Since heterogeneity in depressed patients makes treatment decisions difficult and treatment often unsuccessful, we seek to identify certain subtypes of depression. 30 to 40% of depressed patients... Show moreSince heterogeneity in depressed patients makes treatment decisions difficult and treatment often unsuccessful, we seek to identify certain subtypes of depression. 30 to 40% of depressed patients have anger regulation problems; from irritability to anger attacks. What is the significance of anger in depression? Does it signify a subtype of depression? In the NESDA cohort, we compared a large sample of currently depressed patients with irritability to currently depressed patients without irritability. Irritable depressed patients had more symptoms of depression, more often had comorbid anxiety and had more often attempted suicide than non-irritable depressed patients. In a student sample, we investigated the role of the MAOA genotype and found that women with the high expression variant are possibly more vulnerable to anger or aggression during depression. Using acute tryptophan depletion we temporarily lowered serotonin in remitted depressed patients with and without anger regulation problems during their depression. We found no cognitive differences between the two groups, but the experiment did show us that depressed patients with anger regulation problems may be more serotonergically vulnerable. Further research is needed to elucidate best suited treatment strategies for anger regulation problems in depression Show less
The present thesis concentrates on predictors and outcomes of occupational stress in emergency (ER-) nurses, working in in-hospital emergency wards, ambulance services and fast rescue teams. More... Show moreThe present thesis concentrates on predictors and outcomes of occupational stress in emergency (ER-) nurses, working in in-hospital emergency wards, ambulance services and fast rescue teams. More specifically, this thesis focuses on the relationships between (1) demographic factors, (2) exposure to traumatic events, (3) job characteristics, (4) organizational variables, (5) coping strategies and (5) goal orientation as potential determinants of (a) job satisfaction, (b) turnover intention, (c) burnout, (d) work engagement, (e) post-traumatic stress symptoms (f) fatigue and (g) other somatic complaints. The first part of this chapter gives an overview of the main results of the different studies, followed by an attempt to integrate all these results from a theoretical and methodological point of view, resulting in a set of practical recommendations and directions for future research Show less
In this thesis four studies assessing putative pathways implicated in cognitive models of depression are presented and discussed. In two initial studies the possibility to manipulate attention... Show moreIn this thesis four studies assessing putative pathways implicated in cognitive models of depression are presented and discussed. In two initial studies the possibility to manipulate attention allocation bias using two types of attention bias modification (ABM) procedures was explored. Neither method successfully or consistently modified attention allocation bias in dysphoric individuals. Putative interactions between 5-HTTLPR genotype and life stress were studied in the third study. Adopting an endophenotype approach, effects on measures of biased information processing were assessed. S-allele carriers showed increased recognition of negative mood state as a function of recent negative life events. Hypothesized interactions with childhood emotional abuse or affection attention allocation bias were found non-significant. A main effect of 5-HTTLPR was observed such that s- allele carriers selectively oriented attention towards negative information. In the fourth study the predictive value of cognitive reactivity to sad mood (measured with the LEIDS-r questionnaire) for the first onset of depression was assessed. Among 834 never previously depressed participants, cognitive reactivity predicted first onset of depression over the subsequent two years, even when various other factors, including baseline symptoms and negative life events, were statistically controlled for. Finally, these findings are discussed and related to the existing literature 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
Confidence in a theory increases when it is confirmed by relevant data. Alongside some consistent findings, the data in the prevailing thesis largely detail a lack of confirmation of the... Show moreConfidence in a theory increases when it is confirmed by relevant data. Alongside some consistent findings, the data in the prevailing thesis largely detail a lack of confirmation of the neurotrophin hypothesis. And where expected associations were established (e.g., abnormally low serum BDNF concentrations in the depressed state), the meaning often was not that clear (e.g., reverse causation). I therefore conclude, whilst taking limitations into account and acknowledging that the results are contingent upon imperfect and peripheral measurement, that the most reliable evidence in humans does not corroborate the neurotrophin hypothesis. So, given the data, the final words of this thesis are that solid work over novelty shows that the neurotrophin hypothesis should no longer be credited in its original form. All that glitters is not gold - back to the drawing table 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
