Background A subset of patients with severe COVID-19 develop a hyperinflammatory syndrome, which might contribute to morbidity and mortality. This study explores a specific phenotype of COVID-19-associated hyperinflammation (COV-HI), and its associations with escalation of respiratory support and survival. Methods In this retrospective cohort study, we enrolled consecutive inpatients (aged ≥18 years) admitted to University College London Hospitals and Newcastle upon Tyne Hospitals in the UK with PCR-confirmed COVID-19 during the first wave of community-acquired infection. Demographic data, laboratory tests, and clinical status were recorded from the day of admission until death or discharge, with a minimum follow-up time of 28 days. We defined COV-HI as a C-reactive protein concentration greater than 150 mg/L or doubling within 24 h from greater than 50 mg/L, or a ferritin concentration greater than 1500 μg/L. Respiratory support was categorised as oxygen only, non-invasive ventilation, and intubation. Initial and repeated measures of hyperinflammation were evaluated in relation to the next-day risk of death or need for escalation of respiratory support (as a combined endpoint), using a multi-level logistic regression model. Findings We included 269 patients admitted to one of the study hospitals between March 1 and March 31, 2020, among whom 178 (66%) were eligible for escalation of respiratory support and 91 (34%) patients were not eligible. Of the whole cohort, 90 (33%) patients met the COV-HI criteria at admission. Despite having a younger median age and lower median Charlson Comorbidity Index scores, a higher proportion of patients with COV-HI on admission died during follow-up (36 [40%] of 90 patients) compared with the patients without COV-HI on admission (46 [26%] of 179). Among the 178 patients who were eligible for full respiratory support, 65 (37%) met the definition for COV-HI at admission, and 67 (74%) of the 90 patients whose respiratory care was escalated met the criteria by the day of escalation. Meeting the COV-HI criteria was significantly associated with the risk of next-day escalation of respiratory support or death (hazard ratio 2·24 [95% CI 1·62–2·87]) after adjustment for age, sex, and comorbidity. Interpretation Associations between elevated inflammatory markers, escalation of respiratory support, and survival in people with COVID-19 indicate the existence of a high-risk inflammatory phenotype. COV-HI might be useful to stratify patient groups in trial design. Funding None.

Preparation-vigilance measures were markers of remission, improving concurrently with ADHD symptoms, whereas executive control measures were not sensitive to ADHD persistence/remission. For IQ, the present and previous results combined suggest a role in moderating ADHD outcome. These findings fit with previously identified aetiological separation of the cognitive impairments in ADHD. The strongest candidates for the development of non-pharmacological interventions involving cognitive training and neurofeedback are the preparation-vigilance processes that were markers of ADHD remission.

Children with ADHD show deficits in attentional orienting and inhibitory control whereas children with ASD show abnormalities in conflict monitoring and response preparation. Children with co-morbid ASD + ADHD present as an additive co-occurrence with deficits of both disorders, although non-additive effects are suggested for response preparation. Measuring ERPs that index attention and inhibition is useful in disentangling cognitive markers of ASD and ADHD and elucidating the basis of co-occurring ASD + ADHD to guide clinical assessment.

Bipolar affective disorder is a severe and debilitating psychiatric condition characterized by the alternating mood states of mania and depression. Both the molecular pathophysiology of the disorder and the mechanism of action of the mainstays of its treatment remain largely unknown. Here, 1 H NMR spectroscopy-based metabonomic analysis was performed to identify molecular changes in post-mortem brain tissue (dorsolateral prefrontal cortex) of patients with a history of bipolar disorder. The observed changes were then compared to metabolic alterations identified in rat brain following chronic oral treatment with either lithium or valproate. This is the first study to use 1 H NMR spectroscopy to study post-mortem bipolar human brain tissue, and it is the first to compare changes in disease brain with changes induced in rat brain following mood stabilizer treatment. Several metabolites were found to be concordantly altered in both the animal and human tissues. Glutamate levels were increased in post-mortem bipolar brain, while the glutamate/glutamine ratio was decreased following valproate treatment, and c-aminobutyric acid levels were increased after lithium treatment, suggesting that the balance of excitatory/inhibitory neurotransmission is central to the disorder. Both creatine and myo-inositol were increased in the post-mortem brain but depleted with the medications. Lastly, the level of N-acetyl aspartate, a clinically important metabolic marker of neuronal viability, was found to be unchanged following chronic mood stabilizer treatment. These findings promise to provide new insight into the pathophysiology of bipolar disorder and may be used to direct research into novel therapeutic strategies.

These findings closely resemble those previously found in children with ADHD, suggesting that conflict monitoring and early error processing are also abnormal in adults with ADHD; and share familial influences with ADHD throughout the lifespan. The relationship between different indices of performance monitoring may suggest partly common underlying mechanisms or modulators.

Background Emerging work suggests that academic achievement may be influenced by the management of affect as well as through efficient information processing of task demands. In particular, mathematical anxiety has attracted recent attention because of its damaging psychological effects and potential associations with mathematical problem-solving and achievement. The present study investigated the genetic and environmental factors contributing to the observed differences in the anxiety people feel when confronted with mathematical tasks. In addition, the genetic and environmental mechanisms that link mathematical anxiety with math cognition and general anxiety were also explored. Methods Univariate and multivariate quantitative genetic models were conducted in a sample of 514 12-year-old twin siblings. Results Genetic factors accounted for roughly 40% of the variation in mathematical anxiety, with the remaining being accounted for by child-specific environmental factors. Multivariate genetic analyses suggested that mathematical anxiety was influenced by the genetic and non-familial environmental risk factors associated with general anxiety and additional independent genetic influences associated with math-based problem solving. Conclusions The development of mathematical anxiety may involve not only exposure to negative experiences with mathematics, but also likely involves genetic risks related to both anxiety and math cognition. These results suggest that integrating cognitive and affective domains may be particularly important for mathematics, and may extend to other areas of academic achievement.

Background Attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood, but it remains unclear which childhood factors predict future outcome. Aim To identify childhood predictors of ADHD outcome using both dimensional and categorical approaches. Methods 116 adolescents and young adults with childhood ADHD were followed up on average 6.6 years later. ADHD outcome variables were interview-based parent-reported ADHD symptoms and impairment. Childhood predictors included parent- and teacher-rated ADHD symptoms and co-occurring behaviours; actigraph measures of activity level; socio-economic status (SES); and cognitive measures previously associated with ADHD. Results Of the sample, 79% continued to meet clinical criteria of ADHD in adolescence and young adulthood. Higher parent-rated ADHD symptoms and movement intensity in childhood, but not teacher-rated symptoms, predicted ADHD symptoms at follow up. Co-occurring symptoms of oppositional behaviours, anxiety, social and emotional problems were also significant predictors, but these effects disappeared after controlling for ADHD symptoms. IQ and SES were significant predictors of both ADHD symptoms and impairment at follow up, but no other cognitive measures significantly predicted outcome. Conclusions SES and IQ emerge as potential moderators for the prognosis of ADHD. Childhood severity of ADHD symptoms, as measured by parent ratings and actigraph movement intensity, also predicts later ADHD outcome. These factors should be considered when identifying ADHD children at most risk of poor long-term outcomes and for the development of interventions to improve prognosis.

Background Electrophysiological and hemodynamic activity is altered in attention-deficit/hyperactivity disorder (ADHD) during tasks requiring cognitive control. Frontal midline theta oscillations are a cortical correlate of cognitive control influencing behavioral outcomes including reaction times. Reaction time variability (RTV) is consistently increased in ADHD and is known to share genetic effects with the disorder. The etiological relationship between the cognitive control system, RTV, and ADHD is unknown. In a sample of twins selected for ADHD and matched control subjects, we aimed to quantify the strength of the phenotypic, genetic, and environmental relationships between event-related midline theta oscillations, RTV, and ADHD. Methods Our sample included 134 participants aged 12 to 15 years: 67 twin pairs (34 monozygotic; 33 dizygotic) with concordance or discordance for ADHD symptomatology assessed at 8, 10, and 12 years of age. Our main outcome measures were frontal midline theta activity, derived from both channel and source decomposed electroencephalographic data, and behavioral performance on a response-choice arrow flanker task known to elicit theta activity. Results Variability in stimulus event-related theta phase from frontal midline cortex is strongly related to both RTV and ADHD, both phenotypically and genetically. Conclusions This is the first finding to confirm the genetic link between the frontal midline cognitive control system and ADHD and the first to identify a genetically related neurophysiological marker of RTV in ADHD. Variability in the timing of the theta signal in ADHD may be part of a dysfunctional brain network that impairs regulation of task-relevant responses in the disorder.