Psychological resilience, emotional symptoms, and recovery duration in adolescent sport-related concussion.

OBJECTIVE: This study aimed to explore the relation between resilience, emotional changes following injury, and recovery duration in sport-related concussion. METHODS: Thirty-one high school student-athletes (ages 14-18) with sports-related injuries (concussion, n = 17 orthopedic injury, n = 14) were recruited from a pediatric sports medicine clinic. Participants completed self-report resilience ratings and self- and parent-reported post-concussion symptoms as part of a neuropsychological test battery. Hierarchical regression analyses examined predictors of recovery duration, including: (1) injury group and sex, (2) self- and parent-reported emotional symptom changes, and (3) resilience score. RESULTS: Injury group and sex alone were not predictors of recovery duration (p = .60). When parent and patient reported emotional response to injury were added to the analysis, 35% of the variance in length of recovery was explained, making the model statistically significant (F (2.26) = 3.57, p = .019). Including resilience did not reach statistical significance (p = .443). Post hoc analysis revealed parent-report of emotional changes was significantly associated with recovery duration t(31) = 3.16, p < .01), while self-report was not (p = .54). CONCLUSIONS: Parent-reported emotional change plays a pivotal role in predicting recovery length among adolescents recovering from sport-related concussion and orthopedic injury. These pilot findings highlight the significance of caregiver input in the clinical exam and emphasize the potential for acute interventions supporting psychological resources to enhance recovery outcomes across adolescent sport-related injuries.

Does Anxiety Systematically Bias Estimates of Executive Functioning Deficits in Pediatric Attention-Deficit/Hyperactivity Disorder?

Growing evidence suggests that childhood ADHD is associated with larger impairments in working memory relative to inhibition. However, most studies have not considered the role of co-occurring anxiety on these estimates - a potentially significant confound given prior evidence that anxiety may increase working memory difficulties but decrease inhibition difficulties for these children. The current study extends prior work to examine the extent to which co-occurring anxiety may be systematically affecting recent estimates of the magnitude of working memory/inhibitory control deficits in ADHD. The carefully-phenotyped sample included 197 children with ADHD and 142 children without ADHD between the ages of 8 and 13 years (N = 339; Mage = 10.31, SD = 1.39; 144 female participants). Results demonstrated that ADHD diagnosis predicted small impairments in inhibitory control (d = 0.31) and large impairments in working memory (d = 0.99). However, child trait anxiety assessed dimensionally across multiple informants (child, parent, teacher) did not uniquely predict either executive function, nor did it moderate estimates of ADHD-related working memory/inhibition deficits. When evaluating anxiety categorically and controlling for ADHD, anxiety diagnosis predicted slightly better working memory (d = 0.19) but not inhibitory control for clinically evaluated children generally. Findings from the current study indicate that trait anxiety, measured dimensionally or categorically, does not differentially affect estimates of executive dysfunction in pediatric ADHD. Further, results suggest that trait anxiety is generally not associated with executive dysfunction above and beyond the impact of co-occurring ADHD. Future research is needed to further assess the role of anxiety in ADHD behavioral symptomatology, neurocognitive functioning, and mechanisms underlying these relations.

Development of a machine learning algorithm based on administrative claims data for identification of ED anaphylaxis patient visits.

Background: Epidemiologic studies of anaphylaxis commonly rely on International Classification of Diseases (ICD) codes to identify anaphylaxis cases, which may lead to suboptimal epidemiologic classification. Objective: We sought to develop and assess the accuracy of a machine learning algorithm using ICD codes and other administrative data compared with ICD code-only algorithms to identify emergency department (ED) anaphylaxis visits. Methods: We conducted a retrospective review of ED visits from January 2013 to September 2017. Potential ED anaphylaxis visits were identified using 3 methods: anaphylaxis ICD diagnostic codes (method 1), ICD symptom-based codes with or without a code indicating an allergic trigger (method 2), and ICD codes indicating a potential allergic reaction only (method 3). A machine learning algorithm was developed from administrative data, and test characteristics were compared with ICD code-only algorithms. Results: A total of 699 of 2191 (31.9%) potential ED anaphylaxis visits were classified as anaphylaxis. The sensitivity and specificity of method 1 were 49.1% and 87.5%, respectively. Method 1 used in combination with method 2 resulted in a sensitivity of 53.9% and a specificity of 68.7%. Method 1 used in combination with method 3 resulted in a sensitivity of 98.4% and a specificity of 15.1%. The sensitivity and specificity of the machine learning algorithm were 87.3% and 79.1%, respectively. Conclusions: ICD coding alone demonstrated poor sensitivity in identifying cases of anaphylaxis, with venom-related anaphylaxis missing 96% of cases. The machine learning algorithm resulted in a better balance of sensitivity and specificity and improves upon previous strategies to identify ED anaphylaxis visits.

The relation between executive functions, error-related brain activity, and ADHD symptoms in clinically evaluated school-aged children.

Two event-related potentials (ERPs) elicited following errors, the error-related negativity (ERN) and error positivity (Pe), have been proposed to reflect cognitive control, though the specific processes remain debated. Few studies have examined the ERN and Pe's relations with individual differences in cognitive control/executive functioning using well-validated tests administered separately from the inhibition tasks used to elicit the ERN/Pe. Additionally, neurocognitive tests of executive functions tend to strongly predict ADHD symptoms, but the extent to which task-based and EEG-based estimates of executive functioning/cognitive control account for the same variance in ADHD symptoms remains unclear. The current study addressed these limitations by examining relations between the ERN/Pe and three core executive functions (working memory, inhibitory control, set shifting) in a clinically-evaluated sample of 53 children ages 8-12 (Mage = 10.36, SD = 1.42; 77.4% White/Non-Hispanic; 16 girls) with and without ADHD. Results demonstrated that neither the ERN nor Pe were related to overall cognitive control/executive functioning, or to working memory or set shifting specifically (all 95%CIs include 0.0). In contrast, a larger Pe was associated with better-developed inhibitory control (ß=-.35, 95%CI excludes 0.0), but did not capture aspects of inhibitory control that are important for predicting ADHD symptoms. Neither the ERN nor Pe predicted ADHD symptoms (95%CIs include 0.0). Results were generally robust to control for age, sex, SES, ADHD symptom cluster, and anxiety, and emphasize the need for caution when interpreting the ERN/Pe as indices of broad-based cognitive control/executive functioning, as well as using the ERN/Pe to examine cognitive processes contributing to ADHD symptomatology.

[Formula: see text] Does training working memory or inhibitory control produce far-transfer improvements in set shifting for children with ADHD? A randomized controlled trial.

Children with ADHD show impairments in set shifting task performance. However, the limited available evidence suggests that directly training shifting may not improve shifting performance in this population. We hypothesized that this incongruence may be because impairments exhibited by children with ADHD during shifting tasks are due to deficits in other executive functions, as shifting tasks also engage children's working memory and/or inhibitory control abilities. This randomized controlled trial examined the extent to which neurocognitive training of working memory vs. inhibitory control can produce downstream (far-transfer) improvements in set shifting task performance. Children with ADHD ages 8-12 (M = 10.41, SD = 1.46; 12 girls; 74% White/Non-Hispanic) were randomized to either central executive training (CET; n = 25) or inhibitory control training (ICT; n = 29), two next-generation digital therapeutics previously shown to improve their intended neurocognitive targets. Two criterion set shifting tests were administered at pre- and post-treatment. Results indicated that ICT was superior to CET for improving shifting accuracy (treatmentxtime: p = .03, BF10 = 3.01, η2 = .09, d = 0.63). ICT was also superior to CET for improving shifting speed, albeit on only one of the two outcome tasks (p = .02, BF10 = 4.53, η2 = .08, d = 0.59). CET did not produce improvements in shifting speed or accuracy on either task (p > .52, BF01 > 2.62), but showed evidence for more general (non-shifting-specific) improvement in response times on one of the outcome tasks (shift trials, d = 0.70; non-shift trials, d = 0.68). Taken together, these findings confirm that inhibitory control is important for successful performance on shifting tests, and suggest that training inhibitory control may reflect a method for improving set shifting difficulties in children with ADHD.

Reproducible changes in the anorexia nervosa gut microbiota following inpatient therapy remain distinct from non-eating disorder controls.

The composition of the gut microbiota in patients with anorexia nervosa (AN), and the ability of this microbial community to influence the host, remains uncertain. To achieve a broader understanding of the role of the intestinal microbiota in patients with AN, we collected fecal samples before and following clinical treatment at two geographically distinct eating disorder units (Center of Excellence for Eating Disorders [UNC-CH] and ACUTE Center for Eating Disorders [Denver Health]). Gut microbiotas were characterized in patients with AN, before and after inpatient treatment, and in non-eating disorder (non-ED) controls using shotgun metagenomic sequencing. The impact of inpatient treatment on the AN gut microbiota was remarkably consistent between eating disorder units. Although weight in patients with AN showed improvements, AN microbiotas post-treatment remained distinct from non-ED controls. Additionally, AN gut microbiotas prior to treatment exhibited more fermentation pathways and a lower ability to degrade carbohydrates than non-ED controls. As the intestinal microbiota can influence nutrient metabolism, our data highlight the complex microbial communities in patients with AN as an element needing further attention post inpatient treatment. Additionally, this study defines the effects of renourishment on the AN gut microbiota and serves as a platform to develop precision nutrition approaches to potentially mitigate impediments to recovery.

European Clinical Neuropsychology: Role in Healthcare and Access to Neuropsychological Services.

This study analyzed aspects of the work of clinical neuropsychologists across Europe. There are no published comparisons between European countries regarding the nature of clinical neuropsychologists' work. Forty-one national psychological and neuropsychological societies were approached, of which 31 (76%) responded. Data from seven countries with less than 10 neuropsychologists were excluded. A license is required to practice clinical neuropsychology in 50% of the countries. Clinical neuropsychologists work independently in 62.5%. Diagnostic/assessment work is the most frequently reported activity (54%). Most neuropsychologists work in public hospitals, followed by health centers. Adult neuropsychology was the most frequent area of activity. Services in public institutions are covered by public entities (45.8%), or by a combination of patient funds and public entities (29.2%) and only 4.2% by the patient; whereas services in private institutions are covered by the patient (26.1%) and the combination of patient, public entities (21.7%) or patient and private entities (17.4%). The data suggest that the number of neuropsychologists working across European countries is considerably low in comparison to other medical professionals. The results of the survey identified similar aspects of neuropsychologists' work, despite variations in terms of reimbursement and mechanisms, reflecting economic and healthcare differences. Estimates on the number of clinical neuropsychologists suggest insufficient access to neuropsychological services.

The Eating Disorders Genetics Initiative (EDGI): study protocol.

BACKGROUND: The Eating Disorders Genetics Initiative (EDGI) is an international investigation exploring the role of genes and environment in anorexia nervosa, bulimia nervosa, and binge-eating disorder. METHODS: A total of 14,500 individuals with eating disorders and 1500 controls will be included from the United States (US), Australia (AU), New Zealand (NZ), and Denmark (DK). In the US, AU, and NZ, participants will complete comprehensive online phenotyping and will submit a saliva sample for genotyping. In DK, individuals with eating disorders will be identified by the National Patient Register, and genotyping will occur using bloodspots archived from birth. A genome-wide association study will be conducted within EDGI and via meta-analysis with other data from the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED). DISCUSSION: EDGI represents the largest genetic study of eating disorders ever to be conducted and is designed to rapidly advance the study of the genetics of the three major eating disorders (anorexia nervosa, bulimia nervosa, and binge-eating disorder). We will explicate the genetic architecture of eating disorders relative to each other and to other psychiatric and metabolic disorders and traits. Our goal is for EDGI to deliver "actionable" findings that can be transformed into clinically meaningful insights. TRIAL REGISTRATION: EDGI is a registered clinical trial: clinicaltrials.gov NCT04378101 .

Early impact of COVID-19 on individuals with self-reported eating disorders: A survey of ~1,000 individuals in the United States and the Netherlands.

OBJECTIVE: We evaluated the early impact of COVID-19 on people with self-reported eating disorders. METHOD: Participants in the United States (US, N = 511) and the Netherlands (NL, N = 510), recruited through ongoing studies and social media, completed an online survey that included both quantitative measures and free-text responses assessing the impact of COVID-19 on situational circumstances, eating disorder symptoms, eating disorder treatment, and general well-being. RESULTS: Results revealed strong and wide-ranging effects on eating disorder concerns and illness behaviors that were consistent with eating disorder type. Participants with anorexia nervosa (US 62% of sample; NL 69%) reported increased restriction and fears about being able to find foods consistent with their meal plan. Individuals with bulimia nervosa and binge-eating disorder (US 30% of sample; NL 15%) reported increases in their binge-eating episodes and urges to binge. Respondents noted marked increases in anxiety since 2019 and reported greater concerns about the impact of COVID-19 on their mental health than physical health. Although many participants acknowledged and appreciated the transition to telehealth, limitations of this treatment modality for this population were raised. Individuals with past histories of eating disorders noted concerns about relapse related to COVID-19 circumstances. Encouragingly, respondents also noted positive effects including greater connection with family, more time for self-care, and motivation to recover. DISCUSSIONS: COVID-19 is associated with increased anxiety and poses specific disorder-related challenges for individuals with eating disorders that require attention by healthcare professionals and carers.

Early Impact of COVID-19 on Individuals with Eating Disorders: A survey of ~1000 Individuals in the United States and the Netherlands.

We received rapid ethical permission to evaluate the early impact of COVID-19 on people with eating disorders. Participants in the United States (US, N=511) and the Netherlands (NL, N=510), recruited through ongoing studies and social media, completed an online baseline survey that included both quantitative measures and free-text responses assessing the impact of COVID-19 on situational circumstances, eating disorder symptoms, eating disorder treatment, and general well-being. Results revealed strong and wide-ranging effects on eating disorder concerns and illness behaviors that were consistent with diagnoses. Participants with anorexia nervosa (US 62% of sample; NL 69%) reported increased restriction and fears about being able to find foods consistent with their meal plan. Individuals with bulimia nervosa and binge-eating disorder (US 30% of sample; NL 15%) reported increases in their binge-eating episodes and urges to binge. Respondents noted marked increases in anxiety since 2019 and reported greater concerns about the impact of COVID-19 on their mental health than physical health. Although many participants acknowledged and appreciated the transition to telehealth, limitations of this treatment modality for this population were raised. Individuals with past histories of eating disorders noted concerns about relapse related to COVID-19 circumstances. Encouragingly, respondents also noted positive effects including greater connection with family, more time for self-care, and motivation to recover.

Selectively reduced contrast sensitivity in high schizotypy.

Deficits in the ability to encode small differences in contrast between adjacent parts of an image (contrast sensitivity) are well documented in schizophrenic patients. In the present study, we sought to determine whether contrast sensitivity deficits reported in schizophrenic patients are also evident in those who exhibit high schizotypy scores in a typical (i.e., non-schizophrenic) population. Using the O-Life Questionnaire, we determined the effects of schizotypy on spatial (0.5, 2 and 8 c/deg) and spatiotemporal (0.5 and 8 c/deg at 0.5 and 8 Hz) contrast sensitivity in 73 young (18-26 years), majority female (n = 68) participants. We found differences in contrast sensitivity that were spatial, spatiotemporal and O-Life subscale specific. Spatial contrast sensitivity was significantly lower in high, compared to low schizotypes at low spatial frequencies (0.5 c/deg) in those who scored highly on the Unusual Experiences and Cognitive Disorganisation O-Life subscales. For moving stimuli, individuals with high scores on the Unusual Experiences subscale exhibited lower spatiotemporal contrast sensitivity for 0.5 and 8 c/deg patterns drifting at 8 Hz. Although the effects reported here were relatively small, this is the first report of reduced contrast sensitivity in schizotypy.

The 14q32 maternally imprinted locus is a major source of longitudinally stable circulating microRNAs as measured by small RNA sequencing.

Understanding the normal temporal variation of serum molecules is a critical factor for identifying useful candidate biomarkers for the diagnosis and prognosis of chronic disease. Using small RNA sequencing in a longitudinal study of 66 women with no history of cancer, we determined the distribution and dynamics (via intraclass correlation coefficients, ICCs) of the miRNA profile over 3 time points sampled across 2-5 years in the course of the screening trial, UKCTOCS. We were able to define a subset of longitudinally stable miRNAs (ICC >0.75) that were individually discriminating of women who had no cancer over the study period. These miRNAs were dominated by those originating from the C14MC cluster that is subject to maternal imprinting. This assessment was not significantly affected by common confounders such as age, BMI or time to centrifugation nor alternative methods to data normalisation. Our analysis provides important benchmark data supporting the development of miRNA biomarkers for the impact of life-course exposure as well as diagnosis and prognostication of chronic disease.

Training models and status of clinical neuropsychologists in Europe: Results of a survey on 30 countries.

OBJECTIVE: The aims of the study were to analyze the current European situation of specialist education and training within clinical neuropsychology, and the legal and professional status of clinical neuropsychologists in different European countries. METHOD: An online survey was prepared in 2016 by a Task Force established by the European Federation of Psychological Associations, and representatives of 30 countries gave their responses. Response rate was 76%. RESULTS: Only three countries were reported to regulate the title of clinical neuropsychologist as well as the education and practice of clinical neuropsychologists by law. The most common university degree required to practice clinical neuropsychology was the master's degree; a doctoral degree was required in two countries. The length of the specialist education after the master's degree varied between 12 and 60 months. In one third of the countries, no commonly agreed upon model for specialist education existed. A more systematic training model and a longer duration of training were associated with independence in the work of clinical neuropsychologists. CONCLUSIONS: As legal regulation is mostly absent and training models differ, those actively practicing clinical neuropsychology in Europe have a very heterogeneous educational background and skill level. There is a need for a European standardization of specialist training in clinical neuropsychology. Guiding principles for establishing the common core requirements are presented.

Subjective health among LGBT persons living with disabilities: A qualitative content analysis.

OBJECTIVE: There exist significant health disparities among both lesbian, gay, bisexual, transexual (LGBT) and disability persons; however, there is a dearth of information regarding the subjective health experiences of LGBT persons living with disabilities (LGBTPWD). As such, the purpose of this study was to understand how LGBTPWD subjectively defined and characterized the meaning of health in their lives. METHOD: Using qualitative content analyses procedures outlined by Elo and Kyngäs (2008), we conducted a secondary data analysis using a larger questionnaire study that was administered via the Internet. Participants were originally asked to answer the following prompt, "Describe what it personally means to you to be healthy?" Open-ended responses from 79 participants were thematically analyzed over several inductive and comparative coding iterations by a 3-person research team. Trustworthiness of data analysis was ensured via researcher triangulation, negative case analyses, and researcher reflexivity. RESULTS: Four dimensions of subjective health emerged during the qualitative analytic process: physical wellness, emotional vitality, functionality, and social engagement. CONCLUSIONS/IMPLICATIONS: There are contextually nuanced characteristics that constitute subjective health for LGBTPWD. These findings could help rehabilitation professionals provide culturally competent interventions. Implications for future research and limitations are provided in the discussion section. (PsycINFO Database Record

Reactivation of cocaine reward memory engages the Akt/GSK3/mTOR signaling pathway and can be disrupted by GSK3 inhibition.

RATIONAL: Memories return to a labile state following their retrieval and must undergo a process of reconsolidation to be maintained. Thus, disruption of cocaine reward memories by interference with reconsolidation may be therapeutically beneficial in the treatment of cocaine addiction. OBJECTIVE: The objectives were to elucidate the signaling pathway involved in reconsolidation of cocaine reward memory and to test whether targeting this pathway could disrupt cocaine-associated contextual memory. METHODS: Using a mouse model of conditioned place preference, regulation of the activity of glycogen synthase kinase-3 (GSK3), mammalian target of Rapamycin complex 1 (mTORC1), P70S6K, ß-catenin, and the upstream signaling molecule Akt, was studied in cortico-limbic-striatal circuitry after re-exposure to an environment previously paired with cocaine. RESULT: Levels of phosporylated Akt-Thr308, GSK3α-Ser21, GSK3ß-Ser9, mTORC1, and P70S6K were reduced in the nucleus accumbens and hippocampus 10 min after the reactivation of cocaine cue memories. Levels of pAkt and pGSK3 were also reduced in the prefrontal cortex. Since reduced phosphorylation of GSK3 indicates heightened enzyme activity, the effect of a selective GSK3 inhibitor, SB216763, on reconsolidation was tested. Administration of SB216763 immediately after exposure to an environment previously paired with cocaine abrogated a previously established place preference, suggesting that GSK3 inhibition interfered with reconsolidation of cocaine-associated reward memories. CONCLUSIONS: These findings suggest that the Akt/GSK3/mTORC1 signaling pathway in the nucleus accumbens, hippocampus, and/or prefrontal cortex is critically involved in the reconsolidation of cocaine contextual reward memory. Inhibition of GSK3 activity during memory retrieval can erase an established cocaine place preference.

The GSK3 signaling pathway is activated by cocaine and is critical for cocaine conditioned reward in mice.

The Akt - GSK3 signaling pathway has been recently implicated in psychostimulant-induced behavioral and cellular effects. Here, the ability of cocaine to regulate the activity of Akt and GSK3 was investigated by measuring the phosphorylation states of the two kinases. The anatomical specificity of the response was determined, as was the contributions of dopamine and NMDA receptors to the actions of cocaine. As GSK3 activity was found to be increased by cocaine, subsequent experiments investigated the importance of GSK3 activation in cocaine conditioned reward. Adult male CD-1 mice were injected with cocaine or saline, and levels of phosphorylated Akt and GSK3α/ß were measured 30 minutes later. Acute administration of cocaine significantly decreased the phosphorylation of Akt-Thr308 (pAkt-Thr308) and GSK3ß in the caudate putamen and nucleus accumbens core, without altering pAkt-Ser473 and pGSK3α. To investigate the role of dopamine and NMDA receptors in the regulation of Akt and GSK3 by cocaine, specific receptor antagonists were administered prior to cocaine. Blockade of dopamine D2 receptors with eticlopride prevented the reduction of pAkt-Thr308 produced by cocaine, whereas antagonists at dopamine D1, dopamine D2 or glutamatergic NMDA receptors each blocked cocaine-induced reductions in pGSK3ß. The potential importance of GSK3 activity in the rewarding actions of cocaine was determined using a cocaine conditioned place preference procedure. Administration of the selective GSK3 inhibitor, SB 216763, prior to cocaine conditioning sessions blocked the development of cocaine place preference. In contrast, SB 216763 did not alter the acquisition of a contextual fear conditioning response, demonstrating that SB 216763 did not globally inhibit contextual learning processes. The results of this study indicate that phosphorylation of GSK3ß is reduced, hence GSK3ß activity is increased following acute cocaine, an effect that is contingent upon both dopaminergic and glutamatergic receptors. Further, GSK3 activity is required for the development of cocaine conditioned reward.

Multipotent CD15+ cancer stem cells in patched-1-deficient mouse medulloblastoma.

Subpopulations of tumorigenic cells have been identified in many human tumors, although these cells may not be very rare in some types of cancer. Here, we report that medulloblastomas arising from Patched-1-deficient mice contain a subpopulation of cells that show a neural precursor phenotype, clonogenic and multilineage differentiation capacity, activated Hedgehog signaling, wild-type Patched-1 expression, and the ability to initiate tumors following allogeneic orthotopic transplantation. The normal neural stem cell surface antigen CD15 enriches for the in vitro proliferative and in vivo tumorigenic potential from uncultured medulloblastomas, supporting the existence of a cancer stem cell hierarchy in this clinically relevant mouse model of cancer.