYs) of all medical conditions, which led the European Psychiatric Association to propose a policy paper, pinpointing their unmet health care and research needs. The first part focuses on what can be currently done to improve the care of patients with depression, and then discuss future trends for research and healthcare. Through the narration of clinical cases, the different points are illustrated. The necessary political framework is formulated, to implement such changes to fundamentally improve psychiatric care. The group of European Psychiatrist Association (EPA) experts insist on the need for (1) increased awareness of mental illness in primary care settings, (2) the development of novel (biological) markers, (3) the rapid implementation of machine learning (supporting diagnostics, prognostics, and therapeutics), (4) the generalized use of electronic devices and apps into everyday treatment, (5) the development of the new generation of treatment options, such as plasticity-promoting agents, and (6) the importance of comprehensive recovery approach. At a political level, the group also proposed four priorities, the need to (1) increase the use of open science, (2) implement reasonable data protection laws, (3) establish ethical electronic health records, and (4) enable better healthcare research and saving resources.

The ongoing developments of psychiatric classification systems have largely improved reliability of diagnosis, including that of schizophrenia. However, with an unknown pathophysiology and lacking biomarkers, its validity still remains low, requiring further advancements. Research has helped establish multiple sclerosis (MS) as the central nervous system (CNS) disorder with an established pathophysiology, defined biomarkers and therefore good validity and significantly improved treatment options. Before proposing next steps in research that aim to improve the diagnostic process of schizophrenia, it is imperative to recognize its clinical heterogeneity. Indeed, individuals with schizophrenia show high interindividual variability in terms of symptomatic manifestation, response to treatment, course of illness and functional outcomes. There is also a multiplicity of risk factors that contribute to the development of schizophrenia. Moreover, accumulating evidence indicates that several dimensions of psychopathology and risk factors cross current diagnostic categorizations. Schizophrenia shares a number of similarities with MS, which is a demyelinating disease of the CNS. These similarities appear in the context of age of onset, geographical distribution, involvement of immune-inflammatory processes, neurocognitive impairment and various trajectories of illness course. This article provides a critical appraisal of diagnostic process in schizophrenia, taking into consideration advancements that have been made in the diagnosis and management of MS. Based on the comparison between the two disorders, key directions for studies that aim to improve diagnostic process in schizophrenia are formulated. All of them converge on the necessity to deconstruct the psychosis spectrum and adopt dimensional approaches with deep phenotyping to refine current diagnostic boundaries.

Abstract Background The aim of this study was to assess barriers and facilitators in the pathways toward specialist care for eating disorders (EDs). Methods Eleven ED services located in seven European countries recruited patients with an ED. Clinicians administered an adapted version of the World Health Organization “Encounter Form,” a standardized tool to assess the pathways to care. The unadjusted overall time needed to access the ED unit was described using the Kaplan–Meier curve. Results Four-hundred-nine patients were recruited. The median time between the onset of the current ED episode and the access to a specialized ED care was 2 years. Most of the participants did not directly access the specialist ED unit: primary “points of access” to care were mental health professionals and general practitioners. The involvement of different health professionals in the pathway, seeking help for general psychiatric symptoms, and lack of support from family members were associated with delayed access to ED units. Conclusions Educational programs aiming to promote early diagnosis and treatment for EDs should pay particular attention to general practitioners, in addition to mental health professionals, and family members to increase awareness of these illnesses and of their treatment initiation process.

Abstract Background Patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) are increasingly acknowledged as critical tools for enhancing patient-centred, value-based care. However, research is lacking on the impact of using standardized patient-reported indicators in acute psychiatric care. The aim of this study was to explore whether subjective well-being indicators (generic PROMs) are relevant for evaluating the quality of hospital care, distinct from measures of symptom improvement (disease-specific PROMs) and from PREMs. Methods Two hundred and forty-eight inpatients admitted to a psychiatric university hospital were included in the study between January and June 2021. Subjective well-being was assessed using standardized generic PROMs on well-being, symptom improvement was assessed using standardized disease-specific PROMs, and experience of care using PREMs. PROMs were completed at admission and discharge, PREMs were completed at discharge. Clinicians rated their experience of providing treatment using adapted PREMs items. Results Change in subjective well-being (PROMs) at discharge was significantly (p < 0.001), but moderately (r 2 = 28.5%), correlated to improvement in symptom outcomes, and weakly correlated to experience of care (PREMs) (r 2 = 11.0%), the latter being weakly explained by symptom changes (r 2 = 6.9%). Patients and clinicians assessed the experience of care differently. Conclusions This study supports the case for routinely measuring patients’ subjective well-being to better capture the unmet needs of patients undergoing psychiatric hospital treatment, and the use of standardized patient-reported measures as key indicators of high quality of care across mental health services.

Abstract Quantifying changes in DNA and RNA levels is essential in numerous molecular biology protocols. Quantitative real time PCR (qPCR) techniques have evolved to become commonplace, however, data analysis includes many time-consuming and cumbersome steps, which can lead to mistakes and misinterpretation of data. To address these bottlenecks, we have developed an open-source Python software to automate processing of result spreadsheets from qPCR machines, employing calculations usually performed manually. Auto-qPCR is a tool that saves time when computing qPCR data, helping to ensure reproducibility of qPCR experiment analyses. Our web-based app ( https://auto-q-pcr.com/ ) is easy to use and does not require programming knowledge or software installation. Using Auto-qPCR, we provide examples of data treatment, display and statistical analyses for four different data processing modes within one program: (1) DNA quantification to identify genomic deletion or duplication events; (2) assessment of gene expression levels using an absolute model, and relative quantification (3) with or (4) without a reference sample. Our open access Auto-qPCR software saves the time of manual data analysis and provides a more systematic workflow, minimizing the risk of errors. Our program constitutes a new tool that can be incorporated into bioinformatic and molecular biology pipelines in clinical and research labs.

Gambling Disorder (GD) has a complex etiology that involves biological and environmental aspects. From a genetic perspective, neurotrophic factors (NTFs) polymorphisms have been associated with the risk of developing GD. The aim of this study was to assess the underlying mechanisms implicated in GD severity by considering the direct and mediational relationship between different variables including genetic, psychological, socio-demographic, and clinical factors. To do so, we used genetic variants that were significantly associated with an increased risk for GD and evaluated its relationship with GD severity through pathway analysis. We found that the interaction between these genetic variants and other different biopsychological features predicted a higher severity of GD. On the one hand, the presence of haplotype block 2, interrelated with haplotype block 3, was linked to a more dysfunctional personality profile and a worse psychopathological state, which, in turn, had a direct link with GD severity. On the other hand, having rs3763614 predicted higher general psychopathology and therefore, higher GD severity. The current study described the presence of complex interactions between biopsychosocial variables previously associated with the etiopathogenesis and severity of GD, while also supporting the involvement of genetic variants from the NTF family.

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 Patients with anorexia nervosa (AN) show impaired decision-making ability, but it is still unclear if this is a trait marker (i.e., being associated with AN at any stage of the disease) or a state parameter of the disease (i.e., being present only in acutely ill patients), and if it has endophenotypic characteristics. The aim of this study was to determine the endophenotypic, and state- or trait-associated nature of decision-making impairment in AN. Methods Ninety-one patients with acute AN (A-AN), 90 unaffected relatives (UR), 23 patients remitted from AN (R-AN), and 204 healthy controls (HC) carried out the Iowa gambling task (IGT). Prospective valence learning (PVL) model was employed to distinguish the cognitive dimensions underlying the decision-making process, that is, learning, consistency, feedback sensitivity, and loss aversion. IGT performance and decision-making dimensions were compared among groups to assess whether they had endophenotypic (i.e., being present in A-AN, UR, and R-AN, but not in HC) and/or trait-associated features (i.e., present in A-AN and R-AN but not in HC). Results Patients with A-AN had lower performance at the IGT (p

Introduction: Body image distortion is a core symptom of anorexia nervosa (AN), embodying dissatisfaction and overvaluation of body appearance and weight. Body image distortion is an important factor in the maintenance of weight loss behaviours such as compulsive physical exercise. Conversely, physical exercise seems to have an aggravating effect on body image in patients with AN, but the evidence is still poor. The aim of this study was to examine the relationship between body image distortion and physical exercise in AN in order to understand whether physical exercise may play a specific role in body image distortion beyond psychopathological severity. Methods: Forty patients with AN and 21 healthy controls were tested for body image distortion and different proxies of physical exercise. Univariate correlations tested the relationship between body image distortion and physical exercise in AN and control groups. Then, to experimentally assess the effect of exercise on body image distortion, participants were invited to rate their body image before and after a standardised effort test. Results: In the AN group, a correlation was found between physical activity and body image distortion (p < 0.01), which was still significant after controlling for psychopathological severity. No correlation was found in healthy controls. After a standardised effort, patients with AN had higher increases in body image distortion than healthy controls (almost 4 kg/m2 vs. 0.8 kg/m2) (p < 0.01). Discussion: Physical exercise may contribute to the distortion of body image in anorexia nervosa and explain the paradoxical augmentation of unhealthy exercise despite ongoing weight loss.

Objectives To capture the subjective experience of close family ascendants of acute bacterial meningitis survivors and to explore how they give meaning to this specific experience.Design A qualitative study of indepth interviews using interpretative phenomenological analysis.Primary outcome Main meaning-making processes of participants’ experience.Settings Participants were recruited through two associations of people affected by meningitis and their family ascendants.Participants Convenience sampling of 11 women whose children or grandchildren were between 0.2 and 20 years old at the time of their meningitis diagnosis (M=4.06, SD=7.3). On average, 9.39 (SD=5.4) years had passed between the onset of illness and the interview.Results Six superordinate themes (meningitis disease; healthcare services and professionals; knowledge/ignorance; repercussions of the meningitis experience: ‘life afterwards’; sick child attitudes/behaviour; and sibling attitudes/behaviour) and two main meaning-making processes in relation to participants’ experience of meningitis were identified: (1) the sick child becoming a ‘hero’: comparison with other children; and (2) engaging action/attitude: finding the ‘positive’ of the traumatic experience and engaging action to improve the care system. These two processes underpin the psychological adjustment to meningitis and its consequences.Conclusions This study provides a unique insight into close family members’ first-hand experience with acute bacterial meningitis. Findings highlighted factors characterising the disease experience, the psychological adjustment of meningitis survivors’ families and their meaning-making processes. These findings are important for research and clinical practice, demonstrating the multidimensional impact of the disease on family ascendants, their need for professional psychological support and the importance of direct involvement of parents in identifying key aspects of care.

AbstractBackgroundPatients with schizophrenia spectrum disorders (SSD) have worse physical health and reduced life expectancy compared to the general population. In 2009, the European Psychiatric Association, the European Society of Cardiology and the European Association for the Study of Diabetes published a position paper aimed to improve cardiovascular and diabetes care in patients with severe mental illnesses. However, the initiative did not produce the expected results. Experts in SSD or in cardiovascular and metabolic diseases convened to identify main issues relevant to management of cardiometabolic risk factors in schizophrenia patients and to seek consensus through the Delphi method.MethodsThe steering committee identified four topics: 1) cardiometabolic risk factors in schizophrenia patients; 2) cardiometabolic risk factors related to antipsychotic treatment; 3) differences in antipsychotic cardiometabolic profiles; 4) management of cardiometabolic risk. Twelve key statements were included in a Delphi questionnaire delivered to a panel of expert European psychiatrists.ResultsConsensus was reached for all statements with positive agreement higher than 85% in the first round. European psychiatrists agreed on: 1) high cardiometabolic risk in patients with SSD, 2) importance of correct risk management of cardiometabolic diseases, from lifestyle modification to treatment of risk factors, including the choice of antipsychotic drugs with a favourable cardiometabolic profile. The expert panel identified the psychiatrist as the central coordinating figure of management, possibly assisted by other specialists and general practitioners.ConclusionsThis study demonstrates high level of agreement among European psychiatrists regarding the importance of cardiovascular risk assessment and management in subjects with SSD.

Objectives (1) To capture the subjective experience of meningitis survivors during adolescence and adulthood and (2) To explore how they give meaning to this specific experience.Design A qualitative study of in-depth interviews using interpretative phenomenological analysis.Settings Participants recruited through an association of persons affected by meningitis and their relatives.Participants Convenience sample of nine participants (seven women and two men) between the ages of 18 to 48 years (mean=28.3, SD=11.4), who personally experienced meningitis.Results Eight major themes and three main meaning-making processes in relation to the participants’ experiences of meningitis were identified: (1) the ability to rely on the testimony of others, (2) the impossibility of meaning-making and (3) the possibility of post-traumatic growth. We detailed here five major themes, which appear critical to answering the objective of the study.Conclusions This study provides a unique insight into the first-hand experience of surviving meningitis. Findings highlighted factors characterising the disease experience, the psychological adjustment of meningitis survivors and their meaning-making processes. These findings are important for both research and clinical practice, demonstrating the importance of direct involvement of meningitis survivors in identifying key aspects of care, which include the critical role of relatives, and the importance of investigating the need for training among healthcare providers on how to diagnose meningitis.

Abstract Background Antidepressant medication is commonly used to treat depression. However, many patients do not respond to the first medication prescribed and improvements in symptoms are generally only detectable by clinicians 4–6 weeks after the medication has been initiated. As a result, there is often a long delay between the decision to initiate an antidepressant medication and the identification of an effective treatment regimen. Previous work has demonstrated that antidepressant medications alter subtle measures of affective cognition in depressed patients, such as the appraisal of facial expression. Furthermore, these cognitive effects of antidepressants are apparent early in the course of treatment and can also predict later clinical response. This trial will assess whether an electronic test of affective cognition and symptoms (the Predicting Response to Depression Treatment Test; PReDicT Test) can be used to guide antidepressant treatment in depressed patients and, therefore, hasten treatment response compared to a control group of patients treated as usual. Methods/design The study is a randomised, two-arm, multi-centre, open-label, clinical investigation of a medical device, the PReDicT Test. It will be conducted in five European countries (UK, France, Spain, Germany and the Netherlands) in depressed patients who are commencing antidepressant medication. Patients will be randomised to treatment guided by the PReDicT Test (PReDicT arm) or to Treatment as Usual (TaU arm). Patients in the TaU arm will be treated as per current standard guidelines in their particular country. Patients in the PReDicT arm will complete the PReDicT Test after 1 (and if necessary, 2) weeks of treatment. If the test indicates non-response to the treatment, physicians will be advised to immediately alter the patient’s antidepressant therapy by dose escalation or switching to another compound. The primary outcome of the study is the proportion of patients showing a clinical response (defined as 50% or greater decrease in baseline scores of depression measured using the Quick Inventory of Depressive Symptoms – Self-Rated questionnaire) at week 8. Health economic and acceptability data will also be collected and analysed. Discussion This trial will test the clinical efficacy, cost-effectiveness and acceptability of using the novel PReDicT Test to guide antidepressant treatment selection in depressed patients. Trial registration ClinicalTrials.gov, ID: NCT02790970 . Registered on 30 March 2016.

Anorexia nervosa (AN) is a severe eating disorder where caloric restriction, excessive physical activity and metabolic alterations lead to life-threatening situations. Despite weight restoration after treatment, a significant part of patients experience relapses. In this translational study, we combined clinical and preclinical approaches. We describe preliminary data about the effect of weight gain on the symptomatology of patients suffering from acute AN (n = 225) and partially recovered (n = 41). We measured more precisely physical activity with continuous cardiac monitoring in a sub-group (n = 68). Using a mouse model, we investigated whether a long-term food restriction followed by nutritional recovery associated or not with physical activity may differentially impact peripheral and central homeostatic regulation. We assessed the plasma concentration of acyl ghrelin, desacyl ghrelin and leptin and the mRNA expression of hypothalamic neuropeptides and their receptors. Our data show an effect of undernutrition history on the level of physical activity in AN. The preclinical model supports an important role of physical activity in the recovery process and points out the leptin system as one factor that can drive a reliable restoration of metabolic variables through the hypothalamic regulation of neuropeptides involved in feeding behavior.

Anorexia nervosa (AN) is a dramatic psychiatric disorder characterized by dysregulations in food intake and reward processing, involving molecular and cellular changes in several peripheral cell types and central neuronal networks. Genomic and epigenomic analyses have allowed the identification of multiple genetic and epigenetic modifications highlighting the complex pathophysiology of AN. Behavioral and genetic rodent models have been used to recapitulate and investigate, with some limitations, the cellular and molecular changes that potentially underlie eating disorders. In the last 5 years, the use of induced pluripotent stem cells (IPSCs), combined with CRISPR–Cas9 technology, has led to the generation of specific neuronal cell subtypes engineered from human somatic samples, representing a powerful tool to complement observations made in human samples and data collected from animal models. Systems biology using IPSCs has indeed proved to be a valuable approach for the study of metabolic disorders, in addition to neurodevelopmental and psychiatric disorders. The manuscript, while reviewing the main findings related to the genetic, epigenetic, and cellular bases of AN, will present how new studies published, or to be performed, in the field of IPSC-derived cells should improve our current understanding of the pathophysiology of AN and provide potential therapeutic strategies addressing specific endophenotypes.

Anorexia nervosa (AN) is a severe metabopsychiatric disorder characterised by caloric intake restriction and often excessive physical exercise. Our aim is to assess in female AN patients and in a rodent model, the co-evolution of physical activity and potential dysregulation of acyl—(AG) and desacyl—(DAG) ghrelin plasma concentrations during denutrition and weight recovery. AN inpatients were evaluated at inclusion (T0, n = 29), half—(T1) and total (T2) weight recovery, and one month after discharge (T3, n = 13). C57/Bl6 mice with access to a running wheel, were fed ad libitum or submitted to short—(15 days) or long—(50 days) term quantitative food restriction, followed by refeeding (20 days). In AN patients, AG and DAG rapidly decreased during weight recovery (T0 to T2), AG increased significantly one-month post discharge (T3), but only DAG plasma concentrations at T3 correlated negatively with BMI and positively with physical activity. In mice, AG and DAG both increased during short- and long-term food restriction. After 20 days of ad libitum feeding, DAG was associated to persistence of exercise alteration. The positive association of DAG with physical activity during caloric restriction and after weight recovery questions its role in the adaptation mechanisms to energy deprivation that need to be considered in recovery process in AN.

The management of eating disorders (EDs) is still difficult and few treatments are effective. Recently, several studies have described the important contribution of non-invasive brain stimulation (repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and electroconvulsive therapy) and invasive brain stimulation (deep brain stimulation and vagal nerve stimulation) for ED management. This review summarizes the available evidence supporting the use of brain stimulation in ED. All published studies on brain stimulation in ED as well as ongoing trials registered at clinicaltrials.gov were examined. Articles on neuromodulation research and perspective articles were also included. This analysis indicates that brain stimulation in EDs is still in its infancy. Literature data consist mainly of case reports, cases series, open studies, and only a few randomized controlled trials. Consequently, the evidence supporting the use of brain stimulation in EDs remains weak. Finally, this review discusses future directions in this research domain (e.g., sites of modulation, how to enhance neuromodulation efficacy, personalized protocols).

Schizophrenia is a multifactorial disease associated with widespread cognitive impairment. Although cognitive deficits are one of the factors most strongly associated with functional impairment in schizophrenia (SZ), current treatment strategies hardly tackle these impairments. To develop more efficient treatment strategies in patients, a better understanding of their pathogenesis is needed. Recent progress in genetics, driven by large genome-wide association studies (GWAS) and the use of polygenic risk scores (PRS), has provided new insights about the genetic architecture of complex human traits, including cognition and SZ. Here, we review the recent findings examining the genetic links between SZ and cognitive functions in population-based samples as well as in participants with SZ. The performed meta-analysis showed a negative correlation between the polygenetic risk score of schizophrenia and global cognition (p < 0.001) when the samples rely on general and healthy participants, while no significant correlation was detected when the three studies devoted to schizophrenia patients were meta-analysed (p > 0.05). Our review and meta-analysis therefore argues against universal pleiotropy for schizophrenia alleles and cognition, since cognition in SZ patients would be underpinned by the same genetic factors than in the general population, and substantially independent of common variant liability to the disorder.

Various therapeutic approaches are available for the treatment of gambling disorder (GD), especially cognitive behavioral therapy (CBT; the most widely used treatment). However, CBT has high dropout and relapse rates as well as non-compliance issues, which may be partly due to resistance to changing core characteristics, such as executive functioning, attention, and emotional regulation abnormalities. Finding new therapeutic approaches to treat GD is thus a key challenge. Cognitive remediation (CR) interventions represent a promising approach to GD management, which has recently been demonstrated to have efficacy for treating other addictive disorders. The objective of this review is to describe the possible benefits of CR interventions for GD management. Two systematic searches in MEDLINE and ScienceDirect databases were conducted up until January 2017. Potential neurocognitive targets of CR interventions for GD were reviewed, as is the use and efficacy of such interventions for GD. While there is evidence of several neurocognitive deficits in individuals with GD in terms of impulsive, reflective, and interoceptive processes, the literature on CR interventions is virtually absent. No clinical studies were found in the literature, apart from a trial of a very specific program using Playmancer, a serious videogame, which was tested in cases of bulimia nervosa and GD. However, neurocognitive impairments in individuals with addictive disorders are highly significant, not only affecting quality of life, but also making abstinence and recovery more difficult. Given that CR interventions represent a relatively novel therapeutic approach to addiction and that there is currently a scarcity of studies on clinical populations suffering from GD, further research is needed to examine the potential targets of such interventions and the effectiveness of different training approaches. So far, no consensus has been reached on the optimal parameters of CR interventions (duration, intensity, frequency, group vs. individual, pencil-and-paper vs. computerized delivery, etc.). Although no firm conclusions can be drawn, CR interventions represent a promising adjunct treatment for GD. Such a novel therapy could be associated with common interventions, such as CBT and educational and motivational interventions, in order to make therapies more effective and longer-lasting and to decrease the risk of relapse.

Cognitive deficits such as poor selective attention and executive functions decline have been reported in patients with schizophrenia. Many studies have emphasized the role of dopamine in regulating cognitive functions in the general population as well as in schizophrenia. However, the relationship between cognitive processes, schizophrenia and dopaminergic candidate genes is an original approach given interesting results. The purpose of the current exploratory study was to examine the interaction of dopaminergic genes (coding for dopamine receptor D2, DRD2, and for Catecholamine-O-Methyl-Transferase, COMT) with the diagnostic of schizophrenia in (i) the executive control of attention, (ii) selective attention, and (iii) executive functions.We recruited 52 patients with schizophrenia and 53 healthy controls who performed the Stroop Color-Word Test, the Attention Network Test and the Wisconsin Card Sorting test. Four single nucleotide polymorphisms (SNPs) in the DRD2 gene (rs6275, rs6277, rs2242592 and rs1800497) and two SNPs in the COMT gene (rs4680 and rs165599) have been genotyped. Patients with schizophrenia performed significantly worse than controls in all cognitive performance, taking into account demographic variables. A significant gene by disease interaction was found for the Stroop interference (p = 0.002) for rs6275 of the DRD2 gene. The COMT Val/Val genotype and schizophrenia were associated with increased number of perseverative errors (p = 0.01).In our study, the DRD2 gene is involved in attention while the COMT gene is implicated in executive functions in patients with schizophrenia.

Introduction: Several studies have shown an association between homicide and sexual chromosomal abnormalities, but data are still lacking regarding Klinefelter syndrome. Methods: We retrospectively reviewed two cases of homicide perpetrators who were both diagnosed with Klinefelter syndrome on the basis of a karyotype analysis. A neurocognitive assessment was also performed (MMSE, Frontal Assessment Battery, brain CT, and electroencephalogram). Results: Numerous intermediate risk factors of homicide were shared by our two cases, including dispositional (male gender, young age, low socioeconomic status), historical (prior arrest record and past conviction for any offense), contextual (unemployment), and clinical (alcohol abuse). Conclusion: It is important that clinicians go beyond obvious risk factors, such as chromosomal abnormalities, to pinpoint other meaningful risk factors and potentially facilitate preventive approaches.

BACKGROUND: Growing evidence supports the validity of distinguishing major depressive disorder (MDD) plus a lifetime history of subthreshold hypomania (D(m)) from pure MDD in psychiatric classifications. The present study sought to estimate the proportion of individuals with D(m) that would have been included in RCTs for MDD using typical eligibility criteria, and examine the potential impact of including these participants on internal validity. METHODS: Data were derived from the 2001-2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC), a national representative sample of 43,093 adults of the United States population. We examined the proportion of participants with a current diagnosis of pure MDD and D(m) that would have been eligible in clinical trials for MDD with a traditional set of eligibility criteria, and compared it with that of participants with bipolar 2 disorder if the same set of eligibility criteria was applied. We considered 4 models including different definitions of subthreshold hypomania. RESULTS: We found that more than 7 out of ten participants with pure MDD and with D(m) would have been excluded by at least one classical eligibility criterion. Prevalence rate of individuals with D(m) in RCTs for MDD with traditional eligibility criteria would have ranged from 7.98% to 22.59%. Overall exclusion rate of individuals with MDD plus at least 4 lifetime concomitant hypomanic probes significantly differ from those with pure MDD, whereas it was not significantly different in those with at least 2 lifetime concomitant hypomanic probes compared to those with bipolar 2 disorder. CONCLUSIONS: The current design of clinical trials for MDD may suffer from impaired external validity and potential impaired internal validity, due to the inclusion of a substantial proportion of individuals with subthreshold hypomania presenting with similar pattern of exclusion rates to those with bipolar 2 disorder, possibly resulting in a selection bias.