Depression involves multiple mental problems, including low mood, inability to experience pleasure and emotional, cognitive and behavioral problems. It has a lifetime prevalence of ~15% in the... Show moreDepression involves multiple mental problems, including low mood, inability to experience pleasure and emotional, cognitive and behavioral problems. It has a lifetime prevalence of ~15% in the Dutch population, striking women twice as often as men. The disorder often comprises persisting disturbances in the neuroendocrine stress system, the hypothalamic- pituitary-adrenal (HPA) axis, including disregulation of its end-hormone cortisol. Cortisol normally stimulates emotional, cognitive and behavioral processes in order to cope with a stressor and promotes recovery, learning and memory. This thesis describes the identification of a specific genetic variant of the mineralocorticoid receptor (MR), one of the two receptors for cortisol, which protects against depression. MR transcript expression was found to be lower in postmortem limbic brain regions of depressed patients compared to non-depressed subjects. In addition, a specific and common MR gene variant was identified that results in higher MR expression in vitro. This same variant was found to associate with personality characteristics that predict the risk of depression later in life and with a lower risk of depression itself. All associations were found only in women and not in men. To conclude, the MR is an important determinant of resilience; increased MR expression seems to be protective against depression. Show less
This thesis explores cognitive vulnerability to depression and the interplay between genetic and environmental influences. Cognitive vulnerability to depression is characterized by negative... Show moreThis thesis explores cognitive vulnerability to depression and the interplay between genetic and environmental influences. Cognitive vulnerability to depression is characterized by negative patterns of information processing. One aspect is cognitive reactivity - the tendency to respond with maladaptive thoughts when mood is challenged. Vulnerable individuals also show negative cognitive biases in emotion perception and attention, and impaired decision-making. How one processes personal and socially relevant information plays an important role in the development and maintenance of depression. The first part of the thesis reports how the interplay between genes and environment affects cognitive reactivity and emotional information processing. We observed that genes and environmental stressors interact to determine a person’s vulnerability to depression or resilience. Cognitive reactivity was also found to be a residual vulnerability factor in individuals with history of suicidal tendencies. The second part of the thesis is comprised of two experimental manipulations on emotional cognition. Effects of omega-3 fatty acid supplementation were examined on mood and cognition of healthy participants and recovered depressed individuals. Omega-3 fatty acids can have selective effects on mood and cognition of individuals, but the pathways through which this happens remain to be investigated. 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
This thesis focuses on patients with Binge Eating Disorder. The thesis consists of three parts. In the first part the validity of the diagnosis of BED will be discussed. The results of two... Show moreThis thesis focuses on patients with Binge Eating Disorder. The thesis consists of three parts. In the first part the validity of the diagnosis of BED will be discussed. The results of two literature reviews and an empirical cross-sectional study suggested that BED is a distinct eating disorder and should be added to a next version of the DSM. In the second part results of a randomized controlled trial were described. The effectiveness of cognitive behavioural therapy was compared to a waiting list control group. As expected, objective binge eating frequency, eating disordered psychopathology, and comorbid psychopathology decreased significantly in the CBT group whereas no reduction was found in the control (WLC) group. Mediator analyses indicated that abstinence from binge eating at post treatment was fully mediated by changes in weight concerns and marginally by changes in concerns about shape and eating, depressive symptoms, and more general psychopathological symptoms. In the third and last part the results of two experimental studies were presented. The purpose of the studies was to investigate the causal relationship between negative mood and binge eating. Both experimental studies found evidence for the fact that in individuals with BED depressive symptoms and caloric intake are positively related. Show less
What kinds of personal goals, aspirations and plans do Dutch youths consider important in their lives? And how does experience of setbacks when pursuing these goals and means of coping with these... Show moreWhat kinds of personal goals, aspirations and plans do Dutch youths consider important in their lives? And how does experience of setbacks when pursuing these goals and means of coping with these frustrations influence their psychological well-being and experience of headache? These are some of the main questions addressed in this research project by means of a series of questionnaire and diary studies among high-school students. Goals were most commonly reported in the area of interpersonal relationships, followed by health and body, their future, school, leisure and personal development. Importance of adolescent aspirations and thoughts and emotions related to these goals were shaped to a large extent by personal and contextual characteristics such as gender, age and ethnicity. Goal importance did not differ according to experience of headache, however, youths with weekly headache reported higher levels of frustration in personal goal pursuits compared to their headache-free peers. Frustration in pursuit of especially self and health goals was related to higher depressive symptoms and lower quality of life in a cross-sectional questionnaire study. Furthermore, frustration predicted next-day lower well-being and greater headache complaints in a prospective diary study. Moreover, dwelling on the negative aspects of the situation (catastrophizing), repetitive thoughts about the frustration (rumination) and the belief that one is unable to cope well with the setback predicted next-day poorer psychological well-being. This was one of the first studies to assess the contribution of self and emotion regulation factors to well-being and headache in adolescence and offers insights into possible targets for intervention with youths Show less
To fail or not to fail __ Clinical trials in depression investigates the causes of the high failure rate of clinical trials in depression research. Apart from the difficulties in the search for new... Show moreTo fail or not to fail __ Clinical trials in depression investigates the causes of the high failure rate of clinical trials in depression research. Apart from the difficulties in the search for new antidepressants during drug discovery, faulty clinical trial designs hinder their evaluation during drug development. This thesis focuses on three important aspects of clinical trials in depression: clinical endpoints, data analysis and trial design-related factors. Show less
In Chapter 2, results of a study are reported in which remitted depressed patients are compared to healthy controls to investigate possible residual cognitive impairments that persist into the... Show moreIn Chapter 2, results of a study are reported in which remitted depressed patients are compared to healthy controls to investigate possible residual cognitive impairments that persist into the euthymic phase. Chapter 3 will describe the effects of an alpha-lactalbumin enriched diet on cognitive performance in unmedicated recovered depressed patients and healthy controls. In Chapter 4 the effects of alpha-lactalbumin on mood and stress-induced cortisol response in unmedicated recovered depressed patients and healthy controls are reported. Chapter 5 describes the effects of low-dose and high-dose ATD on mood and neutral as well as emotional information processing in medicated remitted depressed patients. In Chapter 6, the effects of low-dose and high-dose tryptophan depletion on individual plasma tryptophan levels and the ratio tryptophan/LNAA will be discussed. In Chapter 7 the effects of ATD on heart rate variability in medicated remitted depressed patients are reported. A literature overview of studies investigating the effects of serotonin manipulations on emotional information processing and mood is given in Chapter 8. Also, evidence for a possible sequential link between serotonin induced changes in emotional information processing and mood is evaluated. Chapter 9 contains a summary and integration of the main findings, as well as methodological strengths and limitations, directions for future research and clinical implications of the findings reported in this thesis 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
