K-12 Life Skills Education, Independence, and Employment of Autistic Individuals: Giving Voice to Autistic Adults.

Autistic adults are often challenged to engage in and complete life skill tasks independently and are underrepresented in employment. No prior study has explored the perceptions of autistic individuals regarding K-12 life skills experiences and postsecondary employment. As such, the purposes of this study were to explore the association between components of life skills instruction and employment for 12 autistic individuals, and to elicit the perspectives of and experiences in K-12 education and employment of six autistic adults. As this was a mixed methods study, surveys and semi-structured interviews were conducted. Results of Fisher's test indicated no statistically significant associations between employment and instructional components; however, the associations between employment and household chores [Cramer's V = .60]; cooking [Cramer's V = .66]; one-on-one instruction [Cramer's V = .63]; and field trips [Cramer's V = .41]) were large. The associations between employment and job site training [Cramer's V = .33] and token boards [Cramer's V = .33]) were moderate. Three themes and 10 subthemes emerged. Specifically, participants remembered Memorable Components from K-12 instruction: (a) job site training, (b) field trips, and (c) household chores. Participants perceived Beneficial Practices as: (a) job site training and (b) skills learned. Participants described shortcomings of K-12 instruction as need (a) for more skills training, (c) for social skills training, (d) to eliminate unnecessary instruction and (e) to carefully consider student placement. In conclusion, participants described experiences that helped them gain and attain post-secondary employment. More specific individualized programming in K-12 instruction would be beneficial to develop independence and post-secondary employment.

Pathway-specific polygenic scores for Alzheimer's disease are associated with changes in brain structure in younger and older adults.

Genome-wide association studies have identified multiple Alzheimer's disease risk loci with small effect sizes. Polygenic risk scores, which aggregate these variants, are associated with grey matter structural changes. However, genome-wide scores do not allow mechanistic interpretations. The present study explored associations between disease pathway-specific scores and grey matter structure in younger and older adults. Data from two separate population cohorts were used as follows: the Avon Longitudinal Study of Parents and Children, mean age 19.8, and UK Biobank, mean age 64.4 (combined n = 18 689). Alzheimer's polygenic risk scores were computed using the largest genome-wide association study of clinically assessed Alzheimer's to date. Relationships between subcortical volumes and cortical thickness, pathway-specific scores and genome-wide scores were examined. Increased pathway-specific scores were associated with reduced cortical thickness in both the younger and older cohorts. For example, the reverse cholesterol transport pathway score showed evidence of association with lower left middle temporal cortex thickness in the younger Avon participants (P = 0.034; beta = -0.013, CI -0.025, -0.001) and in the older UK Biobank participants (P = 0.019; beta = -0.003, CI -0.005, -4.56 × 10-4). Pathway scores were associated with smaller subcortical volumes, such as smaller hippocampal volume, in UK Biobank older adults. There was also evidence of positive association between subcortical volumes in Avon younger adults. For example, the tau protein-binding pathway score was negatively associated with left hippocampal volume in UK Biobank (P = 8.35 × 10-05; beta = -11.392, CI -17.066, -5.718) and positively associated with hippocampal volume in the Avon study (P = 0.040; beta = 51.952, CI 2.445, 101.460). The immune response score had a distinct pattern of association, being only associated with reduced thickness in the right posterior cingulate in older and younger adults (P = 0.011; beta = -0.003, CI -0.005, -0.001 in UK Biobank; P = 0.034; beta = -0.016, CI -0.031, -0.001 in the Avon study). The immune response score was associated with smaller subcortical volumes in the older adults, but not younger adults. The disease pathway scores showed greater evidence of association with imaging phenotypes than the genome-wide score. This suggests that pathway-specific polygenic methods may allow progress towards a mechanistic understanding of structural changes linked to polygenic risk in pre-clinical Alzheimer's disease. Pathway-specific profiling could further define pathophysiology in individuals, moving towards precision medicine in Alzheimer's disease.

The impact of genetic risk for Alzheimer's disease on the structural brain networks of young adults.

Introduction: We investigated the structural brain networks of 562 young adults in relation to polygenic risk for Alzheimer's disease, using magnetic resonance imaging (MRI) and genotype data from the Avon Longitudinal Study of Parents and Children. Methods: Diffusion MRI data were used to perform whole-brain tractography and generate structural brain networks for the whole-brain connectome, and for the default mode, limbic and visual subnetworks. The mean clustering coefficient, mean betweenness centrality, characteristic path length, global efficiency and mean nodal strength were calculated for these networks, for each participant. The connectivity of the rich-club, feeder and local connections was also calculated. Polygenic risk scores (PRS), estimating each participant's genetic risk, were calculated at genome-wide level and for nine specific disease pathways. Correlations were calculated between the PRS and (a) the graph theoretical metrics of the structural networks and (b) the rich-club, feeder and local connectivity of the whole-brain networks. Results: In the visual subnetwork, the mean nodal strength was negatively correlated with the genome-wide PRS (r = -0.19, p = 1.4 × 10-3), the mean betweenness centrality was positively correlated with the plasma lipoprotein particle assembly PRS (r = 0.16, p = 5.5 × 10-3), and the mean clustering coefficient was negatively correlated with the tau-protein binding PRS (r = -0.16, p = 0.016). In the default mode network, the mean nodal strength was negatively correlated with the genome-wide PRS (r = -0.14, p = 0.044). The rich-club and feeder connectivities were negatively correlated with the genome-wide PRS (r = -0.16, p = 0.035; r = -0.15, p = 0.036). Discussion: We identified small reductions in brain connectivity in young adults at risk of developing Alzheimer's disease in later life.

Anti-cholinergic drug burden in patients with dementia increases after hospital admission: a multicentre cross-sectional study.

BACKGROUND: Anticholinergic medications are drugs that block cholinergic transmission, either as their primary therapeutic action or as a secondary effect. Patients with dementia may be particularly sensitive to the central effects of anticholinergic drugs. Anticholinergics also antagonise the effects of the main dementia treatment, cholinesterase inhibitors. Our study aimed to investigate anticholinergic prescribing for dementia patients in UK acute hospitals before and after admission. METHODS: We included 352 patients with dementia from 17 UK hospital sites in 2019. They were all inpatients on surgical, medical or Care of the Elderly wards. Information about each patient's medications were collected using a standardised form, and the anticholinergic drug burden of each patient was calculated with an evidence-based online calculator. Wilcoxon's rank test was used to look at the correlation between two subgroups upon admission and discharge. RESULTS: On admission to hospital, 37.8% of patients had an anticholinergic burden score ≥ 1 and 5.68% ≥3. On discharge, 43.2% of patients with an anticholinergic burden score ≥ 1 and 9.1% ≥3. The increase in scores was statistically significant (p = 0.001). Psychotropics were the most common group of anticholinergic medications prescribed at discharge. Of those patients taking cholinesterase inhibitors, 44.9% were also prescribed anticholinergic medications. CONCLUSIONS: Our cross-sectional, multicentre study found that people with dementia are commonly prescribed anticholinergic medications, even if concurrently taking cholinesterase inhibitors, and are significantly more likely to be discharged from hospital with a higher anticholinergic burden than on admission.

Comparison of Four Classroom-Based Strategies for Middle School Students With ADHD: A Pilot Randomized Controlled Trial.

Middle school students with ADHD often experience negative academic outcomes. To intervene, schools frequently provide services through special education or section 504. These services include strategies, such as breaks, prompting, and sensory proprioception to remove the impact of construct-irrelevant variance. Student plans rarely include strategies, such as selfmanagement, designed to teach students skills to increase independent functioning. The purpose of this study was to compare the effectiveness of four strategies on engagement, disruptive behavior, and time to initiate tasks. Fifteen sixth and seventh grade students were randomized daily to one of four conditions. Results indicated large statistically significant differences. Social validity data indicated that students found prompting and self-management helpful, but preferred breaks and sensory proprioception. This study builds on a growing empirical base that supports the prioritization of strategies to teach skills over strategies to remove the impact of ADHD on performance.

A novel hybrid scale for the assessment of cognitive and executive function: The Free-Cog.

BACKGROUND: Scales measuring cognitive and executive functions are integral to the assessment and management of patients with suspected cognitive impairment. Some of the most commonly used cognitive tests are now subject to copyright restrictions. Furthermore, no existing scale assesses both executive and cognitive abilities. AIMS: We aimed to develop and validate a novel hybrid scale for use in clinical practice which integrate measures of cognition and executive abilities ('Free-Cog'). METHODS: The instrument was devised through a national collaboration including health professionals, those with lived experience of dementia and researchers. Following ethics committee approval, the Free-Cog was assessed in 25 real-world clinical settings across England, Wales and Scotland. It was compared to three other cognitive tests routinely administered in clinical practice: the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MOCA), and the Addenbrooke's Cognitive Examination (ACE). RESULTS: The Free-Cog was tested in 960 patients with clinical diagnoses of dementia, Mild Cognitive Impairment (MCI), and normal controls. Similar to the MMSE, MOCA and ACE, it discriminated well between the three groups (p < 0.001). It correlated well with the other instruments. Using a receiver operating characteristic curve analysis, Free-Cog achieved an Area Under Curve of 0.94 for dementia versus controls, 0.80 for MCI versus controls and 0.77 for dementia versus MCI. A version of the tool adapted for telephone consultation, the Tele Free-Cog, also discriminated well between patient groups. CONCLUSIONS: Free-Cog is a non-proprietary, empirically derived, concise assessment. Uniquely, it combines cognitive and executive function questions in the one instrument. It could be used to inform the assessment of people presenting with cognitive impairment and is available to anyone interested in trialling it.

Imaging Alzheimer's genetic risk using diffusion MRI: A systematic review.

Diffusion magnetic resonance imaging (dMRI) is an imaging technique which probes the random motion of water molecules in tissues and has been widely applied to investigate changes in white matter microstructure in Alzheimer's Disease. This paper aims to systematically review studies that examined the effect of Alzheimer's risk genes on white matter microstructure. We assimilated findings from 37 studies and reviewed their diffusion pre-processing and analysis methods. Most studies estimate the diffusion tensor (DT) and compare derived quantitative measures such as fractional anisotropy and mean diffusivity between groups. Those with increased AD genetic risk are associated with reduced anisotropy and increased diffusivity across the brain, most notably the temporal and frontal lobes, cingulum and corpus callosum. Structural abnormalities are most evident amongst those with established Alzheimer's Disease. Recent studies employ signal representations and analysis frameworks beyond DT MRI but show that dMRI overall lacks specificity to disease pathology. However, as the field advances, these techniques may prove useful in pre-symptomatic diagnosis or staging of Alzheimer's disease.

Comparison of accommodations and interventions for youth with ADHD: A randomized controlled trial.

School psychologists have a variety of evidence-based interventions from which to choose when recommending classroom-based strategies for students with attention deficit hyperactivity disorder (ADHD); however, strategies frequently found on individualized education plans are accommodations designed to remove barriers to learning, which have limited empirical evidence. As such, the purpose of the current study was to compare the efficacy of three interventions (i.e., organization training, self-management, note-taking instruction) and three accommodations (i.e., organization support, extended time, copy of teacher notes) to address difficulties with organization and maintaining attention during a science lesson and associated independent practice. The study included 64 middle school students with ADHD randomized to either an intervention or an accommodation condition. The intervention group was further divided into two subgroups, consisting of (a) students who were willing to follow intervention procedures and (b) students who were not willing to follow the procedures (behavioral indicators of social validity). Results indicated that adolescents with ADHD in the intervention group were statistically significantly more likely to organize and maintain binder organization and to take complete and accurate notes than those in the accommodation group. In addition, exploratory analyses indicated that adolescents who demonstrated willingness to follow intervention procedures were more likely to be academically engaged during instruction and independent work and to complete independent work accurately than those who resisted the procedures.

From Polygenic Scores to Precision Medicine in Alzheimer's Disease: A Systematic Review.

BACKGROUND: Late-onset Alzheimer's disease (AD) is highly heritable. The effect of many common genetic variants, single nucleotide polymorphisms (SNPs), confer risk. Variants are clustered in areas of biology, notably immunity and inflammation, cholesterol metabolism, endocytosis, and ubiquitination. Polygenic scores (PRS), which weight the sum of an individual's risk alleles, have been used to draw inferences about the pathological processes underpinning AD. OBJECTIVE: This paper aims to systematically review how AD PRS are being used to study a range of outcomes and phenotypes related to neurodegeneration. METHODS: We searched the literature from July 2008-July 2018 following PRISMA guidelines. RESULTS: 57 studies met criteria. The AD PRS can distinguish AD cases from controls. The ability of AD PRS to predict conversion from mild cognitive impairment (MCI) to AD was less clear. There was strong evidence of association between AD PRS and cognitive impairment. AD PRS were correlated with a number of biological phenotypes associated with AD pathology, such as neuroimaging changes and amyloid and tau measures. Pathway-specific polygenic scores were also associated with AD-related biologically relevant phenotypes. CONCLUSION: PRS can predict AD effectively and are associated with cognitive impairment. There is also evidence of association between AD PRS and other phenotypes relevant to neurodegeneration. The associations between pathway specific polygenic scores and phenotypic changes may allow us to define the biology of the disease in individuals and indicate who may benefit from specific treatments. Longitudinal cohort studies are required to test the ability of PGS to delineate pathway-specific disease activity.

#BJPsych and social media - likes, followers and leading?

This article explores the growing interface between social media and academic publishing. We discuss how the British Journal of Psychiatry (BJPsych) and other scientific journals are engaging with social media to communicate in a digital world. A growing body of evidence suggests that public visibility and constructive conversation on social media networks can be beneficial for researchers and clinicians, influencing research in a number of key ways. This engagement presents new opportunities for more widely disseminating information, but also carries risks. We note future prospects and ask where BJPsych should strategically place itself in this rapidly changing environment.Declaration of interestJ.R.H., J.F.H. and D.T. are on the editorial board of the BJPsych. D.T. runs its social media arm.

Fractional anisotropy of the uncinate fasciculus and cingulum in bipolar disorder type I, type II, unaffected siblings and healthy controls.

BACKGROUND: Fractional anisotropy in the uncinate fasciculus and the cingulum may be biomarkers for bipolar disorder and may even be distinctly affected in different subtypes of bipolar disorder, an area in need of further research.AimsThis study aims to establish if fractional anisotropy in the uncinate fasciculus and cingulum shows differences between healthy controls, patients with bipolar disorder type I (BD-I) and type II (BD-II), and their unaffected siblings. METHOD: Fractional anisotropy measures from the uncinate fasciculus, cingulum body and parahippocampal cingulum were compared with tractography methods in 40 healthy controls, 32 patients with BD-I, 34 patients with BD-II, 17 siblings of patients with BD-I and 14 siblings of patients with BD-II. RESULTS: The main effects were found in both the right and left uncinate fasciculus, with patients with BD-I showing significantly lower fractional anisotropy than both patients with BD-II and healthy controls. Participants with BD-II did not differ from healthy controls. Siblings showed similar effects in the left uncinate fasciculus. In a subsequent complementary analysis, we investigated the association between fractional anisotropy in the uncinate fasciculus and polygenic risk for bipolar disorder and psychosis in a large cohort (n = 570) of healthy participants. However, we found no significant association. CONCLUSIONS: Fractional anisotropy in the uncinate fasciculus differs significantly between patients with BD-I and patients with BD-II and healthy controls. This supports the hypothesis of differences in the physiological sub-tract between bipolar disorder subtypes. Similar results were found in unaffected siblings, suggesting the potential for this biomarker to represent an endophenotype for BD-I. However, fractional anisotropy in the uncinate fasciculus seems unrelated to polygenic risk for bipolar disorder or psychosis.Declaration of interestNone.

The use of polygenic risk scores to identify phenotypes associated with genetic risk of bipolar disorder and depression: A systematic review.

BACKGROUND: Identifying the phenotypic manifestations of increased genetic liability for depression (MDD) and bipolar disorder (BD) can enhance understanding of their aetiology. The polygenic risk score (PRS) derived using data from genome-wide-association-studies can be used to explore how genetic risk is manifest in different samples. AIMS: In this systematic review, we review studies that examine associations between the MDD and BD polygenic risk scores and phenotypic outcomes. METHODS: Following PRISMA guidelines, we searched EMBASE, Medline and PsycINFO (from August 2009 - 14th March 2016) and references of included studies. Study inclusion was based on predetermined criteria and data were extracted independently and in duplicate. RESULTS: Twenty-five studies were included. Overall, both polygenic risk scores were associated with other psychiatric disorders (not the discovery sample disorder) such as depression, schizophrenia and bipolar disorder, greater symptom severity of depression, membership of a creative profession and greater educational attainment. Both depression and bipolar polygenic risk scores explained small amounts of variance in most phenotypes (< 2%). LIMITATIONS: Many studies did not report standardised effect sizes. This prevented us from conducting a meta-analysis. CONCLUSIONS: Polygenic risk scores for BD and MDD are associated with a range of phenotypes and outcomes. However, they only explain a small amount of the variation in these phenotypes. Larger discovery and adequately powered target samples are required to increase power of the PRS approach. This could elucidate how genetic risk for bipolar disorder and depression is manifest and contribute meaningfully to stratified medicine.

The use of polygenic risk scores to identify phenotypes associated with genetic risk of schizophrenia: Systematic review.

Studying the phenotypic manifestations of increased genetic liability for schizophrenia can increase our understanding of this disorder. Specifically, information from alleles identified in genome-wide association studies can be collapsed into a polygenic risk score (PRS) to explore how genetic risk is manifest within different samples. In this systematic review, we provide a comprehensive assessment of studies examining associations between schizophrenia PRS (SZ-PRS) and several phenotypic measures. We searched EMBASE, Medline and PsycINFO (from August 2009-14th March 2016) plus references of included studies, following PRISMA guidelines. Study inclusion was based on predetermined criteria and data were extracted independently and in duplicate. Overall, SZ-PRS was associated with increased risk for psychiatric disorders such as depression and bipolar disorder, lower performance IQ and negative symptoms. SZ-PRS explained up to 6% of genetic variation in psychiatric phenotypes, compared to <0.7% in measures of cognition. Future gains from using the PRS approach may be greater if used for examining phenotypes that are more closely related to biological substrates, for scores based on gene-pathways, and where PRSs are used to stratify individuals for study of treatment response. As it was difficult to interpret findings across studies due to insufficient information provided by many studies, we propose a framework to guide robust reporting of PRS associations in the future.

Improving inpatient care for older adults: Implementing Dementia Commissioning for Quality and Innovation (CQUIN).

Dementia is a common condition, and people with dementia occupy around 25% of hospital beds. Commissioning for Quality and Innovation (CQUIN) is an NHS payment framework that links part of English healthcare providers' income to quality improvement. The dementia CQUIN goals are designed to encourage the recognition of dementia in hospital. The Royal Surrey County Hospital, Guildford, introduced new procedures to meet the dementia CQUIN targets. Adherence to the changes was a problem. This project aimed to improve hospital's implementation strategy. At baseline, completion rates for dementia CQUIN assessments were just 27%. Interventions were informed by semi-structured interviews with junior doctors and dementia leads in neighbouring trusts. Progress was measured by regular audits and interventions were made over several months. Changes suggested by junior doctors and nurses proved very effective, and involving the multidisciplinary team produced the most significant improvement. Gradual progress was made until we achieved and maintained 90% completion for dementia assessments. In conclusion, we made changes to working practices to achieve the CQUIN targets and promoted quality care for older adults. Our experience highlighted the importance of involving multidisciplinary frontline staff in the design of service changes.

Alzheimer's disease: the amyloid hypothesis on trial.

The pathogenesis of Alzheimer's disease is complex. The amyloid hypothesis has directed research efforts for many years, but it has recently been questioned after failed drug trials. Here, we review the evidence for and against and suggest that it might be premature to abandon the amyloid hypothesis.

Measuring ADHD and ODD symptoms and impairment using high school teachers' ratings.

We analyzed the results of high school teachers' ratings of symptoms of attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder, as well as school-related impairment of 875 adolescents. One hundred forty-three teachers at 19 high schools across 4 states each rated 6 students from their first-period classes according to selection criteria that led to ratings for 3 male and 3 female students. Factor analyses were conducted on the symptom measure to test hypotheses pertaining to the divergence of impulsivity and hyperactivity dimensions. Normative values for the Disruptive Behavior Disorder-Teacher Rating Scale and Impairment Rating Scale are reported, as well as important differences related to age, race, and gender. Gender and age contrasts revealed that boys were rated as more symptomatic and impaired than girls and younger adolescents were rated as having more problems than older adolescents in most areas. African American adolescents were rated higher on measures of symptoms and impairment than their Caucasian peers. Large differences in normative levels of hyperactivity/impulsivity and inattention are reported that are consistent with a reduced likelihood of a diagnosis of ADHD-C as children get older. Implications for the interpretation of ratings from high school teachers are discussed.

Behaviors that discriminate ADHD in children and adolescents: primary symptoms, symptoms of comorbid conditions, or indicators of functional impairment?

OBJECTIVE: The objectives of this study were to evaluate whether behaviors that differentiate children and adolescents with ADHD from those without are related to the primary diagnostic criteria (i.e., inattention and impulsivity-hyperactivity), symptoms of comorbid conditions, functional impairment, or a combination, and to determine whether behaviors that discriminate are consistent between the key developmental stages of childhood and adolescence. METHOD: Parents and teachers rated children and adolescents with a formal diagnosis of ADHD and those without any mental, physical, or emotional disorders on the multidimensional Behavior Assessment System for Children (2nd ed., BASC-2). RESULTS: Results indicated that behaviors that discriminate children and adolescents with ADHD from those without were associated with primary symptoms, symptoms of comorbid conditions, and indicators of functional impairment. Teachers rated atypicality as the strongest discriminator of children with ADHD from those without and learning problems as the strongest discriminator of adolescents. Parents rated hyperactivity as the strongest discriminator for children and attention problems for adolescents. Activities of daily living was the third strongest discriminator of adolescents as rated by parents. CONCLUSIONS: Findings supported the need for a multidimensional view of ADHD that adds emphasis to issues of functional impairment in routine, daily activities important to success in school and interpersonally. Findings showed that conceptualizing and assessing behaviors demonstrated by children and adolescents with ADHD as a whole instead of only equating a diagnosis of ADHD to hyperactivity, inattention, and impulsivity will establish a foundation for understanding, interpreting, and addressing students' academic and behavioral needs across the home and school.