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
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
In this thesis, we have studied the potential of the zebrafish larval model in studying the ECS, as a complementary model to the existing rodent models. More specifically, we have looked at the... Show moreIn this thesis, we have studied the potential of the zebrafish larval model in studying the ECS, as a complementary model to the existing rodent models. More specifically, we have looked at the role of the ECS in regulating locomotion and anxiety, and its interaction with the hypothalamic-pituitary-interrenal (HPI) axis, or stress axis. This study has provided us with an interesting animal model which allows for pharmacological screening of Cnr1 agonists, and their involvement in the CNS, as shown by a change in locomotion, anxiety-like behavior and HPI axis activity. The zebrafish larval model can be used as a complementary model to the existing rodent animal models, to study the ECS. The zebrafish larval model brings several interesting features, such as optical transparency and possibilities for high-throughput screening. Furthermore, a complete ECS is present, there is lack of endogenous activity, allowing for exogenous compound screening, and zebrafish data is generally in line with rodent literature. Since the ECS is involved in many diseases, more research of this system may result in the discovery of novel drugs and drug targets. Show less
This thesis describes the relation of fear of childbirth (FOC), measured pre- and postpartum, with the preferred and actual place and mode of giving birth and with the use of pharmacological pain... Show moreThis thesis describes the relation of fear of childbirth (FOC), measured pre- and postpartum, with the preferred and actual place and mode of giving birth and with the use of pharmacological pain relief during labour. The studies were embedded in the Dutch obstetric system, where midwives have an independent profession and where home birth is an accepted option for women with a low-risk pregnancy. The general finding, consistent across all studies in this thesis, is that the level of FOC in pregnancy was strongly related to, and predictive of the level of postpartum FOC. Furthermore, women with severe FOC during pregnancy were prone to preferring a hospital birth, having pharmacological pain relief during labour and requesting an elective Caesarean Section. Congruence between one’s own preference (of place or mode of giving birth) and the actual delivery situation was not related to the degree of postpartum FOC. Instead, predictors for high postpartum FOC were: being referred from midwifery-led care to obstetrician-led care, emergency Caesarean Section, and a poor condition of the new-born. For guiding women with severe FOC through pregnancy and childbirth, a close collaboration between the obstetric caregiver and a psychotherapist is advised. Show less
Art therapy is an often provided but little studied treatment option in mental health care.The effectiveness of art therapy in the treatment of anxiety was studied and its working mechanisms were... Show moreArt therapy is an often provided but little studied treatment option in mental health care.The effectiveness of art therapy in the treatment of anxiety was studied and its working mechanisms were explored. Outcomes of a randomised controlled trial (n=59) showed preliminary evidence of the effectiveness of art therapy. The treatment, consisting of three months of anthroposophic art therapy, showed major reduction of anxiety symptom severity in women, compared to a wait list condition. The therapy also improved quality of life and various aspects of self-regulation: higher HRV at rest (which may indicate an overall lower stress level), improvements in emotion regulation and improvements in daily executive functioning.The second part of this PhD research focused on case report methodology and the development of tools for research within this field, with and for therapists in clinical practice, and for education. A publication guideline for case reports was developed and positively evaluated in practice. An exemplary case report of a female client with anxiety was provided.The outcomes of this research support the indication of art therapy in the treatment of anxiety and justify further studying of the effectiveness and mechanisms of art therapy. Show less
The GABAergic system has been implicated in the pathogenesis of various anxiety disorders. Pharmacological treatments, like benzodiazepines, have been proven to target the GABA(A) receptors and... Show moreThe GABAergic system has been implicated in the pathogenesis of various anxiety disorders. Pharmacological treatments, like benzodiazepines, have been proven to target the GABA(A) receptors and exert quick-onset anxiolytic effect in anxiety patients. However, the side effects of these non-selective GABA(A)ergic compounds, such as sedation, postural imbalance, or potential abuse, limit their use for clinical anxiolysis. Based on the understanding of benzodiazepines’ mechanism of action, the emergence of α2,3 subtype-selective GABA(A) modulator is expected to provide a novel pharmacological approach that alleviates anxiety symptoms but spares the common undesired side effects. Most of these compounds are still in early clinical development, in which stage proof-of-mechanism studies are usually performed in healthy volunteers. The findings from our studies consistently present a similar pattern in the pharmacodynamic effect profiles of the α2,3 subtype-selective GABA(A) modulators versus those of the non-selective full GABA(A) agonist, lorazepam. Future application of anxiogenic symptom provocation models that combine subjective measurements and/or neuroendocrine biomarker assays may provide further construct validity for clinical anxiolytic effects of α2,3 subtype-selective GABA(A) modulators. Also, such findings are expected to provide insights into the translation of preclinical pharmacological properties of α2,3-subtype-selective GABA(A)ergic compounds to clinical effects in anxiety patients through human pharmacology studies. Show less
The main focus of the research that makes up this thesis was to translate rodent behavioural assays to larval zebrafish for better time and resource management in biomedical research,... Show moreThe main focus of the research that makes up this thesis was to translate rodent behavioural assays to larval zebrafish for better time and resource management in biomedical research, pharmaceutical research and development. __The larval zebrafish is a useful model in toxicology and drug discovery. However, its predictivity is restricted by compound class. __Light-dark cycle plays an important role in the normal development of the zebrafish embryo, and abnormal lighting regimes during rearing can result in malformations. __The hyperactivity displayed by zebrafish larvae following the onset of sudden darkness is an intrinsic characteristic. Zebrafish larvae quickly habituate with repeated stimuli of onset of darkness with short interstimulus interval. __Zebrafish larvae are able to discriminate colours, and they show a preference for orange and green, but aversion towards red, yellow, blue and black. The larvae also show freezing behaviour in the complex environment which is attenuated with diazepam.. __Zebrafish larvae raised in an abnormal lighting regime changed some aspects of their colour preference, although orange and red remained as preferred and avoided colours respectively. __In short, the zebrafish larvae is a useful complementary animal model in behavioural research amenable to high-throughput screening of compounds and drug discovery 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
The main objective of this thesis is to describe the epidemiology of long term BZD use as well as its long term consequences. This thesis is structured into three sections: In section one, the... Show moreThe main objective of this thesis is to describe the epidemiology of long term BZD use as well as its long term consequences. This thesis is structured into three sections: In section one, the correlates of BZD use, new use, chronic use, inappropriate use, and BZD dependence severity are investigated. The possible influence of the prescribing physicians on patient BZD use is also considered. In section two, the focus is on the physiological consequences of long-term BZDs use on the HPA axis and the ANS. In section three, cognitive effects of BZDs in long-term users are addressed Show less
The aim of this thesis was to clarify which aspects of depression and anxiety are related to an increased metabolic risk, and which factors contribute to these associations. Taken together, our... Show moreThe aim of this thesis was to clarify which aspects of depression and anxiety are related to an increased metabolic risk, and which factors contribute to these associations. Taken together, our findings indicate that people with more severe symptoms of depression and anxiety are at particular risk of progressive dyslipidemia and (abdominal) obesity. The higher rates of smoking and systemic inflammation among people with depression or anxiety partially accounted for their adverse metabolic profile. Dysregulations of the autonomic nervous system partly explained why users of tricyclic antidepressants displayed an increased risk of dyslipidemia and (abdominal) obesity as well, and also of hypertension. These important findings shed light on useful avenues for future research, and on preventive and therapeutic insights and directions. Show less
There is a growing awareness that research of the etiology of depressive and anxiety disorders has been hampered by their strictly categorical definition in the Diagnostic and Statistical Manual ... Show moreThere is a growing awareness that research of the etiology of depressive and anxiety disorders has been hampered by their strictly categorical definition in the Diagnostic and Statistical Manual (DSM). The DSM uses a syndrome approach, which __ although beneficial for standardization - has inherent problems that make it suboptimal for research: high rates of (artificial) comorbidity, diagnostic heterogeneity and the unrealistic assumption of discontinuity between ill and healthy. A dimensional approach that focusses on the relative severity of continuous symptom domains could be more optimal but measurement and the added value of such dimensions has been debated. Therefore, this dissertation was aimed to investigate (1) the internal validity and possibility to measure dimensions and (2) their added value in etiological and clinical research. The results showed that measurement of dimensions can be optimized using self-report questionnaires. In addition, dimensions were shown to have added value in etiological and clinical research. Because of their specific and continuous nature, dimensions could be used to uncover symptom-specific and/or non-linear association. Together, the results suggest that dimensions of depression and anxiety have internal and external validity and have the potential to improve the psychiatric research. Show less
The main purpose of this dissertation was to highlight and address seven challenges related to the measurement of youth cognition, understanding the role of cognitive constructs in anxiety and... Show moreThe main purpose of this dissertation was to highlight and address seven challenges related to the measurement of youth cognition, understanding the role of cognitive constructs in anxiety and school refusal, and the examination of cognitive mediators of cognitive-behavioural treatment outcomes. The studies presented in this dissertation contributed to the empirically valid assessment of constructs of cognitive processing in youth which were until now only present in cognitive theories of Aron Beck. Now, constructs of cognitive processing coming from the cognitive theories of depression and anxiety of Beck and colleagues can be assessed in youth using one single measure. Further, cognitive dimensions of cognitive products and cognitive processes from Beck and colleagues cognitive theories of emotional disorders were found to be important in the etiology of school refusal. The belief that positive treatment outcomes can be achieved through changes in cognition received support. Using innovative statistical approaches to mediation, it was found that enhanced levels of self-efficacy following cognitive-behavioural treatment for school refusal were associated with increased levels of school attendance and decreased levels of school fear. Show less
Doublecortin (DCX) and DCX-domain containing Doublecortin-Like Kinase (DCLK) gene splice variants function during embryonic development, where they play a role in microtubule binding. Although a... Show moreDoublecortin (DCX) and DCX-domain containing Doublecortin-Like Kinase (DCLK) gene splice variants function during embryonic development, where they play a role in microtubule binding. Although a role for the DCLK gene during embryogenesis is clearly established, it encodes multiple, different transcripts, some of which are expressed in the adult brain or in response to neuronal activity. This suggests that the DCLK gene may have additional functions beyond neuronal development. Strikingly, the roles of two DCLK gene products, DCLK-short and CaMK-related peptide (CARP), remain largely elusive. Therefore, we have generated transgenic mice with over-expression of either CARP or a constitutively active form of DCLK-short, called _C-DCLK-short, in the brain. This has opened up the possibility to study the effect of over-expression of these DCLK transcripts in the brain during adulthood. To gain more insight in DCLK gene function in the adult brain we aimed to study and describe the phenotypes of these transgenic mice at different functional levels, such as the genetic, network and behavioural level. Show less
Background: It is assumed that the endogenous subtype of depression is a form of depression with various biological abnormalities and a genetic predisposition. The clinical picture rarely shows... Show moreBackground: It is assumed that the endogenous subtype of depression is a form of depression with various biological abnormalities and a genetic predisposition. The clinical picture rarely shows prior stress and/or an abnormal personality. According to the DSM-IV, this subtype is reproduced as the melancholic subtype, but this subtype has insufficient external validity. This is mainly due to the specific operational method used in the categorical DSM system. Question: Reformulating the melancholic subtype by means of a multidimensional approach. This would be formulated and tested on different external validity levels, which should result in better external validity. An improvement at one level of investigation could lead to improvements in relation to other levels, and vice versa. The development of diagnostic concepts could therefore progress according to a cyclic validation process. For this reason, we also investigated whether a later-found subgroup with above-normal plasma AVP could be a more useful endophenotypic parameter as well. This subtype was also tested on different external validation levels. Results: We found a two-dimensionally based, highly anxious retarded subcategory, with better external validation criteria than the melancholic subtype. We also found a second subtype, namely above normal AVP depression, that also had better external validation criteria. Show less
Arnold, Ingrid Antonette; Waal, Margaretha Wilhelmina Maria de 2006
De huisarts ziet veel patienten met onverklaarde lichamelijke klachten, vaak in combinatie met angst- en depressieve klachten. Dit proefschrift beschrijft de resultaten van een prevalentie studie... Show moreDe huisarts ziet veel patienten met onverklaarde lichamelijke klachten, vaak in combinatie met angst- en depressieve klachten. Dit proefschrift beschrijft de resultaten van een prevalentie studie met een prospectieve follow-up en een daarop volgende behandelstudie. De prevalentie van somatoforme stoornissen (DSM-IV) was 16,1%: één op de zes patienten die de huisarts bezoekt had tenminste zes maanden last van onverklaarde lichamelijk klachten met aanzienlijke beperkingen. De overlap met angst en depressie was substantieel en vergrootte de ernst van de ziektelast. Deze bevindingen onderstrepen het belang van een brede diagnostiek in de huisartspraktijk die zowel angst en depressie als somatoforme stoornissen omvat. Het aantal symptomen, zowel lichamelijk als psychisch, kan een nuttig instrument zijn bij het identificeren van de ernstigste patiënten. Het gegeven dat bijna driekwart van alle patiënten met een somatoforme stoornis langdurig klachten houdt impliceert een grote behoefte aan behandeling. In een gecontroleerde behandelstudie konden we echter niet aantonen dat een cognitief-gedragsmatige interventie volgens het gevolgenmodel door getrainde huisartsen effectiever was dan gebruikelijke zorg. Aangezien de behandelde patiënten vaak ernstige klachten hadden stellen de auteurs voor om een stapsgewijze behandelmethode te ontwikkelen zodat zowel kortdurende als chronische klachten goed aangepakt kunnen worden. Show less
