Socio-demographic, economic and mental health problems were risk factors for suicidal ideation among Kenyan students aged 15 plus

Background: About a third of youth with suicidal ideation develop suicidal plans and about 60% of youth with suicidal plans make suicidal attempts. This study aimed to study different types of suicidal ideation and the risk factors in Kenyan youth. Methods: We studied a total of 9742 high school, college and university students using following selfadministered instruments: -a researcher design socio-demographic questionnaire, Psychiatric Diagnostic Screening Questionnaire (PDSQ) to document psychiatric disorders and various types of suicidal ideas in previous two weeks, Washington Early Recognition Center Affectivity and Psychosis tool to assess stress, affectivity and psychosis, Wealth index questionnaire to document economic indicators based on household items for the families of the students. We used descriptive statistics, univariate analysis, bivariate logistic regression analysis and variables with a p-value of less than <.05 were entered into generalized linear models using logit links to identify independent predictors. Results: The overall prevalence of different types of suicidal ideation was (22.6%), major depression was found in 20.0%, affectivity, psychosis and stress was found in 10.4%, 8.7% and 26.0% respectively. Female gender, major depression, stress, affectivity and psychosis and being in high school were significant (p < 0.05) predictors of suicidal ideation. Limitations: This was a cross sectional study that focused only on suicidal ideas and associated economic factors and mental health disorders. It did not study suicidal behavior. Conclusion: Future studies are needed to study the progression from suicidal ideas to suicidal attempts and the factors associated with that progression

Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification

Familial idiopathic basal ganglia calcification (IBGC) or Fahr's disease is a rare neurodegenerative disorder characterized by calcium deposits in the basal ganglia and other brain regions, which is associated with neuropsychiatric and motor symptoms. Familial IBGC is genetically heterogeneous and typically transmitted in an autosomal dominant fashion. We performed a mutational analysis of SLC20A2, the first gene found to cause IBGC, to assess its genetic contribution to familial IBGC. We recruited 218 subjects from 29 IBGC-affected families of varied ancestry and collected medical history, neurological exam, and head CT scans to characterize each patient's disease status. We screened our patient cohort for mutations in SLC20A2. Twelve novel (nonsense, deletions, missense, and splice site) potentially pathogenic variants, one synonymous variant, and one previously reported mutation were identified in 13 families. Variants predicted to be deleterious cosegregated with disease in five families. Three families showed nonsegregation with clinical disease of such variants, but retrospective review of clinical and neuroimaging data strongly suggested previous misclassification. Overall, mutations in SLC20A2 account for as many as 41 % of our familial IBGC cases. Our screen in a large series expands the catalog of SLC20A2 mutations identified to date and demonstrates that mutations in SLC20A2 are a major cause of familial IBGC. Non-perfect segregation patterns of predicted deleterious variants highlight the challenges of phenotypic assessment in this condition with highly variable clinical presentation

Digital health technologies in the accelerating medicines Partnership® Schizophrenia Program.

Although meta-analytic studies have shown that 25-33% of those at Clinical High Risk (CHR) for psychosis transition to a first episode of psychosis within three years, less is known about estimating the risk of transition at an individual level. Digital phenotyping offers a novel approach to explore the nature of CHR and may help to improve personalized risk prediction. Specifically, digital data enable detailed mapping of experiences, moods and behaviors during longer periods of time (e.g., weeks, months) and offer more insight into patterns over time at the individual level across their routine daily life. However, while novel digital health technologies open up many new avenues of research, they also come with specific challenges, including replicability of results and the adherence of participants. This paper outlines the design of the digital component of the Accelerating Medicines Partnership® Schizophrenia Program (AMP SCZ) project, a large international collaborative project that follows individuals at CHR for psychosis over a period of two years. The digital component comprises one-year smartphone-based digital phenotyping and actigraphy. Smartphone-based digital phenotyping includes 30-item short daily self-report surveys and voice diaries as well as passive data capture (geolocation, on/off screen state, and accelerometer). Actigraphy data are collected via an Axivity wristwatch. The aim of this paper is to describe the design and the three goals of the digital measures used in AMP SCZ to: (i) better understand the symptoms, real-life experiences, and behaviors of those at CHR for psychosis, (ii) improve the prediction of transition to psychosis and other health outcomes in this population based on digital phenotyping and, (iii) serve as an example for replicable and ethical research across geographically diverse regions and cultures. Accordingly, we describe the rationale, protocol and implementation of these digital components of the AMP SCZ project. **Link to video interview: https://vimeo.com/1060935583 *

Pavlovian Reward Prediction and Receipt in Schizophrenia: Relationship to Anhedonia

Reward processing abnormalities have been implicated in the pathophysiology of negative symptoms such as anhedonia and avolition in schizophrenia. However, studies examining neural responses to reward anticipation and receipt have largely relied on instrumental tasks, which may confound reward processing abnormalities with deficits in response selection and execution. 25 chronic, medicated outpatients with schizophrenia and 20 healthy controls underwent functional magnetic resonance imaging using a Pavlovian reward prediction paradigm with no response requirements. Subjects passively viewed cues that predicted subsequent receipt of monetary reward or non-reward, and blood-oxygen-level-dependent signal was measured at the time of cue presentation and receipt. At the group level, neural responses to both reward anticipation and receipt were largely similar between groups. At the time of cue presentation, striatal anticipatory responses did not differ between patients and controls. Right anterior insula demonstrated greater activation for nonreward than reward cues in controls, and for reward than nonreward cues in patients. At the time of receipt, robust responses to receipt of reward vs. nonreward were seen in striatum, midbrain, and frontal cortex in both groups. Furthermore, both groups demonstrated responses to unexpected versus expected outcomes in cortical areas including bilateral dorsolateral prefrontal cortex. Individual difference analyses in patients revealed an association between physical anhedonia and activity in ventral striatum and ventromedial prefrontal cortex during anticipation of reward, in which greater anhedonia severity was associated with reduced activation to money versus no-money cues. In ventromedial prefrontal cortex, this relationship held among both controls and patients, suggesting a relationship between anticipatory activity and anhedonia irrespective of diagnosis. These findings suggest that in the absence of response requirements, brain responses to reward receipt are largely intact in medicated individuals with chronic schizophrenia, while reward anticipation responses in left ventral striatum are reduced in those patients with greater anhedonia severity

Widespread white matter microstructural differences in schizophrenia across 4322 individuals:Results from the ENIGMA Schizophrenia DTI Working Group

The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.Molecular Psychiatry advance online publication, 17 October 2017; doi:10.1038/mp.2017.170

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

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

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

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