Coming dissertations at MedFak
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When extra support is needed
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-540487
Newborn infants exhibit a profound dependency on their primary caregivers to meet their essential needs, which is critical for both development and survival. The World Health Organization’s guideline Early Childhood Development underscores the necessity of responsive care during the early years. When individuals with intellectual disabilities (ID) become parents, unique challenges may arise, resulting in precarious situations. Thus, both parents and children must receive adequate support from healthcare systems and society.
The primary objective of this thesis was to improve perinatal support for both parents and children, particularly for those with ID.
In Paper I, a population-based cohort study involving over 600,000 children revealed that those born to mothers with ID face a significantly higher risk of mental illness, injuries, and violence compared to peers born to mothers without ID.
Paper II employed focus groups in a qualitative study, highlighting that staff working with individuals with ID find discussions about reproductive health and childbirth particularly challenging. They expressed a need for additional support in addressing issues related to sexual and reproductive health rights.
Paper III conducted a psychometric analysis of the Baby Care Questionnaire in Swedish, indicating that the instrument required revision for optimal fit before use.
Paper IV explored whether an educational programme for healthcare professionals, coupled with comprehensive parental education, could enhance the duration of skin-to-skin contact (SSC). The results demonstrated that the quasi-experimental intervention effectively increased the SSC provided by parents.
The thesis highlights that children of mothers with ID and individuals with ID require additional support and resources. Also, the thesis illustrates that healthcare professionals can influence the behaviour of new parents and thereby increase the frequency of SSC, which offers significant benefits.
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Biomarkers for depression: genetic, epigenetic, and expression evidence
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-540129
Depression is a very prevalent disorder affecting between 2 to 21% of the world population. This thesis extends the knowledge on the biological aspects of depression, aiming to identify and validate markers of genetic, epigenetic, and gene expression origin.
In Study I, the main focus was depression-related gene MAD1L1 that was previously linked to depression by SNPs and frequently mentioned as a stress-related marker. We identified that depression-related SNPs in MAD1L1 affect DNA methylation levels at cg02825527, cg18302629, and cg19624444 that were associated with depressive phenotypes in independent cohorts.
In Study II, we investigated whether GWAS catalog depression SNPs located in Olink-detectable genes could be replicated in a UKBiobank cohort and whether these associations are supported by DNA methylation and transcriptome. We validated eight depression SNPs and found very weak evidence that TNXB may be related to depression.
Study III was based on comparison of different depression -OMIC layers, including genetics, DNA methylation, and transcriptome. We explored how the identified genes from different -OMICs overlap, are functionally related and if they could show patterns in drugs and clinical trials. Only three genes were supported by evidence at all three -OMIC levels and included: FOXP1, VPS41, and AKTIP. Different -OMIC levels showed involvement of multiple systems in depression.
In Study IV, we used the Neuro Exploratory panel (Olink) to identify depression proteomic changes in blood. We took antidepressant intake into the account and validated associations in the independent datasets. We identified several proteins that showed nominally different levels between depression risk groups in the adolescent cohort. Validation of identified markers yielded that only PPP3R1 was also differentially expressed in prefrontal cortex and whole blood in the independent open-access cohorts with matching association directions.
In Study V, we used the entire blood DNA methylation as a depression marker. We investigated stability of DNA-methylation in eight independent datasets with meta-analysis and compared common machine learning and deep learning strategies for the depression detection purposes. We found 1987 CpG sites related to depression in both mega- and meta-analysis at the nominal level. Random forest classifiers achieved the best performance in identifying depression based on DNA methylation data in blood (AUC 0.73 and 0.76) in CV and hold-out tests respectively on the batch-level processed data.
Overall, the thesis supports multiple depression genetic, epigenetic, and expression markers. However, identified individual and systemic depression changes show high variability, which is in agreement with previous studies and observations.
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Exploring Disease Patterns in the Long-Term Follow-Up of Juvenile Idiopathic Arthritis : Focus on Psoriasis, HLA-B27, and Temporomandibular Involvement
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-539872
Juvenile idiopathic arthritis (JIA) is an umbrella term encompassing a heterogeneous group of chronic arthritis in children. Many of these have significant differences from adult arthritis, while others possibly represent similar diseases in children and adults. Classification aims to enhance the understanding of the disease’s pathogenesis, patterns of phenotypes, disease trajectories, and treatment responses.
Patient-reported outcome measures (PROMs) are invaluable for assessing disease burden and play an important role in co-producing optimal health care for the child with JIA.
This thesis has its origin in the Nordic JIA study, a population-based, prospective study of 510 children with newly diagnosed JIA who were included between 1997 and 1999. In the 8-year follow-up, we found that features associated with psoriasis were linked to more severe disease progression over time. A significant proportion of children with both psoriasis and arthritis were not classified as having juvenile psoriatic arthritis (JPsA). To ensure that these children receive early, personalized treatment, future classifications should include psoriasis and psoriasis-related characteristics as criteria.
In the 18-year follow-up, we studied temporomandibular joint (TMJ) arthritis. Orofacial symptoms and dysfunctions were common, and two-thirds of participants showed condylar deformities or erosions on cone-beam computed tomography (CBCT). An interdisciplinary approach is recommended to optimize management throughout the course of the disease.
The presence of HLA-B27 was associated with an increased risk of not being in remission off medication after 18 years of disease duration in males but not in females. Uveitis in HLA-B27 positive individuals is not always symptomatic, which clinicians need to be aware of.
The Juvenile Arthritis Multidimensional Assessment Report, JAMAR, was translated into Swedish and validated in a clinical setting. The Swedish JAMAR proved to be a reliable tool that can be used in both routine clinical practice and research. The responses from the questionnaire can also serve as a basis for discussions between patients and caregivers.
In conclusion, JIA is a complex disease requiring attention to multiple aspects. Our results highlight the need for better classification of psoriasis in JIA, the importance of careful and multidisciplinary follow-up for TMJ arthritis, and an association between HLA-B27 positivity and more severe disease. The Swedish version of JAMAR serves as a valuable complement to existing PROMs and has the potential to enhance health care for children with JIA.