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The primary goal of this project is to investigate early patterns of sensory responsiveness (SR) over time, assessed via parent report, in a large sample of young children with an elevated likelihood (EL) of autism spectrum disorder (ASD) and children with a typical likelihood (TL) of ASD. In the current proposal, SR was operationalized by the Infant/Toddler Sensory Profile (ITSP | Dunn, 2002), based on the model of Dunn. This model is one of the most recognized models and assumes an interaction between neurological thresholds and behavioral responses (Dunn, 1997). Both thresholds and behavioral responses may differ based on the different sensory modalities (i.e. visual, auditory, vestibular, tactile, and oral processing). Individuals with low threshold patterns are often described as hyperresponsive, whereas individuals with high threshold patterns are often called hyporesponsive. During the last decades a growing body of literature has focused on the relation between SR and ASD at a very young age (e.g. Damiano-Goodwin et al., 2018; Jones, Dawson, & Webb, 2018; Niedzwiecka, Domasiewicz, Kawa, Tomalski, & Pisula, 2019). These studies indicate that children with ASD, as compared to typically developing groups, show atypical sensory profiles. These atypical profiles already emerge early in life (Wolff et al., 2019), possibly before social-communicative symptoms of ASD can be measured. Although evidence is growing, we know relatively little about how SR changes over time, especially across the first years of life, and how patterns may differ within the group of young children (subsequently) diagnosed with ASD. Most research on sensory patterns in ASD has focused on between-group comparisons of sensory symptom severity in individuals with ASD to those with typical development or other developmental delays, and did not focus on sensory patterns within the ASD population. Given that SR patterns may differ within the EL and TL groups, we are interested in studying who follows which sensory pattern by identifying subgroups within the EL and TL group together, investigating how these subgroups compare to each other, and what the characteristics are of children with specific patterns.

This study investigates (a) group differences in parent-reported infant temperament and observed parent-child interaction between infant siblings of children on the autism spectrum (‘siblings’) and prematurely born infants (‘preterms’) and their mothers, and (b) associations between temperament and parent-child interaction, at 5 and 10 months of child’s (corrected) age. Both siblings and preterms are at elevated likelihood (EL) of autism (Agrawal et al., 2018; Laverty et al., 2021; Messinger et al., 2015; Szatmari et al., 2016; Vermeirsch et al., 2021), but – to our knowledge – these two groups have never been investigated together in a published peer-reviewed study on parent-child interaction and temperament in light of emergent autism. For a more detailed description of our study, we refer to the first step of this pre-registration (https://doi.org/10.17605/OSF.IO/MF4H3).

This study explores whether maternal well-being and group status predict change in reported parenting behaviours among mothers of young children at elevated likelihood (EL) of autism. Two groups of children at EL of autism are included in our sample: (a) infant siblings of children with an established autism spectrum disorder (ASD) diagnosis (Messinger et al., 2015; Ozonoff et al., 2011), (b) children born prematurely, at a gestational age of less than 30 weeks (Agrawal et al., 2018; Laverty et al., 2021). Research findings indicate that lower maternal well-being (i.e., reports of low well-being or more symptoms of depression or parenting stress) is associated with fewer sensitive and responsive parenting behaviours and more disciplinary and critical parenting behaviours, both in the general population (Goodman et al., 2020) and among mothers of autistic children (Boonen et al., 2015; Likhitweerawong et al., 2020; Madarevic et al., 2022; Osborne & Reed, 2010) and children born pre-term (Feldman et al., 2007; Korja et al., 2008; Zengin Akkus et al., 2020). Moreover, parenting behaviours were found to mediate the relationships between well-being and child functioning (Goodman et al., 2020). According to the differential susceptibility theory (Belsky et al., 2007), children who seem most vulnerable to adverse environments, may also benefit the most from enriched environments. Several studies indicate that children at EL of autism may be especially susceptible to their environment, due to their genetic disposition or temperamental reactivity (e.g., Caplan et al., 2021; Gueron-Sela et al., 2015, 2016; Poehlmann et al., 2011, Poehlmann et al., 2012), and may thus benefit the most from sensitive and responsive parenting and be most vulnerable to critical and intrusive parenting. Given that mothers of young children at EL of autism may experience low levels of well-being (e.g., Feldman et al., 2007; Hayes & Watson, 2013; Kersting et al., 2004; Pace et al., 2016; Singer et al., 1999; Tint & Weiss, 2016), an investigation of the role that well-being plays in the course of parenting behaviours is needed. As the determinants of well-being and parenting behaviours may differ between mothers of siblings and pre-terms, an exploration of the influence of EL group could provide a better understanding of the strengths and vulnerabilities in this specific population and may open windows for intervention.

Funder: H2020 European Research Council; doi: http://dx.doi.org/10.13039/100010663, Funder: Research Foundation Flanders, Funder: Universiteit Gent; doi: http://dx.doi.org/10.13039/501100004385, Funder: Marguerite-Marie Delacroix, Funder: Autistica; doi: http://dx.doi.org/10.13039/100011706, Funder: Riksbankens Jubileumsfond; doi: http://dx.doi.org/10.13039/501100004472; Grant(s): NHS14-1802:1, Funder: K.F. Hein Fonds, Funder: Scott Family Junior Research Fellowship, Autism is frequently associated with difficulties with top-down attentional control, which impact on individuals’ mental health and quality of life. The developmental processes involved in these attentional difficulties are not well understood. Using a data-driven approach, 2 samples (N = 294 and 412) of infants at elevated and typical likelihood of autism were grouped according to profiles of parent report of attention at 10, 15 and 25 months. In contrast to the normative profile of increases in attentional control scores between infancy and toddlerhood, a minority (7–9%) showed plateauing attentional control scores between 10 and 25 months. Consistent with pre-registered hypotheses, plateaued growth of attentional control was associated with elevated autism and ADHD traits, and lower adaptive functioning at age 3 years.

Supplemental material, sj-docx-2-aut-10.1177_13623613221080318 for Determinants of satisfaction with the detection process of autism in Europe: Results from the ASDEU study by Quentin Guillon, Sophie Baduel, ��lvaro Bejarano-Mart��n, Ricardo Canal-Bedia, Mar��a Mag��n-Maganto, Clara Fern��ndez-��lvarez, Mar��a Victoria Mart��n-Cilleros, Mar��a Cruz S��nchez-G��mez, Patricia Garc��a-Primo, Mary Rose-Sweeney, Andrew Boilson, Renata Linertov��, Herbert Roeyers, Sara Van der Paelt, Diana Schendel, Christine Kloster Warberg, Susanne Cramer, Antonio Narzisi, Filippo Muratori, Mar��a Luisa Scattoni, Irma Moilanen, Anneli Yliherva, Evald Saemundsen, Sigridur Loa Jonsdottir, Magdalena Efrim-Budisteanu, Aurora Arghir, Sorina Mihaela Papuc, Astrid Vicente, Celia Rasga, Johanna Xenia Kafka, Luise Poustka, Oswald D Kothgassner, Rafal Kawa, Ewa Pisula, Tracey Sellers, Manuel Posada de la Paz and Bernadette Rog�� in Autism

Supplemental material, sj-pdf-1-aut-10.1177_13623613221080318 for Determinants of satisfaction with the detection process of autism in Europe: Results from the ASDEU study by Quentin Guillon, Sophie Baduel, ��lvaro Bejarano-Mart��n, Ricardo Canal-Bedia, Mar��a Mag��n-Maganto, Clara Fern��ndez-��lvarez, Mar��a Victoria Mart��n-Cilleros, Mar��a Cruz S��nchez-G��mez, Patricia Garc��a-Primo, Mary Rose-Sweeney, Andrew Boilson, Renata Linertov��, Herbert Roeyers, Sara Van der Paelt, Diana Schendel, Christine Kloster Warberg, Susanne Cramer, Antonio Narzisi, Filippo Muratori, Mar��a Luisa Scattoni, Irma Moilanen, Anneli Yliherva, Evald Saemundsen, Sigridur Loa Jonsdottir, Magdalena Efrim-Budisteanu, Aurora Arghir, Sorina Mihaela Papuc, Astrid Vicente, Celia Rasga, Johanna Xenia Kafka, Luise Poustka, Oswald D Kothgassner, Rafal Kawa, Ewa Pisula, Tracey Sellers, Manuel Posada de la Paz and Bernadette Rog�� in Autism

Supplemental material, sj-pdf-3-aut-10.1177_13623613221080318 for Determinants of satisfaction with the detection process of autism in Europe: Results from the ASDEU study by Quentin Guillon, Sophie Baduel, ��lvaro Bejarano-Mart��n, Ricardo Canal-Bedia, Mar��a Mag��n-Maganto, Clara Fern��ndez-��lvarez, Mar��a Victoria Mart��n-Cilleros, Mar��a Cruz S��nchez-G��mez, Patricia Garc��a-Primo, Mary Rose-Sweeney, Andrew Boilson, Renata Linertov��, Herbert Roeyers, Sara Van der Paelt, Diana Schendel, Christine Kloster Warberg, Susanne Cramer, Antonio Narzisi, Filippo Muratori, Mar��a Luisa Scattoni, Irma Moilanen, Anneli Yliherva, Evald Saemundsen, Sigridur Loa Jonsdottir, Magdalena Efrim-Budisteanu, Aurora Arghir, Sorina Mihaela Papuc, Astrid Vicente, Celia Rasga, Johanna Xenia Kafka, Luise Poustka, Oswald D Kothgassner, Rafal Kawa, Ewa Pisula, Tracey Sellers, Manuel Posada de la Paz and Bernadette Rog�� in Autism

Supplemental material, sj-docx-2-aut-10.1177_13623613221080318 for Determinants of satisfaction with the detection process of autism in Europe: Results from the ASDEU study by Quentin Guillon, Sophie Baduel, ��lvaro Bejarano-Mart��n, Ricardo Canal-Bedia, Mar��a Mag��n-Maganto, Clara Fern��ndez-��lvarez, Mar��a Victoria Mart��n-Cilleros, Mar��a Cruz S��nchez-G��mez, Patricia Garc��a-Primo, Mary Rose-Sweeney, Andrew Boilson, Renata Linertov��, Herbert Roeyers, Sara Van der Paelt, Diana Schendel, Christine Kloster Warberg, Susanne Cramer, Antonio Narzisi, Filippo Muratori, Mar��a Luisa Scattoni, Irma Moilanen, Anneli Yliherva, Evald Saemundsen, Sigridur Loa Jonsdottir, Magdalena Efrim-Budisteanu, Aurora Arghir, Sorina Mihaela Papuc, Astrid Vicente, Celia Rasga, Johanna Xenia Kafka, Luise Poustka, Oswald D Kothgassner, Rafal Kawa, Ewa Pisula, Tracey Sellers, Manuel Posada de la Paz and Bernadette Rog�� in Autism

Supplemental material, sj-pdf-3-aut-10.1177_13623613221080318 for Determinants of satisfaction with the detection process of autism in Europe: Results from the ASDEU study by Quentin Guillon, Sophie Baduel, ��lvaro Bejarano-Mart��n, Ricardo Canal-Bedia, Mar��a Mag��n-Maganto, Clara Fern��ndez-��lvarez, Mar��a Victoria Mart��n-Cilleros, Mar��a Cruz S��nchez-G��mez, Patricia Garc��a-Primo, Mary Rose-Sweeney, Andrew Boilson, Renata Linertov��, Herbert Roeyers, Sara Van der Paelt, Diana Schendel, Christine Kloster Warberg, Susanne Cramer, Antonio Narzisi, Filippo Muratori, Mar��a Luisa Scattoni, Irma Moilanen, Anneli Yliherva, Evald Saemundsen, Sigridur Loa Jonsdottir, Magdalena Efrim-Budisteanu, Aurora Arghir, Sorina Mihaela Papuc, Astrid Vicente, Celia Rasga, Johanna Xenia Kafka, Luise Poustka, Oswald D Kothgassner, Rafal Kawa, Ewa Pisula, Tracey Sellers, Manuel Posada de la Paz and Bernadette Rog�� in Autism

Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood psychiatric disorder often comorbid with disruptive behavior disorders (DBDs). Here, we report a GWAS meta-analysis of ADHD comorbid with DBDs (ADHD + DBDs) including 3802 cases and 31,305 controls. We identify three genome-wide significant loci on chromosomes 1, 7, and 11. A meta-analysis including a Chinese cohort supports that the locus on chromosome 11 is a strong risk locus for ADHD + DBDs across European and Chinese ancestries (rs7118422, P = 3.15×10−10, OR = 1.17). We find a higher SNP heritability for ADHD + DBDs (h2SNP = 0.34) when compared to ADHD without DBDs (h2SNP = 0.20), high genetic correlations between ADHD + DBDs and aggressive (rg = 0.81) and anti-social behaviors (rg = 0.82), and an increased burden (polygenic score) of variants associated with ADHD and aggression in ADHD + DBDs compared to ADHD without DBDs. Our results suggest an increased load of common risk variants in ADHD + DBDs compared to ADHD without DBDs, which in part can be explained by variants associated with aggressive behavior., ADHD is often found to be comorbid with disruptive behavior disorders, but the genetic loci underlying this comorbidity are unknown. Here, the authors have performed a GWAS meta-analysis of ADHD with disruptive behavior disorders, finding three genome-wide significant loci in Europeans, and replicating one in a Chinese cohort.

Autism is frequently associated with difficulties with top-down attentional control, which impact on individuals' mental health and quality of life. The developmental processes involved in these attentional difficulties are not well understood. Using a data-driven approach, 2 samples (N = 294 and 412) of infants at elevated and typical likelihood of autism were grouped according to profiles of parent report of attention at 10, 15 and 25 months. In contrast to the normative profile of increases in attentional control scores between infancy and toddlerhood, a minority (7-9%) showed plateauing attentional control scores between 10 and 25 months. Consistent with pre-registered hypotheses, plateaued growth of attentional control was associated with elevated autism and ADHD traits, and lower adaptive functioning at age 3 years.

Highlights • The Eurosibs consortium is a nine-site European neurocognitive study of infants with an older sibling with ASD. • Data quality assessments show that that neurocognitive measures hold promise for cross-site consistency in diverse populations. • We present robust data analysis pipelines and highlight challenges and opportunities for future multisite research efforts., Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that affects social communication skills and flexible behaviour. Developing new treatment approaches for ASD requires early identification of the factors that influence later behavioural outcomes. One fruitful research paradigm has been the prospective study of infants with a first degree relative with ASD, who have around a 20% likelihood of developing ASD themselves. Early findings have identified a range of candidate neurocognitive markers for later ASD such as delayed attention shifting or neural responses to faces, but given the early stage of the field most sample sizes are small and replication attempts remain rare. The Eurosibs consortium is a European multisite neurocognitive study of infants with an older sibling with ASD conducted across nine sites in five European countries. In this manuscript, we describe the selection and standardization of our common neurocognitive testing protocol. We report data quality assessments across sites, showing that neurocognitive measures hold great promise for cross-site consistency in diverse populations. We discuss our approach to ensuring robust data analysis pipelines and boosting future reproducibility. Finally, we summarise challenges and opportunities for future multi-site research efforts.

A visual paired comparison eye-tracking paradigm was used to measure preferences for socially relevant faces and subsequent objects in a 5-month-old low- and high-risk group for autism spectrum disorder (ASD). In a first condition the mother's face was presented next to a stranger's face, in the second condition two stranger's faces were presented with direct versus averted gaze. Afterwards two objects were presented at the same places where previously the faces appeared. Both groups showed a similar preference for their mother's face over a stranger's face, while only the low-risk group tended to show a preference for the face with direct gaze over the face with averted gaze. No difference between groups was found for looking at the objects. These findings show that differences in social attention between both groups are subtle and depend on the manipulations used.

Purpose of reviewSubstantial research exists focusing on the various aspects and domains of early human development. However, there is a clear blind spot in early postnatal development when dealing with neurodevelopmental disorders, especially those that manifest themselves clinically only in late infancy or even in childhood.Recent findingsThis early developmental period may represent an important timeframe to study these disorders but has historically received far less research attention. We believe that only a comprehensive interdisciplinary approach will enable us to detect and delineate specific parameters for specific neurodevelopmental disorders at a very early age to improve early detection/diagnosis, enable prospective studies and eventually facilitate randomised trials of early intervention. In this article, we propose a dynamic framework for characterising neurofunctional biomarkers associated with specific disorders in the development of infants and children. We have named this automated detection 'Fingerprint Model', suggesting one possible approach to accurately and early identify neurodevelopmental disorders.

Being sensitive and responsive to others’ internal states is critical for social life. One reliable cue to what others might be feeling is pupil dilation because it is linked to increases in arousal. When adults view an individual with dilated pupils, their pupils dilate in response, suggesting not only sensitivity to pupil size, but a corresponding response as well. However, little is known about the origins or mechanism underlying this phenomenon of pupillary contagion. Here we show that 4- to 6-month-old infants show pupillary contagion when viewing photographs of eyes with varying pupil sizes: their pupils dilate in response to others’ large, but not small or medium pupils. The results suggest that pupillary contagion is likely driven by a transfer of arousal and that it is present very early in life in human infants, supporting the view that it could be an adaptation fundamental for social and emotional development. Correction in: Scientific Reports, 2018, vol. 8, article Number: 4157.DOI: 10.1038/s41598-018-22184-1

Attention-deficit hyperactivity disorder (ADHD) is a complex polygenic disorder. This study aimed to discover common and rare DNA variants associated with ADHD in a large homogeneous Han Chinese ADHD case-control sample. The sample comprised 1,040 cases and 963 controls. All cases met DSM-IV ADHD diagnostic criteria. We used the Affymetrix6.0 array to assay both single nucleotide polymorphisms (SNPs) and copy number variants (CNVs). Genome-wide association analyses were performed using PLINK. SNP-heritability and SNP-genetic correlations with ADHD in Caucasians were estimated with genome-wide complex trait analysis (GCTA). Pathway analyses were performed using the Interval enRICHment Test (INRICH), the Disease Association Protein-Protein Link Evaluator (DAPPLE), and the Genomic Regions Enrichment of Annotations Tool (GREAT). We did not find genome-wide significance for single SNPs but did find an increased burden of large, rare CNVs in the ADHD sample (P=0.038). SNP-heritability was estimated to be 0.42 (standard error, 0.13, P=0.0017) and the SNP-genetic correlation with European Ancestry ADHD samples was 0.39 (SE 0.15, P=0.0072). The INRICH, DAPPLE, and GREAT analyses implicated several gene ontology cellular components, including neuron projections and synaptic components, which are consistent with a neurodevelopmental pathophysiology for ADHD. This study suggested the genetic architecture of ADHD comprises both common and rare variants. Some common causal variants are likely to be shared between Han Chinese and Caucasians. Complex neurodevelopmental networks may underlie ADHD's etiology. (c) 2013 Wiley Periodicals, Inc. Refereed/Peer-reviewed

Objective: To examine the factor structure of attention-deficit/ hyperactivity disorder (ADHD) in a clinical sample of 1,373 children and adolescents with ADHD and their 1,772 unselected siblings recruited from different countries across a large age range. Hierarchical and correlated factor analytic models were compared separately in the ADHD and sibling samples, across three different instruments and across parent and teacher informants. Specific consideration was given to factorial invariance analyses across different ages and different countries in the ADHD sample. Method: A sample of children and adolescents between 5 and 17 years of age with ADHD and their unselected siblings was assessed. Participants were recruited from seven European countries and Israel. ADHD symptom data came from a clinical interview with parents Parental Account of Childhood Symptoms and questionnaires from parents and teachers (Conners Parent and Teacher). Results: A hierarchical general factor model with two specific factors best represented the structure of ADHD in both the ADHD and unselected sibling groups, and across informants and instruments. The model was robust and invariant with regard to age differences in the ADHD sample. The model was not strongly invariant across different national groups in the ADHD sample, likely reflecting severity differences across the different centers and not any substantial difference in the clinical presentation of ADHD. Conclusions: The results replicate previous studies of a model with a unitary ADHD component and separable specific traits of inattention and hyperactivity/impulsivity. The unique contribution of this study was finding support for this model across a large developmental and multinational/multicultural sample and its invariance across ages. © 2011 Association for Child and Adolescent Mental Health.

Publisher's version disponible en: http://hdl.handle.net/20.500.12105/13056 A large number of studies have reported on the validity of autism spectrum disorder (ASD) screening procedures. An overall understanding of these studies' findings cannot be based solely on the level of internal validity of each, since screening instruments might perform differently according to certain factors in different settings. Europe has led the field with the development of the first screening tool and first prospective screening study of autism. This paper seeks to provide an overview of ASD screening studies and ongoing programmes across Europe, and identify variables that have influenced the outcomes of such studies. Results show that, to date, over 70,000 children have been screened in Europe using 18 different screening procedures. Differences among findings across studies have enabled us to identify ten factors that may influence screening results. Although it is impossible to draw firm conclusions as to which screening procedure is most effective, this analysis might facilitate the choice of a screening method that best fits a specific scenario, and this, in turn, may eventually improve early ASD detection procedures. The work of Patricia Garcia-Primo and AnnikaHellendoorn was supported by a Short Term Scientific Mission(STSM) grant from COST Action BM1004. We wish to thank allESSEA COST members and the contacted authors of publishedstudies for their invaluable contribution to the collection of data Sí

Item does not contain fulltext OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable psychiatric disorder. Because of its multifactorial etiology, however, identifying the genes involved has been difficult. The authors followed up on recent findings suggesting that rare copy number variants (CNVs) may be important for ADHD etiology. METHOD: The authors performed a genome-wide analysis of large, rare CNVs (100 kb in size, which segregated into 912 independent loci. Overall, the rate of rare CNVs >100 kb was 1.15 times higher in ADHD case subjects relative to comparison subjects, with duplications spanning known genes showing a 1.2-fold enrichment. In accordance with a previous study, rare CNVs >500 kb showed the greatest enrichment (1.28-fold). CNVs identified in ADHD case subjects were significantly enriched for loci implicated in autism and in schizophrenia. Duplications spanning the CHRNA7 gene at chromosome 15q13.3 were associated with ADHD in single-locus analysis. This finding was consistently replicated in an additional 2,242 ADHD case subjects and 8,552 comparison subjects from four independent cohorts from the United Kingdom, the United States, and Canada. Presence of the duplication at 15q13.3 appeared to be associated with comorbid conduct disorder. CONCLUSIONS: These findings support the enrichment of large, rare CNVs in ADHD and implicate duplications at 15q13.3 as a novel risk factor for ADHD. With a frequency of 0.6% in the populations investigated and a relatively large effect size (odds ratio=2.22, 95% confidence interval=1.5-3.6), this locus could be an important contributor to ADHD etiology. 01 februari 2012

Item does not contain fulltext BACKGROUNd: Emotional lability (EL) is commonly seen in patients with attention-deficit/hyperactivity disorder (ADHD). The reasons for this association remain currently unknown. To address this question, we examined the relationship between ADHD and EL symptoms, and performance on a range of neuropsychological tasks to clarify whether EL symptoms are predicted by particular cognitive and/or motivational dysfunctions and whether these associations are mediated by the presence of ADHD symptoms. METHODS: A large multi-site sample of 424 carefully diagnosed ADHD cases and 564 unaffected siblings and controls aged 6-18 years performed a broad neuropsychological test battery, including a Go/No-Go Task, a warned four-choice Reaction Time task, the Maudsley Index of Childhood Delay Aversion and Digit span backwards. Neuropsychological variables were aggregated as indices of processing speed, response variability, executive functions, choice impulsivity and the influence of energetic and/or motivational factors. EL and ADHD symptoms were regressed on each neuropsychological variable in separate analyses controlling for age, gender and IQ, and, in subsequent regression analyses, for ADHD and EL symptoms respectively. RESULTS: Neuropsychological variables significantly predicted ADHD and EL symptoms with moderate-to-low regression coefficients. However, the association between neuropsychological parameters on EL disappeared entirely when the effect of ADHD symptoms was taken into account, revealing that the association between the neuropsychological performance measures and EL is completely mediated statistically by variations in ADHD symptoms. Conversely, neuropsychological effects on ADHD symptoms remained after EL symptom severity was taken into account. CONCLUSIONS: The neuropsychological parameters examined, herein, predict ADHD more strongly than EL. They cannot explain EL symptoms beyond what is already accounted for by ADHD symptom severity. The association between EL and ADHD cannot be explained by these cognitive or motivational deficits. Alternative mechanisms, including overlapping genetic influences (pleiotropic effects) and/or alternative neuropsychological processes need to be considered.

Background: ADHD is a common and complex genetic disorder.Genetic risk factors are expected to be multiple, have small effect sizes when considered individually and to interact with each other and with environmental factors. Objective: To describe the difficulties involved in the genetic investigation of such a complex disorder and give a prospective for the future. Methods: Review based on empirical literature and project description. Results: considerable progress has been achieved through the association analysis of candidate gene loci. Linkage scans using affected sibling pairs have identified a number of potential loci that may lead to the identification of novel genes of moderate effect size. Quantitative trait locus (QTL approaches provide powerful complementary strategies that have the potential to link the categorical disorder to continuously distributed traits associated more closely with underlying genetic liability in the general population. Success in identifying some associated genes has been complemented by functional studies that seek to understand the mode of action of such genes. Conclusion: Progress in understanding the mechanisms involved has not been straightforward and many inconsistencies have arisen. In order to take advantage of the potential for progress that stems from the genetic findings it will be important to draw upon a variety of approaches and experimental paradigms. A functional genomic approach to ADHD means that investigation of gene function is carried out at various levels of analysis, not only at the level of molecular and cellular function but also at the level of psychological processes, neuronal networks, environmental interactions and behavioural outcomes

Funder: H2020 European Research Council; doi: http://dx.doi.org/10.13039/100010663, Funder: Research Foundation Flanders, Funder: Universiteit Gent; doi: http://dx.doi.org/10.13039/501100004385, Funder: Marguerite-Marie Delacroix, Funder: Autistica; doi: http://dx.doi.org/10.13039/100011706, Funder: Riksbankens Jubileumsfond; doi: http://dx.doi.org/10.13039/501100004472; Grant(s): NHS14-1802:1, Funder: K.F. Hein Fonds, Funder: Scott Family Junior Research Fellowship, Autism is frequently associated with difficulties with top-down attentional control, which impact on individuals' mental health and quality of life. The developmental processes involved in these attentional difficulties are not well understood. Using a data-driven approach, 2 samples (N = 294 and 412) of infants at elevated and typical likelihood of autism were grouped according to profiles of parent report of attention at 10, 15 and 25 months. In contrast to the normative profile of increases in attentional control scores between infancy and toddlerhood, a minority (7-9%) showed plateauing attentional control scores between 10 and 25 months. Consistent with pre-registered hypotheses, plateaued growth of attentional control was associated with elevated autism and ADHD traits, and lower adaptive functioning at age 3 years.

Mutations in FARS2 are known to cause dysfunction of mitochondrial translation due to deficient aminoacylation of the mitochondrial phenylalanine tRNA. Here, we report three novel mutations in FARS2 found in two patients in a compound heterozygous state. The missense mutation c.1082C>T (p.Pro361Leu) was detected in both patients. The mutations c.461C>T (p.Ala154Val) and c.521_523delTGG (p.Val174del) were each detected in one patient. We report abnormal in vitro aminoacylation assays as a functional validation of the molecular genetic findings. Based on the phenotypic data of previously reported subjects and the two subjects reported here, we conclude that FARS2 deficiency can be associated with two phenotypes: (i) an epileptic phenotype, and (ii) a spastic paraplegia phenotype.