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1. Sex differences in social brain neural responses in autism: temporal profiles of configural face-processing within data-driven time windows

Author: Onderwijscentrum, Brain, Psychiatrie_Medisch, Del Bianco, Teresa, Lai, Meng Chuan, Mason, Luke, Johnson, Mark H., Charman, Tony, Loth, Eva, Banaschewski, Tobias, Buitelaar, Jan, Murphy, Declan G.M., Jones, Emily J.H., The AIMS-2-TRIALS LEAP Team, Onderwijscentrum, Brain, Psychiatrie_Medisch, Del Bianco, Teresa, Lai, Meng Chuan, Mason, Luke, Johnson, Mark H., Charman, Tony, Loth, Eva, Banaschewski, Tobias, Buitelaar, Jan, Murphy, Declan G.M., Jones, Emily J.H., and The AIMS-2-TRIALS LEAP Team
Published: 2024

2. Processing of social and monetary rewards in autism spectrum disorders

Author: Baumeister, Sarah; https://orcid.org/0000-0001-9005-0084, Moessnang, Carolin; https://orcid.org/0000-0003-4357-2706, Bast, Nico; https://orcid.org/0000-0001-5721-207X, Hohmann, Sarah, Aggensteiner, Pascal; https://orcid.org/0000-0002-1048-9044, Kaiser, Anna, Tillmann, Julian, Goyard, David, Charman, Tony; https://orcid.org/0000-0003-1993-6549, Ambrosino, Sara, Baron-Cohen, Simon, Beckmann, Christian, Bölte, Sven, Bourgeron, Thomas; https://orcid.org/0000-0001-8164-9220, Rausch, Annika, Crawley, Daisy, Dell'Acqua, Flavio, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Floris, Dorothea L, Frouin, Vincent, Hayward, Hannah, Holt, Rosemary, Johnson, Mark H, Jones, Emily J H, Lai, Meng-Chuan, Lombardo, Michael V, Mason, Luke, Oakley, Bethany, Brandeis, Daniel, et al, Baumeister, Sarah; https://orcid.org/0000-0001-9005-0084, Moessnang, Carolin; https://orcid.org/0000-0003-4357-2706, Bast, Nico; https://orcid.org/0000-0001-5721-207X, Hohmann, Sarah, Aggensteiner, Pascal; https://orcid.org/0000-0002-1048-9044, Kaiser, Anna, Tillmann, Julian, Goyard, David, Charman, Tony; https://orcid.org/0000-0003-1993-6549, Ambrosino, Sara, Baron-Cohen, Simon, Beckmann, Christian, Bölte, Sven, Bourgeron, Thomas; https://orcid.org/0000-0001-8164-9220, Rausch, Annika, Crawley, Daisy, Dell'Acqua, Flavio, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Floris, Dorothea L, Frouin, Vincent, Hayward, Hannah, Holt, Rosemary, Johnson, Mark H, Jones, Emily J H, Lai, Meng-Chuan, Lombardo, Michael V, Mason, Luke, Oakley, Bethany, Brandeis, Daniel, and et al
Abstract: Background: Reward processing has been proposed to underpin the atypical social feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social reward processing in ASD. Aims: Utilising a large sample, we aimed to assess reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD. Method: Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6-30.6 years of age) and 181 typically developing participants (7.6-30.8 years of age). Results: Across social and monetary reward anticipation, whole-brain analyses showed hypoactivation of the right ventral striatum in participants with ASD compared with typically developing participants. Further, region of interest analysis across both reward types yielded ASD-related hypoactivation in both the left and right ventral striatum. Across delivery of social and monetary reward, hyperactivation of the ventral striatum in individuals with ASD did not survive correction for multiple comparisons. Dimensional analyses of autism and attention-deficit hyperactivity disorder (ADHD) scores were not significant. In categorical analyses, post hoc comparisons showed that ASD effects were most pronounced in participants with ASD without co-occurring ADHD. Conclusions: Our results do not support current theories linking atypical social interaction in ASD to specific alterations in social reward processing. Instead, they point towards a generalised hypoactivity of ventral striatum in ASD during anticipation of both social and monetary rewards. We suggest this indicates attenuated reward seeking in ASD independent of social content and that elevated ADHD symptoms may attenuate altered reward seeking in ASD.
Published: 2023

3. Stratifying the autistic phenotype using electrophysiological indices of social perception

Author: Brain, Ontwikkelingsstoornissen Ond., Onderzoek Bob Oranje, Mason, Luke, Moessnang, Carolin, Chatham, Christopher, Ham, Lindsay, Tillmann, Julian, Dumas, Guillaume, Ellis, Claire, Leblond, Claire S, Cliquet, Freddy, Bourgeron, Thomas, Beckmann, Christian, Charman, Tony, Oakley, Beth, Banaschewski, Tobias, Meyer-Lindenberg, Andreas, Baron-Cohen, Simon, Bölte, Sven, Buitelaar, Jan K, Durston, Sarah, Loth, Eva, Oranje, Bob, Persico, Antonio, Dell'Acqua, Flavio, Ecker, Christine, Johnson, Mark H, Murphy, Declan, Jones, Emily J H, Brain, Ontwikkelingsstoornissen Ond., Onderzoek Bob Oranje, Mason, Luke, Moessnang, Carolin, Chatham, Christopher, Ham, Lindsay, Tillmann, Julian, Dumas, Guillaume, Ellis, Claire, Leblond, Claire S, Cliquet, Freddy, Bourgeron, Thomas, Beckmann, Christian, Charman, Tony, Oakley, Beth, Banaschewski, Tobias, Meyer-Lindenberg, Andreas, Baron-Cohen, Simon, Bölte, Sven, Buitelaar, Jan K, Durston, Sarah, Loth, Eva, Oranje, Bob, Persico, Antonio, Dell'Acqua, Flavio, Ecker, Christine, Johnson, Mark H, Murphy, Declan, and Jones, Emily J H
Published: 2022

4. Qualitative differences in the spatiotemporal brain states supporting configural face processing emerge in adolescence in autism

Author: Haartsen, Rianne, Mason, Luke, Garces, Pilar, Gui, Anna, Charman, Tony, Tillmann, Julian, Johnson, Mark H, Buitelaar, Jan K, Loth, Eva, Murphy, Declan, Jones, Emily J H, et al, Brandeis, Daniel, Haartsen, Rianne, Mason, Luke, Garces, Pilar, Gui, Anna, Charman, Tony, Tillmann, Julian, Johnson, Mark H, Buitelaar, Jan K, Loth, Eva, Murphy, Declan, Jones, Emily J H, et al, and Brandeis, Daniel
Abstract: BACKGROUND Studying the neural processing of faces can illuminate the mechanisms of compromised social expertise in autism. To resolve a longstanding debate, we examined whether differences in configural face processing in autism are underpinned by quantitative differences in the activation of typical face processing pathways, or the recruitment of non-typical neural systems. METHODS We investigated spatial and temporal characteristics of event-related EEG responses to upright and inverted faces in a large sample of children, adolescents, and adults with and without autism. We examined topographic analyses of variance and global field power to identify group differences in the spatial and temporal response to face inversion. We then examined how quasi-stable spatiotemporal profiles - microstates - are modulated by face orientation and diagnostic group. RESULTS Upright and inverted faces produced distinct profiles of topography and strength in the topographical analyses. These topographical profiles differed between diagnostic groups in adolescents, but not in children or adults. In the microstate analysis, the autistic group showed differences in the activation strength of normative microstates during early-stage processing at all ages, suggesting consistent quantitative differences in the operation of typical processing pathways; qualitative differences in microstate topographies during late-stage processing became prominent in adults, suggesting the increasing involvement of non-typical neural systems with processing time and over development. CONCLUSIONS These findings suggest that early difficulties with configural face processing may trigger later compensatory processes in autism that emerge in later development.
Published: 2022

5. Attentive brain states in infants with and without later autism

Author: Gui, Anna, Bussu, Giorgia, Tye, C., Elsabbagh, Mayada, Pasco, G., Charman, Tony, Johnson, Mark H., Jones, Emily J. H., Gui, Anna, Bussu, Giorgia, Tye, C., Elsabbagh, Mayada, Pasco, G., Charman, Tony, Johnson, Mark H., and Jones, Emily J. H.
Abstract: Contains fulltext : 246003.pdf (Publisher’s version ) (Open Access)
Published: 2021

6. Development of the pupillary light reflex from 9 to 24 months : association with common autism spectrum disorder (ASD) genetic liability and 3-year ASD diagnosis

Author: Fish, Laurel A., Nyström, Pär, Gliga, Teodora, Gui, Anna, Begum Ali, Jannath, Mason, Luke, Garg, Shruti, Green, Jonathan, Johnson, Mark H., Charman, Tony, Harrison, Rebecca, Meaburn, Emma, Falck-Ytter, Terje, Jones, Emily J. H., Fish, Laurel A., Nyström, Pär, Gliga, Teodora, Gui, Anna, Begum Ali, Jannath, Mason, Luke, Garg, Shruti, Green, Jonathan, Johnson, Mark H., Charman, Tony, Harrison, Rebecca, Meaburn, Emma, Falck-Ytter, Terje, and Jones, Emily J. H.
Abstract: Background: Although autism spectrum disorder (ASD) is heritable, the mechanisms through which genes contribute to symptom emergence remain unclear. Investigating candidate intermediate phenotypes such as the pupillary light reflex (PLR) prospectively from early in development could bridge genotype and behavioural phenotype. Methods: Using eye tracking, we longitudinally measured the PLR at 9, 14 and 24 months in a sample of infants (N = 264) enriched for a family history of ASD; 27 infants received an ASD diagnosis at 3 years. We examined the 9- to 24-month developmental trajectories of PLR constriction latency (onset; ms) and amplitude (%) and explored their relation to categorical 3-year ASD outcome, polygenic liability for ASD and dimensional 3-year social affect (SA) and repetitive/restrictive behaviour (RRB) traits. Polygenic scores for ASD (PGSASD) were calculated for 190 infants. Results: While infants showed a decrease in latency between 9 and 14 months, higher PGSASD was associated with a smaller decrease in latency in the first year (? = ?.16, 95% CI = ?0.31, ?0.002); infants with later ASD showed a significantly steeper decrease in latency (a putative ?catch-up?) between 14 and 24 months relative to those with other outcomes (typical: ? = .54, 95% CI = 0.08, 0.99; other: ? = .53, 95% CI = 0.02, 1.04). Latency development did not associate with later dimensional variation in ASD-related traits. In contrast, change in amplitude was not related to categorical ASD or genetics, but decreasing 9- to 14-month amplitude was associated with higher SA (? = .08, 95% CI = 0.01, 0.14) and RRB (? = .05, 95% CI = 0.004, 0.11) traits. Conclusions: These findings corroborate PLR development as possible intermediate phenotypes being linked to both genetic liability and phenotypic outcomes. Future work should incorporate alternative measures (e.g. functionally informed structural and genetic measures) to test whether distinct neural mechanisms underpin PLR alterations.
Published: 2021
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7. Development of the pupillary light reflex from 9 to 24 months : association with common autism spectrum disorder (ASD) genetic liability and 3-year ASD diagnosis

Author: Fish, Laurel A., Nyström, Pär, Gliga, Teodora, Gui, Anna, Begum Ali, Jannath, Mason, Luke, Garg, Shruti, Green, Jonathan, Johnson, Mark H., Charman, Tony, Harrison, Rebecca, Meaburn, Emma, Falck-Ytter, Terje, Jones, Emily J. H., Fish, Laurel A., Nyström, Pär, Gliga, Teodora, Gui, Anna, Begum Ali, Jannath, Mason, Luke, Garg, Shruti, Green, Jonathan, Johnson, Mark H., Charman, Tony, Harrison, Rebecca, Meaburn, Emma, Falck-Ytter, Terje, and Jones, Emily J. H.
Abstract: Background: Although autism spectrum disorder (ASD) is heritable, the mechanisms through which genes contribute to symptom emergence remain unclear. Investigating candidate intermediate phenotypes such as the pupillary light reflex (PLR) prospectively from early in development could bridge genotype and behavioural phenotype. Methods: Using eye tracking, we longitudinally measured the PLR at 9, 14 and 24 months in a sample of infants (N = 264) enriched for a family history of ASD; 27 infants received an ASD diagnosis at 3 years. We examined the 9- to 24-month developmental trajectories of PLR constriction latency (onset; ms) and amplitude (%) and explored their relation to categorical 3-year ASD outcome, polygenic liability for ASD and dimensional 3-year social affect (SA) and repetitive/restrictive behaviour (RRB) traits. Polygenic scores for ASD (PGSASD) were calculated for 190 infants. Results: While infants showed a decrease in latency between 9 and 14 months, higher PGSASD was associated with a smaller decrease in latency in the first year (? = ?.16, 95% CI = ?0.31, ?0.002); infants with later ASD showed a significantly steeper decrease in latency (a putative ?catch-up?) between 14 and 24 months relative to those with other outcomes (typical: ? = .54, 95% CI = 0.08, 0.99; other: ? = .53, 95% CI = 0.02, 1.04). Latency development did not associate with later dimensional variation in ASD-related traits. In contrast, change in amplitude was not related to categorical ASD or genetics, but decreasing 9- to 14-month amplitude was associated with higher SA (? = .08, 95% CI = 0.01, 0.14) and RRB (? = .05, 95% CI = 0.004, 0.11) traits. Conclusions: These findings corroborate PLR development as possible intermediate phenotypes being linked to both genetic liability and phenotypic outcomes. Future work should incorporate alternative measures (e.g. functionally informed structural and genetic measures) to test whether distinct neural mechanisms underpin PLR alterations.
Published: 2021
Full Text: View/download PDF

8. Attentive brain states in infants with and without later autism

Author: Gui, Anna, Bussu, Giorgia, Tye, C., Elsabbagh, Mayada, Pasco, G., Charman, Tony, Johnson, Mark H., Jones, Emily J. H., Gui, Anna, Bussu, Giorgia, Tye, C., Elsabbagh, Mayada, Pasco, G., Charman, Tony, Johnson, Mark H., and Jones, Emily J. H.
Abstract: Contains fulltext : 246003.pdf (Publisher’s version ) (Open Access)
Published: 2021

9. Attentive brain states in infants with and without later autism

Author: Gui, Anna, Bussu, Giorgia, Tye, C., Elsabbagh, Mayada, Pasco, G., Charman, Tony, Johnson, Mark H., Jones, Emily J. H., Gui, Anna, Bussu, Giorgia, Tye, C., Elsabbagh, Mayada, Pasco, G., Charman, Tony, Johnson, Mark H., and Jones, Emily J. H.
Abstract: Contains fulltext : 246003.pdf (Publisher’s version ) (Open Access)
Published: 2021

10. Development of the pupillary light reflex from 9 to 24 months : association with common autism spectrum disorder (ASD) genetic liability and 3-year ASD diagnosis

Author: Fish, Laurel A., Nyström, Pär, Gliga, Teodora, Gui, Anna, Begum Ali, Jannath, Mason, Luke, Garg, Shruti, Green, Jonathan, Johnson, Mark H., Charman, Tony, Harrison, Rebecca, Meaburn, Emma, Falck-Ytter, Terje, Jones, Emily J. H., Fish, Laurel A., Nyström, Pär, Gliga, Teodora, Gui, Anna, Begum Ali, Jannath, Mason, Luke, Garg, Shruti, Green, Jonathan, Johnson, Mark H., Charman, Tony, Harrison, Rebecca, Meaburn, Emma, Falck-Ytter, Terje, and Jones, Emily J. H.
Abstract: Background: Although autism spectrum disorder (ASD) is heritable, the mechanisms through which genes contribute to symptom emergence remain unclear. Investigating candidate intermediate phenotypes such as the pupillary light reflex (PLR) prospectively from early in development could bridge genotype and behavioural phenotype. Methods: Using eye tracking, we longitudinally measured the PLR at 9, 14 and 24 months in a sample of infants (N = 264) enriched for a family history of ASD; 27 infants received an ASD diagnosis at 3 years. We examined the 9- to 24-month developmental trajectories of PLR constriction latency (onset; ms) and amplitude (%) and explored their relation to categorical 3-year ASD outcome, polygenic liability for ASD and dimensional 3-year social affect (SA) and repetitive/restrictive behaviour (RRB) traits. Polygenic scores for ASD (PGSASD) were calculated for 190 infants. Results: While infants showed a decrease in latency between 9 and 14 months, higher PGSASD was associated with a smaller decrease in latency in the first year (? = ?.16, 95% CI = ?0.31, ?0.002); infants with later ASD showed a significantly steeper decrease in latency (a putative ?catch-up?) between 14 and 24 months relative to those with other outcomes (typical: ? = .54, 95% CI = 0.08, 0.99; other: ? = .53, 95% CI = 0.02, 1.04). Latency development did not associate with later dimensional variation in ASD-related traits. In contrast, change in amplitude was not related to categorical ASD or genetics, but decreasing 9- to 14-month amplitude was associated with higher SA (? = .08, 95% CI = 0.01, 0.14) and RRB (? = .05, 95% CI = 0.004, 0.11) traits. Conclusions: These findings corroborate PLR development as possible intermediate phenotypes being linked to both genetic liability and phenotypic outcomes. Future work should incorporate alternative measures (e.g. functionally informed structural and genetic measures) to test whether distinct neural mechanisms underpin PLR alterations.
Published: 2021
Full Text: View/download PDF

11. Development of the pupillary light reflex from 9 to 24 months : association with common autism spectrum disorder (ASD) genetic liability and 3-year ASD diagnosis

Author: Fish, Laurel A., Nyström, Pär, Gliga, Teodora, Gui, Anna, Begum Ali, Jannath, Mason, Luke, Garg, Shruti, Green, Jonathan, Johnson, Mark H., Charman, Tony, Harrison, Rebecca, Meaburn, Emma, Falck-Ytter, Terje, Jones, Emily J. H., Fish, Laurel A., Nyström, Pär, Gliga, Teodora, Gui, Anna, Begum Ali, Jannath, Mason, Luke, Garg, Shruti, Green, Jonathan, Johnson, Mark H., Charman, Tony, Harrison, Rebecca, Meaburn, Emma, Falck-Ytter, Terje, and Jones, Emily J. H.
Abstract: Background: Although autism spectrum disorder (ASD) is heritable, the mechanisms through which genes contribute to symptom emergence remain unclear. Investigating candidate intermediate phenotypes such as the pupillary light reflex (PLR) prospectively from early in development could bridge genotype and behavioural phenotype. Methods: Using eye tracking, we longitudinally measured the PLR at 9, 14 and 24 months in a sample of infants (N = 264) enriched for a family history of ASD; 27 infants received an ASD diagnosis at 3 years. We examined the 9- to 24-month developmental trajectories of PLR constriction latency (onset; ms) and amplitude (%) and explored their relation to categorical 3-year ASD outcome, polygenic liability for ASD and dimensional 3-year social affect (SA) and repetitive/restrictive behaviour (RRB) traits. Polygenic scores for ASD (PGSASD) were calculated for 190 infants. Results: While infants showed a decrease in latency between 9 and 14 months, higher PGSASD was associated with a smaller decrease in latency in the first year (? = ?.16, 95% CI = ?0.31, ?0.002); infants with later ASD showed a significantly steeper decrease in latency (a putative ?catch-up?) between 14 and 24 months relative to those with other outcomes (typical: ? = .54, 95% CI = 0.08, 0.99; other: ? = .53, 95% CI = 0.02, 1.04). Latency development did not associate with later dimensional variation in ASD-related traits. In contrast, change in amplitude was not related to categorical ASD or genetics, but decreasing 9- to 14-month amplitude was associated with higher SA (? = .08, 95% CI = 0.01, 0.14) and RRB (? = .05, 95% CI = 0.004, 0.11) traits. Conclusions: These findings corroborate PLR development as possible intermediate phenotypes being linked to both genetic liability and phenotypic outcomes. Future work should incorporate alternative measures (e.g. functionally informed structural and genetic measures) to test whether distinct neural mechanisms underpin PLR alterations.
Published: 2021
Full Text: View/download PDF

12. INTERSTAARS: Attention training for infants with elevated likelihood of developing ADHD: a proof-of-concept randomised controlled trial

Author: Goodwin, Amy, Jones, Emily. J H, Salomone, Simona, Mason, Luke, Holman, Rebecca, Begum Ali, Jannath, Hunt, Anna, Ruddock, Martin, Vamvakas, George, Robinson, Emily, Holden, Catherine, Taylor, Chloe, Smith, Tim, Sonuga-Barke, Edmund, Bolton, Patrick, Charman, Tony, Pickles, Andrew, Wass, Sam, Johnson, Mark. H, Goodwin, Amy, Jones, Emily. J H, Salomone, Simona, Mason, Luke, Holman, Rebecca, Begum Ali, Jannath, Hunt, Anna, Ruddock, Martin, Vamvakas, George, Robinson, Emily, Holden, Catherine, Taylor, Chloe, Smith, Tim, Sonuga-Barke, Edmund, Bolton, Patrick, Charman, Tony, Pickles, Andrew, Wass, Sam, and Johnson, Mark. H
Abstract: Attention-deficit/hyperactivity disorder (ADHD) is first diagnosed during middle childhood, when patterns of difficulty are often established. Pre-emptive approaches that strengthen developing cognitive systems could offer an alternative to post-diagnostic interventions. This proof-of-concept randomised controlled trial (RCT) tested whether computerised gaze-based attention training is feasible and improves attention in infants liable to develop ADHD. Forty-three 9- to 16-month-old infants with a first-degree relative with ADHD were recruited (11/2015–11/2018) at two UK sites and randomised with minimisation by site and sex to receive 9 weekly sessions of either (a) gaze-contingent attention training (intervention; n = 20); or (b) infant-friendly passive viewing of videos (control, n = 23). Sessions were delivered at home with blinded outcome assessments. The primary outcome was a composite of attention measures jointly analysed via a multivariate ANCOVA with a combined effect size (ES) from coefficients at baseline, midpoint and endpoint (Registration: ISRCTN37683928). Uptake and compliance was good but intention-to-treat analysis showed no significant differences between 20 intervention and 23 control infants on primary (ES −0.4, 95% CI −0.9 to 0.2; Complier-Average-Causal Effect ES −0.6, 95% CI −1.6 to 0.5) or secondary outcomes (behavioural attention). There were no adverse effects on sleep but a small increase in post-intervention session fussiness. Although feasible, there was no support for short-term effects of gaze-based attention training on attention skills in early ADHD. Longer-term outcomes remain to be assessed. The study highlights challenges and opportunities for pre-emptive intervention approaches to the management of ADHD.
Published: 2021

13. INTERSTAARS: Attention training for infants with elevated likelihood of developing ADHD: a proof-of-concept randomised controlled trial

Author: Goodwin, Amy, Jones, Emily. J H, Salomone, Simona, Mason, Luke, Holman, Rebecca, Begum Ali, Jannath, Hunt, Anna, Ruddock, Martin, Vamvakas, George, Robinson, Emily, Holden, Catherine, Taylor, Chloe, Smith, Tim, Sonuga-Barke, Edmund, Bolton, Patrick, Charman, Tony, Pickles, Andrew, Wass, Sam, Johnson, Mark. H, Goodwin, Amy, Jones, Emily. J H, Salomone, Simona, Mason, Luke, Holman, Rebecca, Begum Ali, Jannath, Hunt, Anna, Ruddock, Martin, Vamvakas, George, Robinson, Emily, Holden, Catherine, Taylor, Chloe, Smith, Tim, Sonuga-Barke, Edmund, Bolton, Patrick, Charman, Tony, Pickles, Andrew, Wass, Sam, and Johnson, Mark. H
Abstract: Attention-deficit/hyperactivity disorder (ADHD) is first diagnosed during middle childhood, when patterns of difficulty are often established. Pre-emptive approaches that strengthen developing cognitive systems could offer an alternative to post-diagnostic interventions. This proof-of-concept randomised controlled trial (RCT) tested whether computerised gaze-based attention training is feasible and improves attention in infants liable to develop ADHD. Forty-three 9- to 16-month-old infants with a first-degree relative with ADHD were recruited (11/2015–11/2018) at two UK sites and randomised with minimisation by site and sex to receive 9 weekly sessions of either (a) gaze-contingent attention training (intervention; n = 20); or (b) infant-friendly passive viewing of videos (control, n = 23). Sessions were delivered at home with blinded outcome assessments. The primary outcome was a composite of attention measures jointly analysed via a multivariate ANCOVA with a combined effect size (ES) from coefficients at baseline, midpoint and endpoint (Registration: ISRCTN37683928). Uptake and compliance was good but intention-to-treat analysis showed no significant differences between 20 intervention and 23 control infants on primary (ES −0.4, 95% CI −0.9 to 0.2; Complier-Average-Causal Effect ES −0.6, 95% CI −1.6 to 0.5) or secondary outcomes (behavioural attention). There were no adverse effects on sleep but a small increase in post-intervention session fussiness. Although feasible, there was no support for short-term effects of gaze-based attention training on attention skills in early ADHD. Longer-term outcomes remain to be assessed. The study highlights challenges and opportunities for pre-emptive intervention approaches to the management of ADHD.
Published: 2021

14. INTERSTAARS: Attention training for infants with elevated likelihood of developing ADHD: a proof-of-concept randomised controlled trial

Author: Goodwin, Amy, Jones, Emily. J H, Salomone, Simona, Mason, Luke, Holman, Rebecca, Begum Ali, Jannath, Hunt, Anna, Ruddock, Martin, Vamvakas, George, Robinson, Emily, Holden, Catherine, Taylor, Chloe, Smith, Tim, Sonuga-Barke, Edmund, Bolton, Patrick, Charman, Tony, Pickles, Andrew, Wass, Sam, Johnson, Mark. H, Goodwin, Amy, Jones, Emily. J H, Salomone, Simona, Mason, Luke, Holman, Rebecca, Begum Ali, Jannath, Hunt, Anna, Ruddock, Martin, Vamvakas, George, Robinson, Emily, Holden, Catherine, Taylor, Chloe, Smith, Tim, Sonuga-Barke, Edmund, Bolton, Patrick, Charman, Tony, Pickles, Andrew, Wass, Sam, and Johnson, Mark. H
Abstract: Attention-deficit/hyperactivity disorder (ADHD) is first diagnosed during middle childhood, when patterns of difficulty are often established. Pre-emptive approaches that strengthen developing cognitive systems could offer an alternative to post-diagnostic interventions. This proof-of-concept randomised controlled trial (RCT) tested whether computerised gaze-based attention training is feasible and improves attention in infants liable to develop ADHD. Forty-three 9- to 16-month-old infants with a first-degree relative with ADHD were recruited (11/2015–11/2018) at two UK sites and randomised with minimisation by site and sex to receive 9 weekly sessions of either (a) gaze-contingent attention training (intervention; n = 20); or (b) infant-friendly passive viewing of videos (control, n = 23). Sessions were delivered at home with blinded outcome assessments. The primary outcome was a composite of attention measures jointly analysed via a multivariate ANCOVA with a combined effect size (ES) from coefficients at baseline, midpoint and endpoint (Registration: ISRCTN37683928). Uptake and compliance was good but intention-to-treat analysis showed no significant differences between 20 intervention and 23 control infants on primary (ES −0.4, 95% CI −0.9 to 0.2; Complier-Average-Causal Effect ES −0.6, 95% CI −1.6 to 0.5) or secondary outcomes (behavioural attention). There were no adverse effects on sleep but a small increase in post-intervention session fussiness. Although feasible, there was no support for short-term effects of gaze-based attention training on attention skills in early ADHD. Longer-term outcomes remain to be assessed. The study highlights challenges and opportunities for pre-emptive intervention approaches to the management of ADHD.
Published: 2021

15. Development of the pupillary light reflex from 9 to 24 months : association with common autism spectrum disorder (ASD) genetic liability and 3-year ASD diagnosis

Author: Fish, Laurel A., Nyström, Pär, Gliga, Teodora, Gui, Anna, Begum Ali, Jannath, Mason, Luke, Garg, Shruti, Green, Jonathan, Johnson, Mark H., Charman, Tony, Harrison, Rebecca, Meaburn, Emma, Falck-Ytter, Terje, Jones, Emily J. H., Fish, Laurel A., Nyström, Pär, Gliga, Teodora, Gui, Anna, Begum Ali, Jannath, Mason, Luke, Garg, Shruti, Green, Jonathan, Johnson, Mark H., Charman, Tony, Harrison, Rebecca, Meaburn, Emma, Falck-Ytter, Terje, and Jones, Emily J. H.
Abstract: Background: Although autism spectrum disorder (ASD) is heritable, the mechanisms through which genes contribute to symptom emergence remain unclear. Investigating candidate intermediate phenotypes such as the pupillary light reflex (PLR) prospectively from early in development could bridge genotype and behavioural phenotype. Methods: Using eye tracking, we longitudinally measured the PLR at 9, 14 and 24 months in a sample of infants (N = 264) enriched for a family history of ASD; 27 infants received an ASD diagnosis at 3 years. We examined the 9- to 24-month developmental trajectories of PLR constriction latency (onset; ms) and amplitude (%) and explored their relation to categorical 3-year ASD outcome, polygenic liability for ASD and dimensional 3-year social affect (SA) and repetitive/restrictive behaviour (RRB) traits. Polygenic scores for ASD (PGSASD) were calculated for 190 infants. Results: While infants showed a decrease in latency between 9 and 14 months, higher PGSASD was associated with a smaller decrease in latency in the first year (? = ?.16, 95% CI = ?0.31, ?0.002); infants with later ASD showed a significantly steeper decrease in latency (a putative ?catch-up?) between 14 and 24 months relative to those with other outcomes (typical: ? = .54, 95% CI = 0.08, 0.99; other: ? = .53, 95% CI = 0.02, 1.04). Latency development did not associate with later dimensional variation in ASD-related traits. In contrast, change in amplitude was not related to categorical ASD or genetics, but decreasing 9- to 14-month amplitude was associated with higher SA (? = .08, 95% CI = 0.01, 0.14) and RRB (? = .05, 95% CI = 0.004, 0.11) traits. Conclusions: These findings corroborate PLR development as possible intermediate phenotypes being linked to both genetic liability and phenotypic outcomes. Future work should incorporate alternative measures (e.g. functionally informed structural and genetic measures) to test whether distinct neural mechanisms underpin PLR alterations.
Published: 2021
Full Text: View/download PDF

16. Temporal Profiles of Social Attention Are Different Across Development in Autistic and Neurotypical People

Author: Del Bianco, Teresa, Mason, Luke, Charman, Tony, Tillman, Julian, Loth, Eva, Hayward, Hannah, Shic, Frederick, Buitelaar, Jan, Johnson, Mark H, Jones, Emily J H, EU-AIMS LEAP Group, Del Bianco, Teresa, Mason, Luke, Charman, Tony, Tillman, Julian, Loth, Eva, Hayward, Hannah, Shic, Frederick, Buitelaar, Jan, Johnson, Mark H, Jones, Emily J H, and EU-AIMS LEAP Group
Abstract: BACKGROUND Sociocommunicative difficulties, including abnormalities in eye contact, are core diagnostic features of autism spectrum disorder (ASD). Many studies have used eye tracking to measure reduced attention to faces in autistic people; however, most of this work has not taken advantage of eye-tracking temporal resolution to examine temporal profiles of attention. METHODS We used growth curve analysis to model attention to static social scenes as a function of time in a large (N = 650) sample of autistic participants and neurotypical participants across a wide age range (6-30 years). RESULTS The model yielded distinct temporal profiles of attention to faces in the groups. Initially, both groups showed a relatively high probability of attending to faces, followed by decline after several seconds. The neurotypical participants, however, were significantly more likely to return their attention to faces in the latter part of each 20-second trial, with increasing probability with age. In contrast, the probability of returning to the face in the autistic participants remained low across development. In participants with ASD, more atypical profiles of attention were associated with lower Vineland Adaptive Behavior Scales communication scores and a higher curvature in one data-driven cluster correlated with symptom severity. CONCLUSIONS These findings show that social attention not only is reduced in ASD, but also differs in its temporal dynamics. The neurotypical participants became more sophisticated in how they deployed their social attention across age, a pattern that was significantly reduced in the participants with ASD, possibly reflecting delayed acquisition of social expertise.
Published: 2021

17. Attenuated anticipation of social and monetary rewards in autism spectrum disorders

Author: the AIMS-2-TRIALS group, Baumeister, Sarah, Mößnang, Carolin Ulrike, Bast, Nico, Hohmann, Sarah, Tillmann, Julian, Goyard, David, Charman, Tony, Ambrosino, Sara, Baron-Cohen, Simon, Beckmann, Christian F., Bölte, Sven, Bourgeron, Thomas, Rausch, Annika, Crawley, Daisy, Dell'Acqua, Flavio, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Floris, Dorothea L., Frouin, Vincent, Hayward, Hannah, Holt, Rosemary, Johnson, Mark H., Jones, Emily J. H., Lai, Meng-Chuan, Lombardo, Michael V., Mason, Luke, Oldehinkel, Marianne, Persico, Tony, San José Cáceres, Antonia, Wolfers, Thomas, Spooren, Willibrordus Philippus Johannes Maria, Loth, Eva, Murphy, Declan G. M., Buitelaar, Jan K., Tost, Heike, Meyer-Lindenberg, Andreas, Banaschewski, Tobias, Brandeis, Daniel, the AIMS-2-TRIALS group, Baumeister, Sarah, Mößnang, Carolin Ulrike, Bast, Nico, Hohmann, Sarah, Tillmann, Julian, Goyard, David, Charman, Tony, Ambrosino, Sara, Baron-Cohen, Simon, Beckmann, Christian F., Bölte, Sven, Bourgeron, Thomas, Rausch, Annika, Crawley, Daisy, Dell'Acqua, Flavio, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Floris, Dorothea L., Frouin, Vincent, Hayward, Hannah, Holt, Rosemary, Johnson, Mark H., Jones, Emily J. H., Lai, Meng-Chuan, Lombardo, Michael V., Mason, Luke, Oldehinkel, Marianne, Persico, Tony, San José Cáceres, Antonia, Wolfers, Thomas, Spooren, Willibrordus Philippus Johannes Maria, Loth, Eva, Murphy, Declan G. M., Buitelaar, Jan K., Tost, Heike, Meyer-Lindenberg, Andreas, Banaschewski, Tobias, and Brandeis, Daniel
Abstract: Background Reward processing has been proposed to underpin atypical social behavior, a core feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social rewards in ASD. Utilizing a large sample, we aimed to assess altered reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD. Methods Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6-30.5 years) and 181 typically developing (TD) participants (7.6-30.8 years). Results Across social and monetary reward anticipation, whole-brain analyses (p<0.05, family-wise error-corrected) showed hypoactivation of the right ventral striatum (VS) in ASD. Further, region of interest (ROI) analysis across both reward types yielded hypoactivation in ASD in both the left and right VS. Across delivery of social and monetary reward, hyperactivation of the VS in individuals with ASD did not survive correction for multiple comparisons. Reward type by diagnostic group interactions, and a dimensional analysis of autism trait scores were not significant during anticipation or delivery. Levels of attention-deficit/hyperactivity disorder (ADHD) symptoms did not affect reward processing in ASD. Conclusions Our results do not support current theories linking atypical social interaction in ASD to specific alterations in processing of social rewards. Instead, they point towards a generalized hypoactivity of VS in ASD during anticipation of both social and monetary rewards. We suggest that this indicates attenuated subjective reward value in ASD independent of social content and ADHD symptoms.
Published: 2020

18. Saccade dysmetria indicates attenuated visual exploration in autism spectrum disorder

Author: Bast, Nico, Mason, Luke, Freitag, Christine. M, Smith, Tim, Portugal, Ana Maria, Poustka, Luise, Banaschewski, Tobias, Johnson, Mark. H, Bast, Nico, Mason, Luke, Freitag, Christine. M, Smith, Tim, Portugal, Ana Maria, Poustka, Luise, Banaschewski, Tobias, and Johnson, Mark. H
Abstract: Background: Visual exploration in autism spectrum disorder (ASD) is characterized by attenuated social attention. The underlying oculomotor function during visual exploration is understudied, whereas oculomotor function during restricted viewing suggested saccade dysmetria in ASD by altered pontocerebellar motor modulation. Methods: Oculomotor function was recorded using remote eye tracking in 142 ASD participants and 142 matched neurotypical controls during free viewing of naturalistic videos with and without human content. The sample was heterogenous concerning age (6–30 years), cognitive ability (60–140 IQ), and male/female ratio (3:1). Oculomotor function was defined as saccade, fixation, and pupil‐dilation features that were compared between groups in linear mixed models. Oculomotor function was investigated as ASD classifier and features were correlated with clinical measures. Results: We observed decreased saccade duration (∆M = −0.50, CI [−0.21, −0.78]) and amplitude (∆M = −0.42, CI [−0.12, −0.72]), which was independent of human video content. We observed null findings concerning fixation and pupil‐dilation features (POWER = .81). Oculomotor function is a valid ASD classifier comparable to social attention concerning discriminative power. Within ASD, saccade features correlated with measures of restricted and repetitive behavior. Conclusions: We conclude saccade dysmetria as ASD oculomotor phenotype relevant to visual exploration. Decreased saccade amplitude and duration indicate spatially clustered fixations that attenuate visual exploration and emphasize endogenous over exogenous attention. We propose altered pontocerebellar motor modulation as underlying mechanism that contributes to atypical (oculo‐)motor coordination and attention function in ASD.
Published: 2020

19. Saccade dysmetria indicates attenuated visual exploration in autism spectrum disorder

Author: Bast, Nico, Mason, Luke, Freitag, Christine. M, Smith, Tim, Portugal, Ana Maria, Poustka, Luise, Banaschewski, Tobias, Johnson, Mark. H, Bast, Nico, Mason, Luke, Freitag, Christine. M, Smith, Tim, Portugal, Ana Maria, Poustka, Luise, Banaschewski, Tobias, and Johnson, Mark. H
Abstract: Background: Visual exploration in autism spectrum disorder (ASD) is characterized by attenuated social attention. The underlying oculomotor function during visual exploration is understudied, whereas oculomotor function during restricted viewing suggested saccade dysmetria in ASD by altered pontocerebellar motor modulation. Methods: Oculomotor function was recorded using remote eye tracking in 142 ASD participants and 142 matched neurotypical controls during free viewing of naturalistic videos with and without human content. The sample was heterogenous concerning age (6–30 years), cognitive ability (60–140 IQ), and male/female ratio (3:1). Oculomotor function was defined as saccade, fixation, and pupil‐dilation features that were compared between groups in linear mixed models. Oculomotor function was investigated as ASD classifier and features were correlated with clinical measures. Results: We observed decreased saccade duration (∆M = −0.50, CI [−0.21, −0.78]) and amplitude (∆M = −0.42, CI [−0.12, −0.72]), which was independent of human video content. We observed null findings concerning fixation and pupil‐dilation features (POWER = .81). Oculomotor function is a valid ASD classifier comparable to social attention concerning discriminative power. Within ASD, saccade features correlated with measures of restricted and repetitive behavior. Conclusions: We conclude saccade dysmetria as ASD oculomotor phenotype relevant to visual exploration. Decreased saccade amplitude and duration indicate spatially clustered fixations that attenuate visual exploration and emphasize endogenous over exogenous attention. We propose altered pontocerebellar motor modulation as underlying mechanism that contributes to atypical (oculo‐)motor coordination and attention function in ASD.
Published: 2020

20. Saccade dysmetria indicates attenuated visual exploration in autism spectrum disorder

Author: Bast, Nico, Mason, Luke, Freitag, Christine. M, Smith, Tim, Portugal, Ana Maria, Poustka, Luise, Banaschewski, Tobias, Johnson, Mark. H, Bast, Nico, Mason, Luke, Freitag, Christine. M, Smith, Tim, Portugal, Ana Maria, Poustka, Luise, Banaschewski, Tobias, and Johnson, Mark. H
Abstract: Background: Visual exploration in autism spectrum disorder (ASD) is characterized by attenuated social attention. The underlying oculomotor function during visual exploration is understudied, whereas oculomotor function during restricted viewing suggested saccade dysmetria in ASD by altered pontocerebellar motor modulation. Methods: Oculomotor function was recorded using remote eye tracking in 142 ASD participants and 142 matched neurotypical controls during free viewing of naturalistic videos with and without human content. The sample was heterogenous concerning age (6–30 years), cognitive ability (60–140 IQ), and male/female ratio (3:1). Oculomotor function was defined as saccade, fixation, and pupil‐dilation features that were compared between groups in linear mixed models. Oculomotor function was investigated as ASD classifier and features were correlated with clinical measures. Results: We observed decreased saccade duration (∆M = −0.50, CI [−0.21, −0.78]) and amplitude (∆M = −0.42, CI [−0.12, −0.72]), which was independent of human video content. We observed null findings concerning fixation and pupil‐dilation features (POWER = .81). Oculomotor function is a valid ASD classifier comparable to social attention concerning discriminative power. Within ASD, saccade features correlated with measures of restricted and repetitive behavior. Conclusions: We conclude saccade dysmetria as ASD oculomotor phenotype relevant to visual exploration. Decreased saccade amplitude and duration indicate spatially clustered fixations that attenuate visual exploration and emphasize endogenous over exogenous attention. We propose altered pontocerebellar motor modulation as underlying mechanism that contributes to atypical (oculo‐)motor coordination and attention function in ASD.
Published: 2020

21. Latent trajectories of adaptive behaviour in infants at high and low familial risk for autism spectrum disorder

Author: Bussu, G., Jones, E.J.H., Charman, T., Johnson, Mark H., Buitelaar, J.K., Bussu, G., Jones, E.J.H., Charman, T., Johnson, Mark H., and Buitelaar, J.K.
Abstract: Contains fulltext : 202067.pdf (publisher's version ) (Open Access)
Published: 2019

22. Latent trajectories of adaptive behaviour in infants at high and low familial risk for autism spectrum disorder

Author: Bussu, G., Jones, E.J.H., Charman, T., Johnson, Mark H., Buitelaar, J.K., Bussu, G., Jones, E.J.H., Charman, T., Johnson, Mark H., and Buitelaar, J.K.
Abstract: Contains fulltext : 202067.pdf (publisher's version ) (Open Access)
Published: 2019

23. Investigating the factors underlying adaptive functioning in autism in the EU-AIMS Longitudinal European Autism Project

Author: Ontwikkelingsstoornissen Ond., Brain, Onderzoek Bob Oranje, Tillmann, Julian, Caceres, Antonia San Jose, Chatham, Chris H., Crawley, Daisy, Holt, Rosemary, Oakley, Bethany, Banaschewski, Tobias, Baron-Cohen, Simon, Boelte, Sven, Buitelaar, Jan K., Durston, Sarah, Ham, Lindsay, Loth, Eva, Simonoff, Emily, Spooren, Will, Murphy, Declan G., Charman, Tony, Ahmad, Jumana, Ambrosino, Sara, Auyeung, Bonnie, Baumeister, Sarah, Beckmann, Christian, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, de Bruijn, Yvette, Chakrabarti, Bhismadev, Cornelissen, Ineke, Dell'Acqua, Flavio, Dumas, Guillaume, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garces, Pilar, Goyard, David, Hayward, Hannah, Hipp, Joerg, Johnson, Mark H., Jones, Emily J. H., Kundu, Prantik, Lai, Meng-Chuan, D'ardhuy, Xavier Liogier, Lombardo, Michael, Lythgoe, David J., Mandl, Rene, Mason, Luke, Meyer-Lindenberg, Andreas, Oranje, Bob, Ontwikkelingsstoornissen Ond., Brain, Onderzoek Bob Oranje, Tillmann, Julian, Caceres, Antonia San Jose, Chatham, Chris H., Crawley, Daisy, Holt, Rosemary, Oakley, Bethany, Banaschewski, Tobias, Baron-Cohen, Simon, Boelte, Sven, Buitelaar, Jan K., Durston, Sarah, Ham, Lindsay, Loth, Eva, Simonoff, Emily, Spooren, Will, Murphy, Declan G., Charman, Tony, Ahmad, Jumana, Ambrosino, Sara, Auyeung, Bonnie, Baumeister, Sarah, Beckmann, Christian, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, de Bruijn, Yvette, Chakrabarti, Bhismadev, Cornelissen, Ineke, Dell'Acqua, Flavio, Dumas, Guillaume, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garces, Pilar, Goyard, David, Hayward, Hannah, Hipp, Joerg, Johnson, Mark H., Jones, Emily J. H., Kundu, Prantik, Lai, Meng-Chuan, D'ardhuy, Xavier Liogier, Lombardo, Michael, Lythgoe, David J., Mandl, Rene, Mason, Luke, Meyer-Lindenberg, Andreas, and Oranje, Bob
Published: 2019

24. Enhanced pupillary light reflex in infancy is associated with autism diagnosis in toddlerhood

Author: Nyström, Pär, Gliga, Teodora, Nilsson Jobs, Elisabeth, Gredebäck, Gustaf, Charman, Tony, Johnson, Mark H., Bölte, Sven, Falck-Ytter, Terje, Nyström, Pär, Gliga, Teodora, Nilsson Jobs, Elisabeth, Gredebäck, Gustaf, Charman, Tony, Johnson, Mark H., Bölte, Sven, and Falck-Ytter, Terje
Abstract: Autism spectrum disorder (ASD) is a neurodevelopmental condition affecting around 1% of the population. We previously discovered that infant siblings of children with ASD had stronger pupillary light reflexes compared to low-risk infants, a result which contrasts sharply with the weak pupillary light reflex typically seen in both children and adults with ASD. Here, we show that on average the relative constriction of the pupillary light reflex is larger in 9–10-month-old high risk infant siblings who receive an ASD diagnosis at 36 months, compared both to those who do not and to low-risk controls. We also found that the magnitude of the pupillary light reflex in infancy is associated with symptom severity at follow-up. This study indicates an important role of sensory atypicalities in the etiology of ASD, and suggests that pupillometry, if further developed and refined, could facilitate risk assessment in infants.
Published: 2018
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25. Enhanced pupillary light reflex in infancy is associated with autism diagnosis in toddlerhood

Author: Nyström, Pär, Gliga, Teodora, Nilsson Jobs, Elisabeth, Gredebäck, Gustaf, Charman, Tony, Johnson, Mark H., Bölte, Sven, Falck-Ytter, Terje, Nyström, Pär, Gliga, Teodora, Nilsson Jobs, Elisabeth, Gredebäck, Gustaf, Charman, Tony, Johnson, Mark H., Bölte, Sven, and Falck-Ytter, Terje
Abstract: Autism spectrum disorder (ASD) is a neurodevelopmental condition affecting around 1% of the population. We previously discovered that infant siblings of children with ASD had stronger pupillary light reflexes compared to low-risk infants, a result which contrasts sharply with the weak pupillary light reflex typically seen in both children and adults with ASD. Here, we show that on average the relative constriction of the pupillary light reflex is larger in 9–10-month-old high risk infant siblings who receive an ASD diagnosis at 36 months, compared both to those who do not and to low-risk controls. We also found that the magnitude of the pupillary light reflex in infancy is associated with symptom severity at follow-up. This study indicates an important role of sensory atypicalities in the etiology of ASD, and suggests that pupillometry, if further developed and refined, could facilitate risk assessment in infants.
Published: 2018
Full Text: View/download PDF

26. Enhanced pupillary light reflex in infancy is associated with autism diagnosis in toddlerhood

Author: Nyström, Pär, Gliga, Teodora, Nilsson Jobs, Elisabeth, Gredebäck, Gustaf, Charman, Tony, Johnson, Mark H., Bölte, Sven, Falck-Ytter, Terje, Nyström, Pär, Gliga, Teodora, Nilsson Jobs, Elisabeth, Gredebäck, Gustaf, Charman, Tony, Johnson, Mark H., Bölte, Sven, and Falck-Ytter, Terje
Abstract: Autism spectrum disorder (ASD) is a neurodevelopmental condition affecting around 1% of the population. We previously discovered that infant siblings of children with ASD had stronger pupillary light reflexes compared to low-risk infants, a result which contrasts sharply with the weak pupillary light reflex typically seen in both children and adults with ASD. Here, we show that on average the relative constriction of the pupillary light reflex is larger in 9–10-month-old high risk infant siblings who receive an ASD diagnosis at 36 months, compared both to those who do not and to low-risk controls. We also found that the magnitude of the pupillary light reflex in infancy is associated with symptom severity at follow-up. This study indicates an important role of sensory atypicalities in the etiology of ASD, and suggests that pupillometry, if further developed and refined, could facilitate risk assessment in infants.
Published: 2018
Full Text: View/download PDF

27. EU-AIMS Longitudinal European Autism Project (LEAP) : The autism twin cohort

Author: Isaksson, Johan, Tammimies, Kristiina, Neufeld, Janina, Cauvet, Élodie, Lundin, Karl, Buitelaar, Jan K., Loth, Eva, Murphy, Declan G.M., Spooren, Will, Bölte, Sven, Ahmad, Jumana, Ambrosino, Sara, Auyeung, Bonnie, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, De Bruijn, Yvette, Chakrabarti, Bhismadev, Charman, Tony, Crawley, Daisy, Cornelissen, Ineke, Dell'Acqua, Flavio, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Frouin, Vincent, Garcés, Pilar, Goyard, David, Ham, Lindsay, Hayward, Hannah, Hipp, Joerg, Holt, Rosemary J., Johnson, Mark H., Jones, Emily J.H., Kundu, Prantik, Lai, Meng Chuan, D'Ardhuy, Xavier Liogier, Lombardo, Michael, Lythgoe, David J., Mandl, René, Mason, Luke, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M., Ruggeri, Barbara, Ruigrok, Amber, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San José, Simonoff, Emily, Tillmann, Julian, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C.R., Wooldridge, Caroline, Zwiers, Marcel P., Isaksson, Johan, Tammimies, Kristiina, Neufeld, Janina, Cauvet, Élodie, Lundin, Karl, Buitelaar, Jan K., Loth, Eva, Murphy, Declan G.M., Spooren, Will, Bölte, Sven, Ahmad, Jumana, Ambrosino, Sara, Auyeung, Bonnie, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, De Bruijn, Yvette, Chakrabarti, Bhismadev, Charman, Tony, Crawley, Daisy, Cornelissen, Ineke, Dell'Acqua, Flavio, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Frouin, Vincent, Garcés, Pilar, Goyard, David, Ham, Lindsay, Hayward, Hannah, Hipp, Joerg, Holt, Rosemary J., Johnson, Mark H., Jones, Emily J.H., Kundu, Prantik, Lai, Meng Chuan, D'Ardhuy, Xavier Liogier, Lombardo, Michael, Lythgoe, David J., Mandl, René, Mason, Luke, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M., Ruggeri, Barbara, Ruigrok, Amber, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San José, Simonoff, Emily, Tillmann, Julian, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C.R., Wooldridge, Caroline, and Zwiers, Marcel P.
Published: 2018

28. Developmental change in look durations predicts later effortful control in toddlers at familial risk for ASD

Author: Hendry, A, Jones, E, Bedford, R, Gliga, T, Charman, T, Johnson, M, Baron-Cohen, S, Blasi, A, Bolton, P, Cheung, H, Davies, K, Elsabbagh, M, Fernandes, J, Gammer, I, Green, J, Guiraud, J, Lloyd-Fox, S, Liew, M, Maris, H, O'Hara, L, Pasco, G, Pickles, A, Ribeiro, H, Salomone, E, Tucker, L, Wass, S, Hendry, Alexandra, Jones, Emily J. H., Bedford, Rachael, Gliga, Teodora, Charman, Tony, Johnson, Mark H., Baron-Cohen, S., Blasi, A., Bolton, P., Cheung, H. M. C., Davies, K., Elsabbagh, M., Fernandes, J., Gammer, I., Green, J., Guiraud, J., Lloyd-Fox, S., Liew, M., Maris, H., O'Hara, L., Pasco, G., Pickles, A., Ribeiro, H., Salomone, E., Tucker, L., Wass, S., Hendry, A, Jones, E, Bedford, R, Gliga, T, Charman, T, Johnson, M, Baron-Cohen, S, Blasi, A, Bolton, P, Cheung, H, Davies, K, Elsabbagh, M, Fernandes, J, Gammer, I, Green, J, Guiraud, J, Lloyd-Fox, S, Liew, M, Maris, H, O'Hara, L, Pasco, G, Pickles, A, Ribeiro, H, Salomone, E, Tucker, L, Wass, S, Hendry, Alexandra, Jones, Emily J. H., Bedford, Rachael, Gliga, Teodora, Charman, Tony, Johnson, Mark H., Baron-Cohen, S., Blasi, A., Bolton, P., Cheung, H. M. C., Davies, K., Elsabbagh, M., Fernandes, J., Gammer, I., Green, J., Guiraud, J., Lloyd-Fox, S., Liew, M., Maris, H., O'Hara, L., Pasco, G., Pickles, A., Ribeiro, H., Salomone, E., Tucker, L., and Wass, S.
Abstract: Background: Difficulties with executive functioning (EF) are common in individuals with a range of developmental disorders, including autism spectrum disorder (ASD). Interventions that target underlying mechanisms of EF early in development could be broadly beneficial, but require infant markers of such mechanisms in order to be feasible. Prospective studies of infants at high familial risk (HR) for ASD have revealed a surprising tendency for HR toddlers to show longer epochs of attention to faces than low-risk (LR) controls. In typical development, decreases in look durations towards the end of the first year of life are driven by the development of executive attention - a foundational component of EF. Here, we test the hypothesis that prolonged attention to visual stimuli (including faces) in HR toddlers reflects early differences in the development of executive attention. Methods: In a longitudinal prospective study, we used eye-tracking to record HR and LR infants' looking behaviour to social and non-social visual stimuli at ages 9 and 15 months. At age 3 years, we assessed children with a battery of clinical research measures and collected parental report of effortful control (EC) - a temperament trait closely associated with EF and similarly contingent on executive attention. Results: Consistent with previous studies, we found an attenuated reduction in peak look durations to faces between 9 and 15 months for the HR group compared with the LR group, and lower EC amongst the HR-ASD group. In line with our hypothesis, change in peak look duration to faces between 9 and 15 months was negatively associated with EC at age 3. Conclusions: We suggest that for HR toddlers, disruption to the early development of executive attention results in an attenuated reduction in looking time to faces. Effects may be more apparent for faces due to early biases to orient towards them; further, attention difficulties may interact with earlier emerging differences in social informat
Published: 2018

29. EU-AIMS Longitudinal European Autism Project (LEAP) : The autism twin cohort

Author: Isaksson, Johan, Tammimies, Kristiina, Neufeld, Janina, Cauvet, Élodie, Lundin, Karl, Buitelaar, Jan K., Loth, Eva, Murphy, Declan G.M., Spooren, Will, Bölte, Sven, Ahmad, Jumana, Ambrosino, Sara, Auyeung, Bonnie, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, De Bruijn, Yvette, Chakrabarti, Bhismadev, Charman, Tony, Crawley, Daisy, Cornelissen, Ineke, Dell'Acqua, Flavio, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Frouin, Vincent, Garcés, Pilar, Goyard, David, Ham, Lindsay, Hayward, Hannah, Hipp, Joerg, Holt, Rosemary J., Johnson, Mark H., Jones, Emily J.H., Kundu, Prantik, Lai, Meng Chuan, D'Ardhuy, Xavier Liogier, Lombardo, Michael, Lythgoe, David J., Mandl, René, Mason, Luke, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M., Ruggeri, Barbara, Ruigrok, Amber, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San José, Simonoff, Emily, Tillmann, Julian, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C.R., Wooldridge, Caroline, Zwiers, Marcel P., Isaksson, Johan, Tammimies, Kristiina, Neufeld, Janina, Cauvet, Élodie, Lundin, Karl, Buitelaar, Jan K., Loth, Eva, Murphy, Declan G.M., Spooren, Will, Bölte, Sven, Ahmad, Jumana, Ambrosino, Sara, Auyeung, Bonnie, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, De Bruijn, Yvette, Chakrabarti, Bhismadev, Charman, Tony, Crawley, Daisy, Cornelissen, Ineke, Dell'Acqua, Flavio, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Frouin, Vincent, Garcés, Pilar, Goyard, David, Ham, Lindsay, Hayward, Hannah, Hipp, Joerg, Holt, Rosemary J., Johnson, Mark H., Jones, Emily J.H., Kundu, Prantik, Lai, Meng Chuan, D'Ardhuy, Xavier Liogier, Lombardo, Michael, Lythgoe, David J., Mandl, René, Mason, Luke, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M., Ruggeri, Barbara, Ruigrok, Amber, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San José, Simonoff, Emily, Tillmann, Julian, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C.R., Wooldridge, Caroline, and Zwiers, Marcel P.
Published: 2018

30. EU-AIMS Longitudinal European Autism Project (LEAP) : The autism twin cohort

Author: Isaksson, Johan, Tammimies, Kristiina, Neufeld, Janina, Cauvet, Élodie, Lundin, Karl, Buitelaar, Jan K., Loth, Eva, Murphy, Declan G.M., Spooren, Will, Bölte, Sven, Ahmad, Jumana, Ambrosino, Sara, Auyeung, Bonnie, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, De Bruijn, Yvette, Chakrabarti, Bhismadev, Charman, Tony, Crawley, Daisy, Cornelissen, Ineke, Dell'Acqua, Flavio, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Frouin, Vincent, Garcés, Pilar, Goyard, David, Ham, Lindsay, Hayward, Hannah, Hipp, Joerg, Holt, Rosemary J., Johnson, Mark H., Jones, Emily J.H., Kundu, Prantik, Lai, Meng Chuan, D'Ardhuy, Xavier Liogier, Lombardo, Michael, Lythgoe, David J., Mandl, René, Mason, Luke, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M., Ruggeri, Barbara, Ruigrok, Amber, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San José, Simonoff, Emily, Tillmann, Julian, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C.R., Wooldridge, Caroline, Zwiers, Marcel P., Isaksson, Johan, Tammimies, Kristiina, Neufeld, Janina, Cauvet, Élodie, Lundin, Karl, Buitelaar, Jan K., Loth, Eva, Murphy, Declan G.M., Spooren, Will, Bölte, Sven, Ahmad, Jumana, Ambrosino, Sara, Auyeung, Bonnie, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, De Bruijn, Yvette, Chakrabarti, Bhismadev, Charman, Tony, Crawley, Daisy, Cornelissen, Ineke, Dell'Acqua, Flavio, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Frouin, Vincent, Garcés, Pilar, Goyard, David, Ham, Lindsay, Hayward, Hannah, Hipp, Joerg, Holt, Rosemary J., Johnson, Mark H., Jones, Emily J.H., Kundu, Prantik, Lai, Meng Chuan, D'Ardhuy, Xavier Liogier, Lombardo, Michael, Lythgoe, David J., Mandl, René, Mason, Luke, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M., Ruggeri, Barbara, Ruigrok, Amber, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San José, Simonoff, Emily, Tillmann, Julian, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C.R., Wooldridge, Caroline, and Zwiers, Marcel P.
Published: 2018

31. Enhanced pupillary light reflex in infancy is associated with autism diagnosis in toddlerhood

Author: Nyström, Pär, Gliga, Teodora, Nilsson Jobs, Elisabeth, Gredebäck, Gustaf, Charman, Tony, Johnson, Mark H., Bölte, Sven, Falck-Ytter, Terje, Nyström, Pär, Gliga, Teodora, Nilsson Jobs, Elisabeth, Gredebäck, Gustaf, Charman, Tony, Johnson, Mark H., Bölte, Sven, and Falck-Ytter, Terje
Abstract: Autism spectrum disorder (ASD) is a neurodevelopmental condition affecting around 1% of the population. We previously discovered that infant siblings of children with ASD had stronger pupillary light reflexes compared to low-risk infants, a result which contrasts sharply with the weak pupillary light reflex typically seen in both children and adults with ASD. Here, we show that on average the relative constriction of the pupillary light reflex is larger in 9–10-month-old high risk infant siblings who receive an ASD diagnosis at 36 months, compared both to those who do not and to low-risk controls. We also found that the magnitude of the pupillary light reflex in infancy is associated with symptom severity at follow-up. This study indicates an important role of sensory atypicalities in the etiology of ASD, and suggests that pupillometry, if further developed and refined, could facilitate risk assessment in infants.
Published: 2018
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32. EU-AIMS Longitudinal European Autism Project (LEAP): The autism twin cohort

Author: Ontwikkelingsstoornissen Ond., Brain, Onderzoeksgroep 8, Onderzoek Bob Oranje, Isaksson, Johan, Tammimies, Kristiina, Neufeld, Janina, Cauvet, Élodie, Lundin, Karl, Buitelaar, Jan K., Loth, Eva, Murphy, Declan G.M., Spooren, Will, Bölte, Sven, Ahmad, Jumana, Ambrosino, Sara, Auyeung, Bonnie, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, De Bruijn, Yvette, Chakrabarti, Bhismadev, Charman, Tony, Crawley, Daisy, Cornelissen, Ineke, Dell'Acqua, Flavio, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Frouin, Vincent, Garcés, Pilar, Goyard, David, Ham, Lindsay, Hayward, Hannah, Hipp, Joerg, Holt, Rosemary J., Johnson, Mark H., Jones, Emily J.H., Kundu, Prantik, Lai, Meng Chuan, D'Ardhuy, Xavier Liogier, Lombardo, Michael, Lythgoe, David J., Mandl, René, Mason, Luke, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M., Ruggeri, Barbara, Ruigrok, Amber, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San José, Simonoff, Emily, Tillmann, Julian, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C.R., Wooldridge, Caroline, Zwiers, Marcel P., Ontwikkelingsstoornissen Ond., Brain, Onderzoeksgroep 8, Onderzoek Bob Oranje, Isaksson, Johan, Tammimies, Kristiina, Neufeld, Janina, Cauvet, Élodie, Lundin, Karl, Buitelaar, Jan K., Loth, Eva, Murphy, Declan G.M., Spooren, Will, Bölte, Sven, Ahmad, Jumana, Ambrosino, Sara, Auyeung, Bonnie, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, De Bruijn, Yvette, Chakrabarti, Bhismadev, Charman, Tony, Crawley, Daisy, Cornelissen, Ineke, Dell'Acqua, Flavio, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Frouin, Vincent, Garcés, Pilar, Goyard, David, Ham, Lindsay, Hayward, Hannah, Hipp, Joerg, Holt, Rosemary J., Johnson, Mark H., Jones, Emily J.H., Kundu, Prantik, Lai, Meng Chuan, D'Ardhuy, Xavier Liogier, Lombardo, Michael, Lythgoe, David J., Mandl, René, Mason, Luke, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M., Ruggeri, Barbara, Ruigrok, Amber, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San José, Simonoff, Emily, Tillmann, Julian, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C.R., Wooldridge, Caroline, and Zwiers, Marcel P.
Published: 2018

33. Developmental change in look durations predicts later effortful control in toddlers at familial risk for ASD

Author: Hendry, A, Jones, E, Bedford, R, Gliga, T, Charman, T, Johnson, M, Baron-Cohen, S, Blasi, A, Bolton, P, Cheung, H, Davies, K, Elsabbagh, M, Fernandes, J, Gammer, I, Green, J, Guiraud, J, Lloyd-Fox, S, Liew, M, Maris, H, O'Hara, L, Pasco, G, Pickles, A, Ribeiro, H, Salomone, E, Tucker, L, Wass, S, Hendry, Alexandra, Jones, Emily J. H., Bedford, Rachael, Gliga, Teodora, Charman, Tony, Johnson, Mark H., Baron-Cohen, S., Blasi, A., Bolton, P., Cheung, H. M. C., Davies, K., Elsabbagh, M., Fernandes, J., Gammer, I., Green, J., Guiraud, J., Lloyd-Fox, S., Liew, M., Maris, H., O'Hara, L., Pasco, G., Pickles, A., Ribeiro, H., Salomone, E., Tucker, L., Wass, S., Hendry, A, Jones, E, Bedford, R, Gliga, T, Charman, T, Johnson, M, Baron-Cohen, S, Blasi, A, Bolton, P, Cheung, H, Davies, K, Elsabbagh, M, Fernandes, J, Gammer, I, Green, J, Guiraud, J, Lloyd-Fox, S, Liew, M, Maris, H, O'Hara, L, Pasco, G, Pickles, A, Ribeiro, H, Salomone, E, Tucker, L, Wass, S, Hendry, Alexandra, Jones, Emily J. H., Bedford, Rachael, Gliga, Teodora, Charman, Tony, Johnson, Mark H., Baron-Cohen, S., Blasi, A., Bolton, P., Cheung, H. M. C., Davies, K., Elsabbagh, M., Fernandes, J., Gammer, I., Green, J., Guiraud, J., Lloyd-Fox, S., Liew, M., Maris, H., O'Hara, L., Pasco, G., Pickles, A., Ribeiro, H., Salomone, E., Tucker, L., and Wass, S.
Abstract: Background: Difficulties with executive functioning (EF) are common in individuals with a range of developmental disorders, including autism spectrum disorder (ASD). Interventions that target underlying mechanisms of EF early in development could be broadly beneficial, but require infant markers of such mechanisms in order to be feasible. Prospective studies of infants at high familial risk (HR) for ASD have revealed a surprising tendency for HR toddlers to show longer epochs of attention to faces than low-risk (LR) controls. In typical development, decreases in look durations towards the end of the first year of life are driven by the development of executive attention - a foundational component of EF. Here, we test the hypothesis that prolonged attention to visual stimuli (including faces) in HR toddlers reflects early differences in the development of executive attention. Methods: In a longitudinal prospective study, we used eye-tracking to record HR and LR infants' looking behaviour to social and non-social visual stimuli at ages 9 and 15 months. At age 3 years, we assessed children with a battery of clinical research measures and collected parental report of effortful control (EC) - a temperament trait closely associated with EF and similarly contingent on executive attention. Results: Consistent with previous studies, we found an attenuated reduction in peak look durations to faces between 9 and 15 months for the HR group compared with the LR group, and lower EC amongst the HR-ASD group. In line with our hypothesis, change in peak look duration to faces between 9 and 15 months was negatively associated with EC at age 3. Conclusions: We suggest that for HR toddlers, disruption to the early development of executive attention results in an attenuated reduction in looking time to faces. Effects may be more apparent for faces due to early biases to orient towards them; further, attention difficulties may interact with earlier emerging differences in social informat
Published: 2018

34. Enhanced pupillary light reflex in infancy is associated with autism diagnosis in toddlerhood

Author: Nyström, Pär, Gliga, Teodora, Nilsson Jobs, Elisabeth, Gredebäck, Gustaf, Charman, Tony, Johnson, Mark H., Bölte, Sven, Falck-Ytter, Terje, Nyström, Pär, Gliga, Teodora, Nilsson Jobs, Elisabeth, Gredebäck, Gustaf, Charman, Tony, Johnson, Mark H., Bölte, Sven, and Falck-Ytter, Terje
Abstract: Autism spectrum disorder (ASD) is a neurodevelopmental condition affecting around 1% of the population. We previously discovered that infant siblings of children with ASD had stronger pupillary light reflexes compared to low-risk infants, a result which contrasts sharply with the weak pupillary light reflex typically seen in both children and adults with ASD. Here, we show that on average the relative constriction of the pupillary light reflex is larger in 9–10-month-old high risk infant siblings who receive an ASD diagnosis at 36 months, compared both to those who do not and to low-risk controls. We also found that the magnitude of the pupillary light reflex in infancy is associated with symptom severity at follow-up. This study indicates an important role of sensory atypicalities in the etiology of ASD, and suggests that pupillometry, if further developed and refined, could facilitate risk assessment in infants.
Published: 2018
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35. Adaptive Behaviour and Cognitive Skills: Stability and Change from 7 Months to 7 Years in Siblings at High Familial Risk of Autism Spectrum Disorder

Author: Salomone, E, Shephard, E, Milosavljevic, B, Johnson, M, Charman, T, Baron-Cohen, S, Bedford, R, Bolton, P, Chandler, S, Elsabbagh, M, Fernandes, J, Garwood, H, Gliga, T, Hudry, K, Jones, E, Pasco, G, Pickles, A, Tucker, L, Volein, A, Salomone, Erica, Shephard, Elizabeth, Milosavljevic, Bosiljka, Johnson, Mark H., Charman, Tony, Baron-Cohen, Simon, Bedford, Rachael, Bolton, Patrick, Chandler, Susie, Elsabbagh, Mayada, Fernandes, Janice, Garwood, Holly, Gliga, Teodora, Hudry, Kristelle, Jones, Emily J. H., Pasco, Greg, Pickles, Andrew, Tucker, Leslie, Volein, Agnes, Salomone, E, Shephard, E, Milosavljevic, B, Johnson, M, Charman, T, Baron-Cohen, S, Bedford, R, Bolton, P, Chandler, S, Elsabbagh, M, Fernandes, J, Garwood, H, Gliga, T, Hudry, K, Jones, E, Pasco, G, Pickles, A, Tucker, L, Volein, A, Salomone, Erica, Shephard, Elizabeth, Milosavljevic, Bosiljka, Johnson, Mark H., Charman, Tony, Baron-Cohen, Simon, Bedford, Rachael, Bolton, Patrick, Chandler, Susie, Elsabbagh, Mayada, Fernandes, Janice, Garwood, Holly, Gliga, Teodora, Hudry, Kristelle, Jones, Emily J. H., Pasco, Greg, Pickles, Andrew, Tucker, Leslie, and Volein, Agnes
Abstract: Cognitive and adaptive behaviour abilities early in life provide important clinical prognostic information. We examined stability of such skills in children at high familial risk for ASD who either met diagnostic criteria for ASD at age 7 years (HR-ASD, n = 15) or did not (HR-non-ASD, n = 24) and low-risk control children (LR, n = 37), prospectively studied from infancy. For both HR groups, cognitive skills were consistently lower across time than those of LR children. HR-ASD children showed increasing difficulties in adaptive behaviour over time compared to LR children, while the HR-non-ASD children showed no such difficulties. This pattern of change may inform our understanding of developmental profiles of HR siblings beyond core ASD symptoms.
Published: 2018

36. Hand, spoon or toothbrush? Towards the understanding of the neuralunderpinnings of affective touch in 5 months-old infants.

Author: Pirazzoli, Laura, Pirazzoli, Laura, Lloyd-Fox, Sarah, Johnson, Mark H., Gliga, Teodora, Pirazzoli, Laura, Pirazzoli, Laura, Lloyd-Fox, Sarah, Johnson, Mark H., and Gliga, Teodora
Abstract: It is known that affective touch leads to broad cortical activations including posterior STS, key region of the so-cial brain. Our goal is to discover if a similar pattern of activation can be observed in 5-months-old infants, or whether thedevelopment of this cortical specialization results from extensive postnatal experience.Over two studies we used functional-Near-InfraRed-Spectroscopy (fNIRS) to compare social touch (a human caress) tonon-social touch (a caress performed with a spoon in study1 -n=22- or with an electric toothbrush in study2 -n=17-).In study1 we found similar patterns of activation to the social and non-social stimulus. In study2 we report broad responsesto the non-social stimulus, but, to our surprise, we found no activations to the human caress.In light of these results we conclude that it is possible that at this age discrimination between social and non-social touch inthe posterior temporal lobe is still undergoing specialization.
Published: 2017

37. Early Visual Evoked Potentials (VEPs) in Infant Siblings of Children with ASD,ADHD and Age-Matched Controls

Author: Piccardi, Elena Serena, Piccardi, Elena Serena, Johnson, Mark H., Gliga, Teodora, Piccardi, Elena Serena, Piccardi, Elena Serena, Johnson, Mark H., and Gliga, Teodora
Abstract: Atypicalities in sensory perception are observed in individuals diagnosed with ASD and ADHD but have rarely beencontrasted in experimental studies. In the visual domain, superior performance on visual search tasks and hypersensitivity toflickering lights have been cited as evidence of unusual sensory profiles.To measure a reliable visual response, black-and-white checkerboards were presented under free-viewing conditions to threegroups of 10-month-olds: siblings of children with ASD (N=47), ADHD (N=21) and controls (N=18). Continuous EEG wasrecorded and VEPs time-locked to checkerboards presentation computed.Analysis of VEPs amplitude and latency revealed statistically significant group differences in the first 200ms post-stimulusonset. Early components were enhanced in amplitude (P100) and delayed in latency (P100-N100) in at-risk infants comparedto controls (p<.05).Atypical VEPs to low-level information might index a domain-general aberration in at-risk populations. The nature of thisatypicality will be further investigated by analyzing its association with background EEG.
Published: 2017

38. How does social touch modulate arousal states? An investigation in earlydevelopment.

Author: Pirazzoli, Laura, Pirazzoli, Laura, Jones, Emily, Gliga, Teodora, Johnson, Mark H., Pirazzoli, Laura, Pirazzoli, Laura, Jones, Emily, Gliga, Teodora, and Johnson, Mark H.
Abstract: Caregiver-infant interaction through touch was shown to have long-term effects on child’s cognitive development,but the mechanisms are poorly understood. Our aim is to investigate how affective touch (slow gentle caressing) affects arousalstates in young infants. Previous work showed that slow-touch decreases heart rate in 9-month-old infants.We tested two groups of 6-months-old (n=26) and 9-months-old infants (n=23). We measured heart rate and saccadic reactiontime while infants performed a visual orienting task, where speed of re-orienting from a central fixation to a peripheral targetwas measured. During the experiment, infants received either slow or fast-touch on their back in blocked trials. We found noeffects of touch on heart rate in either age-group, and only marginal effects of slow-touch on reaction times in 9-month-oldinfants. We are currently testing 2 months-old infants to investigate if these effects are observed earlier in life; these new resultswill be discussed.
Published: 2017

39. The EU-AIMS Longitudinal European Autism Project (LEAP) : design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders.

Author: Loth, Eva, Charman, Tony, Mason, Luke, Tillmann, Julian, Jones, Emily J H, Wooldridge, Caroline, Ahmad, Jumana, Auyeung, Bonnie, Brogna, Claudia, Ambrosino, Sara, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Brammer, Michael, Brandeis, Daniel, Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, de Bruijn, Yvette, Chakrabarti, Bhismadev, Crawley, Daisy, Cornelissen, Ineke, Acqua, Flavio Dell', Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garces, Pilar, Goyard, David, Hayward, Hannah, Ham, Lindsay M, Hipp, Joerg, Holt, Rosemary J, Johnson, Mark H, Isaksson, Johan, Kundu, Prantik, Lai, Meng-Chuan, D'ardhuy, Xavier Liogier, Lombardo, Michael V, Lythgoe, David J, Mandl, René, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M, Ruigrok, Amber N V, Ruggeri, Barbara, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San José, Simonoff, Emily, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C R, Zwiers, Marcel P, Spooren, Will, Murphy, Declan G M, Buitelaar, Jan K, Loth, Eva, Charman, Tony, Mason, Luke, Tillmann, Julian, Jones, Emily J H, Wooldridge, Caroline, Ahmad, Jumana, Auyeung, Bonnie, Brogna, Claudia, Ambrosino, Sara, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Brammer, Michael, Brandeis, Daniel, Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, de Bruijn, Yvette, Chakrabarti, Bhismadev, Crawley, Daisy, Cornelissen, Ineke, Acqua, Flavio Dell', Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garces, Pilar, Goyard, David, Hayward, Hannah, Ham, Lindsay M, Hipp, Joerg, Holt, Rosemary J, Johnson, Mark H, Isaksson, Johan, Kundu, Prantik, Lai, Meng-Chuan, D'ardhuy, Xavier Liogier, Lombardo, Michael V, Lythgoe, David J, Mandl, René, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M, Ruigrok, Amber N V, Ruggeri, Barbara, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San José, Simonoff, Emily, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C R, Zwiers, Marcel P, Spooren, Will, Murphy, Declan G M, and Buitelaar, Jan K
Abstract: BACKGROUND: The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD. METHODS: LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability. RESULTS: Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some 'lessons learnt'. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted). CONCLUSION: We expect that LEAP wil
Published: 2017
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40. The EU-AIMS Longitudinal European Autism Project (LEAP) : clinical characterisation.

Author: Charman, Tony, Loth, Eva, Tillmann, Julian, Crawley, Daisy, Wooldridge, Caroline, Goyard, David, Ahmad, Jumana, Auyeung, Bonnie, Ambrosino, Sara, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, de Bruijn, Yvette, Chakrabarti, Bhismadev, Cornelissen, Ineke, Acqua, Flavio Dell', Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garcés, Pilar, Ham, Lindsay, Hayward, Hannah, Hipp, Joerg, Holt, Rosemary J, Isaksson, Johan, Johnson, Mark H, Jones, Emily J H, Kundu, Prantik, Lai, Meng-Chuan, D'ardhuy, Xavier Liogier, Lombardo, Michael V, Lythgoe, David J, Mandl, René, Mason, Luke, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M, Ruggeri, Barbara, Ruigrok, Amber N V, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San Jóse, Simonoff, Emily, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C R, Zwiers, Marcel P, Spooren, Will, Murphy, Declan G M, Buitelaar, Jan K, Charman, Tony, Loth, Eva, Tillmann, Julian, Crawley, Daisy, Wooldridge, Caroline, Goyard, David, Ahmad, Jumana, Auyeung, Bonnie, Ambrosino, Sara, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, de Bruijn, Yvette, Chakrabarti, Bhismadev, Cornelissen, Ineke, Acqua, Flavio Dell', Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garcés, Pilar, Ham, Lindsay, Hayward, Hannah, Hipp, Joerg, Holt, Rosemary J, Isaksson, Johan, Johnson, Mark H, Jones, Emily J H, Kundu, Prantik, Lai, Meng-Chuan, D'ardhuy, Xavier Liogier, Lombardo, Michael V, Lythgoe, David J, Mandl, René, Mason, Luke, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M, Ruggeri, Barbara, Ruigrok, Amber N V, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San Jóse, Simonoff, Emily, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C R, Zwiers, Marcel P, Spooren, Will, Murphy, Declan G M, and Buitelaar, Jan K
Abstract: BACKGROUND: The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study on biomarkers for autism spectrum disorder (ASD). The current paper describes the clinical characteristics of the LEAP cohort and examines age, sex and IQ differences in ASD core symptoms and common co-occurring psychiatric symptoms. A companion paper describes the overall design and experimental protocol and outlines the strategy to identify stratification biomarkers. METHODS: From six research centres in four European countries, we recruited 437 children and adults with ASD and 300 controls between the ages of 6 and 30 years with IQs varying between 50 and 148. We conducted in-depth clinical characterisation including a wide range of observational, interview and questionnaire measures of the ASD phenotype, as well as co-occurring psychiatric symptoms. RESULTS: The cohort showed heterogeneity in ASD symptom presentation, with only minimal to moderate site differences on core clinical and cognitive measures. On both parent-report interview and questionnaire measures, ASD symptom severity was lower in adults compared to children and adolescents. The precise pattern of differences varied across measures, but there was some evidence of both lower social symptoms and lower repetitive behaviour severity in adults. Males had higher ASD symptom scores than females on clinician-rated and parent interview diagnostic measures but not on parent-reported dimensional measures of ASD symptoms. In contrast, self-reported ASD symptom severity was higher in adults compared to adolescents, and in adult females compared to males. Higher scores on ASD symptom measures were moderately associated with lower IQ. Both inattentive and hyperactive/impulsive ADHD symptoms were lower in adults than in children and adolescents, and males with ASD had higher levels of inattentive and hyperactive/impulsive ADHD symptoms than females. CONCLUSIONS: The esta
Published: 2017
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41. The EU-AIMS Longitudinal European Autism Project (LEAP) : clinical characterisation.

Author: Charman, Tony, Loth, Eva, Tillmann, Julian, Crawley, Daisy, Wooldridge, Caroline, Goyard, David, Ahmad, Jumana, Auyeung, Bonnie, Ambrosino, Sara, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, de Bruijn, Yvette, Chakrabarti, Bhismadev, Cornelissen, Ineke, Acqua, Flavio Dell', Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garcés, Pilar, Ham, Lindsay, Hayward, Hannah, Hipp, Joerg, Holt, Rosemary J, Isaksson, Johan, Johnson, Mark H, Jones, Emily J H, Kundu, Prantik, Lai, Meng-Chuan, D'ardhuy, Xavier Liogier, Lombardo, Michael V, Lythgoe, David J, Mandl, René, Mason, Luke, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M, Ruggeri, Barbara, Ruigrok, Amber N V, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San Jóse, Simonoff, Emily, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C R, Zwiers, Marcel P, Spooren, Will, Murphy, Declan G M, Buitelaar, Jan K, Charman, Tony, Loth, Eva, Tillmann, Julian, Crawley, Daisy, Wooldridge, Caroline, Goyard, David, Ahmad, Jumana, Auyeung, Bonnie, Ambrosino, Sara, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, de Bruijn, Yvette, Chakrabarti, Bhismadev, Cornelissen, Ineke, Acqua, Flavio Dell', Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garcés, Pilar, Ham, Lindsay, Hayward, Hannah, Hipp, Joerg, Holt, Rosemary J, Isaksson, Johan, Johnson, Mark H, Jones, Emily J H, Kundu, Prantik, Lai, Meng-Chuan, D'ardhuy, Xavier Liogier, Lombardo, Michael V, Lythgoe, David J, Mandl, René, Mason, Luke, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M, Ruggeri, Barbara, Ruigrok, Amber N V, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San Jóse, Simonoff, Emily, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C R, Zwiers, Marcel P, Spooren, Will, Murphy, Declan G M, and Buitelaar, Jan K
Abstract: BACKGROUND: The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study on biomarkers for autism spectrum disorder (ASD). The current paper describes the clinical characteristics of the LEAP cohort and examines age, sex and IQ differences in ASD core symptoms and common co-occurring psychiatric symptoms. A companion paper describes the overall design and experimental protocol and outlines the strategy to identify stratification biomarkers. METHODS: From six research centres in four European countries, we recruited 437 children and adults with ASD and 300 controls between the ages of 6 and 30 years with IQs varying between 50 and 148. We conducted in-depth clinical characterisation including a wide range of observational, interview and questionnaire measures of the ASD phenotype, as well as co-occurring psychiatric symptoms. RESULTS: The cohort showed heterogeneity in ASD symptom presentation, with only minimal to moderate site differences on core clinical and cognitive measures. On both parent-report interview and questionnaire measures, ASD symptom severity was lower in adults compared to children and adolescents. The precise pattern of differences varied across measures, but there was some evidence of both lower social symptoms and lower repetitive behaviour severity in adults. Males had higher ASD symptom scores than females on clinician-rated and parent interview diagnostic measures but not on parent-reported dimensional measures of ASD symptoms. In contrast, self-reported ASD symptom severity was higher in adults compared to adolescents, and in adult females compared to males. Higher scores on ASD symptom measures were moderately associated with lower IQ. Both inattentive and hyperactive/impulsive ADHD symptoms were lower in adults than in children and adolescents, and males with ASD had higher levels of inattentive and hyperactive/impulsive ADHD symptoms than females. CONCLUSIONS: The esta
Published: 2017
Full Text: View/download PDF

42. The EU-AIMS Longitudinal European Autism Project (LEAP) : design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders.

Author: Loth, Eva, Charman, Tony, Mason, Luke, Tillmann, Julian, Jones, Emily J H, Wooldridge, Caroline, Ahmad, Jumana, Auyeung, Bonnie, Brogna, Claudia, Ambrosino, Sara, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Brammer, Michael, Brandeis, Daniel, Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, de Bruijn, Yvette, Chakrabarti, Bhismadev, Crawley, Daisy, Cornelissen, Ineke, Acqua, Flavio Dell', Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garces, Pilar, Goyard, David, Hayward, Hannah, Ham, Lindsay M, Hipp, Joerg, Holt, Rosemary J, Johnson, Mark H, Isaksson, Johan, Kundu, Prantik, Lai, Meng-Chuan, D'ardhuy, Xavier Liogier, Lombardo, Michael V, Lythgoe, David J, Mandl, René, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M, Ruigrok, Amber N V, Ruggeri, Barbara, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San José, Simonoff, Emily, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C R, Zwiers, Marcel P, Spooren, Will, Murphy, Declan G M, Buitelaar, Jan K, Loth, Eva, Charman, Tony, Mason, Luke, Tillmann, Julian, Jones, Emily J H, Wooldridge, Caroline, Ahmad, Jumana, Auyeung, Bonnie, Brogna, Claudia, Ambrosino, Sara, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Brammer, Michael, Brandeis, Daniel, Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, de Bruijn, Yvette, Chakrabarti, Bhismadev, Crawley, Daisy, Cornelissen, Ineke, Acqua, Flavio Dell', Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garces, Pilar, Goyard, David, Hayward, Hannah, Ham, Lindsay M, Hipp, Joerg, Holt, Rosemary J, Johnson, Mark H, Isaksson, Johan, Kundu, Prantik, Lai, Meng-Chuan, D'ardhuy, Xavier Liogier, Lombardo, Michael V, Lythgoe, David J, Mandl, René, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M, Ruigrok, Amber N V, Ruggeri, Barbara, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San José, Simonoff, Emily, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C R, Zwiers, Marcel P, Spooren, Will, Murphy, Declan G M, and Buitelaar, Jan K
Abstract: BACKGROUND: The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD. METHODS: LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability. RESULTS: Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some 'lessons learnt'. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted). CONCLUSION: We expect that LEAP wil
Published: 2017
Full Text: View/download PDF

43. The EU-AIMS Longitudinal European Autism Project (LEAP) : clinical characterisation.

Author: Charman, Tony, Loth, Eva, Tillmann, Julian, Crawley, Daisy, Wooldridge, Caroline, Goyard, David, Ahmad, Jumana, Auyeung, Bonnie, Ambrosino, Sara, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, de Bruijn, Yvette, Chakrabarti, Bhismadev, Cornelissen, Ineke, Acqua, Flavio Dell', Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garcés, Pilar, Ham, Lindsay, Hayward, Hannah, Hipp, Joerg, Holt, Rosemary J, Isaksson, Johan, Johnson, Mark H, Jones, Emily J H, Kundu, Prantik, Lai, Meng-Chuan, D'ardhuy, Xavier Liogier, Lombardo, Michael V, Lythgoe, David J, Mandl, René, Mason, Luke, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M, Ruggeri, Barbara, Ruigrok, Amber N V, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San Jóse, Simonoff, Emily, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C R, Zwiers, Marcel P, Spooren, Will, Murphy, Declan G M, Buitelaar, Jan K, Charman, Tony, Loth, Eva, Tillmann, Julian, Crawley, Daisy, Wooldridge, Caroline, Goyard, David, Ahmad, Jumana, Auyeung, Bonnie, Ambrosino, Sara, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, de Bruijn, Yvette, Chakrabarti, Bhismadev, Cornelissen, Ineke, Acqua, Flavio Dell', Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garcés, Pilar, Ham, Lindsay, Hayward, Hannah, Hipp, Joerg, Holt, Rosemary J, Isaksson, Johan, Johnson, Mark H, Jones, Emily J H, Kundu, Prantik, Lai, Meng-Chuan, D'ardhuy, Xavier Liogier, Lombardo, Michael V, Lythgoe, David J, Mandl, René, Mason, Luke, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M, Ruggeri, Barbara, Ruigrok, Amber N V, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San Jóse, Simonoff, Emily, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C R, Zwiers, Marcel P, Spooren, Will, Murphy, Declan G M, and Buitelaar, Jan K
Abstract: BACKGROUND: The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study on biomarkers for autism spectrum disorder (ASD). The current paper describes the clinical characteristics of the LEAP cohort and examines age, sex and IQ differences in ASD core symptoms and common co-occurring psychiatric symptoms. A companion paper describes the overall design and experimental protocol and outlines the strategy to identify stratification biomarkers. METHODS: From six research centres in four European countries, we recruited 437 children and adults with ASD and 300 controls between the ages of 6 and 30 years with IQs varying between 50 and 148. We conducted in-depth clinical characterisation including a wide range of observational, interview and questionnaire measures of the ASD phenotype, as well as co-occurring psychiatric symptoms. RESULTS: The cohort showed heterogeneity in ASD symptom presentation, with only minimal to moderate site differences on core clinical and cognitive measures. On both parent-report interview and questionnaire measures, ASD symptom severity was lower in adults compared to children and adolescents. The precise pattern of differences varied across measures, but there was some evidence of both lower social symptoms and lower repetitive behaviour severity in adults. Males had higher ASD symptom scores than females on clinician-rated and parent interview diagnostic measures but not on parent-reported dimensional measures of ASD symptoms. In contrast, self-reported ASD symptom severity was higher in adults compared to adolescents, and in adult females compared to males. Higher scores on ASD symptom measures were moderately associated with lower IQ. Both inattentive and hyperactive/impulsive ADHD symptoms were lower in adults than in children and adolescents, and males with ASD had higher levels of inattentive and hyperactive/impulsive ADHD symptoms than females. CONCLUSIONS: The esta
Published: 2017
Full Text: View/download PDF

44. The EU-AIMS Longitudinal European Autism Project (LEAP) : design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders.

Author: Loth, Eva, Charman, Tony, Mason, Luke, Tillmann, Julian, Jones, Emily J H, Wooldridge, Caroline, Ahmad, Jumana, Auyeung, Bonnie, Brogna, Claudia, Ambrosino, Sara, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Brammer, Michael, Brandeis, Daniel, Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, de Bruijn, Yvette, Chakrabarti, Bhismadev, Crawley, Daisy, Cornelissen, Ineke, Acqua, Flavio Dell', Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garces, Pilar, Goyard, David, Hayward, Hannah, Ham, Lindsay M, Hipp, Joerg, Holt, Rosemary J, Johnson, Mark H, Isaksson, Johan, Kundu, Prantik, Lai, Meng-Chuan, D'ardhuy, Xavier Liogier, Lombardo, Michael V, Lythgoe, David J, Mandl, René, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M, Ruigrok, Amber N V, Ruggeri, Barbara, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San José, Simonoff, Emily, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C R, Zwiers, Marcel P, Spooren, Will, Murphy, Declan G M, Buitelaar, Jan K, Loth, Eva, Charman, Tony, Mason, Luke, Tillmann, Julian, Jones, Emily J H, Wooldridge, Caroline, Ahmad, Jumana, Auyeung, Bonnie, Brogna, Claudia, Ambrosino, Sara, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Brammer, Michael, Brandeis, Daniel, Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, de Bruijn, Yvette, Chakrabarti, Bhismadev, Crawley, Daisy, Cornelissen, Ineke, Acqua, Flavio Dell', Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garces, Pilar, Goyard, David, Hayward, Hannah, Ham, Lindsay M, Hipp, Joerg, Holt, Rosemary J, Johnson, Mark H, Isaksson, Johan, Kundu, Prantik, Lai, Meng-Chuan, D'ardhuy, Xavier Liogier, Lombardo, Michael V, Lythgoe, David J, Mandl, René, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M, Ruigrok, Amber N V, Ruggeri, Barbara, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San José, Simonoff, Emily, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C R, Zwiers, Marcel P, Spooren, Will, Murphy, Declan G M, and Buitelaar, Jan K
Abstract: BACKGROUND: The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD. METHODS: LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability. RESULTS: Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some 'lessons learnt'. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted). CONCLUSION: We expect that LEAP wil
Published: 2017
Full Text: View/download PDF

45. The EU-AIMS Longitudinal European Autism Project (LEAP) : Clinical characterisation

Author: Charman, Tony, Loth, Eva, Tillmann, Julian, Crawley, Daisy, Wooldridge, Caroline, Goyard, David, Ahmad, Jumana, Auyeung, Bonnie, Ambrosino, Sara, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, De Bruijn, Yvette, Chakrabarti, Bhismadev, Cornelissen, Ineke, Acqua, Flavio Dell, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garcés, Pilar, Ham, Lindsay, Hayward, Hannah, Hipp, Joerg, Holt, Rosemary J., Isaksson, Johan, Johnson, Mark H., Jones, Emily J.H., Kundu, Prantik, Lai, Meng Chuan, D'Ardhuy, Xavier Liogier, Lombardo, Michael V., Lythgoe, David J, Mandl, René, Mason, Luke, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M., Ruggeri, Barbara, Ruigrok, Amber N V, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San Jóse, Simonoff, Emily, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C.R., Zwiers, Marcel P., Spooren, Will, Murphy, Declan G M, Buitelaar, Jan K., Charman, Tony, Loth, Eva, Tillmann, Julian, Crawley, Daisy, Wooldridge, Caroline, Goyard, David, Ahmad, Jumana, Auyeung, Bonnie, Ambrosino, Sara, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, De Bruijn, Yvette, Chakrabarti, Bhismadev, Cornelissen, Ineke, Acqua, Flavio Dell, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garcés, Pilar, Ham, Lindsay, Hayward, Hannah, Hipp, Joerg, Holt, Rosemary J., Isaksson, Johan, Johnson, Mark H., Jones, Emily J.H., Kundu, Prantik, Lai, Meng Chuan, D'Ardhuy, Xavier Liogier, Lombardo, Michael V., Lythgoe, David J, Mandl, René, Mason, Luke, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M., Ruggeri, Barbara, Ruigrok, Amber N V, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San Jóse, Simonoff, Emily, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C.R., Zwiers, Marcel P., Spooren, Will, Murphy, Declan G M, and Buitelaar, Jan K.
Published: 2017

46. The EU-AIMS Longitudinal European Autism Project (LEAP) : Design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders

Author: Loth, Eva, Charman, Tony, Mason, Luke, Tillmann, Julian, Jones, Emily J.H., Wooldridge, Caroline, Ahmad, Jumana, Auyeung, Bonnie, Brogna, Claudia, Ambrosino, Sara, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Brammer, Michael, Brandeis, Daniel, Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, De Bruijn, Yvette, Chakrabarti, Bhismadev, Crawley, Daisy, Cornelissen, Ineke, Acqua, Flavio Dell, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garces, Pilar, Goyard, David, Hayward, Hannah, Ham, Lindsay M., Hipp, Joerg, Holt, Rosemary J., Johnson, Mark H., Isaksson, Johan, Kundu, Prantik, Lai, Meng Chuan, D'Ardhuy, Xavier Liogier, Lombardo, Michael V., Lythgoe, David J, Mandl, René, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M., Ruigrok, Amber N V, Ruggeri, Barbara, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San José, Simonoff, Emily, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C.R., Zwiers, Marcel P., Spooren, Will, Murphy, Declan G M, Buitelaar, Jan K., Loth, Eva, Charman, Tony, Mason, Luke, Tillmann, Julian, Jones, Emily J.H., Wooldridge, Caroline, Ahmad, Jumana, Auyeung, Bonnie, Brogna, Claudia, Ambrosino, Sara, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Brammer, Michael, Brandeis, Daniel, Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, De Bruijn, Yvette, Chakrabarti, Bhismadev, Crawley, Daisy, Cornelissen, Ineke, Acqua, Flavio Dell, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garces, Pilar, Goyard, David, Hayward, Hannah, Ham, Lindsay M., Hipp, Joerg, Holt, Rosemary J., Johnson, Mark H., Isaksson, Johan, Kundu, Prantik, Lai, Meng Chuan, D'Ardhuy, Xavier Liogier, Lombardo, Michael V., Lythgoe, David J, Mandl, René, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M., Ruigrok, Amber N V, Ruggeri, Barbara, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San José, Simonoff, Emily, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C.R., Zwiers, Marcel P., Spooren, Will, Murphy, Declan G M, and Buitelaar, Jan K.
Published: 2017

47. The EU-AIMS Longitudinal European Autism Project (LEAP) : Clinical characterisation

Author: Charman, Tony, Loth, Eva, Tillmann, Julian, Crawley, Daisy, Wooldridge, Caroline, Goyard, David, Ahmad, Jumana, Auyeung, Bonnie, Ambrosino, Sara, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, De Bruijn, Yvette, Chakrabarti, Bhismadev, Cornelissen, Ineke, Acqua, Flavio Dell, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garcés, Pilar, Ham, Lindsay, Hayward, Hannah, Hipp, Joerg, Holt, Rosemary J., Isaksson, Johan, Johnson, Mark H., Jones, Emily J.H., Kundu, Prantik, Lai, Meng Chuan, D'Ardhuy, Xavier Liogier, Lombardo, Michael V., Lythgoe, David J, Mandl, René, Mason, Luke, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M., Ruggeri, Barbara, Ruigrok, Amber N V, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San Jóse, Simonoff, Emily, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C.R., Zwiers, Marcel P., Spooren, Will, Murphy, Declan G M, Buitelaar, Jan K., Charman, Tony, Loth, Eva, Tillmann, Julian, Crawley, Daisy, Wooldridge, Caroline, Goyard, David, Ahmad, Jumana, Auyeung, Bonnie, Ambrosino, Sara, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, De Bruijn, Yvette, Chakrabarti, Bhismadev, Cornelissen, Ineke, Acqua, Flavio Dell, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garcés, Pilar, Ham, Lindsay, Hayward, Hannah, Hipp, Joerg, Holt, Rosemary J., Isaksson, Johan, Johnson, Mark H., Jones, Emily J.H., Kundu, Prantik, Lai, Meng Chuan, D'Ardhuy, Xavier Liogier, Lombardo, Michael V., Lythgoe, David J, Mandl, René, Mason, Luke, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M., Ruggeri, Barbara, Ruigrok, Amber N V, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San Jóse, Simonoff, Emily, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C.R., Zwiers, Marcel P., Spooren, Will, Murphy, Declan G M, and Buitelaar, Jan K.
Published: 2017

48. The EU-AIMS Longitudinal European Autism Project (LEAP) : Design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders

Author: Loth, Eva, Charman, Tony, Mason, Luke, Tillmann, Julian, Jones, Emily J.H., Wooldridge, Caroline, Ahmad, Jumana, Auyeung, Bonnie, Brogna, Claudia, Ambrosino, Sara, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Brammer, Michael, Brandeis, Daniel, Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, De Bruijn, Yvette, Chakrabarti, Bhismadev, Crawley, Daisy, Cornelissen, Ineke, Acqua, Flavio Dell, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garces, Pilar, Goyard, David, Hayward, Hannah, Ham, Lindsay M., Hipp, Joerg, Holt, Rosemary J., Johnson, Mark H., Isaksson, Johan, Kundu, Prantik, Lai, Meng Chuan, D'Ardhuy, Xavier Liogier, Lombardo, Michael V., Lythgoe, David J, Mandl, René, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M., Ruigrok, Amber N V, Ruggeri, Barbara, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San José, Simonoff, Emily, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C.R., Zwiers, Marcel P., Spooren, Will, Murphy, Declan G M, Buitelaar, Jan K., Loth, Eva, Charman, Tony, Mason, Luke, Tillmann, Julian, Jones, Emily J.H., Wooldridge, Caroline, Ahmad, Jumana, Auyeung, Bonnie, Brogna, Claudia, Ambrosino, Sara, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Brammer, Michael, Brandeis, Daniel, Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, De Bruijn, Yvette, Chakrabarti, Bhismadev, Crawley, Daisy, Cornelissen, Ineke, Acqua, Flavio Dell, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garces, Pilar, Goyard, David, Hayward, Hannah, Ham, Lindsay M., Hipp, Joerg, Holt, Rosemary J., Johnson, Mark H., Isaksson, Johan, Kundu, Prantik, Lai, Meng Chuan, D'Ardhuy, Xavier Liogier, Lombardo, Michael V., Lythgoe, David J, Mandl, René, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M., Ruigrok, Amber N V, Ruggeri, Barbara, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San José, Simonoff, Emily, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C.R., Zwiers, Marcel P., Spooren, Will, Murphy, Declan G M, and Buitelaar, Jan K.
Published: 2017

49. The EU-AIMS Longitudinal European Autism Project (LEAP) : Clinical characterisation

Author: Charman, Tony, Loth, Eva, Tillmann, Julian, Crawley, Daisy, Wooldridge, Caroline, Goyard, David, Ahmad, Jumana, Auyeung, Bonnie, Ambrosino, Sara, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, De Bruijn, Yvette, Chakrabarti, Bhismadev, Cornelissen, Ineke, Acqua, Flavio Dell, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garcés, Pilar, Ham, Lindsay, Hayward, Hannah, Hipp, Joerg, Holt, Rosemary J., Isaksson, Johan, Johnson, Mark H., Jones, Emily J.H., Kundu, Prantik, Lai, Meng Chuan, D'Ardhuy, Xavier Liogier, Lombardo, Michael V., Lythgoe, David J, Mandl, René, Mason, Luke, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M., Ruggeri, Barbara, Ruigrok, Amber N V, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San Jóse, Simonoff, Emily, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C.R., Zwiers, Marcel P., Spooren, Will, Murphy, Declan G M, Buitelaar, Jan K., Charman, Tony, Loth, Eva, Tillmann, Julian, Crawley, Daisy, Wooldridge, Caroline, Goyard, David, Ahmad, Jumana, Auyeung, Bonnie, Ambrosino, Sara, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, De Bruijn, Yvette, Chakrabarti, Bhismadev, Cornelissen, Ineke, Acqua, Flavio Dell, Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garcés, Pilar, Ham, Lindsay, Hayward, Hannah, Hipp, Joerg, Holt, Rosemary J., Isaksson, Johan, Johnson, Mark H., Jones, Emily J.H., Kundu, Prantik, Lai, Meng Chuan, D'Ardhuy, Xavier Liogier, Lombardo, Michael V., Lythgoe, David J, Mandl, René, Mason, Luke, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M., Ruggeri, Barbara, Ruigrok, Amber N V, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San Jóse, Simonoff, Emily, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C.R., Zwiers, Marcel P., Spooren, Will, Murphy, Declan G M, and Buitelaar, Jan K.
Published: 2017

50. The EU-AIMS Longitudinal European Autism Project (LEAP) : design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders.

Author: Loth, Eva, Charman, Tony, Mason, Luke, Tillmann, Julian, Jones, Emily J H, Wooldridge, Caroline, Ahmad, Jumana, Auyeung, Bonnie, Brogna, Claudia, Ambrosino, Sara, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Brammer, Michael, Brandeis, Daniel, Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, de Bruijn, Yvette, Chakrabarti, Bhismadev, Crawley, Daisy, Cornelissen, Ineke, Acqua, Flavio Dell', Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garces, Pilar, Goyard, David, Hayward, Hannah, Ham, Lindsay M, Hipp, Joerg, Holt, Rosemary J, Johnson, Mark H, Isaksson, Johan, Kundu, Prantik, Lai, Meng-Chuan, D'ardhuy, Xavier Liogier, Lombardo, Michael V, Lythgoe, David J, Mandl, René, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M, Ruigrok, Amber N V, Ruggeri, Barbara, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San José, Simonoff, Emily, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C R, Zwiers, Marcel P, Spooren, Will, Murphy, Declan G M, Buitelaar, Jan K, Loth, Eva, Charman, Tony, Mason, Luke, Tillmann, Julian, Jones, Emily J H, Wooldridge, Caroline, Ahmad, Jumana, Auyeung, Bonnie, Brogna, Claudia, Ambrosino, Sara, Banaschewski, Tobias, Baron-Cohen, Simon, Baumeister, Sarah, Beckmann, Christian, Brammer, Michael, Brandeis, Daniel, Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, de Bruijn, Yvette, Chakrabarti, Bhismadev, Crawley, Daisy, Cornelissen, Ineke, Acqua, Flavio Dell', Dumas, Guillaume, Durston, Sarah, Ecker, Christine, Faulkner, Jessica, Frouin, Vincent, Garces, Pilar, Goyard, David, Hayward, Hannah, Ham, Lindsay M, Hipp, Joerg, Holt, Rosemary J, Johnson, Mark H, Isaksson, Johan, Kundu, Prantik, Lai, Meng-Chuan, D'ardhuy, Xavier Liogier, Lombardo, Michael V, Lythgoe, David J, Mandl, René, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan, Persico, Antonio M, Ruigrok, Amber N V, Ruggeri, Barbara, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San José, Simonoff, Emily, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve C R, Zwiers, Marcel P, Spooren, Will, Murphy, Declan G M, and Buitelaar, Jan K
Abstract: BACKGROUND: The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD. METHODS: LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability. RESULTS: Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some 'lessons learnt'. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted). CONCLUSION: We expect that LEAP wil
Published: 2017
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