Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings

Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range = –0.45 to –0.73, p < 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES = –0.14 to –0.33, p < 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range = –0.88 to –0.60, p < 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range = –0.13 to –0.38, p < 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range = –0.21 to –0.43, p < 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Efficacy and Safety of Paliperidone Palmitate 6-Month versus Paliperidone Palmitate 3-Month Long-Acting Injectable in European Patients with Schizophrenia: A Post Hoc Analysis of a Global Phase-3 Double-Blind Randomized Non-Inferiority Study

Cesar Giron‐Hernandez,1 Joong Hee Han,2 Roberta Alberio,3 Arun Singh,2 Maria Paz García-Portilla,4 Maurizio Pompili,5 R Karl Knight,2 Ute Richarz,6 Srihari Gopal,2,7 José Antunes8 1EMEA Medical Affairs, Janssen-Cilag, Issy-les-Moulineaux, France; 2Janssen Research & Development, LLC, Titusville, NJ, USA; 3Medical Affairs, Janssen-Cilag, Milan, Italy; 4Department of Psychiatry, Universidad de Oviedo, Instituto Sanitario Del Principado de Asturias (ISPA) and CIBERSAM, Oviedo, Spain; 5Department of Neurosciences, Mental Health, and Sensory Organs, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy; 6Janssen Global Services LLC, Cilag Int., Zug, Switzerland; 7Regeneron Pharmaceuticals, Tarrytown, NY, USA; 8EMEA Medical Affairs, Janssen-Cilag, Porto Salvo, PortugalCorrespondence: José Antunes, EMEA Medical Affairs, Janssen-Cilag, Porto Salvo, Portugal, Email [email protected]: To examine efficacy and safety of paliperidone palmitate (PP) 6-month (PP6M) vs PP3-month (PP3M) long acting injectable (LAI) in patients with schizophrenia from European sites previously stabilized on PP3M or PP1-month (PP1M).Methods: This post-hoc subgroup analysis used data from a global phase-3 double-blind (DB) randomized non-inferiority study (NCT03345342). Patients were randomized (2:1, respectively) to receive dorsogluteal injections of PP6M (700 mg eq. or 1000 mg eq.) or PP3M (350 mg eq. or 525 mg eq.) in the 12-month DB phase. Primary endpoint was time-to-relapse during the DB phase, using a Kaplan–Meier cumulative survival estimate (non-inferiority margin 95% CI lower bound larger than prespecified as − 10%). Treatment emergent adverse events (TEAEs), physical examinations, and laboratory tests were also evaluated.Results: A total of 384 patients who entered the DB phase were included in European sites (PP6M, n = 260; PP3M, n = 124) with a mean age similar in both groups (mean age [SD] years: PP6M, 40.0 [11.39]; PP3M, 38.8 [10.41]). Baseline characteristics were similar across both groups. The number of patients who experienced a relapse during DB phase were PP6M: 18 (6.9%) vs PP3M: 3 (2.4%) with percentage relapse-free difference of − 4.9% (95% CI: − 9.2%, − 0.5%), thus achieving non-inferiority criteria. Secondary efficacy endpoints indicated comparable improvements. Incidence of TEAEs was similar between PP6M (58.8%) and PP3M (54.8%) groups. Nasopharyngitis, headache, increased weight, and injection-site pain were the most common TEAEs.Conclusion: The efficacy of PP6M was non-inferior to that of PP3M in preventing relapse in the European subgroup previously treated with PP1M or PP3M, which was consistent with the global study. No new safety signals were identified.Keywords: Europe, long-acting injectable, paliperidone palmitate 6-month, relapse-free, schizophreni

Gender, age at onset and duration of being ill as predictors for the long-term course and outcome of Schizophrenia: An international multicenter study

Abstract Background The aim of the current study was to explore the effect of gender, age at onset, and duration on the long-term course of schizophrenia. Methods Twenty-nine centers from 25 countries representing all continents participated in the study that included 2358 patients aged 37.21 ± 11.87 years with a DSM-IV or DSM-5 diagnosis of schizophrenia; the Positive and Negative Syndrome Scale as well as relevant clinicodemographic data were gathered. Analysis of variance and analysis of covariance were used, and the methodology corrected for the presence of potentially confounding effects. Results There was a 3-year later age at onset for females (P &lt; .001) and lower rates of negative symptoms (P &lt; .01) and higher depression/anxiety measures (P &lt; .05) at some stages. The age at onset manifested a distribution with a single peak for both genders with a tendency of patients with younger onset having slower advancement through illness stages (P = .001). No significant effects were found concerning duration of illness. Discussion Our results confirmed a later onset and a possibly more benign course and outcome in females. Age at onset manifested a single peak in both genders, and surprisingly, earlier onset was related to a slower progression of the illness. No effect of duration has been detected. These results are partially in accord with the literature, but they also differ as a consequence of the different starting point of our methodology (a novel staging model), which in our opinion precluded the impact of confounding effects. Future research should focus on the therapeutic policy and implications of these results in more representative samples. </jats:sec

Cardiovascular risk assessment in patients with a severe mental illness: a systematic review and meta-analysis.

BACKGROUND: Cardiovascular risk (CVR) has been observed to be higher in patients with severe mental illness (SMI) than in the general population. However, some studies suggest that CVR is not equally increased in different subgroups of SMI. The purposes of this review are to summarise CVR scores of SMI patients and to determine the differences in CVR between patients with different SMIs and between SMI patients and the control-population. METHODS: MEDLINE (via PubMed) was searched for literature published through August 28, 2014, followed by a snowball search in the Web of Science. Observational and experimental studies that reported CVR assessments in SMI patients using validated tools were included. The risk of bias was reported using STROBE and CONSORT criteria. Pooled continuous data were expressed as standardized mean differences (SMD) with 95 % confidence intervals (CI). Two reviewers independently selected studies, extracted data and assessed methodological quality. RESULTS: A total of 3,608 articles were identified, of which 67 full text papers were assessed for eligibility and 35 were finally included in our review, in which 12,179 psychiatric patients and 225,951 comparative patients had been assessed. The most frequent diagnoses were schizophrenia and related diagnoses (45.7 %), depressive disorders (14.7 %), SMI (11.4 %) and bipolar disorders (8.6 %). The most frequent CVR assessment tool used was the Framingham risk score. Subgroups analysis showed a higher CVR in schizophrenia than in depressive disorder or in studies that included patients with multiple psychiatric diagnoses (SMD: 0.63, 0.03, and 0.02, respectively). Six studies were included in the meta-analysis. Total overall CVR did not differ between SMI patients and controls (SMD: 0.35 [95 % CI:-0.02 to 0.71], p = 0.06); high heterogeneity was observed (I (2) = 93 %; p < 0.001). CONCLUSIONS: The summary of results from studies that assessed CVR using validated tools in SMI patients did not find sufficient data (except for limited evidence associated with schizophrenia) to permit any clear conclusions about increased CVR in this group of patients compared to the general population. The systematic review is registered inThis research has been funded by the Ministry of Science and Innovation through the Instituto Carlos III (PI12/00427). This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. LA is funded by the National Institute of Health Research (NIHR) U