Project description:Inattention, impulsivity and hyperactivity are the primary behaviors associated with Attention Deficit / Hyperactivity Disorder (ADHD). Previous studies proved that peripheral blood gene expression signature could mirror central nervous system disease. This study determined if gene expression in blood correlated with inattention, hyperactivity/impulsivity rating scales and/or both in subjects with Tourette syndrome (TS).
Project description:Generating effective therapies for neurodevelopmental disorders has remained elusive. An emerging drug discovery approach for neurodevelopmental disorders is to characterize transcriptome wide dysregulation in an appropriate model system and screen therapeutics based on their capacity to restore functionally relevant expression patterns. We characterized transcriptomic dysregulation in a human model of HNRNPU-related disorder to explore the potential of such a paradigm. We identified widespread dysregulation in functionally relevant pathways and then compared dysregulation in a human model to transcriptomic differences in embryonic and perinatal mice to determine whether dysregulation in an in vitro human model is partially replicated in an in vivo model of HNRNPU-related disorder. Strikingly, we find enrichment of co-dysregulation between 45-day-old human organoids and embryonic, but not perinatal, mice from distinct models of HNRNPU-related disorder. Thus, hnRNPU deficient human organoids may only be suitable to model transcriptional dysregulation in certain cell types within a specific developmental time window.
Project description:Mental disorders have been shown to be associated with a number of general medical conditions (also referred to as somatic or physical conditions). The investigators aim to undertake a comprehensive study of comorbidity among those with treated mental disorders, by using high-quality Danish registers to provide age- and sex-specific pairwise estimates between the ten groups of mental disorders and nine groups of general medical conditions.
The investigators will examine the association between all 90 possible pairs of prior mental disorders and later GMC categories using the Danish national registers. Depending on whether individuals are diagnosed with a specific mental disorder, the investigators will estimate the risk of receiving a later diagnosis within a specific GMC category, between the start of follow-up (January 1, 2000) or at the earliest age at which a person might develop the mental disorder, whichever comes later. Follow-up will be terminated at onset of the GMC, death, emigration from Denmark, or December 31, 2016, whichever came first. Additionally for dyslipidemia, follow-up will be ended if a diagnosis of ischemic heart disease was received. A "wash-out" period will be employed in the five years before follow-up started (1995-1999), to identify and exclude prevalent cases from the analysis. Individuals with the GMC of interest before the observation period will be considered prevalent cases and excluded from the analyses (i.e. prevalent cases were "washed-out"). When estimating the risk of a specific GMC, the investigators will consider all individuals to be exposed or unexposed to the each mental disorder depending on whether a diagnosis is received before the end of follow-up. Persons will be considered unexposed to a mental disorder until the date of the first diagnosis, and exposed thereafter.
Project description:To identify the differential expression of serum microRNA as molecular fingerprints for Arnold-Chiari (AC) and Tourette syndromes (TS), also in comorbid status between both disorders (ACTS). To investigate on differentially expressed miRNA associations with the neuropsychological and neuroimaging parameters for each participant and their potential involvement in AC and TS pathological pathways.