Coming dissertations at Uppsala university
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On the physiology of psychiatric brain stimulation
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-539059
This thesis examines physiological aspects of two psychiatric brain stimulation treatments: electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS).
ECT’s therapeutic effect depends on epileptic seizures that activate subcortical regions, and involves increased gamma-aminobutyric acid (GABA) inhibition. Clinical ECT seizure evaluation parameters show varying correlation to clinical outcome and uncertain correlation to subcortical activation. Serum prolactin and cortisol increase postictally, and postictal prolactin reflects subcortical seizure activation. The GABA-agonistic hormone allopregnanolone affects psychiatric illness and increases postictally in epilepsy, but is unexplored after ECT seizures.
RTMS’s therapeutic effect depends on altering cortical excitability which affects synapse plasticity, subsequently modulating functional neural network activity. Motor cortex excitability measured with TMS paired with electromyography (TMS-EMG), which includes GABA modulated indices, may be altered in psychiatric illness. Prefrontal rTMS affects motor cortex excitability, and TMS-EMG may predict rTMS treatment outcome, but the rTMS protocol intermittent theta burst stimulation (iTBS) is less explored.
Study I analysed correlations between clinical ECT seizure evaluation parameters and prolactin and cortisol serum levels. Ictal tachycardia correlated with postictal prolactin, but not cortisol, suggesting that ictal tachycardia reflects subcortical seizure engagement.
Study II investigated progesterone and allopregnanolone serum levels after an ECT seizure, finding no postictal increase or correlation to seizure evaluation parameters. Postictal progesterone increased in men in a subgroup analysis.
Study III examined GABAA receptor availability measured with positron emission tomography and TMS-EMG indices in participants with depression before and after iTBS. Baseline comparisons showed no difference from healthy. After iTBS, changes in GABAA receptor availability and TMS-EMG motor threshold correlated negatively, indicating GABAA mediated regulation of motor cortex signalling.
Study IV investigated whether iTBS affects TMS-EMG and whether baseline TMS-EMG predicts iTBS outcome on negative symptoms in schizophrenia and depression, with negative results. Compared to participants with depression and healthy, participants with schizophrenia had more GABAB receptor dependent inhibition, which also correlated with antipsychotic medication dose.
These results contribute to the understanding of ECT and rTMS physiology, facilitating future developments for improved efficacy and reduced side effects.
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Necrotizing Enterocolitis in Preterm Infants : Impact on Infant Mortality and a Search for Predictive Biomarkers
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-539265
Necrotizing enterocolitis (NEC) is an intestinal disease with high mortality and morbidity. This thesis aims to identify biomarkers to possibly predict this fatal and increasingly common disease in preterm infants.
In Paper I, we studied cause of death (COD) in preterms treated at in the neonatal intensive care unit at Uppsala University Children’s Hospital, Uppsala, Sweden. From Period 1 (2002-2009; n=105) to Period 2 (2011-2018; n=160), NEC increased as COD. Paper I also found that the autopsy influenced COD determination in 34.9% of cases. In Paper II, we investigated if biomarkers at birth could identify preterms at risk of developing NEC. Blood samples were collected after birth from 40 preterms, gestational age (GA) <28 weeks. 11 infants later developed NEC (NEC-group), while 29 did not (Control-group). 189 biomarkers, reflecting inflammation, apoptosis and vascularisation, were quantified with Proximity Extension Assay (Olink®). No biomarker differed in expression when comparing the NEC-group to the Control-group, and only some biomarkers differed when compared to control sub-groups. These findings suggest that infants may not be predisposed at birth of developing NEC besides being preterm. In Paper III and IV, we analyzed intestinal biopsies from 43 infants operated due to NEC (NEC-group) and 27 infants (Control-group) operated due to conditions such as atresia, volvulus and aganglionosis. The biopsies were immunohistochemically stained for markers of Paneth Cells (DEFA6 and GUCA2A) in Paper III and Goblet cells (REG4) in Paper IV. Marker expression was quantified with a semi-automated digital image analysis (ImageJ®) and compared between the groups. Paper III revealed that the NEC-group had lower DEFA6 expression than the Control-group, while expression of GUCA2A was similar. In a logistic regression analysis, NEC-risk correlated to low DEFA6 expression. This suggests that NEC-infants have intact Paneth cells, as indicated by unaltered GUCA2A expression, but diminished DEFA6 activity. Paper IV showed that low REG4 expression correlated to higher NEC-risk. A multivariable logistic regression analysis with REG4 expression and GA, found that GA and not REG4 correlated to NEC-risk. Thus, low REG4 expression in NEC-patients may be maturity dependent.
In conclusion, our findings suggest that preterms are not predisposed at birth to develop NEC besides being preterm. These studies also deepen our knowledge on Paneth cell and Goblet cell involvement in NEC. Low expression of DEFA6 and REG4 may indicate a risk of developing NEC, and could be further studied as potential blood biomarkers.
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Having a child with non-syndromic craniosynostosis : Parents' experiences of care, need of support and perceived stress
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-539773
Objective: Being a parent of a child with a diagnosis of craniosynostosis that requires surgery can lead to anxiety and emotional distress. The general aim was to explore parents' experiences when their child is diagnosed with and treated for non-syndromic craniosynostosis. This was accomplished by investigating how parents perceived treatment, information, and participation in care, as well as their parental stress, symptoms of anxiety and depression, and health-related quality of life.
Methods: Study I investigated Swedish parents' (n=20) experiences of having a child with craniosynostosis and their perceptions of the care provided by conducting interviews and thematic analysis. Study II explored parents' (n=19) experiences of the time at the hospital and the year after discharge by conducting interviews and content analysis. Study III explored parents´ satisfaction with hospital care and factors that influenced their perception of quality of care using questionnaires (n=98) and interviews (n=19), employing a mixed method. Study IV assessed parents' perceived parental and psychological stress and health-related quality of life before and one year after surgery, using questionnaires (n=29).
Results: Parents rarely had previous knowledge about craniosynostosis. For this reason, the craniofacial team was highlighted as the most important source of information and support. Parents described the time in the hospital and after discharge as challenging but ultimately good, and support from family, peers, and the expert team was considered essential. Parents were generally satisfied with hospital care, and factors existed that either facilitated or impeded their experience of quality of care. No differences regarding parental stress, health-related quality of life, and psychological distress before and one year after the child's surgery were found, but there was an association between parental stress and symptoms of depression both before and one year after surgery.
Conclusions: This thesis provides an understanding of parents' experiences when having a child undergoing craniosynostosis surgery. Most parents were satisfied with the care provided, but areas of improvement were described. There appears to be an association between parental stress and symptoms of depression. The findings highlight that healthcare professionals should be more responsive to parents´ different care needs.