Many common disorders, including depression, dementia and obesity are for a large part heritable. Despite the fact that genome-wide association studies (GWAS) have contributed substantially to... Show moreMany common disorders, including depression, dementia and obesity are for a large part heritable. Despite the fact that genome-wide association studies (GWAS) have contributed substantially to unraveling the genetic architecture of these polygenetic disorders, a large amount of ‘missing heritability’ remains. A possible explanation is that GWAS, aside single-nucleotide polymorphisms cannot assess the contribution of other important genetic polymorphisms, especially tandem repeats. Tandem repeats constitute 3% of the human genome. Nine hereditary neurodegenerative diseases, known as polyglutamine diseases, including Huntington disease (HD), are the most prevalent disorders associated with tandem repeat variations. These diseases are caused by an elongated cytosine-adenine-guanine (CAG) repeat sequence in the respective polyglutamine disease-associated gene (PDAG). In this dissertation, we provide ample evidence that CAG repeat variations within the ‘normal’ range in PDAGs can affect various aspects of disease, including the age of onset in HD, cognitive function, depression and body mass index. Finally, we found a relatively large prevalence of intermediate and pathological PDAG alleles in the general population. Therefore, we provided support for the role of repetitive DNA polymorphisms in elucidating the ‘missing heritability’ of polygenetic disorders and emphasized the necessity to include these variations in future genetic research. Show less
This dissertation contains the results of an RCT into the effectiveness of an online self-help intervention for people living with HIV (PLWH) and depressive symptoms. Many PLWH suffer from... Show moreThis dissertation contains the results of an RCT into the effectiveness of an online self-help intervention for people living with HIV (PLWH) and depressive symptoms. Many PLWH suffer from depressive symptoms. Online interventions to treat depression may have benefits, such as less perceived stigma, a large reach and high accessibility. The online self-help intervention that we investigated is based on cognitive behavioral therapy and contains 4 components: stimulating activities, relaxation exercises, changing negative thoughts and goal attainment. Two meta-analyses were conducted and the results point to the effectiveness of psychosocial interventions for PLWH to improve depressive symptoms, anxiety symptoms, quality of life, psychological well-being, and medication adherence. The most important result of the RCT was that the intervention together with telephone coaching is effective in reducing depressive symptoms, compared to an attention-only control group. It was also found that the intervention may be effective for all PLWH, regardless of certain baseline characteristics. Furthermore, behavioral activation and goal reengagement were found to be mediators of the intervention effect. Also, the intervention is likely to be cost-effective compared to attention only. As eHealth interventions have benefits compared to face-to-face interventions, they should be more widely implemented in the mental healthcare for PLWH. Show less
The main aim of this thesis is to explore risk factors associated to an increased risk of adverse outcomes for heart failure (HF) patients and improve the early re-admission or mortality prediction... Show moreThe main aim of this thesis is to explore risk factors associated to an increased risk of adverse outcomes for heart failure (HF) patients and improve the early re-admission or mortality prediction in HF. Data from two studies (OPERA-HF study in the UK and SAPHIRE study in US) has been used to explore a wide range of variables as potential risk factors. We found that depression is a significant and independent predictor of all-cause mortality among HF patients. Depression was also significantly associated with recurrent events: unplanned readmission or mortality. Other psychosocial or non-clinical variables independently associated with increasing risk of recurrent events in the year following discharge after a HF hospital admission were: presence of frailty, moderate-to-severe anxiety, living alone and the presence of cognitive impairment. We then used data from the OPERA-HF study to develop a 30-day composite outcome model and to explore the added predictive value of non-clinical predictors to early outcomes: 30-day unplanned readmission or mortality. The performance of the model improved by including physical frailty and social support next to clinical variables. The transportability of the model to a different geography was proved in the external validation of the model on the SAPHIRE study data. Show less
