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

Abstract: Activation of the ATP-dependent P2X7 receptor modulates glucose transport in intestinal epithelial cells through the downregulation of glucose transporter GLUT2. In the present study, we show that an increase [...]

Introduction: Cardiac glycosides comprise medications such as digoxin and digitoxin, plants, and even certain toad venoms. Intoxication with cardiac glycosides can lead to hemodynamic instability and cardiac arrest. With this narrative review, our objective was to determine if any therapy used in a near-cardiac arrest state due to cardiac glycoside poisoning could improve survival with favourable functional and neurological outcomes. Methods: We searched the Medline, PubMed, EMBASE and Cochrane Library databases up to February 2022 for controlled trials, observational studies, and case reports. We reviewed studies if participants were exposed to a cardiac glycoside, had hemodynamic instability, and an intervention was attempted to reverse the toxicity. The effect of interventions on (1) survival with favourable functional and neurological outcomes and (2) correction of hemodynamic instability was assessed. Results: Of the 2422 studies found, 73 were included for analysis, of which 58 were case reports or series, and 15 were observational cohorts. Most patients were intoxicated with medication (60 individual cases and 11 observational cohorts). Administration of digoxin immune-Fab fragments was associated with improved hemodynamic status and survival in medication patients. Administration of magnesium, cardioversion, and cardiac pacing was associated with favourable outcomes, while administration of atropine, antiarrhythmics, or calcium was not. Conclusion: In patients with hemodynamic instability due to cardiac glycoside intoxication, digoxin immune-Fab fragments should be given, and magnesium administration, cardioversion, and cardiac pacing can reasonably be attempted.

Abstract Backgrounds Social skills are frequently impaired in neurodevelopmental disorders and genetic conditions, including 22q11.2 deletion syndrome (22q11DS) and autism spectrum disorders (ASD). Although often assessed with questionnaires, direct assessment provides a more valid estimate of the constructs. Role-plays (i.e., simulates situational settings) therefore appear to be an appropriate indicator of social skills in daily life. Methods This co-registered study involved 53 individuals with 22q11DS, 34 individuals with ASD, and 64 typically developing (TD) peers aged 12–30 years. All participants were assessed with role-plays as well as parent-reported questionnaires and clinical interviews focusing on social skills, functioning and anxiety. Results Both clinical groups showed impaired social skills compared to TD, but distinct social profiles emerged between the groups. Individuals with 22q11DS displayed higher social appropriateness and clarity of speech but weaker general argumentation and negotiation skills, with the opposite pattern observed in participants with ASD. No association was found between social skills measured by direct observation and caregiver reports. Social anxiety, although higher in clinical groups than in TD, was not associated with role-plays. Conclusions This study highlights the need to train social skills through tailored interventions to target the specific difficulties of each clinical population. It also highlights the importance of combining measures as they do not necessarily provide the same outcome.

Abstract Congenital heart disease (CHD) affecting the conotruncal region of the heart, occurs in 40–50% of patients with 22q11.2 deletion syndrome (22q11.2DS). This syndrome is a rare disorder with relative genetic homogeneity that can facilitate identification of genetic modifiers. Haploinsufficiency of TBX1, encoding a T-box transcription factor, is one of the main genes responsible for the etiology of the syndrome. We suggest that genetic modifiers of conotruncal defects in patients with 22q11.2DS may be in the TBX1 gene network. To identify genetic modifiers, we analyzed rare, predicted damaging variants in whole genome sequence of 456 cases with conotruncal defects and 537 controls, with 22q11.2DS. We then performed gene set approaches and identified chromatin regulatory genes as modifiers. Chromatin genes with recurrent damaging variants include EP400, KAT6A, KMT2C, KMT2D, NSD1, CHD7 and PHF21A. In total, we identified 37 chromatin regulatory genes, that may increase risk for conotruncal heart defects in 8.5% of 22q11.2DS cases. Many of these genes were identified as risk factors for sporadic CHD in the general population. These genes are co-expressed in cardiac progenitor cells with TBX1, suggesting that they may be in the same genetic network. The genes KAT6A, KMT2C, CHD7 and EZH2, have been previously shown to genetically interact with TBX1 in mouse models. Our findings indicate that disturbance of chromatin regulatory genes impact the TBX1 gene network serving as genetic modifiers of 22q11.2DS and sporadic CHD, suggesting that there are some shared mechanisms involving the TBX1 gene network in the etiology of CHD.

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

Introduction: Canadian Indigenous populations have a high incidence of poisoning; it has been suggested that care provided to the population living in remote areas is suboptimal. Our study aims to compare the continuum of care of poisoned people in Indigenous communities with those in non-Indigenous communities located in rural regions in the province of Québec. Methods: We conducted a multicenter retrospective cohort study using data from the Center Antipoison du Québec (CAPQ) over a 2-year period (2016-2017). We evaluated the care trajectory of Indigenous patients suffering of poisoning as compared to non-Indigenous patients living in rural areas. Our primary outcome was the duration of CAPQ involvement in case management. Our secondary outcome was the symptoms severity at the end of case management. Results: Among 491 identified poisoned patients (238 Indigenous/253 non-Indigenous), the duration of CAPQ involvement in case management was 9.4 h [2.9-21.3] for Indigenous patients versus 5.5 h [0.1-14.4] for non-Indigenous patients. No statistically significant difference was found between groups (geometric means ratio (GMR) adjusted = 1.08; [0.84; 1.38]). Results were consistent by age and sex groups. Most patients, in both Indigenous and non-Indigenous, showed mild to moderate symptoms at follow-up (59% vs 54%). One death was registered in each group. The CAPQ received a limited number of calls from the non-conventioned First Nations during the study period. Conclusions: We did not observe differences on the duration in case management. Perceptions of suboptimal care provided to rural Indigenous population are likely to be related to geographical remoteness rather than ethnicity. Further research is needed to better identify potential factors involved in the continuity of care provided in emergency situations. Another study will be carried out to describe the Indigenous realities and to better understand the results of this study.

Introduction Traumatic brain injury (TBI) is the leading cause of mortality and long-term disability in young adults. Despite the high prevalence of anaemia and red blood cell transfusion in patients with TBI, the optimal haemoglobin (Hb) transfusion threshold is unknown. We undertook a randomised trial to evaluate whether a liberal transfusion strategy improves clinical outcomes compared with a restrictive strategy.Methods and analysis HEMOglobin Transfusion Threshold in Traumatic Brain Injury OptimizatiON is an international pragmatic randomised open label blinded-endpoint clinical trial. We will include 742 adult patients admitted to an intensive care unit (ICU) with an acute moderate or severe blunt TBI (Glasgow Coma Scale ≤12) and a Hb level ≤100 g/L. Patients are randomly allocated using a 1:1 ratio, stratified by site, to a liberal (triggered by Hb ≤100 g/L) or a restrictive (triggered by Hb ≤70 g/L) transfusion strategy applied from the time of randomisation to the decision to withdraw life-sustaining therapies, ICU discharge or death. Primary and secondary outcomes are assessed centrally by trained research personnel blinded to the intervention. The primary outcome is the Glasgow Outcome Scale extended at 6 months. Secondary outcomes include overall functional independence measure, overall quality of life (EuroQoL 5-Dimension 5-Level; EQ-5D-5L), TBI-specific quality of life (Quality of Life after Brain Injury; QOLIBRI), depression (Patient Health Questionnaire; PHQ-9) and mortality.Ethics and dissemination This trial is approved by the CHU de Québec—Université Laval research ethics board (MP-20-2018-3706) and ethic boards at all participating sites. Our results will be published and shared with relevant organisations and healthcare professionals.Trial registration number NCT03260478.

BackgroundCarriers of the 22q11.2 deletion syndrome (22q11DS) have an enhanced risk of developing psychotic disorders. Full-blown psychosis is typically diagnosed by late adolescence/adulthood. However, cognitive decline is already apparent as early as childhood. Recent findings in mice show that antipsychotic medication administered during adolescence has a long-lasting neuroprotective effect. These findings offer promising evidence for implementing preventive treatment in humans at risk for psychosis.MethodsWe conducted a 12-week double-blind randomized controlled clinical trial with individuals with 22q11DS. Recruitment difficulties resulted in a final sample size of 13 participants (n = 6 treated with antipsychotics and n = 7 receiving placebo). We examined the response to treatment and assessed its short- and long-term effects on psychotic symptomatology using the Structured Interview for Psychosis-Risk Syndromes (SIPS) and cognitive measures.ResultsFirst, two treated participants discontinued treatment after experiencing adverse events. Second, treated participants showed a short-term improvement in 33.3% of the SIPS items, mainly those targeting negative symptoms. Third, reliable improvements in at least one measure of working memory and attention were respectively found in 83.3 and 66.7% of treated participants.ConclusionThis is the first double-blind study to investigate the potential neuroprotective effect of antipsychotics in humans at risk for psychosis. Our preliminary results suggest that antipsychotic treatment may prevent long-term deterioration in clinical symptoms and cognitive skills. Yet, given the limited sample size, our findings need to be replicated in larger samples. To do so, future studies may rather adopt open-label or retrospective designs to ensure sufficient power.Clinical trial registration[www.ClinicalTrials.gov], identifier [NCT04639960].

BACKGROUND In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). METHODS We conducted a phase 2, single-cohort, 25-center, global study of tisagenlecleucel in pediatric and young adult patients with CD19+ relapsed or refractory B-cell ALL. The primary end point was the overall remission rate (the rate of complete remission or complete remission with incomplete hematologic recovery) within 3 months. RESULTS For this planned analysis, 75 patients received an infusion of tisagenlecleucel and could be evaluated for efficacy. The overall remission rate within 3 months was 81%, with all patients who had a response to treatment found to be negative for minimal residual disease, as assessed by means of flow cytometry. The rates of event-free survival and overall survival were 73% (95% confidence interval [CI], 60 to 82) and 90% (95% CI, 81 to 95), respectively, at 6 months and 50% (95% CI, 35 to 64) and 76% (95% CI, 63 to 86) at 12 months. The median duration of remission was not reached. Persistence of tisagenlecleucel in the blood was observed for as long as 20 months. Grade 3 or 4 adverse events that were suspected to be related to tisagenlecleucel occurred in 73% of patients. The cytokine release syndrome occurred in 77% of patients, 48% of whom received tocilizumab. Neurologic events occurred in 40% of patients and were managed with supportive care, and no cerebral edema was reported. CONCLUSIONS In this global study of CAR T-cell therapy, a single infusion of tisagenlecleucel provided durable remission with long-term persistence in pediatric and young adult patients with relapsed or refractory B-cell ALL, with transient high-grade toxic effects. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT02435849.) [ABSTRACT FROM AUTHOR]

Abstract Background Cognitive-affective factors influence the perception of pain and disability. These factors can lead to pain behaviors (PB) that can persist and become maladaptive. These maladaptive PB will further increase the risk of chronicity or persistence of symptoms and disability. Thus, clinicians must be prepared to recognize maladaptive PB in a clinical context. To date, in the context of assessment in a rehabilitation setting, PB in clinical settings are poorly documented. The main objective of this study was to identify direct observation methods and critically appraise them in order to propose recommendations for practice. As a secondary objective, we explored and extracted the different observable PB that patients could exhibit and that clinicians could observe. Methods We conducted a comprehensive review on four databases with a generic search strategy in order to obtain the largest range of PB. For the first objective, a two-step critical appraisal used clinical criteria (from qualitative studies on barriers to implement routine measures) and psychometric criteria (from Brink and Louw critical appraisal tool) to determine which observation methods could be recommended for clinical practice. For the second objective, we extracted PB found in the literature to list potential PB that patients could exhibit, and clinicians could observe. Results From the 3362 retrieved studies, 47 met the inclusion criteria for the first objective. The clinical criteria allowed us to select three observation methods. After the psychometric step, two observation methods were retained and recommended for clinical practice: the Behavioral Avoidance Test-Back Pain (BAT-Back) and the Pain Behaviour Scale (PaBS). For the second objective, 107 studies met the inclusion criteria. The extraction of the PB allowed us to list a large range of PB and classify the data in 7 categories of PB. Conclusion Our results allowed us to recommend two observation methods for clinical practice. However, these methods have limitations and are validated only in chronic low back pain populations. With the extraction of PB presented in the literature, we contribute to better prepare clinicians to recognize PB in all patients who are experiencing pain.

Abstract Cognitive deficits in individuals at risk of psychosis represent a significant challenge for research, as current strategies for symptomatic treatment are often ineffective. Recent studies showed that atypical cognitive development predicts the occurrence of psychotic symptoms. Additionally, abnormal brain development is known to predate clinical manifestations of psychosis. Therefore, critical developmental stages may be the best period for early interventions expected to prevent cognitive decline and protect brain maturation. However, it is challenging to identify and treat individuals at risk of psychosis in the general population before the onset of the first psychotic symptoms. 22q11.2 deletion syndrome (22q11DS), the neurogenetic disorder with the highest genetic risk for schizophrenia, provides the opportunity to prospectively study the development of subjects at risk for psychosis. In this retrospective cohort study, we aimed to establish if early treatment with SSRIs in children and adolescents with 22q11DS was associated with long-term effects on cognition and brain development. We included 98 participants with a confirmed diagnosis of 22q11DS followed up 2–4 times (age range: 10–32). Thirty subjects without psychiatric disorders never received psychotropic medications, thirty had psychotic symptoms but were not treated with SSRIs, and 38 received SSRIs treatment. An increase in IQ scores characterized the developmental trajectories of participants receiving treatment with SSRIs, even those with psychotic symptoms. The thickness of frontal regions and hippocampal volume were also relatively increased. The magnitude of the outcomes was inversely correlated to the age at the onset of the treatment. We provide preliminary evidence that early long-term treatment with SSRIs may attenuate the cognitive decline associated with psychosis in 22q11DS and developmental brain abnormalities.

Abstract Background The 22q11.2 deletion syndrome (22q11DS) is a genetic syndrome that results in a highly variable profile of affected individuals of which impairments in the social domain and increased psychopathology are the most prominent. Notably, 25–30% of affected individuals eventually develop schizophrenia/psychosis, predisposing persons with the syndrome to increased risk for this disorder. Because social cognition is considered to underlie social behavior and to be related to psychopathology, this systematic review investigated social cognition in individuals with 22q11DS and examined reported links across its domains with psychopathology and social outcomes. This can provide the basis for a closer understanding of the path from risk to disorder and will inform on the specific domains that can be targeted with preventive intervention strategies. Method Systematic literature review of studies that reported the links between social cognitive domains and psychopathology and/or social outcomes in individuals with 22q11DS. Electronic databases searched were PubMed and PsycINFO. Results Defined eligibility criteria identified a total of ten studies to be included in the present review. Selected studies investigated links between two domains of social cognition (emotion processing and theory of mind (ToM)) and psychopathology and/or social outcomes. With respect to the links to psychopathology, two aspects of social cognition were related primarily to negative symptoms. Results regarding the associations to positive and emotional symptoms (anxiety/depression) are limited and require further investigation. Even though both aspects of social cognition were associated with social outcomes, several studies also found no links between these two domains. Both reports invite for an additional examination of reported results and specific considerations regarding chosen constructs. Conclusion Although equivocal, results of the present review provide sufficient evidence that social cognition is a useful domain for the closer elucidation of clinical outcomes and social difficulties in this population. At the same time, longitudinal studies and consideration of other variables are also necessary for a timely understanding of affected persons in this respect.

Abstract The SARS-CoV-2 pandemic is not only a threat to physical health but is also having severe impacts on mental health. Although increases in stress-related symptomatology and other adverse psycho-social outcomes, as well as their most important risk factors have been described, hardly anything is known about potential protective factors. Resilience refers to the maintenance of mental health despite adversity. To gain mechanistic insights about the relationship between described psycho-social resilience factors and resilience specifically in the current crisis, we assessed resilience factors, exposure to Corona crisis-specific and general stressors, as well as internalizing symptoms in a cross-sectional online survey conducted in 24 languages during the most intense phase of the lockdown in Europe (22 March to 19 April) in a convenience sample of N = 15,970 adults. Resilience, as an outcome, was conceptualized as good mental health despite stressor exposure and measured as the inverse residual between actual and predicted symptom total score. Preregistered hypotheses (osf.io/r6btn) were tested with multiple regression models and mediation analyses. Results confirmed our primary hypothesis that positive appraisal style (PAS) is positively associated with resilience (p

Abstract Disruptions of white matter microstructure have been widely reported in schizophrenia. However, the emergence of these alterations during preclinical stages remains poorly understood. 22q11.2 Deletion Syndrome (22q11.2DS) represents a unique model to study the interplay of different risk factors that may impact neurodevelopment in premorbid psychosis. To identify the impact of genetic predisposition for psychosis on white matter development, we acquired longitudinal MRI data in 201 individuals (22q11.2DS = 101; controls = 100) aged 5–35 years with 1–3 time points and reconstructed 18 white matter tracts using TRACULA. Mixed model regression was used to characterize developmental trajectories of four diffusion measures—fractional anisotropy (FA), axial (AD), radial (RD), and mean diffusivity (MD) in each tract. To disentangle the impact of additional environmental and developmental risk factors on white matter maturation, we used a multivariate approach (partial least squares (PLS) correlation) in a subset of 39 individuals with 22q11.2DS. Results revealed no divergent white matter developmental trajectories in patients with 22q11.2DS compared to controls. However, 22q11.2DS showed consistently increased FA and reduced AD, RD, and MD in most white matter tracts. PLS correlation further revealed a significant white matter-clinical risk factors relationship. These results indicate that while age-related changes are preserved in 22q11.2DS, white matter microstructure is widely disrupted, suggesting that genetic high risk for psychosis involves early occurring neurodevelopmental insults. In addition, multivariate modeling showed that clinical risk factors further impact white matter development. Together, these findings suggest that genetic, developmental, and environmental risk factors may play a cumulative role in altering normative white matter development during premorbid stages of psychosis.

Abstract Background 22q11.2 deletion syndrome (22q11DS) is a genetic disorder associated with an increased risk of psychiatric disorders. Vulnerability for psychopathology has been related to an increased reactivity to stress. Here, we examined affective states, perceived stress, affective and psychotic reactivity to various sources of environmental stress using the experience sampling method (ESM), a structured diary technique allowing repeated assessments in the context of daily life. Methods Adults with 22q11DS (n = 31; age, 34.1 years) and matched healthy controls (HCs; n = 24; age, 39.9 years) were included. ESM was used to assess affective states, perceived stress, and stress reactivity. Data were analyzed using multilevel regression models. Results Adults with 22q11DS displayed overall higher levels of negative affect but comparable levels of positive affect compared to HCs. Higher levels of perceived stress were reported by individuals with 22q11DS. Comparable affective and psychotic reactivity in relation to all types of environmental stress was observed between the two groups. Conclusion The results point toward higher levels of negative affect and differences in the perception of daily hassles in 22q11DS but no difference in affective or psychotic reactivity to stress. This study contributes to the growing literature regarding the impact of stress on the development of psychopathology in the 22q11DS population.

Background: 22q11.2 deletion syndrome (22q11DS) is a neurogenetic condition associated to a high risk for psychiatric disorders, including psychosis. Individuals with 22q11DS are thought to experience increased levels of chronic stress, which could lead to alterations in hypothalamic-pituitary-adrenocortical (HPA)-axis functioning. In the current study, we investigated for the first time diurnal salivary cortisol profiles in adolescents and young adults with 22q11DS as well as their link with stress exposure, coping strategies and psychopathology, including psychotic symptoms. Methods: Salivary cortisol was collected from adolescents and young adults with 22q11DS (n = 30, age = 19.7) and matched healthy controls (HC; n = 36, age = 18.5) six times a day for two days. Exposure to stressful life events, including peer victimization, coping strategies and general psychopathology were assessed with questionnaires. Psychotic symptoms and psychiatric comorbidities were evaluated with clinical interviews. Results: We observed similar daily levels and diurnal profiles of salivary cortisol in adolescents and young adults with 22q11DS compared to HCs. However, participants with 22q11DS reported less frequent exposure to stress than HCs. In 22q11DS, we observed a significant association between the use of non-adaptive coping strategies and the severity of psychotics symptoms. Cortisol level was not associated to severity of psychotic symptoms, but elevated cortisol awakening response (CAR) was found in participants with 22q11DS with higher levels of general psychopathology. Conclusions: Our results do not support earlier propositions of altered HPA-axis functioning in 22q11DS but highlight the need to further investigate diurnal cortisol as an indicator of HPA-axis functioning and its link with (earlier) stress exposure and psychopathology in this population. Interventions should target the development of adaptive coping skills in preventing psychosis in 22q11DS.

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

Causal interactions between specific psychiatric symptoms could contribute to the heterogenous clinical trajectories observed in early psychopathology. Current diagnostic approaches merge clinical manifestations that co-occur across subjects and could significantly hinder our understanding of clinical pathways connecting individual symptoms. Network analysis techniques have emerged as alternative approaches that could help shed light on the complex dynamics of early psychopathology. The present study attempts to address the two main limitations that have in our opinion hindered the application of network approaches in the clinical setting. Firstly, we show that a multi-layer network analysis approach, can move beyond a static view of psychopathology, by providing an intuitive characterization of the role of specific symptoms in contributing to clinical trajectories over time. Secondly, we show that a Graph-Signal-Processing approach, can exploit knowledge of longitudinal interactions between symptoms, to predict clinical trajectories at the level of the individual. We test our approaches in two independent samples of individuals with genetic and clinical vulnerability for developing psychosis. Novel network approaches can allow to embrace the dynamic complexity of early psychopathology and help pave the way towards a more a personalized approach to clinical care.

Adolescence is a vulnerable period for psychopathology development, and certain parenting styles are consistent and robust predictors of a broad range of mental health outcomes. The mechanisms through which maladaptive parenting styles affect the development of psychopathology are assumed to be largely social in nature. Yet, the social mechanisms linking parenting to psychopathology are unexplored at arguably the most important level of functioning: daily life. This study aims to identify the associations between three parenting styles, and the experience of daily-life social interactions. Furthermore, we aim to explore the extent to which these parenting styles and altered daily-life social experiences are associated with psychopathology. In this study, we recruited a sample of N = 1,913 adolescents (63.3% girls; mean age = 13.7, age range = 11 to 20) as part of the first wave of the longitudinal cohort study “SIGMA”. Parenting styles (psychological control, responsiveness, and autonomy support) and psychopathology symptoms were assessed using a retrospective questionnaire battery. The experienced quality of social interactions in different types of company was assessed using the experience sampling method, ten times per day for 6 days. Direct associations between parenting styles and general quality of daily-life social experiences were tested using a three-level linear model, revealing significant associations between social experiences and different parenting styles. When interaction effects were added to this model, we found that maternal responsiveness and paternal psychological control mainly related to altered qualities of social interactions with parents, while paternal autonomy support was associated with better experiences of non-family social interactions. Finally, an exploratory path analysis highlighted how both paternal autonomy support and altered quality of non-family interactions are uniquely associated with psychopathology levels. These findings demonstrate the general and pervasive effects of maladaptive parenting styles, as parenting seems to broadly affect adolescents' interactions with different types of social partners in everyday life. Moreover, they illustrate a potential mediated relationship in which altered daily-life social interactions could drive the development of psychopathology. A stronger focus may be required on the role of altered day-to-day social experiences in the prevention and potentially, the treatment, of adolescent psychopathology.