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