Rachel Blakey

Cleft lip and/or palate (CL/P) is the most common craniofacial congenital anomaly and has been associated with higher risk of neurodevelopmental and behavioural problems indicating potential shared genetic factors between CL/P and neurodevelopmental disorders. In this study, we aimed to determine the prevalence of neurodevelopmental copy number variants (CNV) in children with CL/P and their link to early developmental and behavioural problems. Using data from the Cleft Collective, the largest UK-based national cohort study of children with CL/P, we determined the rates of neurodevelopmental CNVs in children with CL/P comparing them to the general population, explored differences by cleft type and investigated risk of developmental delays and behavioural problems among those with CL/P and neurodevelopmental CNVs. Children with CL/P had a higher prevalence of neurodevelopmental CNVs than participants in four population-based samples (3.7% vs 2.3% in the Avon Longitudinal Study of Parents and Children (ALSPAC), 2.0% in Born in Bradford (BiB), 2.3% in Millenium Cohort Study (MCS), 1.7% in UK Biobank, ORs(95%CIs): ALSPAC= 1.56(1.18-2.06), BiB= 1.84(1.37-2.45), MCS= 1.59(1.19-2.11), UK Biobank= 2.15(1.68–2.71). Children with cleft palate only were 3 times more likely to have a neurodevelopmental CNV (95%CIs1.50-6.59, p=0.03) than children with cleft lip only. Furthermore, children with CL/P and neurodevelopmental CNVs were more likely to experience early developmental delays and behavioural problems by age 5 compared to children with CL/P and without neurodevelopmental CNVs. These findings highlight that genetic testing ascertaining the presence of neurodevelopmental CNVs might be helpful in early identification of developmental needs in children with CL/P.

Objective: Previous population-based studies have identified associations between childhood neurodevelopmental traits and depression in childhood, adolescence, and young adulthood. However, neurodevelopmental traits are highly correlated with each other, which could confound associations when traits are examined in isolation. The authors sought to identify unique associations between multiple neurodevelopmental traits in childhood and depressive symptoms across development, while taking into account co-occurring difficulties, in multivariate analyses. Methods: Data from two U.K. population-based cohorts, the Twins Early Development Study (TEDS) (N=4,407 independent twins) and the Avon Longitudinal Study of Parents and Children (ALSPAC) (N=10,351), were independently analyzed. Bayesian Gaussian graphical models were estimated to investigate pairwise conditional associations between neurodevelopmental traits (autism and ADHD symptoms and general cognitive, learning, and communication abilities), socioenvironmental stressors (academic performance and peer relations), and emotional dysregulation in childhood (ages 7–11) and depressive symptoms across development (ages 12, 16, and 21). Results: In both cohorts, bivariate correlations indicated several associations between neurodevelopmental traits and depressive symptoms across development. However, based on replicated findings across cohorts, these pairs of variables were mostly conditionally independent, and none were conditionally associated, after accounting for socioenvironmental stressors and emotional dysregulation. In turn, socioenvironmental stressors and emotional dysregulation were conditionally associated with both neurodevelopmental traits and depressive symptoms. Based on replicated findings across cohorts, neurodevelopmental traits in childhood could be associated only indirectly with depressive symptoms across development. Conclusions: This study indicates that associations between childhood neurodevelopmental traits and depressive symptoms across development could be explained by socioenvironmental stressors and emotional dysregulation. The present findings could inform future research aimed at the prevention of depression in youths with neurodevelopmental disorders.

Background: Attention deficit hyperactivity disorder (ADHD) and autism, defined as traits or disorders, commonly co‐occur. Developmental trajectories of ADHD and autistic traits both show heterogeneity in onset and course, but little is known about how symptom trajectories co‐develop into adulthood. Methods: Using data from a population cohort, the Avon Longitudinal Study of Parents and Children, we examined correlations between ADHD and autistic traits across development, using the Social Communication Disorders Checklist and ADHD subscale of the Strengths and Difficulties Questionnaire. We modelled joint developmental trajectories of parent‐reported ADHD and autistic traits between 4 and 25 years, then characterised trajectory classes based on sociodemographic, perinatal, psychopathology, cognition and social functioning variables and tested for associations with neurodevelopmental/psychiatric polygenic scores (PGS). Results: Three classes of trajectories were identified; a typically developing majority with low‐stable ADHD‐autistic traits (87%), a male‐predominant subgroup with child/adolescent‐declining traits (6%) and a subgroup with late‐emerging traits (6%). ADHD‐autistic trait correlations were greatest in young adulthood for the two nontypically developing classes. There were higher rates of emotional and conduct problems, low IQ, childhood seizures and poor social functioning in the declining and late‐emerging classes compared to the low‐stable class. Emotional, conduct and peer problems were more prevalent during childhood in the childhood/adolescent‐declining class compared to other classes, but were more prevalent in young adulthood in the late‐emerging class. Neurodevelopmental/psychiatric PGS also differed: both nontypically developing classes showed elevated ADHD PGS compared to the low‐stable group, and the late‐emerging group additionally showed elevated schizophrenia PGS and decreased executive function PGS, whereas the declining group showed elevated broad depression PGS. Conclusions: Distinct patterns of ADHD‐autism co‐development are present across development in the general population, each with different characterising factors and genetic signatures as indexed by PGS.

The COVID-19 pandemic negatively impacted mental health globally. Individuals with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), are at elevated risk of mental health difficulties. Therefore, we investigated the impact of the pandemic on anxiety, depression and mental wellbeing in adults with NDDs using longitudinal data from the Avon Longitudinal Study of Parents and Children study (n=3,058). Mental health data were collected pre-pandemic (age 21-25) and at three timepoints during the pandemic (ages 27-28) using the Short Mood and Feelings Questionnaire, Generalised Anxiety Disorder Assessment-7, and Warwick Edinburgh Mental Wellbeing Scale. ADHD and ASD were defined using validated cut-points of the Strengths and Difficulties Questionnaire and Autism Spectrum Quotient, self-reported at age 25. We used multi-level mixed-effects models to investigate changes in mental health in those with ADHD and ASD compared to those without. Prevalences of depression, anxiety and poor mental wellbeing were higher at all timepoints (pre-pandemic and during pandemic) in those with ADHD and ASD compared to those without. Anxiety increased to a greater extent in those with ADHD (β=0.8 [0.2,1.4], p=0.01) and ASD (β=1.2 [-0.1,2.5], p=0.07), while depression symptoms decreased, particularly in females with ASD (β=-3.1 [-4.6,-1.5], p=0.0001). On average, mental wellbeing decreased in all, but to a lesser extent in those with ADHD (β=1.3 [0.2,2.5], p=0.03) and females with ASD (β=3.0 [0.2,5.9], p=0.04). To conclude, anxiety disproportionately increased in adults with NDDs during the pandemic, however, the related lockdowns may have provided a protective environment for depressive symptoms in the same individuals.