Logo: to the web site of Uppsala University

uu.sePublications from Uppsala University
Change search
Refine search result
1 - 7 of 7
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1. Charman, Tony
    et al.
    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
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry. Karolinska Inst KIND, Ctr Neurodev Disorders, Stockholm, Sweden.
    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
    The EU-AIMS Longitudinal European Autism Project (LEAP): clinical characterisation.2017In: Molecular Autism, ISSN 2040-2392, Vol. 8, article id 27Article in journal (Refereed)
    Abstract [en]

    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 established phenotypic heterogeneity in ASD is well captured in the LEAP cohort. Variation both in core ASD symptom severity and in commonly co-occurring psychiatric symptoms were systematically associated with sex, age and IQ. The pattern of ASD symptom differences with age and sex also varied by whether these were clinician ratings or parent- or self-reported which has important implications for establishing stratification biomarkers and for their potential use as outcome measures in clinical trials.

    Download full text (pdf)
    fulltext
  • 2.
    Isaksson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    Tammimies, Kristiina
    Neufeld, Janina
    Cauvet, Élodie
    Lundin, Karl
    Buitelaar, Jan K
    Loth, Eva
    Murphy, Declan G M
    Spooren, Will
    Bölte, Sven
    EU-AIMS Longitudinal European Autism Project (LEAP): the autism twin cohort2018In: Molecular Autism, ISSN 2040-2392, Vol. 9, article id 26Article in journal (Refereed)
    Abstract [en]

    EU-AIMS is the largest European research program aiming to identify stratification biomarkers and novel interventions for autism spectrum disorder (ASD). Within the program, the Longitudinal European Autism Project (LEAP) has recruited and comprehensively phenotyped a rare sample of 76 monozygotic and dizygotic twins, discordant, or concordant for ASD plus 30 typically developing twins. The aim of this letter is to complete previous descriptions of the LEAP case-control sample, clinically characterize, and investigate the suitability of the sample for ASD twin-control analyses purposes and share some 'lessons learnt.' Among the twins, a diagnosis of ASD is associated with increased symptom levels of ADHD, higher rates of intellectual disability, and lower family income. For the future, we conclude that the LEAP twin cohort offers multiple options for analyses of genetic and shared and non-shared environmental factors to generate new hypotheses for the larger cohort of LEAP singletons, but particularly cross-validate and refine evidence from it.

    Download full text (pdf)
    fulltext
  • 3.
    Liepinsh, Edgars
    et al.
    Latvian Inst Organ Synth, Riga, Latvia.;Riga Stradins Univ, Riga, Latvia..
    Svalbe, Baiba
    Latvian Inst Organ Synth, Riga, Latvia..
    Stelfa, Gundega
    Latvian Inst Organ Synth, Riga, Latvia.;Latvia Univ Life Sci & Technol, Jelgava, Latvia..
    Grinberga, Solveiga
    Latvian Inst Organ Synth, Riga, Latvia..
    Zvejniece, Liga
    Latvian Inst Organ Synth, Riga, Latvia..
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Functional Pharmacology and Neuroscience.
    Dambrova, Maija
    Latvian Inst Organ Synth, Riga, Latvia.;Riga Stradins Univ, Riga, Latvia..
    Knockout of Tmlhe in mice is not associated with autism spectrum disorder phenotypes or motor dysfunction despite low carnitine levels2023In: Molecular Autism, ISSN 2040-2392, Vol. 14, no 1, article id 29Article in journal (Refereed)
    Abstract [en]

    Deletion of exon 2 of the trimethyllysine hydroxylase epsilon (TMLHE) gene was identified in probands with autism spectrum disorder (ASD). TMLHE encodes the first enzyme in carnitine biosynthesis, N6-trimethyllysine dioxygenase (TMLD). Researchers have suggested that carnitine depletion could be important for the development of ASD and cognitive, locomotor and social dysfunctions, but previous findings have been inconclusive regarding the specific role of endogenous carnitine. We developed a mouse knockout model with constitutive TMLD enzyme inactivation that exhibited a significant decrease in the carnitine by more than 90% compared to wild-type (WT) mice. However, we did not observe any significant social, cognitive, or repetitive-behavior changes associated with ASD in the knockout mice; muscle strength and coordination were also not affected. In addition, the life expectancy of knockout mice was similar to that of WT mice. In conclusion, knockout of Tmlh in mice does not induce an ASD phenotype or motor dysfunction despite extremely low carnitine and gamma-butyrobetaine concentrations. Moreover, inactivation of TMLD does not induce a phenotype similar to previously described primary carnitine deficiency; indeed, our results showed that low levels of carnitine sustained adequate energy production, muscle function and social behavior in mice.

    Download full text (pdf)
    FULLTEXT01
  • 4. Loth, Eva
    et al.
    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
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry. Karolinska Inst KIND, Ctr Neurodev Disorders, Stockholm, Sweden.
    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
    The EU-AIMS Longitudinal European Autism Project (LEAP): design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders.2017In: Molecular Autism, ISSN 2040-2392, Vol. 8, article id 24Article in journal (Refereed)
    Abstract [en]

    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 will enable us to confirm, reject and refine current hypotheses of neurocognitive/neurobiological abnormalities, identify biologically and clinically meaningful ASD subgroups, and help us map phenotypic heterogeneity to different aetiologies.

    Download full text (pdf)
    fulltext
  • 5. Mason, L.
    et al.
    Shic, F.
    Falck-Ytter, Terje
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Uppsala University, Swedish Collegium for Advanced Study (SCAS). Center of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research, Department of Women’s and Children’s Health, Karolinska Institutet.;Child and Adolescent Psychiatry, Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden..
    Chakrabarti, B.
    Charman, T.
    Loth, E.
    Tillmann, J.
    Banaschewski, T.
    Baron-Cohen, S.
    Bölte, S.
    Buitelaar, J.
    Durston, S.
    Oranje, B.
    Persico, A. M.
    Beckmann, C.
    Bougeron, T.
    Dell’Acqua, F.
    Ecker, C.
    Moessnang, C.
    Murphy, D.
    Johnson, M. H.
    Jones, E. J. H.
    Ahmad, Jumana
    Ambrosino, Sara
    Baumeister, Sarah
    Bours, Carsten
    Brammer, Michael
    Brandeis, Daniel
    Brogna, Claudia
    de Bruijn, Yvette
    Chatham, Chris
    Cornelissen, Ineke
    Crawley, Daisy
    Dumas, Guillaume
    Faulkner, Jessica
    Frouin, Vincent
    Garcés, Pilar
    Goyard, David
    Ham, Lindsay
    Hipp, Joerg
    Holt, Rosemary
    Lai, Meng-Chuan
    D’ardhuy, Xavier Liogier
    Lombardo, Michael V.
    Lythgoe, David J.
    Mandl, René
    Marquand, Andre
    Mennes, Maarten
    Meyer-Lindenberg, Andreas
    Bast, Nico
    Oakley, Bethany
    O’Dwyer, Laurence
    Oldehinkel, Marianne
    Pandina, Gahan
    Ruggeri, Barbara
    Ruigrok, Amber
    Sabet, Jessica
    Sacco, Roberto
    Cáceres, Antonia San José
    Simonoff, Emily
    Spooren, Will
    Toro, Roberto
    Tost, Heike
    Waldman, Jack
    Williams, Steve C. R.
    Wooldridge, Caroline
    Zwiers, Marcel P.
    Preference for biological motion is reduced in ASD: implications for clinical trials and the search for biomarkers2021In: Molecular Autism, ISSN 2040-2392, Vol. 12, article id 74Article in journal (Refereed)
    Abstract [en]

    Background: The neurocognitive mechanisms underlying autism spectrum disorder (ASD) remain unclear. Progress has been largely hampered by small sample sizes, variable age ranges and resulting inconsistent findings. There is a pressing need for large definitive studies to delineate the nature and extent of key case/control differences to direct research towards fruitful areas for future investigation. Here we focus on perception of biological motion, a promising index of social brain function which may be altered in ASD. In a large sample ranging from childhood to adulthood, we assess whether biological motion preference differs in ASD compared to neurotypical participants (NT), how differences are modulated by age and sex and whether they are associated with dimensional variation in concurrent or later symptomatology.

    Methods: Eye-tracking data were collected from 486 6-to-30-year-old autistic (N = 282) and non-autistic control (N = 204) participants whilst they viewed 28 trials pairing biological (BM) and control (non-biological, CTRL) motion. Preference for the biological motion stimulus was calculated as (1) proportion looking time difference (BM-CTRL) and (2) peak look duration difference (BM-CTRL).

    Results: The ASD group showed a present but weaker preference for biological motion than the NT group. The nature of the control stimulus modulated preference for biological motion in both groups. Biological motion preference did not vary with age, gender, or concurrent or prospective social communicative skill within the ASD group, although a lack of clear preference for either stimulus was associated with higher social-communicative symptoms at baseline.

    Limitations: The paired visual preference we used may underestimate preference for a stimulus in younger and lower IQ individuals. Our ASD group had a lower average IQ by approximately seven points. 18% of our sample was not analysed for various technical and behavioural reasons.

    Conclusions: Biological motion preference elicits small-to-medium-sized case–control effects, but individual differences do not strongly relate to core social autism associated symptomatology. We interpret this as an autistic difference (as opposed to a deficit) likely manifest in social brain regions. The extent to which this is an innate difference present from birth and central to the autistic phenotype, or the consequence of a life lived with ASD, is unclear.

    Download full text (pdf)
    fulltext
  • 6.
    Nyström, Pär
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Gredebäck, Gustaf
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Bolte, Sven
    Falck-Ytter, Terje
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Hypersensitive pupillary light reflex in infants at risk for autism2015In: Molecular Autism, ISSN 2040-2392, Vol. 6, article id 10Article in journal (Refereed)
    Abstract [en]

    Background: Post mortem brain tissue data and animal modeling work indicate cholinergic disruptions in autism. Moreover, the cholinergic system plays a key role in the early neurodevelopmental processes believed to be derailed early in life in individuals with the disorder. Yet, there is no data from human infants supporting a developmentally important role of this neurotransmitter system. Because the pupillary light reflex depends largely on cholinergic synaptic transmission, we assessed this reflex in a sample of infants at risk for autism as well as infants at low (average) risk. Methods: Ten-month-old infants with an older sibling with autism (n = 29, 16 females), and thus a genetic predisposition to developing the disorder themselves, were presented with white flashes on a computer monitor, and pupillary responses were captured using eye tracking. A control group matched on age and developmental level (n = 15, seven females) was also tested. Results: The siblings of children with autism had a faster and stronger pupillary light reflex compared to control infants. Baseline pupil diameter was equal in the two groups, ruling out tonic autonomic imbalance as an explanation for these differences. Conclusions: This study establishes that infant siblings of children with autism have hypersensitive pupillary light reflexes, a result which supports the view that altered sensory processing in infancy is associated with elevated autism risk. Moreover, the study indicates that individual differences in autism susceptibility are linked to differences in the cholinergic system during an early developmental period.

    Download full text (pdf)
    fulltext
  • 7.
    Thorup, Emilia
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Nyström, Pär
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Gredebäck, Gustaf
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Bölte, Sven
    Falck-Ytter, Terje
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Altered gaze following during live interaction in infants at risk for autism: An eye tracking study2016In: Molecular Autism, ISSN 2040-2392, Vol. 7, article id 12Article in journal (Refereed)
    Abstract [en]

    Background: The ability to follow gaze is an important prerequisite for joint attention, which is often compromised in children with autism spectrum disorder (ASD). The direction of both the head and eyes provides cues to other people's attention direction, but previous studies have not separated these factors and their relation to ASD susceptibility. Development of gaze following typically occurs before ASD diagnosis is possible, and studies of high-risk populations are therefore important. Methods: Eye tracking was used to assess gaze following during interaction in a group of 10-month-old infants at high familial risk for ASD (high-risk group) as well as a group of infants with no family history of ASD (low-risk group). The infants watched an experimenter gaze at objects in the periphery. Performance was compared across two conditions: one in which the experimenter moved both the eyes and head toward the objects (Eyes and Head condition) and one that involved movement of the eyes only (Eyes Only condition). Results: A group by condition interaction effect was found. Specifically, whereas gaze following accuracy was comparable across the two conditions in the low-risk group, infants in the high-risk group were more likely to follow gaze in the Eyes and Head condition than in the Eyes Only condition. Conclusions: In an ecologically valid social situation, responses to basic non-verbal orienting cues were found to be altered in infants at risk for ASD. The results indicate that infants at risk for ASD may rely disproportionally on information from the head when following gaze and point to the importance of separating information from the eyes and the head when studying social perception in ASD.

    Download full text (pdf)
    fulltext
1 - 7 of 7
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf