Mental health problems among children and youths are common and have numerous negative consequences for young people and their social network. Therewith, these problems pose a social issue. GPs... Show moreMental health problems among children and youths are common and have numerous negative consequences for young people and their social network. Therewith, these problems pose a social issue. GPs play an important role in early detection and management of these problems. Insight into their clinical decision- making and, as a result, way of working would be helpful to develop methods for providing children and youths with the help they need. Previous literature suggest many doctors(-to-be), of whom some are or will become GPs, have (lived) experience related to mental health problems themselves. Previous studies also suggest having (lived) experience influences GPs’ clinical decision-making, and consequently their way of working. It would have clinical benefits for GPs and patients to explore this process. This thesis is constructed of four different articles, each contributing to answering the main question: ‘How do GPs decide on child and youth mental health problems and what is the influence of their(lived) experience regarding these problems on this decision?’ Article 1: How do GPs make decisions regarding mental health problems in children and youths? For answering this subquestion, a mixed methods design was used: interviews among 14 and an online survey among 15 GPs. GPs were asked about their clinical decision-making process on children and youths with mental health problems using three vignettes describing children and youths with mental health problems representative of clinical practice. The findings suggest GPs differ with regards to their decision- making regarding child and youth mental health problems, and that their decision-making is influenced by factors related to 1) the GP, for example if the GP approaches the problem somatically or psychosocially, if the GP considers themself competent enough to solve the problem with regards to their interest in and knowledge about youth mental health care, 2) the child and its social context, for example if the child or youth has psychiatric (co)morbidity, if the problem is likely to solve itself and if the problem could be assessed as being complex and 3) the GPs’ collaboration with other youth care providers, for example if GPs have existing collaboration agreements with these youth care providers and how they view their collaboration. Article 2: Can GPs’ decisions on child and youth mental health problems be supported by means of a decision-support method?For answering this subquestion, a literature search was conducted to retrieve studies that involved clinical decision support methods for GPs’ clinical decision-making related to mental health problems among children and youths. This systematic review yielded 25 studies on 18 clinical decision-support methods, divided into computer-based methods (such as MyGRaCE), telecommunication methods (such as CAP PC) and methods with a combination of components related to computer-based methods and telecommunication methods (such as Collaborative care for depression intervention). The article provides insight into (possible) beneficial clinical implications of clinical decision-support methods. These methods could give more insight into possible mental health problems, they could provide structured information which can be used by the GP and/or parents during their next consultation with the child or youth, and they could also decrease time and costs spent by the primary care practice and the GP. There are also less beneficial clinical implications, such as an inability for some computer-based methods to be used in emergency situations, when time is short, problems for children and youths when using computer-based methods because of their mental status, and impediment to discuss certain topics freely because the decision-support method gives too much direction to the consultation. The article describes certain considerations for GPs when choosing a decision-support method, which may indirectly have a positive impact on the implementation of such methods into general practice. For example, the GP can take into account their way of working, user flexibility of the method for the GP, the child/youth and their parent(s) with regards to understandability and ease of use, if the GP already uses a clinical decision-support method, if the GP already has collaboration agreements with youth care providers, as well as their own attitude and knowledge regarding mental health problems among children and youths.Article 3: Do doctors-to-be, among whom future GPs, have (lived) experience regarding mental health problems? Study focused on preclinical medical students.For answering this subquestion, self-report questionnaires were sent to 1311 preclinical medical students of Leiden University Medical Center to measure burnout-, depression- and anxiety-related symptoms. The article concludes that symptoms related to mental health problems are common among preclinical medical students. Burnout-related symptoms were found in 46%, depression-related symptoms in 27% and anxiety- related symptoms in 29% of preclinical medical students. Burnout-related symptoms among preclinical medical students were correlated with a sleep duration of less than 6 hours per night, low happiness and a high need for recovery after a day of study. Depression- and anxiety-related symptoms were mainly correlated with low optimism, low happiness, and a high need for recovery after a day of study. These findings suggest preclinical medical students are at risk to develop mental health problems, which can inspire universities to come up with preventive interventions.Article 4: Do doctors-to-be, among whom future GPs, have (lived) experience regarding mental health problems? Study focused on medical interns.For answering this subquestion, self-report questionnaires were sent to 709 medical interns of the same institution mentioned in article 3 to measure burnout-related symptoms. Burnout-related symptoms were found in 30% of medical interns. Burnout-related symptoms among medical interns were related to low dedication with regards to work, a high work pace and quantity, a high need for recovery after a day of work and low optimism. These correlates could be used to prevent mental health problems among medical interns by making adjustments to the medical curriculum. The articles of this thesis suggest GPs’ decision-making on mental health problems in children and youths is multifactorial and consists of objective and subjective components. Furthermore, decision-making seems to differ between GPs, which may be an explanation why there are a variety of clinical decision support methods. Some clinical decision support methods have been implemented in the context of research into general practice, like MyGRaCE, CHICA, Mobiletype, Youth StepCare, consultation-liason method(between GPs and psychiatrists), telepsychiatry consultation practice and the MC3 Program. A clinical implication is GPs can choose a decision-support method which match their personal style of clinical decision-making. However, the validity, trustworthiness and usability of available methods need to be further explored. A clinical implication with regards to medical students’ mental health comprises universities provide accessible proactive mental support to preclinical medical interns and medical interns, because many do not seek help themselves. Furthermore, universities could stimulate a stigma-reducing educational environment, for example in collaboration with the department of (Child- and Adolescent) Psychiatry. Therefore, medical students could be equipped with effective strategies to cope with mental health problems. Also, they might be made aware of their vulnerability, so that they may know their subjectivity and use their personal experiences in practice. The results of this thesis invite more (longitudinal) research on the diagnostic precision, predictive value and cost-efficiency of clinical decision-support methods. Furthermore, more research is needed on the prevalence of mental health problems among graduated doctors, like GPs, and possible effects of these problems on their way of working, their decision-making and their contacts with patients. Strengths of this thesis include exploration of a relatively unknown research area, namely GPs’ clinical decision-making regarding mental health problems among children and youths. Therefore, this thesis used multiple research methodologies and it used a practical scope. This thesis also contains several limitations, such as inclusion of a small GP population, as well as self-selection bias in the studies on preclinical medical students, medical interns and GPs. Finally, interpretation of the results of this thesis was impeded because the research has been conducted in one university, because cause and effect of results could not always be disentangled and because of low statistical power. Because having mental health problems may influence GPs’ clinical decision-making, one could explore how (future) doctors work, study and relax. Therefore, it is recommended to strive for educating balanced doctors: persons who, in collaboration with their colleagues, are – through reflection – aware of their needs and wants between professional boundaries. Show less
The aim of this thesis was to assess the efficacy (part 1) and tolerability (part 2) of antiseizure medications (ASMs) in glioma patients with epilepsy. In addition, we aimed to get insight into... Show moreThe aim of this thesis was to assess the efficacy (part 1) and tolerability (part 2) of antiseizure medications (ASMs) in glioma patients with epilepsy. In addition, we aimed to get insight into the ASM prescription behavior and treatment policy in brain tumor-related epilepsy (part 3).First-line levetiracetam seems to be the most efficacious ASM in glioma patients, with favourable tolerability. This is demonstrated in multicenter retrospective observational cohort studies, a systematic review, and is the opinion among the vast majority of European neuro-oncology professionals. Enzyme-inducing AMSs should be avoided in glioma patients due to the high risk of adverse effects. ASM use was not independently associated with neuropsychiatric symptoms in glioma patients, but alternative factors seem to pose a greater risk for developing neuropsychiatric symptoms. If patients experience uncontrolled seizures on ASM monotherapy, levetiracetam combined with valproic acid has better efficacy than other ASM combinations in glioma patients, while toxicity is similar. Subsequently, potential add-on ASMs in glioma patients experiencing uncontrolled seizures on ASM dual therapy include clobazam, lamotrigine, and lacosamide. Show less
This dissertation focuses on identifying neural mechanisms underlying social evaluations and self-views from a parent-adolescent perspective among adolescents with and without depression, and their... Show moreThis dissertation focuses on identifying neural mechanisms underlying social evaluations and self-views from a parent-adolescent perspective among adolescents with and without depression, and their parents. As part of RE-PAIR, affective and neural responses to praise and criticism about the adolescent child, and neural responses to reliving positive autobiographical memories were assessed, using ecologically valid fMRI-tasks. Particularly criticism seems to be highly salient to parents and adolescents, activating the salience network and decreasing mood. Both praise and reliving positive autobiographical memories activate areas important for self-referential processing in adolescents, which might reflect the ‘positive self’. Aberrant self-related processing when reliving autobiographical memories and increased sensitivity to parental criticism might be key underlying neural mechanisms in adolescent depression. By feeling more negatively, having more negative self-views, interpreting the environment as more negatively, memorizing past experiences in a more negative way, and focusing on negative events more often, adolescents with depression seem to have multiple negativity biases. These negativity biases are likely to negatively impact social relationships, potentially further reinforcing negative feelings and a negative self. Interventions exploring and strengthening the positive self, in particular the positive self aligning with the current self, might be useful for treating, or even preventing adolescent depression. Show less
This thesis leads to empirical insights in the relationship between anger and aggression, on the one hand, and psychopathology, on the other hand, using robust study designs and a broad spectrum of... Show moreThis thesis leads to empirical insights in the relationship between anger and aggression, on the one hand, and psychopathology, on the other hand, using robust study designs and a broad spectrum of anger manifestations. It became clear that the occurrence of anger and aggression are common among both psychiatric outpatients, including individuals with depressive-, anxiety-, and bipolar disorders, and psychiatric inpatients, including individuals with psychotic- and personality disorders. Aggressive behaviour regularly leads to a referral to long-stay inpatient care. As supported by this thesis, the costs of aggression within long-stay wards are high. However, despite the increased awareness and efforts to reduce violence in clinical care among healthcare workers and policymakers, aggression incidents remain highly prevalent in psychiatric inpatient facilities. Research suggests diet to be a modifiable factor affecting mood and behaviour. Yet, the promising effects of nutritional supplementation on aggressive incidents found in previous studies were not replicated in psychiatric inpatients. These results strengthen the need for study of additional preventative and treatment options. Furthermore, our results underline the importance of including vulnerable populations, who are often underrepresented in RCTs, to provide evidence-based care for these groups. Show less
This thesis aimed to lay the foundation for a new set of Dutch mental health instruments to measure depression and anxiety in an efficient, reliable, valid, and responsive manner. More specifically... Show moreThis thesis aimed to lay the foundation for a new set of Dutch mental health instruments to measure depression and anxiety in an efficient, reliable, valid, and responsive manner. More specifically, the Dutch-Flemish PROMIS adult v1.0 item banks for Depression and Anxiety were psychometrically evaluated for computerized adaptive test (CAT) administration in the Dutch clinical and general population. CAT is a modern methodology that can be used to develop instruments that measure both efficiently and reliably as only the most appropriate questions are administered, and assessment terminates as soon as sufficient reliability is achieved. For the PROMIS CAT instruments, this was demonstrated in the thesis: measuring depression and anxiety in Dutch persons was highly efficient and reliable. Moreover, the CAT instruments were shown to measure depression and anxiety sufficiently responsive and valid as well. This even includes longitudinal validity, which has barely been studied for other Dutch mental health instruments. Overall, it was concluded that the new instruments are an improvement over available instruments. Therefore, using the PROMIS CAT instruments in clinical practice may lead to more efficient and reliable measurement that supports professionals and patients in evaluating patients' treatment. Show less
Depression shows a large heterogeneity of symptoms between and within persons over time. However, most outcome studies have assessed depression as a single underlying latent construct, using the... Show moreDepression shows a large heterogeneity of symptoms between and within persons over time. However, most outcome studies have assessed depression as a single underlying latent construct, using the sum score on psychometric scales as a total indicator for depression severity. The present dissertation aimed to expand our knowledge of depression by researching its symptom-specific longitudinal characteristics, its predictive factors, and methods for predicting depression and anxiety while taking individual symptoms into account. We demonstrated that individual depressive symptoms are not synchronized over time within patients and in groups of patients. We found that individual symptoms of depression are associated to different risk factors, as preceding chronicity, neuroticism, and inflammation were related to individual symptoms with vastly different magnitudes. Taken these findings together we have demonstrated that depressive disorder can not be characterized as an unified syndrome. Addressing depression at the syndrome level may obscure insights into both patient and symptom-specific characteristics. Our findings strengthen the idea that employing a symptom-focused approach in both clinical care and research is of value. With this dissertation, we hope to have contributed to the development of alternative ways to define and study depression and its symptoms. Show less
This dissertation describes the findings of six studies on mental health problems in the family context, specifically focusing on the associations with the parent-child relationship, parenting... Show moreThis dissertation describes the findings of six studies on mental health problems in the family context, specifically focusing on the associations with the parent-child relationship, parenting behaviors and experiences of childhood maltreatment. The aim is to better understand the risk factors, development and transmission of common psychological problems in order to contribute to prevention and treatment strategies for common psychological problems such as anxiety and depression.Overall, the findings underline the importance of the family context in the development and levels of mental health problems. In addition to the impact of one's own negative parenting experiences, including lack of warmth and experiences of emotional or physical abuse, negative parenting experiences of one's siblings are also associated with elevated anxiety and depressive symptom levels.We also found that externalizing problems of fathers and children have a negative impact on the parent-child interactions. In addition, we found that children with behavioral problems during early adolescence experience harsher parental discipline, even three years later.In the current treatment guidelines for common mental disorders, most therapies focus on the individual. An (additional) systemic approach and considering past and present family relationships in therapy, can be of additional value. For example, supporting families with interventions to improve the parent-child relationship can be helpful in the short and long term. Moreover, (early) treatment of psychological and behavioral problems of the parent or child might be beneficial for all family members. Show less
Vitamin D is a hormone produced in the skin via a non-enzymatic process involving ultraviolet light.It is well known that the physiology of aging makes older people particularly susceptible to... Show moreVitamin D is a hormone produced in the skin via a non-enzymatic process involving ultraviolet light.It is well known that the physiology of aging makes older people particularly susceptible to vitamin D deficiency and that, if untreated, it can have serious health consequences. This thesis deliberates on the topics of vitamin D supplementation in older people in light of the current guidelines and on the possible additional effects of ultraviolet light beyond vitamin D synthesis on nursing home residents. We present a cross-sectional study in nursing home residents aged 70 years and over designed to evaluate the efficacy of vitamin D supplementation in achieving vitamin D sufficiency. We also discuss the different supplementation strategies for nursing home residents and community dwelling persons aged 70 years and over based on a survey administered to general practitioners and elderly care physicians in the Netherlands.In the second part we concentrate on additional effects of ultraviolet light beyond vitamin D synthesis. We describe our systematic review of literature on the effect of ultraviolet light, when applied to the skin or eyes, on mood, depression and well-being. We present also our randomized controlled trial on the effect of ultraviolet radiation compared with oral vitamin D supplementation on the well-being of nursing home residents with dementia. Further we use the data of the RCT to carry out a post-hoc analysis to compare the effect of vitamin D alone compared with ultraviolet radiation on the blood pressure of old people with dementia. Show less
This PhD project revealed that the female hormonal status – including OC use – and stress vulnerability – as defined by the MR-haplotype – have practical implications in experimental psychological... Show moreThis PhD project revealed that the female hormonal status – including OC use – and stress vulnerability – as defined by the MR-haplotype – have practical implications in experimental psychological research. Furthermore, incorporation of these variables in models of emotional information processing may be of help in understanding and treating mood disorders in women. Namely, even small biases may affect information processing and may contribute to the resilience or proneness to mood-disorders.Our research was among the first to show that the genetic makeup of healthy women may play a role in the influence of the female hormonal status on emotional information processing. Healthy female MR-haplotype 1/3 carriers may be more prone to distress, and may also be more sensitive to (pharmacological) changes which may counteract or sustain their vulnerability. Consistently, we observed subtle markers of depressogenic side-effects of OC only in MR-haplotype 1/3 carriers. Our findings regarding the MR-haplotypes 2 carriers are generally in line with earlier observations. We observed that MR-haplotype 2 carriers – especially homozygotes – are the less susceptible, more optimistic and more rational individuals, also in ‘unstressed’ conditions. However, stress-related psychopathology is very heterogeneous by nature and proteins from multiple genes are likely to interact in the stress-susceptibility phenotype. Last but not least, we should not ignore that the increased vulnerability of women to mood disorders is the result of a plethora of biological, psychological and sociological factors.OC-users had lower affect variability and reduced sensitivity to interpersonal emotional cues. This may be experienced as either a stabilizing or a blunting effect of OC, perhaps depending on the individual’s appraisal. The lower depression scores of OC-users in our longitudinal study suggests a protective effect of monophasic OC on symptoms of reproductive depression. Future studies should investigate (former) OC-users in larger cohorts including novel users, satisfied users and ‘brand-switchers’ in order to control for the survivor effect. Show less
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
In een cross-sectioneel onderzoek is nagegaan hoe het op de lange duur met CVA patiënten gaat die in het Haaglanden Medisch Centrum te Den Haag opgenomen zijn geweest vanwege een beroerte. Er is... Show moreIn een cross-sectioneel onderzoek is nagegaan hoe het op de lange duur met CVA patiënten gaat die in het Haaglanden Medisch Centrum te Den Haag opgenomen zijn geweest vanwege een beroerte. Er is gekeken naar verschillende aspecten zoals handfunctie, werkhervatting, stemmingsproblemen en zorggebruik. Het blijkt dat, ondanks alle behandelingen die gegeven worden, een grote groep van deze mensen restbeperkingen ervaart. Hun partners voelen zich fors belast, vooral als er sprake is van stemmingsproblemen en als werkhervatting niet lukt. Ook jaren later geeft de meerderheid van CVA patiënten aan nog steeds zorgvragen te hebben die niet beantwoord zijn. Ze lijken beter hun weg te vinden in de eerstelijn voor hun fysieke problemen dan voor hun mentale problemen. Er is gekeken naar de mate waarin eerstelijns behandelaars zich hebben georganiseerd met betrekking tot chronische behandeling en begeleiding van CVA patiënten. Een goed georganiseerd netwerk, met een visie op kwaliteitsaspecten en scholing, is maar op enkele plaatsen in het land beschikbaar. Er zijn aanbevelingen geformuleerd om de ontwikkeling van eerstelijns netwerken voor CVA patiënten te stimuleren. Show less
Hoewel voorheen al onderzoek is verschenen naar verschillende onderdelen van de migrainedriehoek: chronificatie, depressie, en medicatieafhankelijkheid, waren er nog altijd ontbrekende stukken van... Show moreHoewel voorheen al onderzoek is verschenen naar verschillende onderdelen van de migrainedriehoek: chronificatie, depressie, en medicatieafhankelijkheid, waren er nog altijd ontbrekende stukken van de puzzel. Dit proefschrift onderzocht verschillende aspecten van deze driehoeksrelatie, waarbij wij ons richtten op:• klinische determinanten van depressie in migrainepatiënten (hoofdstuk 2 en 3),• de associatie van depressie met migraine aanvalsfrequentie, zowel in dwarsdoorsnede onderzoek (hoofdstuk 2) als in longitudinale studieopzet (hoofdstuk 3),• de rol van allodynie van de huid in zowel de comorbiditeit met depressie alsook migraine chronificatie (hoofdstuk 2 en 3),• symptoomdimensies van affectieve stoornissen in migrainepatiënten, in vergelijking met personen zonder migraine met en zonder affectieve aandoeningen (hoofdstuk 5),• de comorbiditeit van depressie in hemiplegische migraine, als een monogenetisch migraine fenotype (hoofdstuk 4),• genetische factoren die betrokken zijn bij migraine chronificatie (hoofdstuk 7),• de comorbiditeit van depressie in clusterhoofdpijn, als een ernstige episodische primaire hoofdpijnvorm anders dan migraine (hoofdstuk 8), en• de behandeling van medicatieafhankelijke hoofdpijn. Show less
In this thesis, longitudinal analyses have been performed on the PROPARK-Cohort, a hospital-based cohort of 421 patients followed for a period of five years. The main focus of this thesis was... Show moreIn this thesis, longitudinal analyses have been performed on the PROPARK-Cohort, a hospital-based cohort of 421 patients followed for a period of five years. The main focus of this thesis was to determine which predictors and associated factors contributed to the development of certain non-motor symptoms in Parkinson’s disease (PD). Strengths of our cohort study include the length of the follow-up period, broad clinical characterization, limited loss-to-follow-up and the large cohort size. The following non-motor symptoms have been addressed in this thesis: psychosis (hallucinations), dementia, excessive daytime sleepiness (EDS), insomnia, depression and anxiety. We found that while certain non-motor symptoms are inherent components of PD that increase in severity as the disease progresses, others symptoms such as excessive daytime sleepiness are inarguably caused by antiparkinsonian medication. For the future, we hope to see more longitudinal data on the disease progression in PD from large cohorts. Knowledge from longitudinal studies does not only contribute to more insight in the underlying pathobiology of PD, but it could also help the caregiver to monitor patients with particular risk factors more closely and adjust treatment if necessary. Show less
This thesis investigates different aspects of apathy - as a distinct clinical syndrome assessed with the Apathy Scale- in older persons with and without concurrent depression. In Chapter 2,... Show moreThis thesis investigates different aspects of apathy - as a distinct clinical syndrome assessed with the Apathy Scale- in older persons with and without concurrent depression. In Chapter 2, clinically relevant subtypes of apathy according to the Apathy Scale in older persons from the PROMODE study are examined, using data-driven Latent Class Analysis (LCA). Further, specific characteristics across the classes identified by LCA are investigated. Then, in Chapter 3, cross-sectionally the prevalence, severity and clinical profile of apathy in depressed and non-depressed older persons, in relation to various possible determinants is described. Chapter 4 examines which characteristics predict, over a 2-year period, the incidence and course of apathy in at baseline depressed older persons from the NESDO study. Chapter 5, using data of the NESDO and NESDA, investigates the presence of apathy in late-life compared to early-life depression, and various determinants of clinically relevant apathy in older compared to younger depressed persons. In Chapter 6 the association of the presence of apathy among community-dwelling older persons from the PROMODE study and a diminished quality of life is examined. All results are placed a current perspective in Chapter 7 that also discusses clinical implications, and makes some recommendations for future research. Show less
The overriding aim of my thesis was to study the relationship between blood pressure (BP) and cognitive and psychological functioning in older persons. Observational studies indicate that lower BP... Show moreThe overriding aim of my thesis was to study the relationship between blood pressure (BP) and cognitive and psychological functioning in older persons. Observational studies indicate that lower BP increases risk for cognitive decline in older persons. Older persons are at risk for impaired cerebral autoregulation, and lowering their BP may compromise cerebral blood flow and cognitive function. Contradictory to our hypothesis, the Discontinuation of Antihypertensive Treatment in Elderly people (DANTE) Study Leiden, a community-based randomized clinical trial in older persons (aged ≥75 years) with mild cognitive deficits, did not show that discontinuation of antihypertensive treatment improves cognitive functioning. The lack of the effect of this trial may be due to the unintentional inclusion of persons with a relatively intact cerebral autoregulation. Furthermore, we demonstrated that older persons with mild cognitive deficits and with orthostatic hypotension, who discontinued all their antihypertensive medication had an increased probability of being free from orthostatic hypotension 4 months later, compared to persons who continued their medication. Finally, in the DANTE MRI sub study, the relationship between BP and both conventional features of small vessel disease (SVD) and microstructural damage was explored, as well as the relation between microstructural damage and cognitive and psychological dysfunction. Show less
One of the main findings of the current thesis is the fact that psychosocial factors such as life events and low social support are not primarily predictors of subsequent mood symptoms, but also... Show moreOne of the main findings of the current thesis is the fact that psychosocial factors such as life events and low social support are not primarily predictors of subsequent mood symptoms, but also seem to occur as a result of mood symptoms . Over the last decades longitudinal studies have proven their great value for research in BD. These studies provided ample knowledge about the bipolar disease course and its associated factors. The current study contributed to this knowledge by adding different research approaches to analyse and interpret these complex longitudinal associations. These results implicate that it is difficult, and maybe not even very useful, to determine cause and effect when studying the ongoing interaction between the course of bipolar disorder and psychosocial factors. Consequently, models in which strict monocausal directions of causality are abandoned might lead to a closer approximation of the reality of the disorder and its complex interactions with the environment. The network approach may turn out to be a suitable statistical method to analyse and understand such complex associations. Show less
In this thesis the epidemiology of suicidal ideation and suicide attempts (together referred to as 'suicidality') in Huntington's disease (HD) is investigated and coping styles and support... Show moreIn this thesis the epidemiology of suicidal ideation and suicide attempts (together referred to as 'suicidality') in Huntington's disease (HD) is investigated and coping styles and support strategies that may serve to help suicidal HD mutation carriers are explored. Suicidality frequently occurs in HD, with a 1-month prevalence of up to 20%. Mutation carriers who were most likely to currently experience suicidal ideation or suicidality had a shorter disease duration, were anxious, aggressive, previously attempted suicide, used antidepressants, and had a depressed mood. The presence of a depressed mood and use of benzodiazepines were the only significant independent predictors of incident suicidal ideation or suicidality. Biological parameters, in particular functioning of the immune system and the hypothalamus-pituitary-adrenal axis were not found to be associated with suicidality in HD. In a qualitative study it was shown that suicidal HD mutation carriers generally used four strategies to cope with suicidality: talking about suicidality, employing self-management activities, using medication, and discussing end-of-life wishes. Lastly, in a meta-analysis, we examined whether the expression of suicidal ideation predicted subsequent completed suicide. Effect estimates differed substantially among different populations, but none of the included studies investigated this association in HD. Show less
In this thesis Marcelo Gerona and Silvana Sosa undertake an analysis of the Great Depression (1928-1934) in a sample of three highly interconnected South American countries: Argentina, Brazil and... Show moreIn this thesis Marcelo Gerona and Silvana Sosa undertake an analysis of the Great Depression (1928-1934) in a sample of three highly interconnected South American countries: Argentina, Brazil and Uruguay (ABU). The problem tackled in this work is the relative vulnerabilities of ABU, which contributed to the strong impact of the Great Depression, as well as the nature of the policy responses to the economic emergency. In this context, the hypothesis is that ABU were highly vulnerable to the Great Depression, and among them the smallest country, Uruguay, was the most vulnerable of all. This research is original not only for having assessed jointly these three scarcely analysed countries from a historical-comparative perspective during this uneasy period of time, but also because of the introduction of a new eclectic conception of ‘complex vulnerability’ that involves many paradigms and points of view. Furthermore, the historic research along with a comparative reference to the Financial Crisis of 2008 helps the reader to understand the role of the semi-periphery, in an effort that is appealing for both historians and policymakers worldwide. Show less
