Negative Symptoms in Early-Onset Psychosis and Their Association With Antipsychotic Treatment Failure.

This is the author accepted manuscript. The final version is available from OUP via the DOI in this recordThe prevalence of negative symptoms (NS) at first episode of early-onset psychosis (EOP), and their effect on psychosis prognosis is unclear. In a sample of 638 children with EOP (aged 10-17 y, 51% male), we assessed (1) the prevalence of NS at first presentation to mental health services and (2) whether NS predicted eventual development of multiple treatment failure (MTF) prior to the age of 18 (defined by initiation of a third trial of novel antipsychotic due to prior insufficient response, intolerable adverse-effects or non-adherence). Data were extracted from the electronic health records held by child inpatient and community-based services in South London, United Kingdom. Natural Language Processing tools were used to measure the presence of Marder Factor NS and antipsychotic use. The association between presenting with ≥2 NS and the development of MTF over a 5-year period was modeled using Cox regression. Out of the 638 children, 37.5% showed ≥2 NS at first presentation, and 124 (19.3%) developed MTF prior to the age of 18. The presence of NS at first episode was significantly associated with MTF (adjusted hazard ratio 1.62, 95% CI 1.07-2.46; P = .02) after controlling for a number of potential confounders including psychosis diagnostic classification, positive symptoms, comorbid depression, and family history of psychosis. Other factors associated with MTF included comorbid autism spectrum disorder, older age at first presentation, Black ethnicity, and family history of psychosis. In EOP, NS at first episode are prevalent and may help identify a subset of children at higher risk of responding poorly to antipsychotics.J.D. received supported by a Medical Research Council (MRC) Clinical Research Training Fellowship (MR/L017105/1) and Psychiatry Research Trust Peggy Pollak Research Fellowship in Developmental Psychiatry. H.D. and S.L. have received salary support from the Foundation of Professional Services to Adolescents, UK. R.D.H. was funded by an MRC Fellowship (MR/J01219X/1). R.P. was funded by an MRC CRTF (MR/K002813/1). C.A., L.P-C., and C.M.D-C. have held grants from the Spanish Ministry of Economy, Industry and Competitiveness. Instituto de Salud Carlos III, co-financed by ERDF Funds from the European Commission, “A way of making Europe,” CIBERSAM, Madrid Regional Government (S2010/BMD-2422 AGES), European Union Structural Funds and European Union Seventh Framework Program under grant agreements FP7-HEALTH-2009-2.2.1-2-241909 (EU-GEI), FP7-HEALTH-2009-2.2.1-3-242114 (OPTiMISE), FP7-HEALTH-2013-2.2.1-2-603196 (PSYSCAN)and FP7- HEALTH-2013-2.2.1-2-602478 (METSY); European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No-115916; PRISM); Fundación Alicia Koplowitz and Fundación Mutua Madrileña. M.H., J.H.M. and H.S. receive salary support from the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health

Obstetric complications and clinical presentation in first episode of psychosis

Objective: Psychotic disorders exhibit a complex aetiology that combines genetic and environmental factors. Among the latter, obstetric complications (OCs) have been widely studied as risk factors, but it is not yet well understood how OCs relate to the heterogeneous presentations of psychotic disorders. We assessed the clinical phenotypes of individuals with a first episode of psychosis (FEP) in relation to the presence of OCs. Methods: Two-hundred seventy-seven patients with an FEP were assessed for OCs using the Lewis–Murray scale, with data stratified into three subscales depending on the timing and the characteristics of the obstetric event, namely: complications of pregnancy, abnormal foetal growth and development and difficulties in delivery. We also considered other two groups: any complications during the pregnancy period and all OCs taken altogether. Patients were clinically evaluated with the Positive and Negative Syndrome Scale for schizophrenia. Results: Total OCs and difficulties in delivery were related to more severe psychopathology, and this remained significant after co-varying for age, sex, traumatic experiences, antipsychotic dosage and cannabis use. Conclusions: Our results highlight the relevance of OCs for the clinical presentation of psychosis. Describing the timing of the OCs is essential in understanding the heterogeneity of the clinical presentation

Identifying clinical clusters with distinct trajectories in first-episode psychosis through an unsupervised machine learning technique

The extreme variability in symptom presentation reveals that individuals diagnosed with a first-episode psychosis (FEP) may encompass different sub-populations with potentially different illness courses and, hence, different treatment needs. Previous studies have shown that sociodemographic and family environment factors are associated with more unfavorable symptom trajectories. The aim of this study was to examine the dimensional structure of symptoms and to identify individuals’ trajectories at early stage of illness and potential risk factors associated with poor outcomes at follow-up in non-affective FEP. One hundred and forty-four non-affective FEP patients were assessed at baseline and at 2-year follow-up. A Principal component analysis has been conducted to identify dimensions, then an unsupervised machine learning technique (fuzzy clustering) was performed to identify clinical subgroups of patients. Six symptom factors were extracted (positive, negative, depressive, anxiety, disorganization and somatic/cognitive). Three distinct clinical clusters were determined at baseline: mild; negative and moderate; and positive and severe symptoms, and five at follow-up: minimal; mild; moderate; negative and depressive; and severe symptoms. Receiving a low-dose antipsychotic, having a more severe depressive symptomatology and a positive family history for psychiatric disorders were risk factors for poor recovery, whilst having a high cognitive reserve and better premorbid adjustment may confer a better prognosis. The current study provided a better understanding of the heterogeneous profile of FEP. Early identification of patients who could likely present poor outcomes may be an initial step for the development of targeted interventions to improve illness trajectories and preserve psychosocial functioning

Cognitive clusters in first-episode psychosis

Impairments in a broad range of cognitive domains have been consistently reported in some individuals with first-episode psychosis (FEP). Cognitive deficits can be observed during the prodromal stage. However, the course of cognitive deficits is still unclear. The aim of this study was to identify cognitive subgroups over time and to compare their sociodemographic, clinical and functional profiles. A total of 114 patients with Schizophrenia Spectrum Disorders were included in the present study. We assessed subjects through psychiatric scales and eight neuropsychological tests at baseline and at two-year follow-up visit. We performed the Partition Around Medoids algorithm with all cognitive variables. Furthermore, we performed a logistic regression to identify the predictors related to the different cognitive clusters at follow-up. Two distinct subgroups were found: the first cluster characterized by cognitive impairment and a second cluster had relatively intact cognition in comparison with norms. Up to 54.7% of patients with cognitive deficits at baseline tended to improve during the first two years of treatment. Patients with intact cognition at follow-up had a higher socioeconomic status, later age of onset, lower negative symptoms and a higher cognitive reserve (CR) at baseline. CR and age of onset were the baseline variables that predicted cognitive impairment. This research allows us to obtain a better understanding of the heterogeneous profile of psychotic disorders. Identifying the characteristics of patients who will present a cognitive impairment could improve early detection and intervention. These results suggest that enhancing CR could contribute to improving the course of the illness. © 2021 Elsevier B.V

Do adults with high functioning autism or Asperger Syndrome differ in empathy and emotion recognition?

The present study examined whether adults with high functioning autism (HFA) showed greater difficulties in (i) their self-reported ability to empathise with others and/or (ii) their ability to read mental states in others’ eyes than adults with Asperger syndrome (AS). The Empathy Quotient (EQ) and ‘Reading the Mind in the Eyes’ Test (Eyes Test) were compared in 43 adults with AS and 43 adults with HFA. No significant difference was observed on EQ score between groups, while adults with AS performed significantly better on the Eyes Test than those with HFA. This suggests that adults with HFA may need more support, particularly in mentalizing and complex emotion recognition, and raises questions about the existence of subgroups within autism spectrum conditions

Deficits in neurite density underlie white matter structure abnormalities in first-episode psychosis

Background: Structural abnormalities across multiple white matter tracts are recognised in people with early psychosis, consistent with dysconnectivity as a neuropathological account of symptom expression. We applied advanced neuroimaging techniques to characterise microstructural white matter abnormalities for a deeper understanding of the developmental aetiology of psychosis. Methods: Thirty-five first-episode psychosis patients, and 19 healthy controls, participated in a quantitative neuroimaging study using Neurite Orientation Dispersion and Density Imaging (NODDI), a multi-shell diffusion-weighted MRI technique that distinguishes white matter fibre arrangement and geometry from changes in neurite density. Fractional anisotropy (FA) and mean diffusivity images were also derived. Tract-based spatial statistics compared white matter structure between patients and controls and tested associations with age, symptom severity and medication. Results: Patients with first-episode psychosis had lower regional FA in multiple commissural, corticospinal, and association tracts. These abnormalities predominantly colocalized with regions of reduced neurite density, rather than aberrant fibre bundle arrangement (orientation dispersion index). There was no direct relationship with active symptomatology. FA decreased and orientation dispersion index increased with age in patients, but not controls, suggesting accelerated effects of white matter geometry change. Conclusions: Deficits in neurite density appear fundamental to abnormalities in white matter integrity in early psychosis. In the first application of NODDI in psychosis, we found that processes compromising axonal fibre number, density, and myelination, rather than processes leading to spatial disruption of fibre organisation, are implicated in the aetiology of the disorder. This accords with a neurodevelopmental origin of aberrant brain-wide structural connectivity predisposing individuals to psychosis

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations

Evidence for the Higgs-boson Yukawa coupling to tau leptons with the ATLAS detector

Results of a search for H → τ τ decays are presented, based on the full set of proton-proton collision data recorded by the ATLAS experiment at the LHC during 2011 and 2012. The data correspond to integrated luminosities of 4.5 fb−1 and 20.3 fb−1 at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV respectively. All combinations of leptonic (τ → `νν¯ with ` = e, µ) and hadronic (τ → hadrons ν) tau decays are considered. An excess of events over the expected background from other Standard Model processes is found with an observed (expected) significance of 4.5 (3.4) standard deviations. This excess provides evidence for the direct coupling of the recently discovered Higgs boson to fermions. The measured signal strength, normalised to the Standard Model expectation, of µ = 1.43 +0.43 −0.37 is consistent with the predicted Yukawa coupling strength in the Standard Model

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured