THE PREDICTION OF SYMPTOM SEVERITY IN CHILDREN AND PARENTS IN A CLINICAL COHORT OF FAMILIES WITH CHILDREN WITH NEURODEVELOPMENTAL PROBLEMS

Neurodevelopmental issues in children, such as Attention Deficit Hyperactivity Disorder or Autism Disorder, tend to co-occur. Moreover, anxiety and depression symptoms are often present. Higher severity of symptoms and comorbidity are related to worse outcomes. Co-occurring parental symptoms at baseline are also associated with persistence of the children's symptoms as well as their own symptoms. To identify families at risk for an unfavourable course, a transdiagnostic, dimensional approach could be useful. We analysed data from 411 children and 475 parents that were assessed in a child development clinic in Australia for neurodevelopmental problems. In addition to genotype data, ADHD, ASD and depression symptoms were assessed in the children and ADHD, avoidant personality and depression symptoms in the parents. We explored the association with polygenic scores (PGS) based on the most recent genome wide association studies for psychiatric disorders, cross-disorder factors, gastro-oesophageal reflux diseases (GORD), Irritable Bowel Syndrome (IBS) and BMI. In the univariate analyses, ADHD, educational attainment, BMI, GORD, IBS and Factor 5 PGS associated with ADHD symptoms in the children. In the multiple regression, including the significant BMI, GORD and F5 PGS remained significant. The PGS for GORD was associated with ASD symptoms in children under 6 years. While the ASD and F3 PGS was associated with ASD symptoms in univariate analyses in children aged over 6, none were significant in the multiple regression analysis. Depression symptoms in children (affective scores) were associated with BMI, GORD, F4, F5, F PGS in univariate models, with BMI PGS significant in the multiple regression models. In parents, PGS for MDD, F4 and the general Factor (F) was associated with ADHD symptoms, however these were non-significant in the multiple regression analysis. Parental depression symptoms were associated with MDD, BMI, GORD, F4, F5 and F PGS. MDD and GORD remained significant in the multiple regression analysis. Parental avoidant symptoms were associated with MDD, F4 and F PGS, with MDD remaining significant in the multivariate analysis. We replicated the results in the ADHD Oregon 1000 cohort, a US case-control cohort consisting of children with a diagnosis of ADHD and autism. In this cohort, ADHD symptoms were significantly associated with PGS for ADHD, ASD, GORD and MDD. In multiple regression analysis child ADHD scores remained significantly associated with the PGS for ADHD and GORD. Child ASD symptoms were associated with PGS for ADHD, ASD and GORD, in the final multiple regression analysis ASD symptoms were associated with the PGS for ASD and nominally significant for GORD. In conclusion, in addition to PGS based on psychiatric disorders, symptom severity was associated with GORD PGS in parents and children. This points to a genetic association with gastro-intestinal problems. The underlying mechanism is unclear. The results further indicate that PGS can be useful in a clinical cohort to predict severity in transdiagnostic symptoms in parents and children enabling improved identification of families at increased risk for poor outcome.