Psychopathology in mothers of children with pathogenic Copy Number Variants.

BACKGROUND: Caring for children with pathogenic neurodevelopmental Copy Number Variants (CNVs) (ie, deletions and duplications of genetic material) can place a considerable burden on parents and their quality of life. Our study is the first to examine the frequency of psychiatric diagnoses in mothers of children with CNVs compared with the frequency of psychiatric problems in age-matched mothers from a large community study. METHODS: Case-control study. 268 mothers of children with a CNV diagnosed in a medical genetics clinic and 2680 age-matched mothers taking part in the Avon Longitudinal Study of Parents and Children study. RESULTS: Mothers of children with CNVs reported higher frequency of depression, anorexia, bulimia, alcohol abuse and drug addiction problems compared with the age-matched mothers from the community sample. Focusing on psychiatric problems arising immediately after the birth of the index child, we found that the levels of depression symptoms were similar between the two groups (48% in mothers of children with CNVs vs 44% in mothers of the community sample, p=0.43), but mothers of children with CNVs had higher frequency of anxiety symptoms (55%) compared with mothers from the community sample (30%, p=0.03). CONCLUSION: Our study highlights the need for healthcare providers to devise treatment plans that not only focus on meeting the child's needs but also assess and, if needed, address the mental health needs of the parent.

Effects of copy number variations on brain structure and risk for psychiatric illness: Large-scale studies from the ENIGMA working groups on CNVs.

The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population. The 22q-ENIGMA WG includes 12 international research centers that assessed over 533 individuals with a confirmed 22q11.2 deletion syndrome, 40 with 22q11.2 duplications, and 333 typically developing controls, creating the largest-ever 22q11.2 CNV neuroimaging data set. In this review, we outline the ENIGMA infrastructure and procedures for multi-site analysis of CNVs and MRI data. So far, ENIGMA has identified effects of the 22q11.2, 16p11.2 distal, 15q11.2, and 1q21.1 distal CNVs on subcortical and cortical brain structures. Each CNV is associated with differences in cognitive, neurodevelopmental and neuropsychiatric traits, with characteristic patterns of brain structural abnormalities. Evidence of gene-dosage effects on distinct brain regions also emerged, providing further insight into genotype-phenotype relationships. Taken together, these results offer a more comprehensive picture of molecular mechanisms involved in typical and atypical brain development. This "genotype-first" approach also contributes to our understanding of the etiopathogenesis of brain disorders. Finally, we outline future directions to better understand effects of CNVs on brain structure and behavior.

Assessment of emotions and behaviour by the Developmental Behaviour Checklist in young people with neurodevelopmental CNVs.

BACKGROUND: A number of genomic conditions caused by copy number variants (CNVs) are associated with a high risk of neurodevelopmental and psychiatric disorders (ND-CNVs). Although these patients also tend to have cognitive impairments, few studies have investigated the range of emotion and behaviour problems in young people with ND-CNVs using measures that are suitable for those with learning difficulties. METHODS: A total of 322 young people with 13 ND-CNVs across eight loci (mean age: 9.79 years, range: 6.02-17.91, 66.5% male) took part in the study. Primary carers completed the Developmental Behaviour Checklist (DBC). RESULTS: Of the total, 69% of individuals with an ND-CNV screened positive for clinically significant difficulties. Young people from families with higher incomes (OR = 0.71, CI = 0.55-0.91, p = .008) were less likely to screen positive. The rate of difficulties differed depending on ND-CNV genotype (χ2 = 39.99, p < 0.001), with the lowest rate in young people with 22q11.2 deletion (45.7%) and the highest in those with 1q21.1 deletion (93.8%). Specific patterns of strengths and weaknesses were found for different ND-CNV genotypes. However, ND-CNV genotype explained no more than 9-16% of the variance, depending on DBC subdomain. CONCLUSIONS: Emotion and behaviour problems are common in young people with ND-CNVs. The ND-CNV specific patterns we find can provide a basis for more tailored support. More research is needed to better understand the variation in emotion and behaviour problems not accounted for by genotype.

Coordination difficulties, IQ and psychopathology in children with high-risk copy number variants.

BACKGROUND: The prevalence and impact of motor coordination difficulties in children with copy number variants associated with neurodevelopmental disorders (ND-CNVs) remains unknown. This study aims to advance understanding of motor coordination difficulties in children with ND-CNVs and establish relationships between intelligence quotient (IQ) and psychopathology. METHODS: 169 children with an ND-CNV (67% male, median age = 8.88 years, range 6.02-14.81) and 72 closest-in-age unaffected siblings (controls; 55% male, median age = 10.41 years, s.d. = 3.04, range 5.89-14.75) were assessed with the Developmental Coordination Disorder Questionnaire, alongside psychiatric interviews and standardised assessments of IQ. RESULTS: The children with ND-CNVs had poorer coordination ability (b = 28.98, p < 0.001) and 91% of children with an ND-CNV screened positive for suspected developmental coordination disorder, compared to 19% of controls (OR = 42.53, p < 0.001). There was no difference in coordination ability between ND-CNV genotypes (F = 1.47, p = 0.184). Poorer coordination in children with ND-CNV was associated with more attention deficit hyperactivity disorder (ADHD) (ß = -0.18, p = 0.021) and autism spectrum disorder trait (ß = -0.46, p < 0.001) symptoms, along with lower full-scale (ß = 0.21, p = 0.011), performance (ß = -0.20, p = 0.015) and verbal IQ (ß = 0.17, p = 0.036). Mediation analysis indicated that coordination ability was a full mediator of anxiety symptoms (69% mediated, p = 0.012), and a partial mediator of ADHD (51%, p = 0.001) and autism spectrum disorder trait symptoms (66%, p < 0.001) as well as full scale IQ (40%, p = 0.002), performance IQ (40%, p = 0.005) and verbal IQ (38%, p = 0.006) scores. CONCLUSIONS: The findings indicate that poor motor coordination is highly prevalent and closely linked to risk of mental health disorder and lower intellectual function in children with ND-CNVs. Future research should explore whether early interventions for poor coordination ability could ameliorate neurodevelopmental risk.

Altered white matter microstructure in 22q11.2 deletion syndrome: a multisite diffusion tensor imaging study.

22q11.2 deletion syndrome (22q11DS)-a neurodevelopmental condition caused by a hemizygous deletion on chromosome 22-is associated with an elevated risk of psychosis and other developmental brain disorders. Prior single-site diffusion magnetic resonance imaging (dMRI) studies have reported altered white matter (WM) microstructure in 22q11DS, but small samples and variable methods have led to contradictory results. Here we present the largest study ever conducted of dMRI-derived measures of WM microstructure in 22q11DS (334 22q11.2 deletion carriers and 260 healthy age- and sex-matched controls; age range 6-52 years). Using harmonization protocols developed by the ENIGMA-DTI working group, we identified widespread reductions in mean, axial and radial diffusivities in 22q11DS, most pronounced in regions with major cortico-cortical and cortico-thalamic fibers: the corona radiata, corpus callosum, superior longitudinal fasciculus, posterior thalamic radiations, and sagittal stratum (Cohen's d's ranging from -0.9 to -1.3). Only the posterior limb of the internal capsule (IC), comprised primarily of corticofugal fibers, showed higher axial diffusivity in 22q11DS. 22q11DS patients showed higher mean fractional anisotropy (FA) in callosal and projection fibers (IC and corona radiata) relative to controls, but lower FA than controls in regions with predominantly association fibers. Psychotic illness in 22q11DS was associated with more substantial diffusivity reductions in multiple regions. Overall, these findings indicate large effects of the 22q11.2 deletion on WM microstructure, especially in major cortico-cortical connections. Taken together with findings from animal models, this pattern of abnormalities may reflect disrupted neurogenesis of projection neurons in outer cortical layers.

Epilepsy and seizures in young people with 22q11.2 deletion syndrome: Prevalence and links with other neurodevelopmental disorders.

OBJECTIVE: The true prevalence of epileptic seizures and epilepsy in 22q11.2 deletion syndrome (22q11.2DS) is unknown, because previous studies have relied on historical medical record review. Associations of epilepsy with other neurodevelopmental manifestations (eg, specific psychiatric diagnoses) remain unexplored. METHODS: The primary caregivers of 108 deletion carriers (mean age 13.6 years) and 60 control siblings (mean age 13.1 years) completed a validated epilepsy screening questionnaire. A subsample (n = 44) underwent a second assessment with interview, prolonged electroencephalography (EEG), and medical record and epileptologist review. Intelligence quotient (IQ), psychopathology, and other neurodevelopmental problems were examined using neurocognitive assessment and questionnaire/interview. RESULTS: Eleven percent (12/108) of deletion carriers had an epilepsy diagnosis (controls 0%, P = 0.004). Fifty-seven of the remaining 96 deletion carriers (59.4%) had seizures or seizurelike symptoms (controls 13.3%, 8/60, P < 0.001). A febrile seizure was reported for 24.1% (26/107) of cases (controls 0%, P < 0.001). One deletion carrier with a clinical history of epilepsy was diagnosed with an additional type of unprovoked seizure during the second assessment. One deletion carrier was newly diagnosed with epilepsy, and two more with possible nonmotor absence seizures. A positive screen on the epilepsy questionnaire was more likely in deletion carriers with lower performance IQ (odds ratio [OR] 0.96, P = 0.018), attention-deficit/hyperactivity disorder (ADHD) (OR 3.28, P = 0.021), autism symptoms (OR 3.86, P = 0.004), and indicative motor coordination disorder (OR 4.56, P = 0.021). SIGNIFICANCE: Even when accounting for deletion carriers diagnosed with epilepsy, reports of seizures and seizurelike symptoms are common. These may be "true" epileptic seizures in some cases, which are not recognized during routine clinical care. Febrile seizures were far more common in deletion carriers compared to known population risk. A propensity for seizures in 22q11.2DS was associated with cognitive impairment, psychopathology, and motor coordination problems. Future research is required to determine whether this reflects common neurobiologic risk pathways or is a consequence of recurrent seizures.

Developmental coordination disorder, psychopathology and IQ in 22q11.2 deletion syndrome.

BACKGROUND: 22q11.2 deletion syndrome (22q11.2DS) is associated with high rates of neurodevelopmental disorder, however, the links between developmental coordination disorder (DCD), intellectual function and psychiatric disorder remain unexplored. Aims To establish the prevalence of indicative DCD in children with 22q11.2DS and examine associations with IQ, neurocognition and psychopathology. METHOD: Neurocognitive assessments and psychiatric interviews of 70 children with 22q11.2DS (mean age 11.2, s.d. = 2.2) and 32 control siblings (mean age 11.5, s.d. = 2.1) were carried out in their homes. Nine children with 22q11.2DS and indicative DCD were subsequently assessed in an occupational therapy clinic. RESULTS: Indicative DCD was found in 57 (81.4%) children with 22q11.2DS compared with 2 (6.3%) control siblings (odds ratio (OR) = 36.7, P < 0.001). Eight of nine (89%) children with indicative DCD met DSM-5 criteria for DCD. Poorer coordination was associated with increased numbers of anxiety, (P < 0.001), attention-deficit hyperactivity disorder (ADHD) (P < 0.001) and autism-spectrum disorder (ASD) symptoms (P < 0.001) in children with 22q11.2DS. Furthermore, 100% of children with 22q11.2DS and ADHD had indicative DCD (20 of 20), as did 90% of children with anxiety disorder (17 of 19) and 96% of children who screened positive for ASD (22 of 23). The Developmental Coordination Disorder Questionnaire score was related to sustained attention (P = 0.006), even after history of epileptic fits (P = 0.006) and heart problems (P = 0.009) was taken into account. CONCLUSIONS: Clinicians should be aware of the high risk of coordination difficulties in children with 22q11.2DS and its association with risk of mental disorder and specific neurocognitive deficits. Declaration of interest None.

Chronicling menstrual cycle patterns across the reproductive lifespan with real-world data.

The intricate hormonal and physiological changes of the menstrual cycle can influence health on a daily basis. Although prior studies have helped improve our understanding of the menstrual cycle, they often lack diversity in the populations included, sample size, and the span of reproductive and life stages. This paper aims to describe the dynamic differences in menstrual cycle characteristics and associated symptoms by age in a large global cohort of period-tracking application users. This work aims to contribute to our knowledge and understanding of female physiology at varying stages of reproductive aging. This cohort study included self-reported menstrual cycle and symptom information in a sample of Flo application users aged 18-55. Cycle and period length and their variability, and frequency of menstrual cycle symptom logs are described by the age of the user. Based on data logged by over 19 million global users of the Flo app, the length of the menstrual cycle and period show clear age-associated patterns. With higher age, cycles tend to get shorter (Cycle length: D ¯ = 1.85 days, Cohen's D = 0.59) and more variable (Cycle length SD: D ¯ = 0.42 days, Cohen's D = 0.09), until close to the chronological age (40-44) suggesting menopausal transition, when both cycles and periods become longer (Cycle length: D ¯ = 0.86 days, t = 48.85, Cohen's D = 0.26; Period length: D ¯ = 0.08, t = 15.6, Cohen's D = 0.07) and more variable (Cycle length SD: D ¯ = 2.80 days, t = 111.43, d = 0.51; Period length SD: D ¯ = 0.23 days, t = 67.81, Cohen's D = 0.31). The proportion of individuals with irregular cycles was highest in participants aged 51-55 (44.7%), and lowest in the 36-40 age group (28.3%). The spectrum of common menstrual cycle-related symptoms also varies with age. The frequency of logging of cramps and acne is lower in older participants, while logs of headache, backache, stress, and insomnia are higher in older users. Other symptoms show different patterns, such as breast tenderness and fatigue peaking between the ages of 20-40, or mood swings being most frequently logged in the youngest and oldest users. The menstrual cycle and related symptoms are not static throughout the lifespan. Understanding these age-related differences in cycle characteristics and symptoms is essential in understanding how best to care for and improve the daily experience for menstruators across the reproductive life span.

Atypical cortical networks in children at high-genetic risk of psychiatric and neurodevelopmental disorders.

Although many genetic risk factors for psychiatric and neurodevelopmental disorders have been identified, the neurobiological route from genetic risk to neuropsychiatric outcome remains unclear. 22q11.2 deletion syndrome (22q11.2DS) is a copy number variant (CNV) syndrome associated with high rates of neurodevelopmental and psychiatric disorders including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and schizophrenia. Alterations in neural integration and cortical connectivity have been linked to the spectrum of neuropsychiatric disorders seen in 22q11.2DS and may be a mechanism by which the CNV acts to increase risk. In this study, magnetoencephalography (MEG) was used to investigate electrophysiological markers of local and global network function in 34 children with 22q11.2DS and 25 controls aged 10-17 years old. Resting-state oscillatory activity and functional connectivity across six frequency bands were compared between groups. Regression analyses were used to explore the relationships between these measures, neurodevelopmental symptoms and IQ. Children with 22q11.2DS had altered network activity and connectivity in high and low frequency bands, reflecting modified local and long-range cortical circuitry. Alpha and theta band connectivity were negatively associated with ASD symptoms while frontal high frequency (gamma band) activity was positively associated with ASD symptoms. Alpha band activity was positively associated with cognitive ability. These findings suggest that haploinsufficiency at the 22q11.2 locus impacts short and long-range cortical circuits, which could be a mechanism underlying neurodevelopmental and psychiatric vulnerability in this high-risk group.

Efficacy of the Flo App in Improving Health Literacy, Menstrual and General Health, and Well-Being in Women: Pilot Randomized Controlled Trial.

BACKGROUND: Reproductive health literacy and menstrual health awareness play a crucial role in ensuring the health and well-being of women and people who menstruate. Further, awareness of one's own menstrual cycle patterns and associated symptoms can help individuals identify and manage conditions of the menstrual cycle such as premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). Digital health products, and specifically menstrual health apps, have the potential to effect positive change due to their scalability and ease of access. OBJECTIVE: The primary aim of this study was to measure the efficacy of a menstrual and reproductive health app, Flo, in improving health literacy and health and well-being outcomes in menstruating individuals with and without PMS and PMDD. Further, we explored the possibility that the use of the Flo app could positively influence feelings around reproductive health management and communication about health, menstrual cycle stigma, unplanned pregnancies, quality of life, work productivity, absenteeism, and body image. METHODS: We conducted 2 pilot, 3-month, unblinded, 2-armed, remote randomized controlled trials on the effects of using the Flo app in a sample of US-based (1) individuals who track their cycles (n=321) or (2) individuals who track their cycles and are affected by PMS or PMDD (n=117). RESULTS: The findings revealed significant improvements at the end of the study period compared to baseline for our primary outcomes of health literacy (cycle tracking: D̄=1.11; t311=5.73, P<.001; PMS or PMDD: D̄=1.20; t115=3.76, P<.001) and menstrual health awareness (D̄=3.97; t311=7.71, P<.001), health and well-being (D̄=3.44; t311=5.94, P<.001), and PMS or PMDD symptoms burden (D̄=-7.08; t115=-5.44, P<.001). Improvements were also observed for our secondary outcomes of feelings of control and management over health (D̄=1.01; t311=5.08, P<.001), communication about health (D̄=0.93; t311=2.41, P=.002), menstrual cycle stigma (D̄=-0.61; t311=-2.73, P=.007), and fear of unplanned pregnancies (D̄=-0.22; t311=-2.11, P=.04) for those who track their cycles, as well as absenteeism from work and education due to PMS or PMDD (D̄=-1.67; t144=-2.49, P=.01). CONCLUSIONS: These pilot randomized controlled trials demonstrate that the use of the Flo app improves menstrual health literacy and awareness, general health and well-being, and PMS or PMDD symptom burden. Considering the widespread use and affordability of the Flo app, these findings show promise for filling important gaps in current health care provisioning such as improving menstrual knowledge and health. TRIAL REGISTRATION: OSF Registries osf.io/pcgw7; https://osf.io/pcgw7 ; OSF Registries osf.io/ry8vq; https://osf.io/ry8vq.

Feasibility of using intermittent active monitoring of vital signs by smartphone users to predict SARS-CoV-2 PCR positivity.

Early detection of highly infectious respiratory diseases, such as COVID-19, can help curb their transmission. Consequently, there is demand for easy-to-use population-based screening tools, such as mobile health applications. Here, we describe a proof-of-concept development of a machine learning classifier for the prediction of a symptomatic respiratory disease, such as COVID-19, using smartphone-collected vital sign measurements. The Fenland App study followed 2199 UK participants that provided measurements of blood oxygen saturation, body temperature, and resting heart rate. Total of 77 positive and 6339 negative SARS-CoV-2 PCR tests were recorded. An optimal classifier to identify these positive cases was selected using an automated hyperparameter optimisation. The optimised model achieved an ROC AUC of 0.695 ± 0.045. The data collection window for determining each participant's vital sign baseline was increased from 4 to 8 or 12 weeks with no significant difference in model performance (F(2) = 0.80, p = 0.472). We demonstrate that 4 weeks of intermittently collected vital sign measurements could be used to predict SARS-CoV-2 PCR positivity, with applicability to other diseases causing similar vital sign changes. This is the first example of an accessible, smartphone-based remote monitoring tool deployable in a public health setting to screen for potential infections.

Assessment of a Digital Symptom Checker Tool's Accuracy in Suggesting Reproductive Health Conditions: Clinical Vignettes Study.

BACKGROUND: Reproductive health conditions such as endometriosis, uterine fibroids, and polycystic ovary syndrome (PCOS) affect a large proportion of women and people who menstruate worldwide. Prevalence estimates for these conditions range from 5% to 40% of women of reproductive age. Long diagnostic delays, up to 12 years, are common and contribute to health complications and increased health care costs. Symptom checker apps provide users with information and tools to better understand their symptoms and thus have the potential to reduce the time to diagnosis for reproductive health conditions. OBJECTIVE: This study aimed to evaluate the agreement between clinicians and 3 symptom checkers (developed by Flo Health UK Limited) in assessing symptoms of endometriosis, uterine fibroids, and PCOS using vignettes. We also aimed to present a robust example of vignette case creation, review, and classification in the context of predeployment testing and validation of digital health symptom checker tools. METHODS: Independent general practitioners were recruited to create clinical case vignettes of simulated users for the purpose of testing each condition symptom checker; vignettes created for each condition contained a mixture of condition-positive and condition-negative outcomes. A second panel of general practitioners then reviewed, approved, and modified (if necessary) each vignette. A third group of general practitioners reviewed each vignette case and designated a final classification. Vignettes were then entered into the symptom checkers by a fourth, different group of general practitioners. The outcomes of each symptom checker were then compared with the final classification of each vignette to produce accuracy metrics including percent agreement, sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: A total of 24 cases were created per condition. Overall, exact matches between the vignette general practitioner classification and the symptom checker outcome were 83% (n=20) for endometriosis, 83% (n=20) for uterine fibroids, and 88% (n=21) for PCOS. For each symptom checker, sensitivity was reported as 81.8% for endometriosis, 84.6% for uterine fibroids, and 100% for PCOS; specificity was reported as 84.6% for endometriosis, 81.8% for uterine fibroids, and 75% for PCOS; positive predictive value was reported as 81.8% for endometriosis, 84.6% for uterine fibroids, 80% for PCOS; and negative predictive value was reported as 84.6% for endometriosis, 81.8% for uterine fibroids, and 100% for PCOS. CONCLUSIONS: The single-condition symptom checkers have high levels of agreement with general practitioner classification for endometriosis, uterine fibroids, and PCOS. Given long delays in diagnosis for many reproductive health conditions, which lead to increased medical costs and potential health complications for individuals and health care providers, innovative health apps and symptom checkers hold the potential to improve care pathways.

Smartphone movement sensors for the remote monitoring of respiratory rates: Technical validation.

Background: Mobile health (mHealth) offers potential benefits to both patients and healthcare systems. Existing remote technologies to measure respiratory rates have limitations such as cost, accessibility and reliability. Using smartphone sensors to measure respiratory rates may offer a potential solution to these issues. Objective: The aim of this study was to conduct a comprehensive assessment of a novel mHealth smartphone application designed to measure respiratory rates using movement sensors. Methods: In Study 1, 15 participants simultaneously measured their respiratory rates with the app and a Food and Drug Administration-cleared reference device. A novel reference analysis method to allow the app to be evaluated 'in the wild' was also developed. In Study 2, 165 participants measured their respiratory rates using the app, and these measures were compared to the novel reference. The usability of the app was also assessed in both studies. Results: The app, when compared to the Food and Drug Administration-cleared and novel references, respectively, showed a mean absolute error of 1.65 (SD = 1.49) and 1.14 (1.44), relative mean absolute error of 12.2 (9.23) and 9.5 (18.70) and bias of 0.81 (limits of agreement = -3.27 to 4.89) and 0.08 (-3.68 to 3.51). Pearson correlation coefficients were 0.700 and 0.885. Ninety-three percent of participants successfully operated the app on their first use. Conclusions: The accuracy and usability of the app demonstrated here in individuals with a normal respiratory rate range show promise for the use of mHealth solutions employing smartphone sensors to remotely monitor respiratory rates. Further research should validate the benefits that this technology may offer patients and healthcare systems.

Accelerometer-derived sleep onset timing and cardiovascular disease incidence: a UK Biobank cohort study.

Aims: Growing evidence suggests that poor sleep health is associated with cardiovascular risk. However, research in this area often relies upon recollection dependent questionnaires or diaries. Accelerometers provide an alternative tool for measuring sleep parameters objectively. This study examines the association between wrist-worn accelerometer-derived sleep onset timing and cardiovascular disease (CVD). Methods and results: We derived sleep onset and waking up time from accelerometer data collected from 103 712 UK Biobank participants over a period of 7 days. From this, we examined the association between sleep onset timing and CVD incidence using a series of Cox proportional hazards models. A total of 3172 cases of CVD were reported during a mean follow-up period of 5.7 (±0.49) years. An age- and sex-controlled base analysis found that sleep onset time of 10:00 p.m.-10:59 p.m. was associated with the lowest CVD incidence. An additional model, controlling for sleep duration, sleep irregularity, and established CVD risk factors, did not attenuate this association, producing hazard ratios of 1.24 (95% confidence interval, 1.10-1.39; P < 0.005), 1.12 (1.01-1.25; P = 0.04), and 1.25 (1.02-1.52; P = 0.03) for sleep onset <10:00 p.m., 11:00 p.m.-11:59 p.m., and ≥12:00 a.m., respectively, compared to 10:00 p.m.-10:59 p.m. Importantly, sensitivity analyses revealed this association with increased CVD risk was stronger in females, with only sleep onset <10:00 p.m. significant for males. Conclusions: Our findings suggest the possibility of a relationship between sleep onset timing and risk of developing CVD, particularly for women. We also demonstrate the potential utility of collecting information about sleep parameters via accelerometry-capable wearable devices, which may serve as novel cardiovascular risk indicators.

Using kinematic analyses to explore sensorimotor control impairments in children with 22q11.2 deletion syndrome.

BACKGROUND: The 22q11.2 deletion is associated with psychiatric and behavioural disorders, intellectual disability and multiple physical abnormalities. Recent research also indicates impaired coordination skills may be part of the clinical phenotype. This study aimed to characterise sensorimotor control abilities in children with 22q11.2 deletion syndrome (22q11.2DS) and investigate their relationships with co-occurring IQ impairments and psychopathology. METHODS: Fifty-four children with 22q11.2DS and 24 unaffected sibling controls, comparable in age and gender, underwent kinematic analysis of their hand movements, whilst performing a battery of three visuo-manual coordination tasks that measured their tracking, aiming and steering abilities. Additionally, standardised assessments of full-scale IQ (FSIQ), attention deficit hyperactivity disorder, indicative autism spectrum disorder (ASD) and anxiety disorder symptomatology were conducted. RESULTS: Children with 22q11.2DS showed deficits on seven of eight kinematic descriptors of movement quality across the three coordination tasks, compared to controls. Within 22q11.2DS cases, the extent of impairment on only three kinematic descriptors was significantly related to FSIQ after correction for multiple testing. Moreover, only error whilst visuo-manually tracking was nominally associated with ADHD symptom counts. CONCLUSIONS: Impairments in sensorimotor control are seen on a range of visuo-manual tasks in children with 22q11.2DS but the extent of these impairments are largely unrelated to the severity of other psychopathological and intellectual impairments commonly found in children with 22q11.2DS.