Exploration of ADHD Subtype Definitions and Co-Occurring Psychopathology in a Missouri Population-Based Large Sibship Sample

Background: There is some debate regarding the utility of Attention-Deficit/ Hyperactivity Disorder (ADHD) subtypes as currently defined. Differences in co-occurring psychopathology among subtypes would support the validity of subtype definitions.Objective: To explore how ADHD subtype relates to co-occurring psychopathology in a large population-based sample of children and adolescents (n=5744).Method: Parents completed the Strengths and Weaknesses of ADHD-symptoms and Normal behavior (SWAN) questionnaire, the Child Behavior Checklist (CBCL) and the Social Responsiveness Scale (SRS). Methods including discriminant analysis, principal components analysis, and fractional polynomial regression were used to examine the relationship between ADHD diagnostic subtypes and co-occurring psychopathology.Results: Children with different ADHD subtypes show differences on several CBCL subscales. A combination of CBCL subscales and SRS score had good ability to discriminate ADHD subtypes. Conversely, for the same overall number of ADHD symptoms, individuals who present with both inattentive and hyperactive/impulsive symptoms exhibit higher severity of co-occurring psychopathology on a summary measure derived from principal components analysis of the CBCL subscales and SRS. This includes some subjects who fail to meet the DSM-IV-TR ADHD symptom criterion due to having less than 6 inattentive and less than six hyperactive-impulsive symptoms, yet have ADHD symptom severity similar to those with the inattentive or hyperactive-impulsive subtype.Conclusions: Several convergent lines of analysis provide support for the continued use of ADHD subtypes (or current presentation symptom profiles), as evidenced by differences in co-existing psychopathlogy. We also found that current diagnostic criteria may fail to identify a potentially impaired group of individuals who have low-to-moderate levels of both inattention and hyperactivity/impulsivity. Under the upcoming DSM-5, it will be important for clinicians to consider the option of giving an ADHD “not elsewhere classified” diagnosis to such children

Association between antidepressant use and ED or hospital visits in outpatients with SARS-CoV-2

Antidepressants have previously been associated with better outcomes in patients hospitalized with COVID-19, but their effect on clinical deterioration among ambulatory patients has not been fully explored. The objective of this study was to assess whether antidepressant exposure was associated with reduced emergency department (ED) or hospital visits among ambulatory patients with SARS-CoV-2 infection. This retrospective cohort study included adult patients (N = 25 034) with a positive SARS-CoV-2 test performed in a non-hospital setting. Logistic regression analyses tested associations between home use of antidepressant medications and a composite outcome of ED visitation or hospital admission within 30 days. Secondary exposures included individual antidepressants and antidepressants with functional inhibition of acid sphingomyelinase (FIASMA) activity. Patients with antidepressant exposure were less likely to experience the primary composite outcome compared to patients without antidepressant exposure (adjusted odds ratio [aOR] 0.89, 95% CI 0.79-0.99, p = 0.04). This association was only observed with daily doses of at least 20 mg fluoxetine-equivalent (aOR 0.87, 95% CI 0.77-0.99, p = 0.04), but not with daily doses lower than 20 mg fluoxetine-equivalent (aOR 0.94, 95% CI 0.80-1.11, p = 0.48). In exploratory secondary analyses, the outcome incidence was also reduced with exposure to selective serotonin reuptake inhibitors (aOR 0.87, 95% CI 0.75-0.99, p = 0.04), bupropion (aOR 0.70, 95% CI 0.55-0.90, p = 0.005), and FIASMA antidepressant drugs (aOR 0.87, 95% CI 0.77-0.99, p = 0.03). Antidepressant exposure was associated with a reduced incidence of emergency department visitation or hospital admission among SARS-CoV-2 positive patients, in a dose-dependent manner. These data support the FIASMA model of antidepressants\u27 effects against COVID-19

Antidepressant use and its association with 28-day mortality in inpatients with SARS-CoV-2: Support for the FIASMA model against COVID-19

To reduce Coronavirus Disease 2019 (COVID-19)-related mortality and morbidity, widely available oral COVID-19 treatments are urgently needed. Certain antidepressants, such as fluvoxamine or fluoxetine, may be beneficial against COVID-19. We included 388,945 adult inpatients who tested positive for SARS-CoV-2 at 36 AP-HP (Assistance Publique-Hôpitaux de Paris) hospitals from 2 May 2020 to 2 November 2021. We compared the prevalence of antidepressant use at admission in a 1:1 ratio matched analytic sample with and without COVID-19 (N = 82,586), and assessed its association with 28-day all-cause mortality in a 1:1 ratio matched analytic sample of COVID-19 inpatients with and without antidepressant use at admission (N = 1482). Antidepressant use was significantly less prevalent in inpatients with COVID-19 than in a matched control group of inpatients without COVID-19 (1.9% versus 4.8%; Odds Ratio (OR) = 0.38; 95%CI = 0.35-0.41

Selective cognitive and psychiatric manifestations in Wolfram Syndrome

BACKGROUND: Wolfram Syndrome (WFS) is known to involve diabetes mellitus, diabetes insipidus, optic nerve atrophy, vision loss, hearing impairment, motor abnormalities, and neurodegeneration, but has been less clearly linked to cognitive, sleep, and psychiatric abnormalities. We sought to determine whether these abnormalities are present in children, adolescents, and young adults with WFS compared to age- and gender-matched individuals with and without type 1 diabetes using standardized measures. METHODS: Individuals with genetically-confirmed WFS (n = 19, ages 7–27) were compared to age- and gender- equivalent groups of individuals with type 1 diabetes (T1DM; n = 25), and non-diabetic healthy controls (HC: n = 25). Cognitive performance across multiple domains (verbal intelligence, spatial reasoning, memory, attention, smell identification) was assessed using standardized tests. Standardized self- and parent-report questionnaires on psychiatric symptoms and sleep disturbances were acquired from all groups and an unstructured psychiatric interview was performed within only the WFS group. RESULTS: The three groups were similar demographically (age, gender, ethnicity, parental IQ). WFS and T1DM had similar duration of diabetes but T1DM had higher Hb(A1C) levels than WFS and as expected both groups had higher levels than HC. The WFS group was impaired on smell identification and reported sleep quality, but was not impaired in any other cognitive or self-reported psychiatric domain. In fact, the WFS group performed better than the other two groups on selected memory and attention tasks. However, based upon a clinical evaluation of only WFS patients, we found that psychiatric and behavioral problems were present and consisted primarily of anxiety and hypersomnolence. CONCLUSIONS: This study found that cognitive performance and psychological health were relatively preserved WFS patients, while smell and sleep abnormalities manifested in many of the WFS patients. These findings contradict past case and retrospective reports indicating significant cognitive and psychiatric impairment in WFS. While many of these patients were diagnosed with anxiety and hypersomnolence, self-reported measures of psychiatric symptoms indicated that the symptoms were not of grave concern to the patients. It may be that cognitive and psychiatric issues become more prominent later in life and/or in later stages of the disease, but this requires standardized assessment and larger samples to determine. In the relatively early stages of WFS, smell and sleep-related symptoms may be useful biomarkers of disease and should be monitored longitudinally to determine if they are good markers of progression as well. TRIAL REGISTRATION: Current Clinicaltrials.gov Trial NCT02455414

NCSX Toroidal Field Coil Design

The National Compact Stellarator Experiment (NCSX) is an experimental device whose design and construction is underway at the Department of Energy's Princeton Plasma Physics Laboratory (PPPL). The primary coil systems for the NCSX device consist of the twisted plasma-shaping Modular Coils, the Poloidal Field Coils, and the Toroidal Field (TF) Coils. The TF Coils are D-shaped coils wound from hollow copper conductor, and vacuum impregnated with a glass-epoxy resin system. There are 18 identical, equally spaced TF coils providing 1/R field at the plasma. They operate within a cryostat, and are cooled by LN2, nominally, to 80K. Wedge shaped castings are assembled to the inboard face of these coils, so that inward radial loads are reacted via the nesting of each of the coils against their adjacent partners. This paper outlines the TF Coil design methodology, reviews the analysis results, and summarizes how the design and analysis support the design requirements

PDD symptoms in ADHD, an independent familial trait?

The aims of this study were to investigate whether subtle PDD symptoms in the context of ADHD are transmitted in families independent of ADHD, and whether PDD symptom familiality is influenced by gender and age. The sample consisted of 256 sibling pairs with at least one child with ADHD and 147 healthy controls, aged 5-19 years. Children who fulfilled criteria for autistic disorder were excluded. The Children's Social Behavior Questionnaire (CSBQ) was used to assess PDD symptoms. Probands, siblings, and controls were compared using analyses of variance. Sibling correlations were calculated for CSBQ scores after controlling for IQ, ADHD, and comorbid anxiety. In addition, we calculated cross-sibling cross-trait correlations. Both children with ADHD and their siblings had higher PDD levels than healthy controls. The sibling correlation was 0.28 for the CSBQ total scale, with the CSBQ stereotyped behavior subscale showing the strongest sibling correlation (r = 0.35). Sibling correlations remained similar in strength after controlling for IQ and ADHD, and were not confounded by comorbid anxiety. Sibling correlations were higher in female than in male probands. The social subscale showed stronger sibling correlations in elder than in younger sibling pairs. Cross-sibling cross-trait correlations for PDD and ADHD were weak and not-significant. The results confirm that children with ADHD have high levels of PDD symptoms, and further suggest that the familiality of subtle PDD symptoms in the context of ADHD is largely independent from ADHD familiality

The strengths and difficulties questionnaire as a predictor of parent-reported diagnosis of autism spectrum disorder and attention deficit hyperactivity disorder

notes: PMCID: PMC3848967This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.The Strengths and Difficulties Questionnaire (SDQ) is widely used as an international standardised instrument measuring child behaviour. The primary aim of our study was to examine whether behavioral symptoms measured by SDQ were elevated among children with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) relative to the rest of the population, and to examine the predictive value of the SDQ for outcome of parent-reported clinical diagnosis of ASD/ADHD. A secondary aim was to examine the extent of overlap in symptoms between children diagnosed with these two disorders, as measured by the SDQ subscales. A cross-sectional secondary analysis of data from the Millennium Birth Cohort (n = 19,519), was conducted. Data were weighted to be representative of the UK population as a whole. ADHD or ASD identified by a medical doctor or health professional were reported by parents in 2008 and this was the case definition of diagnosis; (ADHD n = 173, ASD n = 209, excluding twins and triplets). Study children's ages ranged from 6.3-8.2 years; (mean 7.2 years). Logistic regression was used to examine the association between the parent-reported clinical diagnosis of ASD/ADHD and teacher and parent-reported SDQ subscales. All SDQ subscales were strongly associated with both ASD and ADHD. There was substantial co-occurrence of behavioral difficulties between children diagnosed with ASD and those diagnosed with ADHD. After adjustment for other subscales, the final model for ADHD, contained hyperactivity/inattention and impact symptoms only and had a sensitivity of 91% and specificity of 90%; (AUC) = 0.94 (95% CI, 0.90-0.97). The final model for ASD was composed of all subscales except the 'peer problems' scales, indicating of the complexity of behavioural difficulties that may accompany ASD. A threshold of 0.03 produced model sensitivity and specificity of 79% and 93% respectively; AUC = 0.90 (95% CI, 0.86-0.95). The results support changes to DSM-5 removing exclusivity clauses.ESRCNational Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsul

NCSX Construction Progress and Research Plans

Stellarators use 3D plasma and magnetic field shaping to produce a steady-state disruption-free magnetic confinement configuration. Compact stellarators have additional attractive properties — quasi-symmetric magnetic fields and low aspect ratio. The National Compact Stellarator Experiment (NCSX) is being constructed at the Princeton Plasma Physics Laboratory (PPPL) in partnership with the Oak Ridge National Laboratory (ORNL) to test the physics of a high-beta compact stellarator with a lowripple, tokamak-like magnetic configuration. The engineering challenges of NCSX stem from its complex geometry requirements. These issues are addressed in the construction project through manufacturing R&D and system engineering. As a result, the fabrication of the coil winding forms and vacuum vessel are proceeding in industry without significant technical issues, and preparations for winding the coils at PPPL are in place. Design integration, analysis, and dimensional control are functions provided by system engineering to ensure that the finished product will satisfy the physics requirements, especially accurate realization of the specified coil geometries. After completion of construction in 2009, a research program to test the expected physics benefits will start