Genetic, neurodevelopmental and psychiatric studies of Turner syndrome

Sammanfattning: Turner Syndrome (TS) is a genetic condition characterized by the partial or complete loss of one sex chromosome. Associations with neurodevelopmental and psychiatric disorders has been suggested in TS, but findings are inconsistent. An uneven cognitive profile and challenges in social skills and executive function are described in TS but interactions between domains are unclear and studies in adult women with TS are scarce. It has been proposed that the phenotype of TS is affected by the parental origin of the retained X chromosome, but evidence is conflicting. Thus, the overarching aim of this thesis was to examine the neurodevelopmental, psychiatric, cognitive, and psychosocial aspects in TS. The methods used to achieve these aims were the following: Study I, a populationbased retrospective cohort study using registers to examine associations between TS and diagnoses of neurodevelopmental and psychiatric disorders. Study II, a cross-sectional study where standardized questionnaires and psychological testing were used for assessments in adult women TS. Study III a cross-sectional case-control study with an experimental manipulation of social and non-social feedback in a reinforcement learning tasks, examining choice behaviors in adult women with TS. Study IV, a cross-sectional retrospective study where diagnoses were extracted from medical records, sociodemographic variables and school-age experiences was assessed in self-report questionnaires and the parental origin of the X chromosome was identified in molecular analyses for comparisons between groups. Findings revealed that Individuals with TS are at increased risk for certain neurodevelopmental and psychiatric disorders (Study I). The cognitive profile of TS in adulthood is associated with a clinically significant uneven cognitive profile, but the split does not correlate with symptoms of neurodevelopmental disorders (Study II). Social feedback in the reinforcement learning task led to a more explorative choice behavior in the control group compared to the group with TS, where no effects of social feedback on learning was found (Study III). No differences emerge based on the X chromosomes origin or karyotype (Study IV). Results in medical record review indicated a trend of increased number of diagnoses in depression, anxiety, and stress-related disorders in adult woman with TS and self-reported questionnaires revealed challenges academically and socially during their school age. However, the sociodemographic outcomes of educational achievements and occupation showed no differences compared to general population of adult woman (Study IV)