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
In this thesis, we used qualitative and quantitative research methods to gain insight in treatment decision-making for depression- and anxiety disorders in specialized mental health care. We... Show moreIn this thesis, we used qualitative and quantitative research methods to gain insight in treatment decision-making for depression- and anxiety disorders in specialized mental health care. We identified what factors are important in the decisional process, to both patients and clinicians, and how they determine decision-making outcomes, i.e., the decision to opt for: pharmacotherapy, psychotherapy, or a combination of both. We determined what preferences patients and clinicians have regarding the treatment of depression and anxiety disorders, which treatments are selected, and which factors are involved in the formation of such treatment preferences and treatment selection. Additionally, we determined what preferences patients and clinicians have regarding their role in the decisional process, their experienced decision-making roles, and the level of concordance between preferred and experienced role of patients. Finally, we examined the extent of Shared Decision-Making (SDM) in clinical practice and explored possible target points to improve SDM. Show less
De uitkomsten beschreven in dit proefschrift dragen bij aan de bestaande overtuiging dat een verfijndere classificatie voor depressie, op basis van symptoomprofielen en hun mogelijke biologische... Show moreDe uitkomsten beschreven in dit proefschrift dragen bij aan de bestaande overtuiging dat een verfijndere classificatie voor depressie, op basis van symptoomprofielen en hun mogelijke biologische onderbouwing, overwogen dient te worden. Inmiddels wordt adipositas in de dagelijkse praktijk op meer dan alleen het BMI beoordeeld, namelijk ook de tailleomtrek en het lipidenprofiel. Echter, dergelijke aandacht bestaat nog niet voor de heterogeniteit van depressie. Een grotere bewustwording van de verschillende manifestaties van depressie-symptomatologie, die het gevolg kunnen zijn van uiteenlopende pathofysiologische mechanismen, is van essentieel belang. Wanneer een patiënt met depressie een atypisch energie-gerelateerd symptoomprofiel heeft, kan het nuttig zijn om diens metabole biomarkers te controleren om mogelijke ontwikkeling van cardiometabole ziekten te voorkomen. In de klinische praktijk moeten wij ons bij de behandeling van patiënten met depressie ook meer bewust worden van de correlatie tussen symptoomprofielen van depressie en afzonderlijke biologische en klinische manifestaties. Het is cruciaal om goed te kijken naar de symptomen die bij elke patiënt tot uiting komen. De resultaten van dit proefschrift tonen aan dat patiënten met een depressie die atypische energie-gerelateerde depressieve symptomen vertonen, genetisch en klinisch kwetsbaar zijn voor aan insulineresistentie gerelateerde ziekten (namelijk adipositas, metabole ontregelingen en diabetes mellitus type 2). Een gepersonaliseerde aanpak kan behulpzaam zijn in preventie van deze chronische en complexe ziekten. Hierbij dient er rekening gehouden worden met de heterogeniteit van depressie en de associatie tussen atypische energie-gerelateerde symptomen van depressie en deze ziekten. 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 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
It is well known that military deployment can lead to mental health problems in veterans, but the long-term impact is still unclear. This thesis discusses the results of the PRISMO-study, a large... Show moreIt is well known that military deployment can lead to mental health problems in veterans, but the long-term impact is still unclear. This thesis discusses the results of the PRISMO-study, a large cohort study in a group of Dutch Afghanistan veterans with a follow-up period of ten years. It shows that at ten years post-deployment, 8% of the cohort reported severe symptoms of posttraumatic stress disorder (PTSD). Agoraphobia, anxiety, depression, and hostility symptoms are also reported more frequently at ten years post-deployment compared to pre-deployment. Furthermore, this thesis demonstrates the large heterogeneity in PTSD symptom development among veterans. Of note is the delayed onset group that experienced increasing symptom levels between five and ten years post-deployment and did not show significant symptom reduction. The results from this thesis also show that various psychological factors, such as social support, and biological factors, such as DNA methylation, are associated with the development of PTSD or other mental health symptoms after deployment. Combining these factors in a prediction model for PTSD symptoms has not led to a useful screening instrument. It does, however, offer important leads for the identification of risk factors for PTSD and the development of intervention programs. 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
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
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
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
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
In this dissertation clinical genetic investigations on migraine, related syndromes and comorbid conditions are described. The first migraine syndrome studied is Familial Hemiplegic Migraine (FHM),... Show moreIn this dissertation clinical genetic investigations on migraine, related syndromes and comorbid conditions are described. The first migraine syndrome studied is Familial Hemiplegic Migraine (FHM), a monogenic migraine variant. The clinical spectrum of FHM1-3 and the relation with closely related diseases such as Alternating hemiplegia of Chilhood, Early Seizures and Cerebral Edema after Trivial Head Trauma, epilepsy and episodic ataxia were investigated. The second monogenic migraine syndrome studied is Retinal Vasculopathy with Cerebral Leukodystrophy (later renamed CHARIOT), where common migraine is part of the clinical spectrum. The identification of TREX1 as the causal gene for RVCL is described. Investigation of the clinical spectrum showed retinal, cerebral and internal organ involvement, without an apparent genotype-phenotype correlation. Endothelial dysfunction of large arteries was shown in RVCL patients and is proposed as a possible disease mechanism. Lastly, migraine patients were identified in a Dutch genetic isolate and the relation with depression and atherosclerosis was assessed. For depression it was shown that shared genetic factors, at least partly, underlie the comorbidity with migraine, in particular migraine with aura. These studies improve our insight in genetic factors and pathofysiological mechanisms involved in migraine, which may ultimately contribute to better treatment options for migraine patients Show less
The primary aim of the NormQuest study described in this thesis was to generate evidencebased, reference values for 19 self-report and observational questionnaires. The focus was on questionnaires... Show moreThe primary aim of the NormQuest study described in this thesis was to generate evidencebased, reference values for 19 self-report and observational questionnaires. The focus was on questionnaires measuring mood, anxiety, and somatoform (MAS) disorders used in Routine Outcome Monitoring (ROM). The set of cut-off values of the ROM reference group (__healthy__) can be used in specialized mental health care by therapists to support the decision whether a patient is sufficiently recovered to be considered as a member of the healthy population, and no longer as a member of the patient population. These reference values are suitable as decision support for referral back to primary care physicians. Additionally, the set of the ROM patient group (__clinically ill__) cut-off values can be used by primary care physicians as decision support for referral to the specialized mental health care. To allow determination of cut-off points for skewed distributions, percentile scores were used. In addition, we assessed the discriminative power of the questionnaire scores by means of Receiver Operating Characteristics (ROC) analyses. Finally, we calculated reference values in separate strata of gender and age. The secondary aim of the NormQuest study concerned the need for the development of public domain questionnaires. In the NormQuest study, the generic Symptom Questionnaire-48 (SQ-48), aimed at broad applicability in patients with MAS disorders, was developed. Also, for the SQ-48 reference values were calculated Show less
Research into the relation between psychopathology and etiological factors has not yet resulted in clear findings. One of the probable causes is that most researchers use the categorical DSM-IV... Show moreResearch into the relation between psychopathology and etiological factors has not yet resulted in clear findings. One of the probable causes is that most researchers use the categorical DSM-IV Classification of mental disorders. A dimensional system has several advantages compared to categorical systems: comorbidity, lack of diagnostic agreement and arbitrary nature of used boundaries are no longer a problem. Our aim was to develop a model with dimensions that can adequately describe patients with mood- and anxiety disorders. This project used data collected through Routine Outcome Monitoring (ROM), a monitoring system for patient care. First, we validated a Dutch adaptation of an instrument based on the tripartite model. Next, we formulated an extension of this model with 5 dimensions. Consequently we presented a second model with 6 dimensions: feelings of worthlessness, fatigue, somatic arousal, anxious apprehension, phobic fear and tension. We used several analysis techniques to create a valid and reliable dimensional model. Each individual factor and the total of factors can be regarded as unidimensional measurement scales. This model can describe the clinical state of patients more specifically than the tripartite model, and can be used in subsequent research into etiological factors of psychopathology (e.g. endophenotype, genotype, trauma's, personality). Show less
When a child is often scolded or threatened by his parents (emotional abuse) and /or when a child is structurally ignored or isolated by his parents (emotional neglect) we call this childhood... Show moreWhen a child is often scolded or threatened by his parents (emotional abuse) and /or when a child is structurally ignored or isolated by his parents (emotional neglect) we call this childhood emotional maltreatment (CEM). CEM is the most common form of child abuse, however, CEM is also the most hidden, underreported and least studied form of child abuse. An important reason for this may be because that the consequences of CEM are underestimated (e.g. __Sticks and Stones may break bones, but words will never hurt me__). However, this thesis shows that CEM is related with a persistent negative impact on cognition and the brain. We discovered that individuals that report CEM show differential structure and function of a brain area (the medial prefrontal cortex) that is crucial for role in responding to stress and thinking about yourself. Individuals with CEM also showed more activity in an area that signals threat (the amygdala) which may represent a persistent vigilance towards the detection of threat from others. These brain changes may underlie our other findings that individuals with CEM think more negatively about themselves and others. Negative thoughts can evoke negative thoughts and in new situations, which reinforces more negative memories. Due to this process, emotionally abused individuals may be more vulnerable to develop a depressive and/or anxiety disorder. Our findings warrant scientific and policital investments to increase societal awareness about the detrimental impact of CEM on cognition and the brain. Increased societal knowledge will hopefully lead to better awareness, reports, and subsequent interventions for individuals with CEM. Show less
