Kristiina Tammimies

Autismspektrumstörning (härifrån autism) med intellektuell funktionsnedsättning (IF) är en allvarlig neuropsykiatrisk funktionsnedsätting. Studier visar samstämt att barn till utrikesfödda har en påtagligt förhöjd risk, men att utrikesföddas barn använder tillgänglig vård i lägre utsträckning än barn till svenskfödda föräldrar. Med bakgrund i detta har vi två separata men sammanlänkade generella forskningsidéer. 1) Att studera de komplexa orsakerna till den ökade risk för autism med IF hos utrikesföddas barn för att minska riskerna. 2) Att samskapa, testa, utvärdera och implementera insatser för att öka kunskapen om autism med IF i högriskgrupper för att minska stigmatisering och öka användningen av tillgänglig vård. I Sverige har barn med somalisk härkomst, i linje med internationella studier, en påtagligt mycket högre förekomst av autism med IF jämfört med icke-somaliska barn. Somaliska föräldrar har en stark önskan att förstå varför förekomsten är så hög bland deras barn och att barnen ska få bättre hjälp och stöd. Syftet här är att tillsammans med somaliska föräldrar till barn med autism och IF, förgrundsgestalter inom den somaliska gruppen och vårdpersonal samskapa en färdplan för forskning. Arbetsplan, metoder och genomförande Projektet kommer att ha sin bas i Järva där många födda i Somalia bor. Inom projektet finns ett brett nätverk av personer med kunskap och kontakter. Tillsammans med tre somalisktalande forskarassistenter kommer vi under sommaren 2025 att göra fokusgruppsintervjuer. Resultaten av fokusgruppsintervjuerna kommer att publiceras i en rapport skriven på ett lättillgängligt språk och översättas till somaliska. Rapporten ska sedan att ligga till grund för en workshop följt av aktiviteter för att samskapa färdplanen. Samhällsrelevans och nyttiggörande Autism med IF innebär en allvarlig funktionsnedsättning med omfattande konsekvenser för den enskilde, personens familj och samhället. Barn med somalisk härkomst i höginkomstländer har en kraftigt ökad förekomst och deras föräldrar undrar varför deras barn är så oproportionerligt drabbade. Forskning om orsakerna till autism med IF och insatser för att barn med dessa funktionsnedsättningar att utvecklas optimalt måste inkludera och ta hjälp de drabbade för att inte förbise möjliga riskfaktorer men öka sannolikheten att forskningen kommer till nytta.

Autism is a neurodevelopmental condition diagnosed in 1-2% of children. Hundreds of genes have been implicated in autism, but a relatively low percentage of autistic individuals have an identifiable single-gene cause for their condition. A combination of other genetic information, such as polygenic risk scores (PRS), is not used in clinical settings yet. Additional investigations are needed to improve the use of genetic information, such as using biological information to improve the genetics scores. Limited information on the effects of high PRS on molecular and cellular phenotypes in neural development. Here, we aim to estimate better how to use biological information such as gene ontology to calculate genetic risk scores from both common and rare variants in autism. We specifically hypothesize that these genetic scores calculated for genes encoding for RNA regulators are associated with co-occurring conditions and severity. Furthermore, we will obtain the multi-omic profiles of neural cells and cerebral organoids generated from induced pluripotent stem cells of carriers with high common RNA regulator PRS and compare these with already available single-gene cellular models. Lastly, we will use genomic and molecular data to identify putative drug targets for subgroups in ASD. Our project will hopefully lead to a better understanding of autism at the genetic and molecular level and improve the use of the data in clinical settings.

ARID1B is the most frequently mutated single gene in neurodevelopmental disorders (NDDs) that are not inherited, with an approximated prevalence of one in 9,500 individuals. ARID1B-related disorder (ARID1B-RD) manifests in early childhood as moderate to severe developmental delay, and children and adults with the disorder have intellectual disability and are often diagnosed with autism alongside many other clinical signs. Despite ARID1B-RD’s high prevalence and extensive debilitating effects, the current understanding of how the disorder develops over time is strikingly limited. The proposed project will address this gap by employing a prospective longitudinal multi-method design. Specifically, we will monitor the development of 135 children and adolescents aged 2-18 with ARID1B-RD for 30 months. Monitoring will involve a) administration of standardized NDD assessments by clinicians complemented by caregivers’ reports

b) evaluation of biological aspects of ARID1B-RD, and c) collection daily life data via caregivers’ reports, and auditory and activity data using microphones and smartwatches. The project team brings a diverse complementary skills and collaborates with leading patient advocacy organizations. The project will generate a comprehensive picture of the progression of ARID1B-RD. The generated data will allow identifying and validating measurable targets for interventions, thus facilitating the development of effective treatments for thousands of children worldwide.

ARID1B is the most frequently mutated single gene among neurodevelopmental disorders (NDDs) that are not inherited, with an approximated prevalence of one in 9,500 individuals. ARID1B-related disorder (ARID1B-RD) manifests in early childhood as moderate to severe developmental delay, and children and adults with the disorder have intellectual disability (ID) and are often diagnosed with autism spectrum disorder along with many other clinical signs. Despite ARID1B-RD’s high prevalence and extensive debilitating effects, the current understanding of how the disorder develops over time is strikingly limited. The proposed project will address this gap by employing a prospective longitudinal multi-method design. Specifically, in six sites, we will monitor the development of 100 children and adolescents aged 2-18 with ARID1B-RD for three years. Monitoring will involve (a) administration of standardized NDD assessments complemented by ARID1B-RD-specific tools

(b) evaluation of biological aspects of ARID1B-RD (for example, electric brain activity)

and (c) collection of daily life data via caregivers’ reports, and audio and movement data using smartwatches and microphones. The project team brings a diverse set of complementary skills and collaborates with a leading patient advocacy organization. The project will generate a comprehensive picture of the progression of ARID1B-RD . The data will allow identifying and validating measurable targets for interventions, thus facilitating the development of effective treatments for thousands of children worldwide.

Preterm birth occurs in 6-12% of pregnancies globally. Intensive care of preterm infants has made major advance over the last decades resulting in dramatically increased survival rates for the most immature infants and a whole new generation of children entering school. While incidence of cerebral palsy decrease, the incidence of neurodevelopmental disorders including intellectual dysfunction, ADHD and autism spectrum disorder now increase and risks are related to immaturity at birth. In children born before 28 weeks´ gestation, two thirds eventually have neurodevelopmental impairments affecting their daily life and academic achievements. To improve outcomes, there is a need for identifying early signs of adverse brain development and to find effective early interventions.The overarching aim is to examine the relations between modifiable perinatal risks, family risk, brain development, neurodevelopment and neurodevelopmental outcomes in children born extremely preterm to improve early prediction and outcomes. In a randomized controlled study, we coach parents to support their preterm born infant´s development in the first year of life and then evaluate neurodevelopmental outcomes. Based on the study results and prediction models we plan to further individualize the intervention.

Autism is a neurodevelopmental condition diagnosed in 1-2% of children. Hundreds of genes have been implicated in autism, but a relatively low percentage of autistic individuals have an identifiable single-gene cause for their condition. A combination of other genetic information, such as polygenic risk scores (PRS), is not used in clinical settings yet. Additional investigations are needed to improve the use of genetic information, such as using biological information to improve the genetics scores. Limited information on the effects of high PRS on molecular and cellular phenotypes in neural development. Here, we aim to estimate better how to use biological information such as gene ontology to calculate genetic risk scores from both common and rare variants in autism. We specifically hypothesize that these genetic scores calculated for genes encoding for RNA regulators are associated with co-occurring conditions and severity. Furthermore, we will obtain the multi-omic profiles of neural cells and cerebral organoids generated from induced pluripotent stem cells of carriers with high common RNA regulator PRS and compare these with already available single-gene cellular models. Lastly, we will use genomic and molecular data to identify putative drug targets for subgroups in ASD. Our project will hopefully lead to a better understanding of autism at the genetic and molecular level and improve the use of the data in clinical settings.