Translating discoveries in Attention-Deficit/Hyperactivity Disorder genomics to an outpatient child and adolescent psychiatric cohort

Objective Genomic discoveries should be investigated in generalizable child psychiatric samples to justify and inform studies that will evaluate their use for specific clinical purposes. In youth consecutively referred for neuropsychiatric evaluation, we examined: 1) the convergent and discriminant validity of attention-deficit/hyperactivity disorder (ADHD) polygenic risk scores (PRS) in relation to DSM-based ADHD phenotypes; 2) the association of ADHD PRS with phenotypes beyond ADHD that share its liability and have implications for outcome; and 3) the extent to which youth with high ADHD PRS manifest a distinctive clinical profile. Method Participants were 433 youth, ages 7 to 18, from the Longitudinal Study of Genetic Influences on Cognition. We used logistic/linear regression and mixed effects models to examine associations with ADHD-related polygenic variation from the largest ADHD GWAS to date. We replicated key findings in 5140 adult patients from a local health system biobank. Results Among referred youth, ADHD PRS associated with ADHD diagnoses, cross-diagnostic ADHD symptoms and academic impairment (OR’s ∼1.4; R2‘s ∼2-3%) as well as cross-diagnostic variation in aggression and working memory. In adults, ADHD PRS associated with ADHD and phenotypes beyond the condition that have public health implications. Finally, youth with a high ADHD polygenic burden showed a more severe clinical profile than those with low burden (beta’s∼.2). Conclusion Among child and adolescent outpatients, ADHD polygenic risk associated with ADHD and related phenotypes as well as clinical severity. Results extend the scientific foundation for studies of ADHD polygenic risk in the clinical setting and highlight directions for further research

Relationship between chronic pain and cognition in cognitively intact older persons and patients with Alzheimer's disease; the need to control for mood

Background: Brain areas that are involved in cognition and mood also play a role in pain processing. Objective: The goal of the present study was to examine the relationship between chronic pain and cognition [executive functions (EF) and memory], while controlling for mood, in cognitively intact older persons and in patients with Alzheimer's disease (AD). Methods: Two groups of subjects participated: 20 older persons without dementia and 19 patients in an early stage of probable AD who suffered from arthrosis/arthritis. Pain intensity and pain affect were assessed by the Colored Analogue Scale for Pain Intensity and for Pain Affect, the Faces Pain Scale (FPS) and the Number of Words Chosen-Affective (NWC-A). Level of depression and anxiety were evaluated by questionnaires. EF and memory were assessed by neuropsychological tests. Results: The results show that significant correlations between specific cognitive functions, pain intensity and pain affect were lacking in the cognitively intact older persons. Cognition, in particular memory, appeared to be related to depressive symptoms. In contrast, a significant positive correlation was observed between EF, pain intensity and pain affect measured by the FPS in the AD group. Conclusions: Although older persons with depression were excluded, in studies on pain and cognition one should control for the presence of depressive symptoms in older persons with and without dementia. Copyright © 2008 S. Karger AG

Psychological Distress and Widespread Pain Contribute to the Variance of the Central Sensitization Inventory:A Cross-Sectional Study in Patients with Chronic Pain

Objectives: Central sensitization (CS) implies increased sensitivity of the nervous system, resulting in increased pain sensitivity as well as widespread pain. Recently, the Central Sensitization Inventory (CSI) was developed to assess symptoms of CS and central sensitivity syndromes. The aim of this study was to examine the convergent validity of the CSI by comparing the outcome to psychosocial factors and clinical features of CS. Methods: In a cross-sectional explorative study, patients with chronic pain completed multiple questionnaires, including the CSI, Pain Catastrophizing Scale, and Symptom Checklist 90, for psychological distress, duration of pain, intensity of pain, widespread pain, and lateralization of pain. Based on bivariate correlations, relevant predictors of CS were selected and used to fit an exploratory structural equation model (SEM) of CS. Results: In total, 114 patients with chronic pain were included, 56.1% being women. The average pain duration was 88 months. The mean total score on the CSI was 36.09 (15.26). The CSI was strongly related to known contributing and related factors of CS. SEM analysis showed that both psychological distress and widespread pain contributed significantly to the variance in symptoms of CS in patients with chronic pain. Conclusion: In this study, the convergent validity of the CSI was measured with demonstration of a strong relationship between contributing factors and clinical features of CS. These findings of convergent validity, considering former studies of the CSI, underline the use of the questionnaire in the clinical practice

Glutamine effects on brain growth in very preterm children in the first year of life

Glutamine supplementation in the neonatal period has been associated with increased brain structure volumes at school-age in very preterm children. The aim of this study was to clarify the emergence and specificity of differences in brain structure volumes, using growth trajectories of head circumference, weight, and length. Sixty-five very preterm ( <32 weeks gestation) children, who originally took part in a randomized controlled trial on glutamine supplementation, participated. Head circumference, weight, and length, were measured at the neonatal intensive care unit, and at routine follow-up assessments at the outpatient clinic and well baby clinics. Magnetic Resonance Imaging was used to determine brain structure volumes at school-age. Growth trajectories were investigated using multilevel modeling analyses. Head circumference in the first year of life was positively associated with white matter volume and grey matter volume (range r = 0.55-0.81, all p <0.002) at school-age. Furthermore, neonatal glutamine supplementation was associated with increased head circumference growth (p = 0.008) in the first year of life, but not with increased growth in weight (p = 0.44) and length (p = 0.73). This study indicates a specific increase in head circumference growth in very preterm children that received neonatal glutamine supplementation, and suggests that group differences in brain structure volumes at school-age may have emerged during the first year of lif

Cardiac function and cognition in older community-dwelling cardiac patients

Background: Cognitive deficits have been reported in older cardiac patients. An underlying mechanism for these findings may be reduced cardiac function. The relationship between cardiac function as represented by different echocardiographic measures and different cognitive function domains in older cardiac patients remains unknown. Methods: An older (≥70 years) heterogeneous group of 117 community-dwelling cardiac patients under medical supervision by a cardiologist underwent thorough echocardiographic assessment including left ventricular ejection fraction, cardiac index, left atrial volume index, left ventricular mass index, left ventricular diastolic function, and valvular calcification. During a home visit, a neuropsychological assessment was performed within 7.1 ± 3.8 months after echocardiographic assessment; the neuropsychological assessment included three subtests of a word-learning test (encoding, recall, recognition) to examine one memory function domain and three executive function tests, including digit span backwards, Trail Making Test B minus A, and the Stroop colour–word test. Results: Regression analyses showed no significant linear or quadratic associations between any of the echocardiographic functions and the cognitive function measures. Conclusions: None of the echocardiographic measures as representative of cardiac function was correlated with memory or executive function in this group of community-dwelling older cardiac patients. These findings contrast with those of previous studies

Allocation of substance use disorder patients to appropriate levels of care: feasibility of matching guidelines in routine practice in Dutch treatment centres

AIMS: To examine the feasibility of implementing evidence-based guidelines for patient-treatment-matching to levels of care in two Dutch substance abuse treatment centres. DESIGN: Multi-centre observational follow-up study. SETTING: Two large substance abuse treatment centres (SATCs). PARTICIPANTS: All 4394 referrals to the two SATCs in 2003. MEASUREMENTS: Baseline patient characteristics needed for treatment allocation according to protocol, treatment allocation according to matching protocol, treatment allocation according to actual level of care (LOC) entered. ANALYSIS: Comparison of recommended and actual LOC entered. Evaluation of reasons for observed differences between recommended and actual LOC entered. FINDINGS: Data needed for treatment allocation according to protocol were available for 2269 (51.6%) patients. Data needed for evaluation of actual LOC entered were available for 1765 (40.2%) patients. Of these patients, 1089 (60.8%) were allocated according to protocol: 48.4% based on the guideline algorithm and 12.4% based on clinically justified deviations from this algorithm. The main reason for deviation was a different appraisal of addiction severity, made by the intake counsellor compared to the protocol. CONCLUSION: The feasibility of guideline-based treatment allocation is seriously limited due to inadequate data collection of patient characteristics and suboptimal guideline-based treatment allocation. As a consequence, only 24.4% of the patients could be evaluated as being matched properly to the treatment planned. The results indicate several barriers which limit the adequate implementation of patient-treatment-matching guidelines: problems in the infrastructure of data collection and storage and the inertia of intake staff who did not adhere to the guidelines for assessment and matchin

Integrating questionnaire measures for transdiagnostic psychiatric phenotyping using word2vec.

BACKGROUND:Recent initiatives in psychiatry emphasize the utility of characterizing psychiatric symptoms in a multidimensional manner. However, strategies for applying standard self-report scales for multiaxial assessment have not been well-studied, particularly where the aim is to support both categorical and dimensional phenotypes. METHODS:We propose a method for applying natural language processing to derive dimensional measures of psychiatric symptoms from questionnaire data. We utilized nine self-report symptom measures drawn from a large cellular biobanking study that enrolled individuals with mood and psychotic disorders, as well as healthy controls. To summarize questionnaire results we used word embeddings, a technique to represent words as numeric vectors preserving semantic and syntactic meaning. A low-dimensional approximation to the embedding space was used to derive the proposed succinct summary of symptom profiles. To validate our embedding-based disease profiles, these were compared to presence or absence of axis I diagnoses derived from structured clinical interview, and to objective neurocognitive testing. RESULTS:Unsupervised and supervised classification to distinguish presence/absence of axis I disorders using survey-level embeddings remained discriminative, with area under the receiver operating characteristic curve up to 0.85, 95% confidence interval (CI) (0.74,0.91) using Gaussian mixture modeling, and cross-validated area under the receiver operating characteristic curve 0.91, 95% CI (0.88,0.94) using logistic regression. Derived symptom measures and estimated Research Domain Criteria scores also associated significantly with performance on neurocognitive tests. CONCLUSIONS:Our results support the potential utility of deriving dimensional phenotypic measures in psychiatric illness through the use of word embeddings, while illustrating the challenges in identifying truly orthogonal dimensions

Development of Repeated Sprint Ability in Talented Youth Basketball Players

te Wierike, SCM, de Jong, MC, Tromp, EJY, Vuijk, PJ, Lemmink, KAPM, Malina, RM, Elferink-Gemser, MT, and Visscher, C. Development of repeated sprint ability in talented youth basketball players. J Strength Cond Res 28(4): 928-934, 2014-Factors affecting repeated sprint ability (RSA) were evaluated in a mixed-longitudinal sample of 48 elite basketball players 14-19 years of age (16.1 +/- 1.7 years). Players were observed on 6 occasions during the 2008-09 and 2009-10 seasons. Three following basketball-specific field tests were administered on each occasion: the shuttle sprint test for RSA, the vertical jump for lower body explosive strength (power), and the interval shuttle run test for interval endurance capacity. Height and weight were measured; body composition was estimated (percent fat, lean body mass). Multilevel modeling of RSA development curve was used with 32 players (16.0 +/- 1.7 years) who had 2 or more observations. The 16 players (16.1 +/- 1.8 years) measured on only 1 occasion were used as a control group to evaluate the appropriateness of the model. Age, lower body explosive strength, and interval endurance capacity significantly contributed to RSA (p = 0.05). The results suggest a potentially important role for the training of lower body explosive strength and interval endurance capacity in the development of RSA among youth basketball players. Age-specific reference values for RSA of youth players may assist basketball coaches in setting appropriate goals for individual players

Polygenic association between attention-deficit/hyperactivity disorder liability and cognitive impairments

Background. A recent genome-wide association study (GWAS) identified 12 independent loci significantly associated with attention-deficit/hyperactivity disorder (ADHD). Polygenic risk scores (PRS), derived from the GWAS, can be used to assess genetic overlap between ADHD and other traits. Using ADHD samples from several international sites, we derived PRS for ADHD from the recent GWAS to test whether genetic variants that contribute to ADHD also influence two cognitive functions that show strong association with ADHD: attention regulation and response inhibition, captured by reaction time variability (RTV) and commission errors (CE). Methods. The discovery GWAS included 19 099 ADHD cases and 34 194 control participants. The combined target sample included 845 people with ADHD (age: 8-40 years). RTV and CE were available from reaction time and response inhibition tasks. ADHD PRS were calculated from the GWAS using a leave-one-study-out approach. Regression analyses were run to investigate whether ADHD PRS were associated with CE and RTV. Results across sites were combined via random effect meta-analyses. Results. When combining the studies in meta-analyses, results were significant for RTV (R2 = 0.011, β = 0.088, p = 0.02) but not for CE (R2 = 0.011, β = 0.013, p = 0.732). No significant association was found between ADHD PRS and RTV or CE in any sample individually ( p > 0.10). Conclusions. We detected a significant association between PRS for ADHD and RTV (but not CE) in individuals with ADHD, suggesting that common genetic risk variants for ADHD influence attention regulatio