Arbeitsgedächtnisleistung und Hirnaktivierung bei Patienten mit Schizophrenie und bipolar I Erkrankung: eine vergleichende Studie mittels funktioneller Magnetresonanztomographie

Arbeitsgedächtnisdefizite sind ein möglicher Endophänotyp der Schizophrenie und gehen mit Aktivierungsdefiziten in präfrontalen Arealen einher. In der vorliegenden Studie wurde die Hypothese geprüft, dass sich Patienten mit Schizophrenie, mit bipolarer affektiver Störung sowie gesunde Kontrollprobanden hinsichtlich cerebraler Aktivierungen im dorsolateralen präfrontalen, ventrolateralen präfrontalen und anterior cingulären Cortex, sowie im Hippocampus und Thalamus unterscheiden. Dabei sollten auch die Hypothesen einer örtlichen Dissoziation (stärkere Aktivierungsdefizite bei Schizophrenie präfrontal) und zeitlichen Dissoziation (stärkere Aktivierungsdefizite bei Patienten mit Schizophrenie bereits während der Enkodierungsphase) geprüft werden. Mittels funktioneller Magnetresonanztomographie wurde die Hirnaktivierung während eines Sternberg Paradigmas bei 32 Patienten mit Schizophrenie (in Remission), 16 Patienten mit bipolar I Erkrankung (euthym, mit früheren psychotischen Symptomen) und 36 gesunden Kontrollprobanden untersucht. Beide Patientengruppen zeigten auf Verhaltensebene Defizite, Patienten mit Schizophrenie besonders bei zusätzlicher Manipulationskomponente. Direkte Gruppenvergleiche bestätigten die Hypothese einer dorsolateral und ventrolateral präfrontalen Minderaktivierung bei Patienten mit Schizophrenie im Vergleich zu den anderen Gruppen während des Enkodierens. Während der Delayphase zeigten Patienten hippocampale/parahippocampale sowie thalamische Aktivierungsdefizite, bei Schizophrenie stärker bzw. räumlich ausgedehnter. Unter zusätzlicher Manipulationskomponente zeigten beide Patientengruppen (medial)präfrontale Mehraktivierungen. Diese Studie zeigt somit die neuronalen Mechanismen von Arbeitsgedächtnisdefiziten bei Schizophrenie auch im direkten Vergleich zu einer psychiatrischen Kontrollgruppe auf, wobei ähnlichen hippocampalen Aktivierungsdefiziten divergierende dorsolateral/ventrolateral präfrontale Aktivierungsdefizite gegenüberstehen

Community Perception and Communication of Volcanic Risk from the Cotopaxi Volcano in Latacunga, Ecuador

he inhabitants of Latacunga living in the surrounding of the Cotopaxi volcano (Ecuador) are exposed to several hazards and related disasters. After the last 2015 volcanic eruption, it became evident once again how important it is for the exposed population to understand their own social, physical, and systemic vulnerability. Effective risk communication is essential before the occurrence of a volcanic crisis. This study integrates quantitative risk and semi-quantitative social risk perceptions, aiming for risk-informed communities. We present the use of the RIESGOS demonstrator for interactive exploration and visualisation of risk scenarios. The development of this demonstrator through an iterative process with the local experts and potential end-users increases both the quality of the technical tool as well as its practical applicability. Moreover, the community risk perception in a focused area was investigated through online and field surveys. Geo-located interviews are used to map the social perception of volcanic risk factors. Scenario-based outcomes from quantitative risk assessment obtained by the RIESGOS demonstrator are compared with the semi-quantitative risk perceptions. We have found that further efforts are required to provide the exposed communities with a better understanding of the concepts of hazard scenario and intensity

Pride and confidence at work: potential predictors of occupational health in a hospital setting

BACKGROUND: This study focuses on determinants of a healthy work environment in two departments in a Swedish university hospital. The study is based on previously conducted longitudinal studies at the hospital (1994–2001), concerning working conditions and health outcomes among health care personnel in conjunction with downsizing processes. Overall, there was a general negative trend in relation to mental health, as well as long-term sick leave during the study period. The two departments chosen for the current study differed from the general hospital trend in that they showed stable health development. The aim of the study was to identify and analyse experiential determinants of healthy working conditions. METHODS: Thematic open-ended interviews were carried out with seventeen managers and key informants, representing different groups of co-workers in the two departments. The interviews were transcribed verbatim and an inductive content analysis was made. RESULTS: In the two studied departments the respondents perceived that it was advantageous to belong to a small department, and to work in cooperation-oriented care. The management approaches described by both managers and co-workers could be interpreted as transformational, due to a strain of visionary, delegating, motivating, confirmative, supportive attitudes and a strongly expressed solution-oriented attitude. The daily work included integrated learning activities. The existing organisational conditions, approaches and attitudes promoted tendencies towards a work climate characterised by trust, team spirit and professionalism. In the description of the themes organisational conditions, approaches and climate, two core determinants, work-pride and confidence, for healthy working conditions were interpreted. Our core determinants augment the well-established concepts: manageability, comprehensiveness and meaningfulness. These favourable conditions seem to function as a buffer against the general negative effects of downsizing observed elsewhere in the hospital, and in the literature. CONCLUSION: Research illuminating health-promoting aspects is rather unusual. This study could be seen as explorative. The themes and core dimensions we found could be used as a basis for further intervention studies in similar health-care settings. The result could also be used in future health promotion studies in larger populations. One of the first steps in such a strategy is to formulate relevant questions, and we consider that this study contributes to this

Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ):Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals.</p

Development of the PSYCHS: Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS

Aim: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). Methods: The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences. Results: Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and modest harmonization for CHR-P criteria. The semi-structured interview, named Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS. Conclusions: Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses

Sample ascertainment and clinical outcome measures in the Accelerating Medicines Partnership® Schizophrenia Program.

Clinical ascertainment and clinical outcome are key features of any large multisite study. In the ProNET and PRESCIENT research networks, the Accelerating Medicines Partnership® Schizophrenia (AMP®SCZ) Clinical Ascertainment and Outcome Measures Team aimed to establish a harmonized clinical assessment protocol across these two research networks and to define ascertainment criteria and primary and secondary endpoints. In addition to developing the assessment protocol, the goals of this aspect of the AMP SCZ project were: (1) to implement and monitor clinical training, ascertainment of participants, and clinical assessments; (2) to provide expert clinical input to the Psychosis Risk Evaluation, Data Integration and Computational Technologies: Data Processing, Analysis, and Coordination Center (PREDICT-DPACC) for data collection, quality control, and preparation of data for the analysis of the clinical measures; and (3) to provide ongoing support to the collection, analysis, and reporting of clinical data. This paper describes the (1) protocol clinical endpoints and outcomes, (2) rationale for the selection of the clinical measures, (3) extensive training of clinical staff, (4) preparation of clinical measures for a multisite study which includes several sites where English is not the native language; and (5) the assessment of measure stability over time in the AMP SCZ observational study comparing clinical ratings at baseline and at the 2-month follow up. Watch Dr. Jean Addington discuss her work and this article: https://vimeo.com/1040425281

The MR neuroimaging protocol for the Accelerating Medicines Partnership® Schizophrenia Program.

Neuroimaging with MRI has been a frequent component of studies of individuals at clinical high risk (CHR) for developing psychosis, with goals of understanding potential brain regions and systems impacted in the CHR state and identifying prognostic or predictive biomarkers that can enhance our ability to forecast clinical outcomes. To date, most studies involving MRI in CHR are likely not sufficiently powered to generate robust and generalizable neuroimaging results. Here, we describe the prospective, advanced, and modern neuroimaging protocol that was implemented in a complex multi-site, multi-vendor environment, as part of the large-scale Accelerating Medicines Partnership® Schizophrenia Program (AMP® SCZ), including the rationale for various choices. This protocol includes T1- and T2-weighted structural scans, resting-state fMRI, and diffusion-weighted imaging collected at two time points, approximately 2 months apart. We also present preliminary variance component analyses of several measures, such as signal- and contrast-to-noise ratio (SNR/CNR) and spatial smoothness, to provide quantitative data on the relative percentages of participant, site, and platform (i.e., scanner model) variance. Site-related variance is generally small (typically &lt;10%). For the SNR/CNR measures from the structural and fMRI scans, participant variance is the largest component (as desired; 40-76%). However, for SNR/CNR in the diffusion scans, there is substantial platform-related variance (&gt;55%) due to differences in the diffusion imaging hardware capabilities of the different scanners. Also, spatial smoothness generally has a large platform-related variance due to inherent, difficult to control, differences between vendors in their acquisitions and reconstructions. These results illustrate some of the factors that will need to be considered in analyses of the AMP SCZ neuroimaging data, which will be the largest CHR cohort to date.Watch Dr. Harms discuss this article at https://vimeo.com/1059777228?share=copy#t=0

Cognitive assessment in the Accelerating Medicines Partnership® Schizophrenia Program:harmonization priorities and strategies in a diverse international sample

Cognitive impairment occurs at higher rates in individuals at clinical high risk (CHR) for psychosis relative to healthy peers, and it contributes unique variance to multivariate prediction models of transition to psychosis. Such impairment is considered a core biomarker of schizophrenia. Thus, cognition is a key domain measured in the Accelerating Medicines Partnership® program for Schizophrenia (AMP SCZ initiative). The aim of this paper is to describe the rationale, processes, considerations, and final harmonization of the cognitive battery used in AMP SCZ across the two data collection networks. This battery comprises tests of general intellect and specific cognitive domains. We estimate premorbid intelligence at baseline and measure current intelligence at baseline and 2 years. Eight tests from the Penn Computerized Neurocognitive Battery (PennCNB), which measure verbal learning and memory, sensorimotor ability, attention, emotion recognition, working memory, processing speed, verbal memory, visual memory, and motor speed are administered repeatedly at baseline, and four follow-up timepoints over 2 years.</p

Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals

Cortical Gyrification, Psychotic-Like Experiences, and Cognitive Performance in Nonclinical Subjects

Abstract Background Psychotic-like experiences (PLE) are present in nonclinical populations, yet their association with brain structural variation, especially markers of early neurodevelopment, is poorly understood. We tested the hypothesis that cortical surface gyrification, a putative marker of early brain development, is associated with PLE in healthy subjects. Methods We analyzed gyrification from 3 Tesla MRI scans (using CAT12 software) and PLE (positive, negative, and depressive symptom dimensions derived from the Community Assessment of Psychic Experiences, CAPE) in 103 healthy participants (49 females, mean age 29.13 ± 9.37 years). A subsample of 63 individuals completed tasks from the Wechsler Adult Intelligence Scale and Controlled Oral Word Association Test. Estimated IQ and a composite neuropsychological score were used to explore mediation pathways via cognition. Results Positive PLE distress was negatively associated with gyrification of the left precuneus. PLE depression dimension showed a negative association with gyrification in the right supramarginal and temporal region. There was no significant mediating effect of cognition on these associations. Conclusion Our results support a neurobiological psychosis spectrum, for the first time linking an early developmental imaging marker (rather than volume) to dimensional subclinical psychotic symptoms. While schizophrenia risk, neurodevelopment, and cognitive function might share genetic risk factors, additional mediation analyses did not confirm a mediating effect of cognition on the gyrification-psychopathology correlation. </jats:sec