| 1. |
- Johansson, Fred
(författare)
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Aspects of the aetiology of mental health problems among university students
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mental disorders are among the leading causes of years lost due to disability in young people globally. Students are no exception, both mental disorders and mental health problems are common among university students with dramatic increases reported in recent years. The aetiology of mental disorders and mental health problems is generally assumed to be multicausal, with factors at different levels contributing to their development. Given the complexity of the causal network underlying mental health problems, it has been argued that a clear causal framework is needed when studying the aetiology of mental health problems. This thesis aimed to investigate some aspects of the potential aetiology of mental health problems among university students. Specifically, it focuses on four exposures at the psychosocial level presented in four studies: 1) the coronavirus disease (COVID-19) pandemic, 2) poor sleep quality, 3) procrastination and 4) sexual harassment and sexual violence. In addition to the discussion provided in each respective paper, this thesis discusses limitations and possible interpretations of our results from a modern causal inference perspective.The four studies of this thesis are based on The Sustainable University Life (SUN) cohort. The SUN cohort followed 4262 university students from eight universities in and around Stockholm, Sweden, with web-surveys at five time-points over one year.In Study I, we aimed to determine the mean trajectories of depression, anxiety, and stress symptoms among university students in Stockholm before and during the first months of the COVID-19 pandemic. For this, we included a subsample of 1836 university students that entered the SUN cohort before the outbreak of the COVID-19 pandemic, and were followed during the months before the pandemic, during the first wave of the pandemic and in the summer, months following the first wave of the pandemic. We found that mean depression, anxiety, and stress symptom levels were largely stable during the first wave compared to the months before the pandemic and decreased slightly during the following summer months. Our results indicate that mean levels of mental health symptoms did not change much during the early phase of the pandemic compared to before the pandemic.In Study II, we aimed to determine whether sleep quality statistically interacts cross-sectionally with loneliness, risky alcohol use, perfectionistic concerns and/or physical inactivity in relation to depressive symptoms in university students. We conducted a cross-sectional study using baseline-data from all 4262 participants in the SUN cohort. We found that while all factors were associated with depressive symptoms, only perfectionistic concerns interacted with sleep quality in its relation to depression. This interaction was quite weak and explainedonly a small proportion of the variance in depressive symptoms. Overall, we did not find support for our hypothesis that poor sleep quality could interact with several different potential risk factors for depressive symptoms.In Study III, we aimed to evaluate the associations between procrastination and sixteen subsequent health outcomes (including mental health symptoms, disabling pain, lifestyle behaviours and psychosocial health factors), measured 9 months later, among university students. We used data from all participants responding to the first follow-up in the SUN cohort (n=3525) and found that procrastination was related to several subsequent health outcomes, including symptoms of depression, anxiety and stress, while controlling for multiple potential confounders. Although we cannot rule out non-causal explanations for these associations, the results indicate that procrastination could have an effect on health outcomes among students, but that it is likely to be rather small for any specific health outcome.In Study IV, we investigated the impact of recent exposure to different forms of sexual harassment and sexual violence; 1) unwanted sexual attention, 2) offensive sexual remarks, 3) presentation or distribution of sexist material, 4) uncomfortable touching, 5) being offered benefits for sex and 6) sex against ones will, along with a wide definition of sexual harassment: sexual harassment (wide subjective definition) on levels of depression and anxiety symptoms three, six and nine months later, for women and men, respectively. We conducted a cohort study using data from all women and men responding to the first follow-up in the SUNcohort (n= 3503). Our results showed that women recently exposed to 1) sexual harassment (wide definition), 2) unwanted sexual attention and 3) sex against ones will showed higher subsequent levels of depression and/or anxiety symptoms. The general trend was that all exposures were related to higher symptom levels at three months, but that this difference between exposed and unexposed diminished over time, although these trends are uncertain with wide confidence intervals. The exception was exposure to sex against ones will, where exposed showed elevated symptom levels throughout the follow-up period. For men, the estimates were uncertain overall, and we refrain from interpreting these results. Our results indicate that recent exposure to different forms of sexual harassment and sexual violence may impact later depression and anxiety symptoms among women, and that there could be differences in the strength and long-term impact on mental health between different forms of sexual harassment and sexual violence. Again, we cannot, with certainty rule out non-causal reasons for these associations.Interpreting any of these results as causal effects rests on multiple assumptions, which are discussed in the thesis. Determination of causal effects preferably relies on triangulation of results from different studies with different methodology. Overall, however, I believe that this thesis has strengthened the evidence that procrastination and sexual harassment and sexual violence may be causes of mental health problems among university students. An equally important finding, is that mental health seemed rather stable during COVID-19 pandemic, indicating that the pandemic may not have caused increased mental health problems on the group level.
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| 2. |
- Kullenberg, Helena
(författare)
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Insulin-degrading enzyme : A link between insulin resistance and Alzheimer's disease
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Prior research has demonstrated an elevated risk of Alzheimer's disease (AD) among individuals diagnosed with type 2 diabetes mellitus (T2DM). Insulin resistance is a potential common link between these conditions, and it is associated with AD due to the insulin-degrading enzyme (IDE), which also degrades amyloid-β (Aβ) in the brain. It has been suggested that high insulin levels may hinder IDE's effective degradation of Aβ, contributing to plaque formation. IDE is measurable in blood and is a promising biomarker for AD risk assessment and diagnosis. IDE has been demonstrated to decrease in blood from patients with cognitive impairment, but the overall knowledge about IDE in human blood is sparse. The aim of the thesis was to increase knowledge of the relationship between insulin resistance and AD, focusing on IDE as a biomarker for risk assessment and diagnosis of AD.Study participants: In study I, we included patients with type 2 diabetes (n=46) and compared them with patients without metabolic diseases (n=18). Serum samples were obtained from the Sophiahemmet biobank. In study II, we used post-mortem plasma samples from patients with Alzheimer's disease (n=18) and compared them with non-demented controls (n=6). These samples were obtained from the Netherlands Brain Bank. In study III, where we had three groups, we recruited patients with Alzheimer's disease (n=9) from a dementia care facility and healthy volunteers from Sophiahemmet University and Sophiahemmet Health Center (n=64). The serum samples from these individuals were then compared with serum samples from patients diagnosed with type 2 diabetes from Study I.In Study IV, we utilized data from the Swedish BPSD (Behavioral and Psychological Symptoms of Dementia) registry. This registry is used by healthcare units that work with patients with neurocognitive disorders and contains information about the patient's diagnosis, drug treatment, and behavioral and psychological symptoms. We selected a group of AD patients prescribed some form of antidiabetic drug treatment and analyzed whether the type of treatment impacted the registered behavioral and psychological symptoms.Methods: In study I-III, ELISA was used to analyze blood samples for levels of IDE and other metabolic markers. In study II, Luminex multiplex was used to measure inflammatory markers. These biomarkers and clinical data were analyzed statistically to investigate differences between groups and correlations between variables. In study IV, the association between BPSD and antidiabetic drug treatment was investigated using a bivariate logistic regression model, adjusted for age, sex, specific diagnosis, and drug treatment.Results: The results showed that patients with T2DM had higher serum IDE levels than patients without metabolic diseases, patients diagnosed with AD, and healthy volunteers. The results also indicated that higher IDE levels were associated with older age, higher weight, and elevated blood glucose. In the samples from the brain bank, we found that higher IDE levels were correlated to increased levels of inflammatory markers and total tau.In the analysis of registry data, we found that the prescription of metformin, one of the most common drugs for type 2 diabetes, was associated with lower odds for symptoms of depression and anxiety. This association was not observed for any other antidiabetic drug.Conclusion: The results suggest that IDE may be an essential factor in metabolic function but may also be associated with significant risk factors for neurocognitive disorders, such as inflammation. Although based on smaller studies, these findings contribute to the limited knowledge of IDE in human blood. Reduced IDE levels have been linked to an increased risk of AD. If patients diagnosed with T2DM have elevated IDE levels, a decrease in IDE levels possibly would indicate that the patient is at higher risk of or even in an early stage of AD. As interest in blood-based biomarkers grows, IDE emerges as a stable and reliable candidate in this thesis. Additionally, the research raises attractive possibilities for enhancing treatment strategies for AD patients experiencing affective symptoms. Metformin is believed to increase IDE levels and has previously been suggested to treat affective disorders and AD. Further investigation is needed to explore this promising avenue.
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| 3. |
- Onell, Clara
(författare)
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Lifestyle behaviors and musculoskeletal conditions in university students and high school athletes
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Musculoskeletal conditions impose a large burden of disability in young populations. University students are prone to neck and back pain, with potential negative impact on physical, mental, and academic functioning. In adolescent athletes, musculoskeletal injuries are common and may result in discontinued sports participation as well as impaired physical and mental health. University students and adolescent athletes tend to have unhealthy lifestyle behaviors. University students report unhealthy behaviors such as high sitting time, low physical activity levels and unhealthy dietary habits. Adolescent athletes are physically active but tend to have inadequate dietary habits in relation to their physiological demands, including insufficient intakes of total energy and carbohydrates.Identifying modifiable risk factors for musculoskeletal conditions is the first step towards prevention, and knowledge about the role of lifestyle behaviors for these conditions is limited. The overarching purpose with this doctoral thesis was to deepen the knowledge about lifestyle behaviors and their role for the risk of musculoskeletal conditions in university students and high school athletes.Methods, results, and conclusions: Study I and II are based on the Sustainable UNiversity Life (SUN) study, a cohort study including 4262 students at Swedish universities. The participants reported different aspects of health, lifestyle behaviors and attitudes through web-surveys every third month for one year in 2019-2021.In Study I, the aim was to assess changes in lifestyle behaviors during the COVID-19 pandemic, compared to before, in 1877 university students (73% women, mean age 26.5 ± 6.8 years). Physical activity levels, sitting time, meal frequency and risk use of alcohol, tobacco and illicit drugs were measured at a pre-pandemic baseline and at two periods during the first six months of the pandemic, the follow-up 1 (FU1) and follow-up 2 (FU2). Population means and differences with 95% confidence interval (CI) in lifestyle behaviors were calculated with generalized estimating equations. The study found that weekly exercise decreased by -7.7 minutes (95% CI -12.6, -2.8) whereas weekly daily activities increased by 14.2 minutes (95% CI 7.9, 20.5) between the pre-pandemic baseline and FU2. Furthermore, daily sitting time decreased by -1.4 hours (95% CI -1.7, -1.2) during this period. Small changes were observed for meal frequency, whereas for risk use of alcohol, tobacco and illicit drugs, changes were only minor. The conclusion of Study I is that lifestyle behaviors in Swedish university students slightly improved during the first six months of the COVID-19 pandemic compared to before.In Study II, the aim was to assess the association between an unhealthy lifestyle and incident activity-limiting neck/back problems (ALNBP) in university students. Physical inactivity, high sitting time, meal skipping, and risky use of alcohol, tobacco and illicit drugs were combined into an unhealthy lifestyle, categorized as ≥3 unhealthy lifestyle behaviors. A total of 3492 university students (60% women, mean age 24.5 ± 6.0 years) without ALNBP the past three months at baseline were included. Cox regression models were built to assess the association between an unhealthy lifestyle and incident ALNBP, reported as a hazard rate ratio (HRR). Being exposed to an unhealthy lifestyle generated a HRR of 1.35 (95% CI 1.12 to 1.63) of ALNBP, compared to not being exposed to an unhealthy lifestyle. The conclusion of Study II is that an unhealthy lifestyle is associated with incident activity-limiting neck/back problems in university students.Study III and IV are based on the Swedish Handball Cohort (SHC), a cohort study including 1334 adolescent handball players enrolled to a handball-profiled high school in Sweden. Participants responded to a baseline web-survey with questions about current and previous injuries, training, and dietary habits, among others, in the beginning of the handball season in 2020/2021, 2021/2022 and 2022/2023.Participants were monitored weekly throughout the handball season with questions about their amount of handball training and matches the preceding week, sleep habits, injuries, and injury consequences, among others, reported through a mobile application.In Study III, the aim was to describe dietary habits in 1040 adolescent handball players enrolled in the SHC seasons 2020/2021 or 2021/2022 (51% males, mean age 16.6 ± 0.9 years). Differences with respect to sex and school grade were estimated with generalized linear models, generating a prevalence ratio (PR) and 95% CI. Overall, 70% and 90% of the participants met recommendations for meal frequency and meal timing, respectively, whereas adherence to recommended provision of carbohydrates was met by 17%. Sixteen percent adhered to the Nordic Nutrition Recommendations (NNR) for fruits/vegetables of ≥500 grams per week, whereas 37% adhered to the recommendations for fish/seafood of ≥2 times per week. Use of dietary supplements was reported by 28% of the participants, and 20% reported food exclusions due to other reasons than intolerances. Females reported a lower frequency of all meals, especially morning snacks and evening snacks. Also, a higher prevalence of food exclusions was observed in females, with a PR of 1.66 (95% CI 1.31to 2.01) for exclusions due to intolerances and a PR of 1.36 (95% CI 1.08, 1.64) for exclusions due to other reasons. Females also reported a higher adherence to fruits/vegetables recommendations with a PR of 2.30 (95% CI 1.98, 2.62) and use of micronutrient supplements to a larger extent with a PR of 1.72 (95% CI 1.43, 2.00), compared to their male counterparts. Small differences were observed with respect to school grade. The conclusion of Study III is that Swedish adolescent handball players’ dietary habits are somewhat in accordance with sports nutrition recommendations whereas adherence to provision of carbohydrates during matches and the NNR for fruit/vegetables and fish/seafood is low. Females seem to display more restrictive dietary habits compared to males.In Study IV, the aim was to assess the association between dietary habits and incident knee/shoulder injuries in 1144 adolescent handball players in season 2020/2021, 2021/2022 and 2022/2023 of the SHC without a knee or shoulder injury at baseline (1703 player seasons, 53% males, mean age 16.7 ± 0.9 years). Cox regression analyses estimated a HRR with the first event of a knee/shoulder injury as the outcome. A moderate-high nutritional quality, in accordance with the NNR, generated a HRR of 1.46 (95% CI 1.08, 1.98) for knee/shoulder injuries compared to low nutritional quality in adolescent female handball players. Also, ≥2 unfavorable dietary habits in relation to sports nutrition recommendations generated a HRR of 1.38 (95% CI 1.02, 1.86) compared to 1 unfavorable dietary habit in females. For poor meal timing, adjusted analyses generated a HRR of 1.20 (95% CI 0.90, 1.61) in females, compared to adequate meal timing. In adolescent male handball players, analyses generated a HRR of 1.23 (95% CI 0.69, 2.17) for low meal frequency compared to high meal frequency and a HRR of 0.83 (95% CI 0.60, 1.15) for poor meal timing. Menstrual dysfunction was assessed in females with no use of hormonal contraceptives, as a proxy for low energy availability, however, no associations were found between menstrual dysfunction and incident injuries in these females. The conclusion of Study IV is that a moderate-high nutritional quality and having more than one unfavorable dietary habit is associated with higher rate of incident knee/shoulder injuries in adolescent female handball players, while there are no or unprecise associations for meal frequency, meal timing and menstrual dysfunction. In adolescent male handball players, there are no clear associations between dietary habits and incident injuries.Overall conclusion: This doctoral thesis sheds light on aspects of lifestyle behaviors in university students and high school athletes. Population-specific unhealthy lifestyle behaviors are common in university students and high school athletes. These behaviors seem to be of importance for the risk of musculoskeletal conditions.
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| 4. |
- Wijk, Ingrid
(författare)
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Experiences of living with type 1 diabetes and improving psychological flexibility through an Acceptance and Commitment Therapy (ACT) intervention
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Impaired psychological health in type 1 diabetes is prevalent and associated with elevated glycaemic outcomes. International evidence-based guidelines have defined glycaemic treatment targets to prevent acute and long-term complications. In addition, the guidelines encourage screening for the elevated distress that living with type 1 diabetes may imply. There is a need to gain further understanding of what it means to live with type 1 diabetes as an adult with elevated HbA1c and to develop interventions to promote psychological and physiological health.Aim: The overall aim of the thesis was to describe experiences of living with type 1 diabetes as an adult with elevated HbA1c and furthermore to evaluate the impact of an Acceptance and Commitment Therapy programme for people living with type 1 diabetes. The thesis also aimed to examine the Swedish version of Acceptance and Action Diabetes Questionnaire (AADQ), which is a questionnaire for psychological flexibility related to diabetes.Method and result: In Study I we included 81 adults with type 1 diabetes and HbA1c > 60 mmol/mol in a randomised controlled trial. A seven-session programme based on Acceptance and Commitment Therapy was conducted and the impact on HbA1c, self-management and psychosocial factors was evaluated. No effect was demonstrated in the linear mixed model analysis on HbA1c or the secondary outcomes. Nevertheless, a significant statistical improvement in psychological flexibility was noted one and two years after the intervention. A large drop-out rate was observed in the study. In Study II, the psychometric properties of a translated version of the AADQ were examined through Rasch analysis. A total of 120 adults with type 1 diabetes were included. The Swedish version of the ADDQ showed acceptable psychometric properties such as fit to the Rasch model and person separation index. However, we also found indications on a malfunctioning categorisation of the response categories. A collapsed three category rating was examined. In Study III, two categories of experiences were described in the qualitative interviews: constraining and manageable. Through content analysis, an overarching theme was created "a life-long follower". The theme describes the unrelenting existence of type 1 diabetes that impact life in various degrees.Conclusion: No impact on HbA1c or secondary outcomes could be demonstrated through the Acceptance and Commitment Therapy based programme. At the same time, a key component in psychological health, psychological flexibility, was improved. The Swedish version of the AADQ showed acceptable psychometric quality. However, uncertainties regarding the categorisation should be further examined. The experiences of living with type 1 diabetes as an adult and elevated HbA1c is widely diverse. A person-centred care approach is therefore crucial to support the needs of each unique person with type 1 diabetes.
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| 5. |
- Nordström, Axel
(författare)
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Exploring eicosanoids as biomarkers in severe chronic rhinosinusitis with nasal polyps
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic rhinosinusitis (CRS) is one of the most common inflammatory chronic conditions, leading to a persistent nasal congestion, nasal discharge, and a loss of smell. Despite sinus surgery and frequent use of oral corticosteroids, a large proportion of individuals with CRS are difficult to treat and have recurrent inflammation. They are usually referred to as individuals with recalcitrant disease and having recurrent nasal polyps (NPs; CRSwNP). The disease poses a significant impact on the patients' health-related quality of life (HrQoL), mainly because of a complete loss of smell. Pharmacological treatment with biological therapies has recently been developed, targeting mediators of the type 2 inflammatory response. However, not everyone benefits from the biological therapy, and it has proven difficult to identify and characterise patients that are responsive to these new medications. Eicosanoids, being arachidonic acid derived bioactive lipid mediators, has been shown to be implicated in CRSwNP. Although there is a clear link between an imbalanced biosynthesis of pro- and anti-inflammatory eicosanoids and type 2 inflammation, to date research has not focused on them as biomarkers in CRSwNP.The overall aim of this thesis was to explore the potential role of eicosanoids as biomarkers and characterise changes over time in HrQoL as well as the degree of smell loss in patients with severe recalcitrant CRSwNP. The project involved immunoassay analysis of levels of various inflammatory mediators, including a selection of eicosanoids, in nasal tissue, nasal secretions and urine from patients with CRSwNP as well as gene expression analyses regarding biosynthetic enzymes and receptors for eicosanoids in nasal tissues. HrQoL was assessed with SNOT-22 and RAND-36, along with point-of-care tests as eosinophil blood count, fractional exhaled nitric oxide (FeNO) and smell tests with Burghart Sniffin’ Sticks.Levels of eicosanoids in nasal secretions were found to associate with the disease severity, defined as the extent of NP growth (paper I). One of the eicosanoids, leukotriene E4 (LTE4), were correlated to the degree of smell loss (paper I). An increase in LTE4 between six and 12 months after surgery was demonstrated in patients with recurrent NPs (paper II). Recurrent NPs were identified endoscopically 12 months after surgery and a distinct eicosanoid profile involving LTE4, prostaglandin D2 and 15(S) hydroxyeicosatetraenoic acid was found to be more common in those with recurrence (paper II). A similar eicosanoid profile, based on measurements from nasal tissue samples instead, was also associated with NP recurrence (paper III).Levels of eicosanoids in nasal tissue and nasal secretions were correlated suggesting that analysis of biomarkers in nasal secretions reflects release from the nasal tissue (paper III). Patients with recurrent NPs had elevated blood eosinophil counts before their surgery, and their sense of smell was significantly impaired both before and after (paper IV). This finding suggests that loss of smell may be the first symptom during recurrence. Although measures of HrQoL could not distinguish patients with recurrent NPs, there was a strong correlation to the degree of smell loss suggesting that loss of smell has a significant impact on the HrQoL (paper IV).In summary, the results from this thesis contribute to an extended knowledge regarding characteristics relevant for identifying severe recalcitrant CRSwNP. Characteristics of interest included a distinct eicosanoid profile, severe loss of smell and eosinophil involvement, all of which may be possible prognostic markers for severe recalcitrant CRSwNP with rapid NP growth. It may be concluded that such biomarkers can guide the choice of treatment for these severely ill patients – repeated surgery or pharmacological treatment with the newly developed biological therapies.
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