Prediction of transition to psychosis in patients with a clinical high risk for psychosis: a systematic review of methodology and reporting

To enhance indicated prevention in patients with a clinical high risk (CHR) for psychosis, recent research efforts have been increasingly directed towards estimating the risk of developing psychosis on an individual level using multivariable clinical prediction models. The aim of this study was to systematically review the methodological quality and reporting of studies developing or validating such models.; A systematic literature search was carried out (up to 14 March 2016) to find all studies that developed or validated a clinical prediction model predicting the transition to psychosis in CHR patients. Data were extracted using a comprehensive item list which was based on current methodological recommendations.; A total of 91 studies met the inclusion criteria. None of the retrieved studies performed a true external validation of an existing model. Only three studies (3.5%) had an event per variable ratio of at least 10, which is the recommended minimum to avoid overfitting. Internal validation was performed in only 14 studies (15%) and seven of these used biased internal validation strategies. Other frequently observed modeling approaches not recommended by methodologists included univariable screening of candidate predictors, stepwise variable selection, categorization of continuous variables, and poor handling and reporting of missing data.; Our systematic review revealed that poor methods and reporting are widespread in prediction of psychosis research. Since most studies relied on small sample sizes, did not perform internal or external cross-validation, and used poor model development strategies, most published models are probably overfitted and their reported predictive accuracy is likely to be overoptimistic

Two-Loop Planar Corrections to Heavy-Quark Pair Production in the Quark-Antiquark Channel

We evaluate the planar two-loop QCD diagrams contributing to the leading color coefficient of the heavy-quark pair production cross section, in the quark-antiquark annihilation channel. We obtain the leading color coefficient in an analytic form, in terms of one- and two-dimensional harmonic polylogarithms of maximal weight 4. The result is valid for arbitrary values of the Mandelstam invariants s and t, and of the heavy-quark mass m. Our findings agree with previous analytic results in the small-mass limit and numerical results for the exact amplitude.Comment: 30 pages, 5 figures. Version accepted by JHE

Latent state-trait structure of BPRS subscales in clinical high-risk state and first episode psychosis.

To investigate the longitudinal latent state-trait structure of the different dimensions of psychosis symptoms in clinical high-risk state (CHRS) and first episode psychosis (FEP) individuals over a one year time-span. This paper examines if the symptom clusters Positive Symptoms, Negative Symptoms, Affectivity, Resistance, Activation, and Excitement according to the Brief Psychiatric Rating Scale (BPRS) differ in their trait and state characters in 196 CHRS and 131 FEP individuals. Statistical analysis was performed using latent state-trait analysis. On average, trait differences accounted for 72.2% of Positive Symptoms, 81.1% of Negative Symptoms, 57.0% of Affectivity, and 69.2% of Activation, whereas 15.0% of the variance of Resistance and 13.2% of the variance of Excitement were explained by trait differences. Explorative analyses showed a trait components' increase of 0.408 in Positive Symptoms from baseline up to the 9th month and an increase of 0.521 in Affectivity from baseline up to the 6th month. Negative Symptoms had the highest trait component levels of all subscales between baseline and 6 months. The finding that an increasing proportion of psychosis symptoms is persisting over time underlines the importance of early intervention programs in individuals with psychotic disorders

Kann Cannabis das Risiko fur schizophrene Psychosen erhöhen?

Hintergrund: Cannabis wurde in den letzten Jahren zunehmend als einer der wichtigsten umweltbezogenen Risikofaktoren für die Entstehung von schizophrenen Psychosen diskutiert. Dies ist hauptsächlich auf folgende Beobachtungen zurückzuführen: 1. Bei hohen Dosen kann Cannabis auch bei gesunden Personen vorübergehend akute psychotische Symptome auslösen. 2. Patienten mit schizophrenen Psychosen missbrauchen Cannabis deutlich häufiger als altersvergleichbare gesunde Kontrollpersonen. Fragestellung: Es ist weiterhin umstritten, ob Cannabis kausal an der Entstehung von schizophrenen Psychosen beteiligt ist. In der vorliegenden Arbeit wurden deshalb die wichtigsten Evidenzen, die für oder gegen einen kausalen Zusammenhang zwischen Cannabiskonsum und Auslösung schizophrener Psychosen sprechen, gesichtet und kritisch überprüft. Methodik: Systematische Literaturrecherche in den Datenbanken PubMed, ISI Web of Science und PsycINFO zu den Schlüsselwörtern cannabis, marijuana, THC, hashish, psychosis, schizophrenia. Schlussfolgerungen: Es zeigte sich, dass ein kausaler Zusammenhang zwar nicht eindeutig belegbar, aber doch zumindest plausibel ist. Die Ergebnisse wiesen auch darauf hin, dass der Konsum von Cannabis insbesondere bei einem niedrigen Einstiegsalter das Risiko für schizophrene Psychosen erhöht. BACKGROUND: In recent years, cannabis has been increasingly discussed as one of the most important environmental risk factors for developing schizophrenic psychoses. This is mainly due to the following observations. (i) Cannabis at high doses can cause acute transient psychotic symptoms even in healthy individuals. (ii) Patients with schizophrenia abuse cannabis more often than age-matched healthy controls. OBJECTIVES: It is still controversial whether cannabis use can cause schizophrenic psychoses that would not have occurred otherwise. In our review, we have critically evaluated the evidence for a causal link between cannabis use and schizophrenic psychoses. METHODS: A systematic literature review in PubMed, ISI Web of Science and PsycINFO was carried out using the following keywords: cannabis, marijuana, THC, hashish, psychosis, schizophrenia. CONCLUSIONS: We have concluded that although a causal relationship between cannabis use and schizophrenic psychoses cannot be definitely proven, the available evidence strongly supports its plausibility. Furthermore, the results of the review indicate that cannabis might cause psychosis especially in individuals with a predisposition for schizophrenia and in adolescents with an early onset of cannabis use

Cannabis use and cognitive functions in at-risk mental state and first episode psychosis

Background: Meta-analyses suggest that schizophrenia patients with a history of cannabis use have less impaired cognitive functioning compared to patients without cannabis use. Aims: The objective of this study was to assess the association between recency and frequency of cannabis use and cognitive functioning in at-risk mental state for psychosis (ARMS) and first episode psychosis (FEP) individuals. Methods: One hundred thirty-six participants completed a cognitive test battery and were assessed for current and past cannabis use. Analyses of covariance models were applied to evaluate the main effects of cannabis use and patient group (ARMS vs. FEP) as well as their interactions on cognitive functioning. Results: No differences were observed in cognitive performance between current, former, and never users, and there were no significant interactions between cannabis use and patient group. Furthermore, within the group of current cannabis users, the frequency of cannabis use was not significantly associated with cognitive functioning. Conclusion: The results of the present study do not support the notion that FEP patients and ARMS individuals with a history of cannabis use have less impaired cognitive functioning compared to those without cannabis us

Cannabis use and cognitive functions in at-risk mental state and first episode psychosis

BACKGROUND: Meta-analyses suggest that schizophrenia patients with a history of cannabis use have less impaired cognitive functioning compared to patients without cannabis use. AIMS: The objective of this study was to assess the association between recency and frequency of cannabis use and cognitive functioning in at-risk mental state for psychosis (ARMS) and first episode psychosis (FEP) individuals. METHODS: One hundred thirty-six participants completed a cognitive test battery and were assessed for current and past cannabis use. Analyses of covariance models were applied to evaluate the main effects of cannabis use and patient group (ARMS vs. FEP) as well as their interactions on cognitive functioning. RESULTS: No differences were observed in cognitive performance between current, former, and never users, and there were no significant interactions between cannabis use and patient group. Furthermore, within the group of current cannabis users, the frequency of cannabis use was not significantly associated with cognitive functioning. CONCLUSION: The results of the present study do not support the notion that FEP patients and ARMS individuals with a history of cannabis use have less impaired cognitive functioning compared to those without cannabis use

Das Basler Interview für Psychosen (BIP): Struktur, Reliabilität und Validität

Hintergrund: Obwohl in den letzten Jahren zahlreiche Instrumente entwickelt worden sind, um Psychoserisikopersonen und Psychoseersterkrankte zu identifizieren, gab es bisher keine geeigneten Instrumente, um solche Personen ausführlicher über ihren Krankheitsverlauf sowie die Risikofaktoren und frühen Indikatoren der Erkrankung zu befragen. Wir haben deshalb das Basler Interview für Psychosen (BIP) entwickelt. Ziel der vorliegenden Arbeit ist es, die Entwicklung und den Aufbau des BIP zu beschreiben sowie über seine psychometrischen Eigenschaften zu berichten. Methoden: Das BIP ist ein halbstrukturiertes klinisches Anamneseinterview, das im Rahmen des Basler Projekts zur Früherkennung von Psychosen (FePsy) auf der Basis der wichtigsten in der Literatur beschriebenen Risikofaktoren und Indikatoren für Psychosen und unter Berücksichtigung schon existierender Fragebögen entwickelt wurde. Es gliedert sich in sechs Bereiche: 1. Soziale und körperliche Entwicklung/Familie, 2. Anzeichen und Symptome, 3. Vulnerabilität, 4. Hilfesucheverhalten, 5. Krankheitseinsicht, 6. Interviewereinschätzung. Um die Interrater-Reliabilität der Items der Abschnitte 2 und 3 zu bestimmen, wurden 20 Patienten von insgesamt 8 unterschiedlichen Ratern beurteilt. Die faktorielle Struktur des Abschnitts 2.3 „Prodromi und Symptome“ wurde in einer Stichprobe von 120 Psychoserisikopersonen und 77 Erstpsychosepatienten untersucht. Auf der Basis der gefundenen Faktorstruktur wurden neue Skalen gebildet und auf ihre Reliabilität und Validität untersucht. Ergebnisse: Von 153 untersuchten Items der Abschnitte 2 und 3 wurden 150 (98 %) mit ausreichend hoher Übereinstimmung (Interrater-Reliabilität > 0,4) eingeschätzt. Die Items des Abschnitts 2.3 „Prodromi und Symptome“ konnten zu 5 Subskalen gruppiert werden. Die Subskalen wiesen überwiegend gute bis sehr gute interne Konsistenzen, Homogenitäten und diskriminante und konvergente Validitäten auf. Für die Subskalen „Positive psychotische Symptome“ und „Störungen des Denkens“ sowie den Gesamtscore konnte zudem eine prädiktive Validität nachgewiesen werden. Diskussion: Mit dem BIP haben wir erstmals ein halbstrukturiertes klinisches Anamneseinterview konstruiert und validiert, das geeignet ist, Psychoserisikopatienten und Psychoseersterkrankte detailliert über Psychoserisikofaktoren und -indikatoren sowie den psychopathologischen Verlauf seit der Kindheit zu befragen. Wir konnten zeigen, dass das BIP hervorragende psychometrische Eigenschaften aufweist. BACKGROUND: Although several instruments have been developed to identify patients with an at-risk mental state (ARMS) for psychosis and first episode of psychosis (FEP), up to now there were no instruments for a detailed assessment of risk factors and indicators of emerging psychosis and the temporal development of psychiatric symptoms over the whole life span in these patients. We therefore developed the Basle Interview for Psychosis (BIP). The aim of this study is to describe the development of the BIP and to report about its psychometric properties. METHODS: The BIP is a comprehensive semi-structured interview that was developed for the Basel early detection of psychoses (FePsy) study. Its items were derived from the most important risk factors and indicators of psychosis described in the literature and from several existing instruments. It contains the following six sections: 1) social and physical development and family, 2) signs and symptoms, 3) vulnerability, 4) help-seeking behavior, 5) illness insight, 6) evaluation of the interview. To estimate the inter-rater reliabilities of the items of sections 2 and 3, 20 interviews were conducted and rated by 8 well-trained raters. The factorial structure of the BIP section "signs and symptoms" was explored in a sample of 120 ARMS and 77 FEP patients. On the basis of the discovered factorial structure, we created new subscales and assessed their reliabilities and validities. RESULTS: Of the 153 studied items of sections 2 and 3, 150 (98 %) were rated with sufficiently high agreement (inter-rater reliability > 0.4). The items of section "signs and symptoms" could be grouped into 5 subscales with predominantly good to very good internal consistencies, homogeneities, and discriminant and convergent validities. Predictive validities could be demonstrated for the subscales "Positive Psychotic Symptoms", "Disturbance of Thinking" and the total score. DISCUSSION: The BIP is the first interview for comprehensively assessing risk factors and indicators of emerging psychosis and the temporal development of psychiatric symptoms over the whole life span, which has been validated in ARMS and FEP patients. We could show that the BIP has excellent psychometric properties

Slepton pair production in the POWHEG BOX

We present an implementation for slepton pair production at hadron colliders in the POWHEG BOX, a framework for combining next-to-leading order QCD calculations with parton-shower Monte-Carlo programs. Our code provides a SUSY Les Houches Accord interface for setting the supersymmetric input parameters. Decays of the sleptons and parton-shower effects are simulated with PYTHIA. Focussing on a representative point in the supersymmetric parameter space we show results for kinematic distributions that can be observed experimentally. While next-to-leading order QCD corrections are sizable for all distributions, the parton shower affects the color-neutral particles only marginally. Pronounced parton-shower effects are found for jet distributions.Comment: 10 pages, 4 figure

Hippocampal volume in subjects at high risk of psychosis: a longitudinal MRI study

The hippocampal formation has been studied extensively in schizophrenic psychoses and alterations in hippocampal anatomy have been consistently reported. Chronic schizophrenia seems to be associated with bilateral hippocampal volume (HV) reduction, while in patients with an at-risk mental state (ARMS) there are contradictory results. This is the first region of interest (ROI) based follow-up MRI study of hippocampal volume comparing ARMS individuals with and without transition to psychosis. The aim was to investigate the timing of HV changes in ARMS in the early phase of psychosis. METHODS: Magnetic resonance imaging data from 18 antipsychotic-naive individuals with an ARMS were collected within the FePsy-clinic for early detection of psychoses. During follow-up 8 subjects transitioned to psychosis (ARMS-T) and 10 did not (ARMS-NT). Subjects were re-scanned after the onset of psychosis or at the end of the follow-up if they did not develop psychosis. RESULTS: Across both groups there was a significant decrease in HV over time (p<0.05). There was no significant difference in progression between ARMS-T and ARMS-NT. Antipsychotic medication at follow up was associated with increased HV (p<0.05). CONCLUSIONS: We found a decrease of HV over time in subjects with an ARMS, independently of clinical outcome. We may speculate that the decrease of HV over time might reflect brain degeneration processes

Hepta-Cuts of Two-Loop Scattering Amplitudes

We present a method for the computation of hepta-cuts of two loop scattering amplitudes. Four dimensional unitarity cuts are used to factorise the integrand onto the product of six tree-level amplitudes evaluated at complex momentum values. Using Gram matrix constraints we derive a general parameterisation of the integrand which can be computed using polynomial fitting techniques. The resulting expression is further reduced to master integrals using conventional integration by parts methods. We consider both planar and non-planar topologies for 2 to 2 scattering processes and apply the method to compute hepta-cut contributions to gluon-gluon scattering in Yang-Mills theory with adjoint fermions and scalars.Comment: 37 pages, 6 figures. version 2 : minor updates, published versio