Highlights d Three groups of highly genetically-related disorders among 8 psychiatric disorders d Identified 109 pleiotropic loci affecting more than one disorder d Pleiotropic genes show heightened expression beginning in 2 nd prenatal trimester d Pleiotropic genes play prominent roles in neurodevelopmental processes Authors Cross-Disorder Group of the Psychiatric Genomics Consortium

Higher cognitive inhibitory and attention functions have been shown to develop throughout adolescence, presumably concurrent with anatomical brain maturational changes. The relatively scarce developmental functional imaging literature on cognitive control, however, has been inconsistent with respect to the neurofunctional substrates of this cognitive development, finding either increased or decreased executive prefrontal function in the progression from childhood to adulthood. Such inconsistencies may be due to small subject numbers or confounds from age-related performance differences in block design functional MRI (fMRI). In this study, rapid, randomized, mixed-trial event-related fMRI was used to investigate developmental differences of the neural networks mediating a range of motor and cognitive inhibition functions in a sizeable number of adolescents and adults. Functional brain activation was compared between adolescents and adults during three different executive tasks measuring selective motor response inhibition (Go/no-go task), cognitive interference inhibition (Simon task), and attentional set shifting (Switch task). Adults compared with children showed increased brain activation in task-specific frontostriatal networks, including right orbital and mesial prefrontal cortex and caudate during the Go/no-go task, right mesial and inferior prefrontal cortex, parietal lobe, and putamen during the Switch task and left dorsolateral and inferior frontotemporoparietal regions and putamen during the Simon task. Whole-brain regression analyses with age across all subjects showed progressive age-related changes in similar and extended clusters of task-specific frontostriatal, frontotemporal, and frontoparietal networks. The findings suggest progressive maturation of task-specific frontostriatal and frontocortical networks for cognitive control functions in the transition from childhood to mid-adulthood.

Background We describe post-COVID symptomatology in a non-hospitalised, national sample of adolescents aged 11–17 years with PCR-confirmed SARS-CoV-2 infection compared with matched adolescents with negative PCR status. Methods In this national cohort study, adolescents aged 11–17 years from the Public Health England database who tested positive for SARS-CoV-2 between January and March, 2021, were matched by month of test, age, sex, and geographical region to adolescents who tested negative. 3 months after testing, a subsample of adolescents were contacted to complete a detailed questionnaire, which collected data on demographics and their physical and mental health at the time of PCR testing (retrospectively) and at the time of completing the questionnaire (prospectively). We compared symptoms between the test-postive and test-negative groups, and used latent class analysis to assess whether and how physical symptoms at baseline and at 3 months clustered among participants. This study is registered with the ISRCTN registry (ISRCTN 34804192). Findings 23 048 adolescents who tested positive and 27 798 adolescents who tested negative between Jan 1, 2021, and March 31, 2021, were contacted, and 6804 adolescents (3065 who tested positive and 3739 who tested negative) completed the questionnaire (response rate 13·4%). At PCR testing, 1084 (35·4%) who tested positive and 309 (8·3%) who tested negative were symptomatic and 936 (30·5%) from the test-positive group and 231 (6·2%) from the test-negative group had three or more symptoms. 3 months after testing, 2038 (66·5%) who tested positive and 1993 (53·3%) who tested negative had any symptoms, and 928 (30·3%) from the test-positive group and 603 (16·2%) from the test-negative group had three or more symptoms. At 3 months after testing, the most common symptoms among the test-positive group were tiredness (1196 [39·0%]), headache (710 [23·2%]), and shortness of breath (717 [23·4%]), and among the test-negative group were tiredness (911 [24·4%]), headache (530 [14·2%]), and other (unspecified; 590 [15·8%]). Latent class analysis identified two classes, characterised by few or multiple symptoms. The estimated probability of being in the multiple symptom class was 29·6% (95% CI 27·4–31·7) for the test-positive group and 19·3% (17·7–21·0) for the test-negative group (risk ratio 1·53; 95% CI 1·35–1·70). The multiple symptoms class was more frequent among those with positive PCR results than negative results, in girls than boys, in adolescents aged 15–17 years than those aged 11–14 years, and in those with lower pretest physical and mental health. Interpretation Adolescents who tested positive for SARS-CoV-2 had similar symptoms to those who tested negative, but had a higher prevalence of single and, particularly, multiple symptoms at the time of PCR testing and 3 months later. Clinicians should consider multiple symptoms that affect functioning and recognise different clus...

The 1999 British Child and Adolescent Mental Health Survey, a nationwide epidemiological study of rates of psychiatric disorder in children aged 5 to 15 years, provided the opportunity to investigate the mental health of children with epilepsy. These children and their families experience disability specifically because of additional emotional, behavioural, and relationship problems, and this is the first epidemiological study that directly measures these impairments. Information was obtained by interviewing a main carer and teacher for 10,316 children; 67 children with epilepsy were identified (35 males, 32 females; mean age 10 years 2 months, SD 2 years 11 months, range 5 to 15 years), and compared with the 47 children with diabetes (27 females, 20 males; mean age 10 years 4 months, SD 3 years 4 months, range 5 to 15 years) and 10,202 controls (50% male; mean age 9 years 11 months, SD 3 years 1 month, range 5 to 15 years). DSM-IV psychiatric diagnoses were derived from the Development and Well-Being Assessment in combination with the interview and a specialist clinician rating. Parental reports of emotional and behavioural problems, their impact, and associated peer problems were also obtained. Rates of psychiatric disorder were 37% (95% confidence interval [CI] 22 to 49) in epilepsy, 11% (95% CI 2 to 19%) in diabetes, and 9% (95% CI 9 to 10%) in control children. Parents of children with epilepsy consistently reported more problems, with greater impact and associated peer problems. Epilepsy, but not diabetes, was independently (adjusted for age, sex, and severe learning difficulties) associated with all behavioural variables in regression analyses. Emotional, behavioural, and relationship difficulties are common in children with epilepsy, and constitute a significant burden to the children and their families, indicating the need for effective mental health services for these children.

Patients with ADHD compared to those with OCD have both common and distinct dysfunctions during inhibitory control. The most consistently reported functional abnormality in children with ADHD in right inferior prefrontal cortex during inhibitory control appears to be disorder-specific when compared to patients with OCD and may be a specific neurofunctional biomarker of ADHD.