Browsing by Author "Jonsson, Lina"

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    Association between polygenic risk scores and outcome of electroconvulsive therapy
    (2022) Sigström, Robert; Kowalec, Kaarina; Jonsson, Lina; Clements, Caitlin C; Karlsson, Robert; Nordenskjöld, Axel; Pålsson, Erik; Sullivan, Patrick F; Landén, Mikael
    Identifying biomarkers associated with response to electroconvulsive therapy (ECT) may aid clinical decisions. The authors examined whether greater polygenic liabilities for major depressive disorder, bipolar disorder, and schizophrenia are associated with improvement following ECT for a major depressive episode.Between 2013 and 2017, patients who had at least one treatment series recorded in the Swedish National Quality Register for ECT were invited to provide a blood sample for genotyping. The present study included 2,320 participants (median age, 51 years; 62.8% women) who had received an ECT series for a major depressive episode (77.1% unipolar depression), who had a registered treatment outcome, and whose polygenic risk scores (PRSs) could be calculated. Ordinal logistic regression was used to estimate the effect of PRS on Clinical Global Impressions improvement scale (CGI-I) score after each ECT series.Greater PRS for major depressive disorder was significantly associated with less improvement on the CGI-I (odds ratio per standard deviation, 0.89, 95% CI=0.82, 0.96; R2=0.004), and greater PRS for bipolar disorder was associated with greater improvement on the CGI-I (odds ratio per standard deviation, 1.14, 95% CI=1.05, 1.23; R2=0.005) after ECT. PRS for schizophrenia was not associated with improvement. In an overlapping sample (N=1,207) with data on response and remission derived from the self-rated version of the Montgomery-Åsberg Depression Rating Scale, results were similar except that schizophrenia PRS was also associated with remission.Improvement after ECT is associated with polygenic liability for major depressive disorder and bipolar disorder, providing evidence of a genetic component for ECT clinical response. These liabilities may be considered along with clinical predictors in future prediction models of ECT outcomes.
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    Genetic studies of autism and autistic-like traits
    (2015-01-09) Jonsson, Lina
    Autism spectrum disorder (ASD) is characterized by impairment in social interaction, language impairment and repetitive behavior with varying degrees of severity. ASD represents the lower end on a continuously distributed measure of autistic-like traits (ALTs). Although a strong genetic component has repeatedly been identified in ASD, the genetic cause of ASD is still unknown for the majority of ASD cases. One of the main interests in this thesis is the neurobiology of melatonin, this interest is based on findings indicating lower levels of melatonin in children with ASD. In our investigations of rare mutations in melatonin related genes in subjects with ASD, we identified a previously reported mutation that has been shown to decrease the activity of one of the enzymes involved in the melatonin synthesis: the acetylserotonin O-methyltransferase (ASMT) (paper I). In the analysis of five common variations in the ASMT gene in relation to ALTs in the general population we found association between a single nucleotide polymorphism and social interaction impairment in girls (paper II). To broaden the analysis of genetic influences on ALTs, we have performed association analyses between ALTs in the general population and common variation in genes previously found to be associated with ASD (RELN, CNTNAP2, SHANK3 and CDH9/10 region) (paper III). Although these regions have previously been suggested to be strong ASD candidate regions, our results do not suggest a major influence of the investigated common variations on ALTs. In the final paper, rare inherited genetic variations were investigated in a large family with autism and language disorders. In this study, we used several techniques, including whole exome sequencing and copy number variation analysis (paper IV). In the family, several rare genetic variations which may partly explain the genetic etiology for autism in this family were identified. We performed functional analyses for a mutation identified in the CYP11A1 gene, indicating a gain of function mutation. The CYP11A1 gene encodes the first enzyme in the steroid hormone biosynthesis, thus our results may be in line with previous findings that have shown an elevated prenatal steroidogenic activity in ASD. In conclusion, we have identified both common and rare genetic variation that may increase the genetic susceptibility for ASD. Our analyses have highlighted the importance of taking both rare and common genetic susceptibility factors, as well as different symptoms of the disorders, into account when elucidating the complex inheritance of ASDs.