Jens Richardt Møllegaard Jepsen’s research while affiliated with Child and Adolescent Mental Health Services and other places

IMPORTANCE Maternal inflammation during pregnancy has been associated with an increased risk of neurodevelopmental disorders (NDDs), such as attention-deficit/hyperactivity disorder (ADHD) and autism, and cognitive deficits in early childhood. However, little is known about the contributions of a wider range of inflammatory proteins to this risk. OBJECTIVE To determine whether maternal inflammatory proteins during pregnancy are associated with the risk of NDDs and executive functions (EF) in middle childhood and to identify protein patterns associated with NDDs and EF. DESIGN, SETTING, AND PARTICIPANTS This was a 10-year follow-up cohort study of the Danish Copenhagen Prospective Studies on Asthma 2010 mother-child birth cohort, using plasma samples collected at week 24 in pregnancy, where 92 inflammatory proteins were assessed. NDDs and EF were assessed in the offspring at age 10 years, between January 2019 and December 2021. Mother-offspring dyads with available maternal prenatal inflammatory proteins during pregnancy and offspring NDD psychopathology data at follow-up were included. Data analyses took place between December 2023 and August 2024. EXPOSURES Levels of 92 inflammatory proteins from panel collected at week 24 during pregnancy. MAIN OUTCOMES AND MEASURES Categorical and dimensional psychopathology of NDDs (primary outcome) and EF (secondary outcome). RESULTS A total of 555 mothers (mean [SD] age, 32.4 [4.3] years) and their children (285 male [51%]) were included. The principal component analysis showed that higher levels of maternal inflammatory proteins depicted in principal component 1 were associated with a higher risk of any NDD (OR, 1.49; 95% CI, 1.15-1.94; P = .003), particularly autism (OR, 2.76; 95% CI, 1.45-5.63; P = .003) and ADHD with predominantly inattentive presentation (OR, 1.57; 95% CI, 1.05-2.39; P = .03). The single protein analysis showed that 18 of 92 proteins reached false discovery rate (FDR) 5% significance after adjustment. Vascular endothelial growth factor A, C-C motif chemokine ligand, CD5, interleukin 12B, fibroblast growth factor-23, and monocyte chemoattractant protein-1 emerged as top proteins associated with risk of NDDs. The sparse partial least squares approach identified 34 proteins associated with any NDD, and 39 with ADHD with predominantly inattentive presentation. There were no associations with EF after FDR correction. CONCLUSIONS AND RELEVANCE The maternal inflammatory proteome during pregnancy was associated with NDDs risks in offspring at age 10 years. Further research is warranted to elucidate the specific pathways involving these proteins during pregnancy that could be targeted with prevention strategies to reduce risk of NDDs in children.

Introduction Autism Spectrum Condition (ASC) is characterised by difficulties in social communication and interaction, which may pose significant challenges to daily functioning throughout life. While current diagnostic methods for ASC often rely on measures based on subjective reports, there is a growing need for objective, quantifiable measures to support current clinical assessment of ASC. Eye-tracking technology records eye and gaze movements in real time and provides a direct and objective method for assessing social attention. Integrating eye-tracking within virtual reality (VR) environments presents a novel approach for capturing gaze behaviour in dynamic, ecologically valid social scenarios. This study aims to investigate whether VR-based eye information can reveal group differences in gaze behaviour between autistic adults and neurotypical controls in simulated social interactions. Methods This case-control study will include 140 adults diagnosed with ASC and 50 neurotypical controls, matched by age and gender. Participants will engage in six VR-based social scenarios, which vary in social complexity and the presence of non-social distractors. Eye information will be measured using eye-tracking technology integrated into a head-mounted display. Gaze behaviour will be analysed through fixation-based metrics on parameters including number of fixations, mean fixation time, and dwell time, on predetermined Areas of Interest. Analysis Statistical analyses will assess between-group differences in gaze behaviour as well as correlations between gaze metrics and clinical measures of social functioning, social cognition and symptom severity. Discussion This study utilises VR-based eye-tracking to investigate novel paradigms for assessing gaze behaviour in ASC in immersive, interactive environments and aims to advance the current understanding of visual social attention in ASC. Positive outcomes from this study may support further research into VR- based eye-tracking to supplement existing clinical assessment methods.

Background Neurofibromatosis type 1 (NF1) is a genetic condition characterized by various somatic manifestations and cognitive impairments, but the latter are sparsely described in adults. This study aimed at characterizing potential impairments of neurocognitive functions using neuropsychological tests as well as a self-report questionnaire. Methods In a nationwide, population-based study including 103 adults with NF1 and 38 age- and gender-matched NF1-free comparisons, we used a comprehensive neurocognitive test battery to assess intelligence and visual short-term memory, immediate visuospatial recall, reaction time, sustained attention, motor speed, planning, planning time, working memory as well as multitasking and a questionnaire to assess executive functions. Descriptive statistics, multivariate analysis of variance (MANOVA), and general linear models with repeated measure analysis of variance (ANOVA) were used. Results We observed a statistically significant difference in overall performance-based cognitive functioning. Adults with NF1 showed significant, moderate-to-severe impairments in intelligence, visual short-term memory, immediate visuospatial recall, sustained attention ( p < 0.0001–0.002), and some executive functions ( p = 0.008 − 0.001), whereas other cognitive functions (multitasking, reaction time, motor speed, spatial working memory, planning time, and planning efficacy as well as some self-reported executive functions) were unimpaired. Conclusions This is the first study with a population-based sample of persons with NF1 and the results show impairments of intelligence and other cognitive functions. The pattern of both significant cognitive impairments and non-significantly different cognitive functions suggests a cognitive profile of selective rather than generalized cognitive deficits in NF1.

Background Children of parents with a severe mental illness have an increased risk of developing a lifetime mental illness. We aimed to compare the effects of a preventive family‐based intervention, VIA Family, with treatment as usual (TAU) on these children's global functioning. Methods Between 2017 and 2021, we conducted a pragmatic, rater‐blinded, two‐arm parallel‐group superiority trial in Denmark. Families with at least one child aged 6–12 years and at least one biological parent with schizophrenia spectrum disorder, bipolar disorder, or recurrent major or moderate depression were included. We randomly allocated 95 families with their 113 children to VIA Family or TAU (ratio 1:1). VIA Family was individually tailored and based on case management. The intervention included options for psychoeducation, parental support, and treatment for emerging child psychiatric symptoms. Blinded raters assessed children and their families at baseline and after 18 months. The primary outcome was the difference in change between groups at end‐of‐treatment in daily global functioning measured with the Children's Global Assessment Scale. Secondary outcomes were emotional and behavioral problems and days absent from school. We analyzed data blinded to allocation. Results At post‐intervention, differences in mean change from baseline between VIA Family and TAU were non‐significant (CGAS: −1.20, 95% CI = −6.61; 4.21, p = 0.66), as were the differences on the secondary and exploratory outcomes. Conclusion Contrary to our hypothesis, we did not find a superior effect of VIA Family compared with TAU. The short follow‐up period and large sample heterogeneity might explain the null findings. Therefore, a possible long‐term, preventive treatment effect has yet to be explored.

Atypical neurocognitive functioning has been found in adult patients with obsessive–compulsive disorder (OCD). However, little work has been done in children and adolescents with OCD. In this study, we investigated neurocognitive functioning in a large and representative sample of newly diagnosed children and adolescents with OCD compared to non-psychiatric controls. Children and adolescents with OCD (n = 119) and non-psychiatric controls (n = 90) underwent psychopathological assessment, intelligence testing, and a neurocognitive test battery spanning cognitive flexibility, planning and decision-making, working memory, fluency, and processing speed. The MANOVA main effect revealed that children and adolescents with OCD performed significantly worse than the control group (p < .001, ηp2${\eta }_{p}^{2}$ = 0.256). Atypical patient performance was particularly found for indices of cognitive flexibility, decision-making, working memory, and processing speed. We found no evidence of differences in planning or fluency. Moreover, we found no significant associations between neurocognitive performance and OCD symptom severity or comorbidity status. Our results indicate that children and adolescents with OCD show selective atypical neurocognitive functioning. These difficulties do not appear to drive their OCD symptoms. However, they may contribute to lifespan difficulties and interfere with treatment efficacy, an objective of our research currently.