Biology subjects

Happe, F.

Publications and source records attributed to Happe, F..

4 recordsLinked to original sources

bioRxiv2025

Epigenome-wide analysis reveals novel DNA methylation signatures significantly associated with the infant pupillary light reflex, a candidate intermediate phenotype for autism.

Autism is a highly heterogeneous neurodevelopmental condition, currently diagnosed based on behavioural characteristics. Candidate early intermediate phenotypes, such as the Pupillary Light Reflex (PLR), a reflexive constriction of the pupil in response to increased optical luminance, may provide insights into etiological factors and potential biomarkers, such as DNA methylation (DNAm), involved in the emergence of autism. We conducted epigenome-wide DNAm association analyses of 9-, 14-, 24-month PLR onset latency and constriction amplitude in a sample of 51 infants enriched for autism family history, using buccal DNA collected at 9-months. Our epigenome-wide analysis (EWAS) identified four stringently significant differentially methylated probes (p < 2.4 x 10-7) associated with cross-section PLR latency measurements at 14- and 24-months, and with 14-to 24-month PLR latency developmental change. Differentially methylated probes associated with PLR amplitude were identified, but at a less stringent discovery threshold (p < 5 x 10-5). Our region analyses identified several significant differentially methylated regions associated with both PLR latency and amplitude Downstream exploratory pathway analysis identified enrichment for multiple developmental biological processes, as well as several susceptibility genes to autism and related neurodevelopmental conditions including NR4A2, HNRNPU and NAV2. Our findings provide novel insight into the role of DNAm in PLR development and illuminate biological mechanisms underpinning altered PLR in infancy in emerging autism.

neuroscience↗

bioRxiv2022

Exploring cognitive, behavioural and autism trait network topology in very preterm and term-born children

Compared to full-term (FT) born peers, children who were born very preterm (VPT; <32 weeks gestation) are likely to display more cognitive and behavioural difficulties, including inattention, anxiety and socio-communication problems. In the published literature, such difficulties tend to be studied independently, thus failing to account for how different aspects of child development interact. The current study aimed to investigate childrens cognitive and behavioural outcomes as interconnected, dynamically related facets of development that influence one another. Participants were 93 VPT and 55 FT children (median age 8.79 years). IQ was evaluated with the Wechsler Intelligence Scale for Children - 4th edition (WISC-IV), autism spectrum condition (ASC) traits with the Social Responsiveness Scale - 2nd edition (SRS-2), behavioural and emotional problems with the Strengths and Difficulties Questionnaire (SDQ), temperament with the Temperament in Middle Childhood Questionnaire (TMCQ) and executive function with the Behaviour Rating Inventory of Executive Functioning (BRIEF-2). Outcome measures were studied in VPT and FT children using Network Analysis, a method that graphically represents partial correlations between variables and yields information on each variables propensity to form a bridge between other variables. Results showed that VPT and FT children exhibited marked topological differences. Bridges (i.e., the variables most connected to others) in the VPT group network were: SDQ Conduct Problems scale and BRIEF-2 Organisation of Materials scale. In the FT group network, the most important bridges were: the BRIEF-2 Initiate, SDQ Emotional Problems and SDQ Prosocial Behaviours scales. These findings highlight the importance of targeting different aspects of development to support VPT and FT children in person-based interventions.

developmental biology↗

bioRxiv2020

Sweet anticipation: Predictability of familiar music in autism

Autism has been characterised by different behavioural and cognitive profiles compared to typically developing (TD) individuals, and increasingly these differences have been associated with differences in structural and functional brain connectivity. It is currently unknown as to whether autistic and TD listeners process music in the same way: emotionally, mnemonically, and perceptually. The present study explores the brains dynamical landscape linked to music familiarity in an fMRI dataset from autistic and TD individuals. Group analysis using leading eigenvector dynamics analysis (LEiDA) revealed significantly higher probability of occurrence of a brain network in TD compared to autistic individuals during listening to familiar music. This network includes limbic and paralimbic areas (amygdala, hippocampus, parahippocampal gyrus, and temporal pole). No significant differences were found between autistic and TD individuals while listening to a scrambled, i.e. unfamiliar and more unpredictable, version of the same music track. These findings provide novel neuroimaging insights into how autistic prediction monitoring may shape brain networks during listening to familiar musical excerpts.

neuroscience↗

bioRxiv2019

ADHD symptoms and their neurodevelopmental correlates in children born very preterm

This study investigated the association between attention-deficit/hyperactivity disorder (ADHD) symptomatology in preschool-aged children who were born very preterm (<32 weeks) and cognitive outcomes, clinical risk and socio-demographic characteristics. 119 very preterm children who participated in the Evaluation of Preterm Imaging Study at term-equivalent age were assessed at a mean age of 4.5 years. Parents completed the ADHD Rating Scale IV, a norm-referenced checklist that evaluates ADHD symptomatology according to diagnostic criteria, and the Behavior Rating Inventory of Executive Function-Preschool version. Children completed the Wechsler Preschool and Primary Scales of Intelligence and the Forward Digit Span task. Longitudinal data including perinatal clinical, qualitative MRI classification, socio-demographic variables and neurodevelopmental disabilities were investigated in relation to ADHD symptomatology. All results were corrected for multiple comparisons using false discovery rate. Results showed that although the proportion of very preterm children with clinically significant ADHD did not differ from normative data after excluding those with neurodevelopmental disabilities, 32.7% met criteria for subthreshold ADHD inattentive type and 33.6% for combined type, which was higher than the expected 20% in normative samples. Higher ADHD symptom scores (all) were associated with greater executive dysfunction (inhibitory self-control, flexibility, and emergent metacognition, corrected p<0.001 for all tests). Higher inattentive ADHD symptom scores were associated with lower IQ ({rho}=-0.241, p=0.036) and higher perinatal clinical risk (more days on mechanical ventilation ({rho}=0.206, p=0.025) and more days on parenteral nutrition ({rho}=0.223, p=0.015)). Higher hyperactive ADHD symptom scores instead were associated with lower socio-economic status ({rho}=0.278, p=0.002). These results highlight the importance of monitoring and supporting the development of very preterm children throughout the school years, as subthreshold ADHD symptoms represent risk factors for psychosocial problems and for receiving a future clinical diagnosis of ADHD.

neuroscience↗