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BackgroundADHD and autism are neurodevelopmental conditions, for which non-specific precursors or early signs include difficulties with language and motor skills, and differences in temperament in the first and second year of life. These early features have also been linked to later diagnosis of schizophrenia which is widely considered to have neurodevelopmental origins. Given that ADHD, autism and schizophrenia are all highly heritable, we tested the hypothesis that in the general population, measures of toddler language development, motor development and temperament are associated with genetic liability to ADHD, autism and/or schizophrenia.MethodsData were analysed from the Avon Longitudinal Study of Parents and Children (ALSPAC) which included motor development scores at age 18 months and language development and temperament scores at age 24 months (N = 7498). Genetic liability was indexed by polygenic risk scores (PGS) for ADHD, autism and schizophrenia.ResultsADHD PGS were associated with specific temperament scales (higher activity β = 0.07, 95% CI = 0.04, 0.09 and lower withdrawal β = −0.05, 95% CI = −0.07, −0.02) as well as better gross motor scores (β = 0.04, 95% CI = 0.01, 0.06). Schizophrenia PGS were associated with one specific temperament scale (negative mood β = 0.04, 95% CI = 0.02, 0.07). We did not find strong evidence of association of autism PGS with any of the toddler measures; there was also not strong evidence of association with motor or language delays for any of the PGS.ConclusionsThis study suggests that some specific aspects of early temperament and gross motor differences in the general population could represent part of the early manifestation of genetic liability to neurodevelopmental conditions.Key pointsPrecursors or early signs of ADHD, autism and schizophrenia include difficulties with language and motor skills, and differences in temperament in the first 2 years of lifeWe investigated associations for genetic liability to ADHD, autism and schizophrenia with motor, language and temperament scores at 18–24 monthsWe found ADHD genetic liability to be associated with better gross motor scores, higher activity and lower withdrawal and schizophrenia genetic liability to be associated with increased negative mood; we did not find strong evidence of association for autism genetic liabilitySpecific aspects of toddler temperament and gross motor differences in the general population could represent part of the early manifestation of genetic liability to neurodevelopmental conditions

Deficits in effective executive function, including inhibitory control are associated with risk for a number of psychiatric disorders and significantly impact everyday functioning. These complex traits have been proposed to serve as endophenotypes, however their genetic architecture is not yet well understood. To identify the common genetic variation associated with inhibitory control in the general population we performed the first trans-ancestry genome wide association study (GWAS) combining data across 8 sites and four ancestries (N=14,877) using behavioural traits derived from the stop-signal task, namely – go reaction time (GoRT), go reaction time variability (GoRT SD) and stop signal reaction time (SSRT). Although we did not identify genome wide significant associations for any of the three traits, GoRT SD and SSRT demonstrated significant and similar SNP heritability of 8.2%, indicative of an influence of genetic factors. Power analyses demonstrated that the number of common causal variants contributing to the heritability of these phenotypes is relatively high and larger sample sizes are necessary to robustly identify associations. The polygenic risk for ADHD was significantly associated with GoRT SD further supporting its suggested utility as an endophenotype for ADHD. Together these findings provide the first evidence indicating the influence of common genetic variation in the genetic architecture of inhibitory control quantified using objective behavioural traits derived from the stop-signal task.

It is widely agreed that the DSM-5, the handbook of psychiatric diagnosis, suffers from both high overlap among its putative disorders and high heterogeneity (variability) within each disorder. While these may appear to be opposite problems, in fact both may stem from failure to recognize transdiagnostic dimensions of emotion, cognition, and personality, among others, that inform psychopathology. These fundamental nosological challenges are exemplified in the case of attention-deficit/hyperactivity disorder (ADHD). In ADHD, broad clinical heterogeneity has defied easy clinical prediction of outcomes or clean statistical differentiation of meaningful, biologically informative sub-groups. Progress for ADHD heterogeneity looks promising, however, when we consider dimensions of trait affectivity such as surgency and negative affectivity, their constituent lower order traits such as irritability, and the integrative function of self-regulation. Focusing on developments in the study of temperament traits and ADHD as they relate to emotional dysregulation, several lines of investigation are proving useful. Utilization of selective computational models, biological validators, and longitudinal analyses points toward potential improvements in nosology and clinical assessment in the future by taking temperament traits into account.

The aperiodic exponent of the electroencephalogram (EEG) power spectrum has received growing attention as a physiological marker of neurodevelopmental psychopathology, including attention-deficit/hyperactivity disorder (ADHD). However, its use as a marker of ADHD risk across development, and particularly in very young children, is limited by unknown reliability, difficulty in aligning canonical band-based measures across development periods, and unclear effects of treatment in later development. Here, we investigate the internal consistency of the aperiodic EEG power spectrum slope and its association with ADHD risk in both infants (n = 69, 1-month-old) and adolescents (n = 262, ages 11-17 years). Results confirm good to excellent internal consistency in infancy and adolescence. In infancy, a larger aperiodic exponent was associated with greater family history of ADHD. In contrast, in adolescence, ADHD diagnosis was associated with a smaller aperiodic exponent, but only in children with ADHD who had not received stimulant medication treatment. Results suggest that disruptions in cortical development associated with ADHD risk may be detectable shortly after birth via this approach. Together, findings imply a dynamic developmental shift in which the developmentally normative flattening of the EEG power spectrum is exaggerated in ADHD, potentially reflecting imbalances in cortical excitation and inhibition that could contribute to long-lasting differences in brain connectivity.

Peripheral epigenetic marks hold promise for understanding psychiatric illness and may represent fingerprints of gene–environment interactions. We conducted an initial examination of CpG methylation variation in children with or without attention-deficit/hyperactivity disorder (ADHD).