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Abstract Depression is a serious mental illness that affects millions worldwide and consequently has attracted considerable research interest in recent years. Within the field of automated depression estimation, most researchers focus on neural network architectures while ignoring other research directions. Within this paper, we explore an alternate approach and study the impact of input representations on the learning ability of the models. In particular, we work with graph-based representations to highlight different aspects of input transcripts, both at the interview and corpus levels. We use sentence similarity graphs and keyword correlation graphs to exemplify the advantages of graphical representations over sequential models for binary classification problems within depression estimation. Additionally, we design multi-view architectures that split interview transcripts into question and answer views in order to take into account dialogue structure. Our experiments show the benefits of multi-view based graphical input encodings over sequential models and provide new state-of-the-art results for binary classification on the gold standard DAIC-WOZ dataset. Further analysis establishes our method as a means for generating meaningful insights and visual summaries of interview transcripts that can be used by medical professionals.

Summary: Background: No study has compared the virological and immunological status of young people with perinatally-acquired HIV infection (P-HIV) with that of people with HIV adulthood (A-HIV) having a similar duration of infection. Methods: 5 French cohorts of P-HIV and A-HIV patients with a known date of HIV-infection and receiving antiretroviral treatment (ART), were used to compare the following proportions of: virological failure (VF) defined as plasma HIV RNA ≥ 50 copies/mL, CD4 cell percentages and CD4:CD8 ratios, at the time of the most recent visit since 2012. The analysis was stratified on time since infection, and multivariate models were adjusted for demographics and treatment history. Findings: 310 P-HIV were compared to 1515 A-HIV (median current ages 20.9 [IQR:14.4–25.5] and 45.9 [IQR:37.9–53.5] respectively). VF at the time of the most recent evaluation was significantly higher among P-HIV (22.6%, 69/306) than A-HIV (3.3%, 50/1514); p ≤ 0.0001. The risk of VF was particularly high among the youngest children (2–5 years), adolescents (13–17 years) and young adults (18–24 years), compared to A-HIV with a similar duration of infection: adjusted Odds-Ratio (aOR) 7.0 [95% CI: 1.7; 30.0], 11.4 [4.2; 31.2] and 3.3 [1.0; 10.8] respectively. The level of CD4 cell percentages did not differ between P-HIV and A-HIV. P-HIV aged 6–12 and 13–17 were more likely than A-HIV to have a CD4:CD8 ratio ≥ 1: 84.1% vs. 58.8% (aOR = 3.5 [1.5; 8.3]), and 60.9% vs. 54.7% (aOR = 1.9 [0.9; 4.2]) respectively. Interpretation: P-HIV were at a higher risk of VF than A-HIV with a similar duration of infection, even after adjusting for treatment history, whereas they were not at a higher risk of immunological impairment. Exposure to viral replication among young patients living with HIV since birth or a very early age, probably because of lower adherence, could have an impact on health, raising major concerns about the selection of resistance mutations and the risk of HIV transmission. Funding: Inserm - ANRS MIE.

Auditory verbal hallucinations (AVHs) are among the most common and disabling symptoms of schizophrenia. They involve the superior temporal sulcus (STS), which is associated with language processing; specific STS patterns may reflect vulnerability to auditory hallucinations in schizophrenia. STS sulcal pits are the deepest points of the folds in this region and were investigated here as an anatomical landmark of AVHs. This study included 53 patients diagnosed with schizophrenia and past or present AVHs, as well as 100 healthy control volunteers. All participants underwent a 3-T magnetic resonance imaging T1 brain scan, and sulcal pit differences were compared between the two groups. Compared with controls, patients with AVHs had a significantly different distributions for the number of sulcal pits in the left STS, indicating a less complex morphological pattern. The association of STS sulcal morphology with AVH suggests an early neurodevelopmental process in the pathophysiology of schizophrenia with AVHs.

PurposeThe purpose of this study was to compare the natural history of visual function change in cohorts of patients affected with retinal degeneration due to biallelic variants in Bardet-Biedl syndrome genes: BBS1 and BBS10.MethodsPatients were recruited from nine academic centers from six countries (Belgium, Canada, France, New Zealand, Switzerland, and the United States). Inclusion criteria were: (1) female or male patients with a clinical diagnosis of retinal dystrophy, (2) biallelic disease-causing variants in BBS1 or BBS10, and (3) measures of visual function for at least one visit. Retrospective data collected included genotypes, age, onset of symptoms, and best corrected visual acuity (VA). When possible, data on refractive error, fundus images and autofluorescence (FAF), optical coherence tomography (OCT), Goldmann kinetic perimetry (VF), electroretinography (ERG), and the systemic phenotype were collected.ResultsSixty-seven individuals had variants in BBS1 (n = 38; 20 female patients and 18 male patients); or BBS10 (n = 29; 14 female patients and 15 male patients). Missense variants were the most common type of variants for patients with BBS1, whereas frameshift variants were most common for BBS10. When ERGs were recordable, rod-cone dystrophy (RCD) was observed in 82% (23/28) of patients with BBS1 and 73% (8/11) of patients with BBS10; cone-rod dystrophy (CORD) was seen in 18% of patients with BBS1 only, and cone dystrophy (COD) was only seen in 3 patients with BBS10 (27%). ERGs were nondetectable earlier in patients with BBS10 than in patients with BBS1. Similarly, VA and VF declined more rapidly in patients with BBS10 compared to patients with BBS1.ConclusionsRetinal degeneration appears earlier and is more severe in BBS10 cases as compared to those with BBS1 variants. The course of change of visual function appears to relate to genetic subtypes of BBS.

Albinism is a genetically heterogeneous disease in which 21 genes are known so far. Its inheritance mode is autosomal recessive except for one X-linked form. The molecular analysis of exonic sequences of these genes allows for about a 70% diagnostic rate. About half (15%) of the unsolved cases are heterozygous for one pathogenic or probably pathogenic variant. Assuming that the missing variant may be located in non-coding regions, we performed sequencing for 122 such heterozygous patients of either the whole genome (27 patients) or our NGS panel (95 patients) that includes, in addition to all exons of the 21 genes, the introns and flanking sequences of five genes, TYR, OCA2, SLC45A2, GPR143 and HPS1. Rare variants (MAF < 0.01) in trans to the first variant were tested by RT-PCR and/or minigene assay. Of the 14 variants tested, nine caused either exon skipping or the inclusion of a pseudoexon, allowing for the diagnosis of 11 patients. This represents 9.8% (12/122) supplementary diagnosis for formerly unsolved patients and 75% (12/16) of those in whom the candidate variant was in trans to the first variant. Of note, one missense variant was demonstrated to cause skipping of the exon in which it is located, thus shedding new light on its pathogenic mechanism. Searching for non-coding variants and testing them for an effect on RNA splicing is warranted in order to increase the diagnostic rate.

Schizophrenia is associated with changes in white matter (WM) integrity and with reduced life expectancy, in part because of the cardiometabolic side effects of antipsychotics. Physical activity (PA) has emerged as a candidate lifestyle intervention that is safe and effective. The study aimed to assess how an adapted PA program delivered remotely by web (e-APA) improved WM integrity in patients with schizophrenia (SZPs) and healthy controls (HCs) and to evaluate associations among WM integrity, cardiorespiratory fitness, and symptom severity. This longitudinal study was conducted over 16 weeks with 31 participants (18 SZPs and 13 HCs). Diffusion tensor imaging and tract-based spatial statistics were employed to assess WM integrity. Cardiorespiratory fitness was measured by maximal oxygen uptake (VO2max), and assessments for clinical symptoms included the Positive and Negative Syndrome Scale, Self-evaluation of Negative Symptoms and the Brief Negative Syndrome Scale (BNSS). Only the SZPs had significantly increased WM integrity after the e-APA program, with increased fractional anisotropy and decreased radial diffusivity in fasciculi involved in motor functions and language process. Furthermore, decreased negative symptoms assessed with BNSS were associated with greater WM integrity following the program. These findings suggest that e-APA may improve WM integrity abnormalities and support e-APA as a promising therapeutic strategy.

Purpose: To report the effect of internal limiting membrane (ILM) peeling prior to Voretigen Neparvovec-ryzl (VN) subretinal injection on focal chorioretinal atrophy development in patients presenting with RPE65-mediated Leber congenital amaurosis (LCA). Design: Retrospective case series. Methods: Three patients who underwent bilateral subretinal VN injection for RPE65-mediated LCA were followed up for 18–24 months. ILM peeling was performed unilaterally in patients 1 and 2 and bilaterally in patient 3. Chorioretinal atrophy was identified on fundus biomicroscopy, non-mydriatic retinography and/or ultrawide field fundus imaging. Best corrected visual acuity (BCVA), spectral-domain optical coherence tomography (SD-OCT), visual fields, full-field stimulus threshold (FST) and visual functioning questionnaire score (NEI-VFQ-25) were reported. Outcome measures were changes in BCVA, visual fields, FST, NEI-VFQ-25, and chorioretinal atrophy location. Results: Chorioretinal atrophy at the injection site exclusively developed in eyes which did not undergo prior ILM peeling. In patient 3, bilateral pre-operative nummular chorioretinal alterations progressed toward epithelial atrophic patches in the mid and extreme retinal periphery 18 months after VN injection. BCVA and visual fields improved bilaterally. NEI_VFQ 25 remained stable in patient 1 and improved in patient 2 and 3. FST test improved bilaterally in patient 3. Conclusions: ILM peeling prior to VN injection seems to be a smoother and safer technique to administer VN treatment and may prevent secondary focal atrophy development at the injection site. However, another type of more extended chorioretinal atrophy might exist and could be related to LCA evolution or to incompletely understood adverse effect of VN product.

Abstract Background Bardet–Biedl syndrome is a rare genetic disease associated with hyperphagia and early-onset, severe obesity. There is limited evidence on how hyperphagia and obesity affect health-related quality of life in patients with Bardet–Biedl syndrome, and on how management of these symptoms may influence disease burden. This analysis evaluated changes in health-related quality of life in adults and children with Bardet–Biedl syndrome in a Phase 3 trial following 1 year of setmelanotide treatment (ClinicalTrials.gov identifier: NCT03746522). Methods Patients with Bardet–Biedl syndrome and obesity received 52 weeks of treatment with setmelanotide and completed various self-reported health-related quality of life measures. Patients aged

Abstract Background Postoperative pain is one of the main factors that delays recovery after prosthetic knee surgery. The use of sufentanil sublingual tablet systems (SSTS) can effectively relieve postoperative pain, but their value in facilitating early mobilization has been little studied so far. Our aim here was to assess whether their use could facilitate recovery after knee arthroplasty in an enhanced recovery program. Case presentation In a prospective observational single-center study, thirty patients operated on for primary knee arthroplasty in the enhanced recovery pathway were included. Patients who received the SSTS (n=15) were compared with those who received an intravenous morphine patient-controlled analgesia (PCA) (n=15). Our recovery program included in particular the use of an adductor canal block, periarticular infiltration of local anesthetic by the surgeon, removal of the venous cannula from the recovery room if possible, the use of an SSTS when available or an IV morphine PCA otherwise, and early physiotherapy. Recovery parameters including the Timed-Up and Go test, pain scores at rest and on exertion, knee flexions, complications, and lengths of hospital stay were not significantly different between the two groups. However, the postoperative opioid consumption in morphine equivalents was significantly greater in the SL-sufentanil group and these patients had their venous cannula removed earlier than in IV-morphine group. Conclusion In our center, the use of a SSTS was suitable for treating postoperative pain after knee arthroplasty, but it did not improve early recovery in comparison with a morphine PCA.

The unique membrane composition of cilia is maintained by a diffusion barrier at the transition zone that is breached when the BBSome escorts signaling receptors out of cilia. Understanding how the BBSome removes proteins from cilia has been hampered by a lack of structural information. Here, we present a nearly complete Cα model of BBSome purified from cow retina. The model is based on a single-particle cryo-electron microscopy density map at 4.9-Å resolution that was interpreted with the help of comprehensive Rosetta-based structural modeling constrained by crosslinking mass spectrometry data. We find that BBSome subunits have a very high degree of interconnectivity, explaining the obligate nature of the complex. Furthermore, like other coat adaptors, the BBSome exists in an autoinhibited state in solution and must thus undergo a conformational change upon recruitment to membranes by the small GTPase ARL6/BBS3. Our model provides the first detailed view of the machinery enabling ciliary exit.

The Human Phenotype Ontology (HPO)-a standardized vocabulary of phenotypic abnormalities associated with 7000+ diseases-is used by thousands of researchers, clinicians, informaticians and electronic health record systems around the world. Its detailed descriptions of clinical abnormalities and computable disease definitions have made HPO the de facto standard for deep phenotyping in the field of rare disease. The HPO's interoperability with other ontologies has enabled it to be used to improve diagnostic accuracy by incorporating model organism data. It also plays a key role in the popular Exomiser tool, which identifies potential disease-causing variants from whole-exome or whole-genome sequencing data. Since the HPO was first introduced in 2008, its users have become both more numerous and more diverse. To meet these emerging needs, the project has added new content, language translations, mappings and computational tooling, as well as integrations with external community data. The HPO continues to collaborate with clinical adopters to improve specific areas of the ontology and extend standardized disease descriptions. The newly redesigned HPO website (www.human-phenotype-ontology.org) simplifies browsing terms and exploring clinical features, diseases, and human genes.

Amelogenesis imperfecta (AI) is a heterogeneous group of genetic rare diseases disrupting enamel development (Smith et al., Front Physiol, 2017a, 8, 333). The clinical enamel phenotypes can be described as hypoplastic, hypomineralized or hypomature and serve as a basis, together with the mode of inheritance, to Witkop’s classification (Witkop, J Oral Pathol, 1988, 17, 547–553). AI can be described in isolation or associated with others symptoms in syndromes. Its occurrence was estimated to range from 1/700 to 1/14,000. More than 70 genes have currently been identified as causative.Objectives: We analyzed using next-generation sequencing (NGS) a heterogeneous cohort of AI patients in order to determine the molecular etiology of AI and to improve diagnosis and disease management.Methods: Individuals presenting with so called “isolated” or syndromic AI were enrolled and examined at the Reference Centre for Rare Oral and Dental Diseases (O-Rares) using D4/phenodent protocol (www.phenodent.org). Families gave written informed consents for both phenotyping and molecular analysis and diagnosis using a dedicated NGS panel named GenoDENT. This panel explores currently simultaneously 567 genes. The study is registered under NCT01746121 and NCT02397824 (https://clinicaltrials.gov/).Results: GenoDENT obtained a 60% diagnostic rate. We reported genetics results for 221 persons divided between 115 AI index cases and their 106 associated relatives from a total of 111 families. From this index cohort, 73% were diagnosed with non-syndromic amelogenesis imperfecta and 27% with syndromic amelogenesis imperfecta. Each individual was classified according to the AI phenotype. Type I hypoplastic AI represented 61 individuals (53%), Type II hypomature AI affected 31 individuals (27%), Type III hypomineralized AI was diagnosed in 18 individuals (16%) and Type IV hypoplastic-hypomature AI with taurodontism concerned 5 individuals (4%). We validated the genetic diagnosis, with class 4 (likely pathogenic) or class 5 (pathogenic) variants, for 81% of the cohort, and identified candidate variants (variant of uncertain significance or VUS) for 19% of index cases. Among the 151 sequenced variants, 47 are newly reported and classified as class 4 or 5. The most frequently discovered genotypes were associated with MMP20 and FAM83H for isolated AI. FAM20A and LTBP3 genes were the most frequent genes identified for syndromic AI. Patients negative to the panel were resolved with exome sequencing elucidating for example the gene involved ie ACP4 or digenic inheritance.Conclusion: NGS GenoDENT panel is a validated and cost-efficient technique offering new perspectives to understand underlying molecular mechanisms of AI. Discovering variants in genes involved in syndromic AI (CNNM4, WDR72, FAM20A … ) transformed patient overall care. Unravelling the genetic basis of AI sheds light on Witkop’s AI classification.

Abstract: Background Physical activity (PA) has emerged as an interesting adjuvant non-pharmacological intervention in patients with schizophrenia (SZPs). The vast majority of programs are face-to-face without considering the patients’ physiological capacities and their difficulty to achieve the programs. The aim of this study was to demonstrate the efficacy of PA on clinical variables and brain plasticity. Its originality was to adapt PA on the cardiorespiratory and physical capacities (APA) and to deliver PA remotely by a videoconference coach (e-APA). Methods This longitudinal study included 35 SZPs (DSM-5) randomized either in an e-APA group or in a control group (health education training (e-HE)). Both programs were delivered in the same conditions, remotely via the web with a professional, for two 60-minute sessions per week during 16 weeks. Cardiorespiratory capacity measured by VO2max, clinical symptoms assessed with PANSS, BNSS and SNS, total hippocampus (HCP) volumes and their subfields, were evaluated in pre- (session 1) and post- interventions (session 2). High-resolution T1-weighted and two high-resolution T2w brain volumes were proceeded at session 1 and 2 (MRI 3-T, Philips). ANCOVAs were performed to determine intervention and/or diagnostic effects on relative variation (RV) of cardiorespiratory capacity, clinical symptoms and HCP volumes. Results The retention rate of SZPs in the study was 88.6%. SZPs of e-APA group presented a greater RV of VO2max (+7.3%) compared to SPZs-HE (-3.9%) (p = 0.024). No significant effect of the e-APA compared to the e-HE was demonstrated regarding the RV of the clinical symptoms. However, between 1 and 2 sessions, total PANSS scores, positive and general PANSS sub-scores significantly decreased in both groups while total SNS and BNSS scores only decreased in e-APA group. Finally, a positive and greater RV of the left subiculum volume was observed in e-APA (+3.4%) compared to e-HE (-2.5%) (p = 0.0005). Conclusion This study is the first one demonstrating the feasibility and acceptability of a remote APA program in SZPs with high participation rates. Our results show that e-APA induces brain plasticity reflected by an increase of HCP subfield volume and improves the cardiorespiratory capacity in SZPs. This study underlines that remote APA represents an innovative, original, safe and effective adjunctive therapeutic strategy in schizophrenia. Disclosure of Interest None Declared

Introduction Auditory verbal hallucinations (AVH) are experienced by approximately 70% of patients with schizophrenia. At the present time, there are no self-evaluation scales for auditory verbal hallucinations. They would allow the patient to self-assess their hallucinations when they occur, taking into account the great variability over time. Moreover, self-assessment allows the patients to better recognize their symptoms and to be more engaged in their treatment. In this context, we have developed a digital device (MIMO) allowing the patient to self-evaluate his/her AVH and to declare his/her hallucinatory crisis at any time. This device contains a self-assessment of auditory verbal hallucinations (SAVH) with 13 questions, 9 of which concern the frequency, the severity, the content and the impact of hallucinations. These 9 questions are rated on a 5-point scale ranging from 0 (absent) to 5 (severe). The patients and practitioners can have an online feedback on the scores as well as on their temporal changes. Objectives The aim of this study was to validate the SAVH scale as well the digital tool, to demonstrate the acceptability by the patients and to prove the feasibility in using such a digital device (mobile phone or tablet). Methods Forty one patients with schizophrenia or schizoaffective disorder (DSM-5) with AVH loaded this application on their own mobile or on a loaned one. AVH was also assessed with the Auditory Hallucination Rating Scale associated with the Brief Psychiatric Rating Scale and the self-assessment of insight. Moreover, a questionnaire included a visual analogic scale on the global satisfaction of the device scoring from 0 (“Not at all satisfied”) to 10 (“Very satisfied”) and 22 questions concerning the conditions of use, the acceptability and the content of the app, its impact on mental health, and questions related to the declaration of hallucinatory crisis. Moreover, statistical analyses were carried out testing internal, external and construct validities of the SAVH. Results 56.1% and 36.6% of patients found the app to be easy and very easy to use, respectively. 61% and 29.3% of the patients considered that the questions were respectively rather adapted and very adapted to the evaluation of auditory hallucinations. 46.3% of patients found the questions quite easy to understand. The majority of patients felt that the MIMO app could be useful to them. Overall satisfaction was 8.073+-3.8 indicating very good overall patient satisfaction of the app. Statistical tests revealed significant convergence and divergence validities as well as good internal consistency of the SAVH. Conclusions This study demonstrated good psychometric properties of the SAVH and very good acceptability of this kind of assessment by digital device in patients with schizophrenia. Such a device can be quite useful to assess the efficacy of the treatment of AVH and to increase the patient’s empowerment. Disclosure of Interest None Declared

Introduction Adapted physical activity (APA) has beneficial neurobiological impact but the underlying pathophysiological mechanisms remain poorly described. APA is currently recognized as an adjuvant therapy to antipsychotic treatments in patients with schizophrenia (SCZs) to reduce the severity of negative symptoms and cognitive impairment. SCZs exhibit hippocampal N-acetylaspartate (NAA) reduction, a marker of neuronal viability and integrity whose concentrations can be assessed by proton magnetic resonance spectroscopy (1H-MRS). Objectives The purpose of this study was to evaluate the impact of remote physical activity (e-APA) via the web on the NAA relative variations in the left hippocampus in SCZs compared to a patient control group benefiting from an health education program (HE). This study concerns one of the secondary objectives of the PEPsy V@SI study co-financed by the Pierre Deniker Foundation, the European Union and the Normandy Region within the framework of the FEDER/FSE 2014-2020 operational program. Methods Thirty-five SCZs were randomized in the e-APA active group or in the control group (HE). Participants received the interventions during 16 weeks, with two visioconference sessions per week. A 1H-MRS sequence positioned on the left hippocampus (MRI-3T) was acquired before and after both interventions. Absolute NAA concentrations in the left hippocampus were obtained using Osprey software after partial volume correction. After checking the quality criteria, the spectra of 6 SCZs in the e-APA group and 8 SCZs in the HE group were analyzed. To test the difference between interventions on the NAA relative variations, a Wilcoxon-Mann-Whitney test and effect size were performed. Paired Wilcoxon tests were used in each group before and after the interventions. Results No significant difference was found in NAA relative variations in the left hippocampus between the e-APA group and the HE group (p = 0.18), although the effect size was 0.38 (considered as moderate). However, a trend towards an increase of NAA was observed in the e-APA group (before intervention: 12.08 International Units (I.U); after: 13.81 I.U) (p = 0.06) but not in the HE group (before intervention: 13.75 I.U ; after: 13.85 I.U) (p = 0.84). Conclusions Our results showed a NAA significant increase in SCZs after an e-APA program, indicating a beneficial impact of e-APA on neuronal viability that might reflect an hippocampal plasticity. However, this increase did not differ significantly between active and control groups probably due to a weak statistical power. Disclosure of Interest L. Metivier: None Declared, F. Briend: None Declared, M. Tréhout: None Declared, L. Bigot: None Declared, G. Quarck: None Declared, A. Herbinet: None Declared, E. Leroux: None Declared, S. Dollfus Consultant of: Fabre,Gedeon,Roche and Takeda, inivited Conferences by Lundbeck, Otsuka, Janssen ; at contracts with Prophase MedAvances and NeuroCogTrials

A new method to reliably simulate the PDE and jitter tail for realistic three-dimensional SPAD devices is presented. The simulation method is based on the use of electric field lines to mimic the carriers’ trajectories, and on one-dimensional models for avalanche breakdown probability and charges transport. This approach allows treating a three-dimensional problem as several one-dimensional problems along each field line. The original approach is applied to the McIntyre model for avalanche breakdown probability to calculate PDE, but also for jitter prediction using a dedicated advection-diffusion model. The results obtained numerically are compared with an extensive series of measurements and show a good agreement on a wide variety of device designs.

Abstract Background One out of three patients with schizophrenia failed to respond adequately to antipsychotics and continue to experience debilitating symptoms such as auditory hallucinations and negative symptoms. The development of additional therapeutic approaches for these persistent symptoms constitutes a major goal for patients. Here, we develop a randomized-controlled trial testing the efficacy of high-frequency transcranial random noise stimulation (hf-tRNS) for the treatment of resistant/persistent symptoms of schizophrenia in patients with various profiles of symptoms, cognitive deficits and illness duration. We also aim to investigate the biological and cognitive effects of hf-tRNS and to identify the predictors of clinical response. Methods In a randomized, double-blind, 2-arm parallel-group, controlled, multicentre study, 144 patients with schizophrenia and persistent symptoms despite the prescription of at least one antipsychotic treatment will be randomly allocated to receive either active (n = 72) or sham (n = 72) hf-tRNS. hf-tRNS (100–500 Hz) will be delivered for 20 min with a current intensity of 2 mA and a 1-mA offset twice a day on 5 consecutive weekdays. The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left temporoparietal junction. Patients’ symptoms will be assessed prior to hf-tRNS (baseline), after the 10 sessions, and at 1-, 3- and 6-month follow-up. The primary outcome will be the number of responders defined as a reduction of at least 25% from the baseline scores on the Positive and Negative Syndrome Scale (PANSS) after the 10 sessions. Secondary outcomes will include brain activity and connectivity, source monitoring performances, social cognition, other clinical (including auditory hallucinations) and biological variables, and attitude toward treatment. Discussion The results of this trial will constitute a first step toward establishing the usefulness of hf-tRNS in schizophrenia whatever the stage of the illness and the level of treatment resistance. We hypothesize a long-lasting effect of active hf-tRNS on the severity of schizophrenia symptoms as compared to sham. This trial will also have implications for the use of hf-tRNS as a preventive intervention of relapse in patients with schizophrenia. Trial registration ClinicalTrials.gov NCT02744989. Prospectively registered on 20 April 2016

Abstract Aim The Self-evaluation of Negative Symptoms (SNS) has been developed to allow schizophrenia patients to evaluate themselves in five dimensions of negative symptoms. The present study aimed to examine psychometric properties of the Persian version of SNS. Methods A group of 50 patients with schizophrenia and a group of 50 healthy controls received the Persian-SNS. Severity of negative symptoms were evaluated by the Scale for Assessment of Negative symptoms (SANS) and the Brief Psychiatric Rating Scale (BPRS). Results The results showed that the Cronbach’s alpha for the Persian SNS was 0.95. The Persian-SNS and its subscales showed significant positive correlations with the total SANS score and SANS subscales as well as BPRS negative subscale, thus confirming the validity of the scale. Finally, the Persian-SNS showed the ability to discriminate patients with schizophrenia from healthy controls. Conclusion The acceptable properties of the Persian version of SNS demonstrated that it is a practical tool for screening negative symptoms in Persian-speaking schizophrenia patients.

Léa Dormegny,1,2 Reana Velizarova,1 Carmen M Schroder,1,3 Ulker Kilic-Huck,1,3 Henri Comtet,1,3 Hélène Dollfus,4 Patrice Bourgin,1,3 Elisabeth Ruppert1,3 1Centre des Troubles du Sommeil - CIRCSom, Hôpital Civil, University of Strasbourg, Strasbourg, 67091, France; 2Department of Ophthalmology, Hôpital Civil, University of Strasbourg, Strasbourg, 67091, France; 3Institute for Cellular and Integrative Neurosciences, CNRS - UPR 3212, Strasbourg, 67000, France; 4Centre des Affections Rares en Génétique Ophtalmologique (CARGO), University of Strasbourg, Strasbourg, 67091, FranceCorrespondence: Elisabeth RuppertCentre des Troubles du Sommeil - CIRCSom - Hôpital Civil, 1, place de l’Hôpital, BP 426, Cedex, Strasbourg, 67091, FranceTel +33 3 88 11 64 30Fax +33 3 88 11 51 53Email elisabeth.ruppert@chru-strasbourg.frObjective/Background: Bardet–Biedl syndrome (BBS) is a rare but well-recognized ciliopathy with high genetic and phenotypic heterogeneity. Cardinal features include obesity, diabetes and high blood pressure (HBP), which are often associated with sleep-disordered breathing. Also, the high prevalence of blindness due to retinal dystrophy could affect circadian sleep–wake rhythms. We characterized in this cohort of adult BBS patients sleep-disordered breathing, sleep quality, daytime sleepiness and chronotype.Patients and Methods: Thirty-two patients with genetically confirmed BBS were included in this observational single center study. Overnight respiratory polygraphy was performed for sleep apnea syndrome (SAS) in 30 patients. Quality of sleep, daytime sleepiness, fatigue and chronotype were assessed in 25 patients using Pittsburgh sleep quality index (PSQI), 14-day sleep diary (SD), Epworth sleepiness scale (ESS), Pichot fatigue scale (PFS) and Horne and Ostberg morningness-eveningness questionnaire (MEQ).Results: Patients’ mean age was 32± 11 years and mean BMI 32.6± 7.7 kg/m2. Eleven (35%) patients had HBP and 7 (22%) diabetes. Moderate to severe sleep apnea syndrome (SAS) was present in 5 (17%) and was not associated with altered sleep, daytime sleepiness or fatigue. Most of the patients (63%) evaluated their sleep as of good quality (PSQI ≤ 5). Median scores of sleep quality, daytime sleepiness and fatigue were normal (PSQI of 3.0 [2.0– 6.0], ESS of 9.0 [6.0– 13.0] and PFS of 8.0 [3.0– 13.0], respectively). Predominant chronotypes according to MEQ were either “intermediate” (57%) or “moderate morning” (29%). None had a free running sleep–wake cycle. 14-day SD revealed overall few awakenings at night and low daytime napping.Conclusions: Given the cardiovascular risk factors, systematic screening for SAS should be considered in BBS patients, regardless of sleep and daytime vigilance complaints. None of these highly visually impaired patients had a circadian sleep–wake rhythm disorder. Further objective assessments are needed to better characterize sleep and circadian rhythms in BBS patients.Keywords: Bardet–Biedl syndrome, ciliopathy, sleep disordered breathing, sleep apnea syndrome, chronotype, circadian rhythm sleep wake disorder

Abstract Dominant optic atrophy (DOA) is genetically heterogeneous and most commonly caused by mutations in OPA1. To distinguish between the classical OPA1-related and the recently identified SSBP1-related DOAs, the retina and fovea of 27 patients carrying the SSBP1 p.Arg38Gln variant were scrutinized using 20° × 20° macular cube and 30° and 55° field fundus autofluorescence photographs. Age of onset, visual acuity, retinal nerve fiber layer and macular thicknesses were recorded. Three SSBP1-patients were asymptomatic, 10 had isolated DOA, and 12 had a combined DOA plus foveopathy. The foveopathy, with a tiny defect of the ellipsoid and interdigitation lines, was similar in all patients, independent of age. There were no significant statistical differences in terms of visual acuity and SD-OCT measurements between patients with isolated DOA (mean visual acuity in decimals: 0.54 ± 0.41) and those with combined foveopathy (0.50 ± 0.23). Two patients over 50 years of age developed a progressive rod-cone dystrophy, leading to severe visual impairment. SSBP1-related DOA shares similarities with OPA1-related DOA with an incomplete penetrance and an early childhood visual impairment. Nevertheless, the presence of a congenital foveopathy with no impact on visual acuity is a major criterion to distinguish SSBP1 cases and orient the appropriate genetic analysis.

Abstract Cohen syndrome (CS) is a rare syndromic form of rod-cone dystrophy. Recent case reports have suggested that cystoid maculopathy (CM) could affect CS patients with an early onset and high prevalence. Our study aims at improving our understanding and management of CM in CS patients through a retrospective case series of ten CS patients with identified pathogenic variants in VPS13B. Longitudinal optical coherence tomography (OCT) imaging was performed and treatment with carbonic anhydrase inhibitors (CAI) was provided to reduce the volume of cystoid spaces. CM affected eight out of ten patients in our cohort. The youngest patient showed a strong progression of macular cysts from the age of 4.5 to 5 years despite oral CAI medication. Other teenage and young adult patients showed stable macular cysts with and without treatment. One patient showed a moderate decrease of cystoid spaces in the absence of treatment at 22 years of age. Through a correlative analysis we found that the volume of cystoid spaces was positively correlated to the thickness of peripheral and macular photoreceptor-related layers. This study suggests that CAI treatments may not suffice to improve CM in CS patients, and that CM may resolve spontaneously during adulthood as photoreceptor dystrophy progresses.