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
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