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
De uitkomsten beschreven in dit proefschrift dragen bij aan de bestaande overtuiging dat een verfijndere classificatie voor depressie, op basis van symptoomprofielen en hun mogelijke biologische... Show moreDe uitkomsten beschreven in dit proefschrift dragen bij aan de bestaande overtuiging dat een verfijndere classificatie voor depressie, op basis van symptoomprofielen en hun mogelijke biologische onderbouwing, overwogen dient te worden. Inmiddels wordt adipositas in de dagelijkse praktijk op meer dan alleen het BMI beoordeeld, namelijk ook de tailleomtrek en het lipidenprofiel. Echter, dergelijke aandacht bestaat nog niet voor de heterogeniteit van depressie. Een grotere bewustwording van de verschillende manifestaties van depressie-symptomatologie, die het gevolg kunnen zijn van uiteenlopende pathofysiologische mechanismen, is van essentieel belang. Wanneer een patiënt met depressie een atypisch energie-gerelateerd symptoomprofiel heeft, kan het nuttig zijn om diens metabole biomarkers te controleren om mogelijke ontwikkeling van cardiometabole ziekten te voorkomen. In de klinische praktijk moeten wij ons bij de behandeling van patiënten met depressie ook meer bewust worden van de correlatie tussen symptoomprofielen van depressie en afzonderlijke biologische en klinische manifestaties. Het is cruciaal om goed te kijken naar de symptomen die bij elke patiënt tot uiting komen. De resultaten van dit proefschrift tonen aan dat patiënten met een depressie die atypische energie-gerelateerde depressieve symptomen vertonen, genetisch en klinisch kwetsbaar zijn voor aan insulineresistentie gerelateerde ziekten (namelijk adipositas, metabole ontregelingen en diabetes mellitus type 2). Een gepersonaliseerde aanpak kan behulpzaam zijn in preventie van deze chronische en complexe ziekten. Hierbij dient er rekening gehouden worden met de heterogeniteit van depressie en de associatie tussen atypische energie-gerelateerde symptomen van depressie en deze ziekten. Show less
This dissertation focuses on identifying neural mechanisms underlying social evaluations and self-views from a parent-adolescent perspective among adolescents with and without depression, and their... Show moreThis dissertation focuses on identifying neural mechanisms underlying social evaluations and self-views from a parent-adolescent perspective among adolescents with and without depression, and their parents. As part of RE-PAIR, affective and neural responses to praise and criticism about the adolescent child, and neural responses to reliving positive autobiographical memories were assessed, using ecologically valid fMRI-tasks. Particularly criticism seems to be highly salient to parents and adolescents, activating the salience network and decreasing mood. Both praise and reliving positive autobiographical memories activate areas important for self-referential processing in adolescents, which might reflect the ‘positive self’. Aberrant self-related processing when reliving autobiographical memories and increased sensitivity to parental criticism might be key underlying neural mechanisms in adolescent depression. By feeling more negatively, having more negative self-views, interpreting the environment as more negatively, memorizing past experiences in a more negative way, and focusing on negative events more often, adolescents with depression seem to have multiple negativity biases. These negativity biases are likely to negatively impact social relationships, potentially further reinforcing negative feelings and a negative self. Interventions exploring and strengthening the positive self, in particular the positive self aligning with the current self, might be useful for treating, or even preventing adolescent depression. Show less
The overarching goal of this dissertation was to investigate parenting processes in relation to affective well-being in families in the daily flow of life from different perspectives (i.e.,... Show moreThe overarching goal of this dissertation was to investigate parenting processes in relation to affective well-being in families in the daily flow of life from different perspectives (i.e., adolescent, mother, father), on different levels (i.e., objective, momentary, and daily), and in a clinical sample (families with an adolescent with a depression) in addition to community samples. Our findings underline the importance of daily parental warmth and criticism of mothers and fathers for adolescents’ well-being. In addition, we showed that adolescents, parents, and their perceptions of parenting influence each other and that becoming more attuned to each other’s intention and needs is essential. Importantly, we consistently demonstrated that not only the extent and direction of the dynamic processes between parenting and affect in daily life differs between, but also within persons and families. This stresses the need for research focusing on individual processes and combining quantitative with qualitative measures. The use of more idiographic approaches would not only enable gaining more insight into these differences between individuals, but also contribute to identifying parenting practices that work for almost all adolescents. This would facilitate the development of interventions combining universal parenting principles with suggestions for tailoring it to individual- or family-specific situations. Show less
This thesis aimed to lay the foundation for a new set of Dutch mental health instruments to measure depression and anxiety in an efficient, reliable, valid, and responsive manner. More specifically... Show moreThis thesis aimed to lay the foundation for a new set of Dutch mental health instruments to measure depression and anxiety in an efficient, reliable, valid, and responsive manner. More specifically, the Dutch-Flemish PROMIS adult v1.0 item banks for Depression and Anxiety were psychometrically evaluated for computerized adaptive test (CAT) administration in the Dutch clinical and general population. CAT is a modern methodology that can be used to develop instruments that measure both efficiently and reliably as only the most appropriate questions are administered, and assessment terminates as soon as sufficient reliability is achieved. For the PROMIS CAT instruments, this was demonstrated in the thesis: measuring depression and anxiety in Dutch persons was highly efficient and reliable. Moreover, the CAT instruments were shown to measure depression and anxiety sufficiently responsive and valid as well. This even includes longitudinal validity, which has barely been studied for other Dutch mental health instruments. Overall, it was concluded that the new instruments are an improvement over available instruments. Therefore, using the PROMIS CAT instruments in clinical practice may lead to more efficient and reliable measurement that supports professionals and patients in evaluating patients' treatment. Show less
This dissertation describes the findings of six studies on mental health problems in the family context, specifically focusing on the associations with the parent-child relationship, parenting... Show moreThis dissertation describes the findings of six studies on mental health problems in the family context, specifically focusing on the associations with the parent-child relationship, parenting behaviors and experiences of childhood maltreatment. The aim is to better understand the risk factors, development and transmission of common psychological problems in order to contribute to prevention and treatment strategies for common psychological problems such as anxiety and depression.Overall, the findings underline the importance of the family context in the development and levels of mental health problems. In addition to the impact of one's own negative parenting experiences, including lack of warmth and experiences of emotional or physical abuse, negative parenting experiences of one's siblings are also associated with elevated anxiety and depressive symptom levels.We also found that externalizing problems of fathers and children have a negative impact on the parent-child interactions. In addition, we found that children with behavioral problems during early adolescence experience harsher parental discipline, even three years later.In the current treatment guidelines for common mental disorders, most therapies focus on the individual. An (additional) systemic approach and considering past and present family relationships in therapy, can be of additional value. For example, supporting families with interventions to improve the parent-child relationship can be helpful in the short and long term. Moreover, (early) treatment of psychological and behavioral problems of the parent or child might be beneficial for all family members. Show less
This PhD project revealed that the female hormonal status – including OC use – and stress vulnerability – as defined by the MR-haplotype – have practical implications in experimental psychological... Show moreThis PhD project revealed that the female hormonal status – including OC use – and stress vulnerability – as defined by the MR-haplotype – have practical implications in experimental psychological research. Furthermore, incorporation of these variables in models of emotional information processing may be of help in understanding and treating mood disorders in women. Namely, even small biases may affect information processing and may contribute to the resilience or proneness to mood-disorders.Our research was among the first to show that the genetic makeup of healthy women may play a role in the influence of the female hormonal status on emotional information processing. Healthy female MR-haplotype 1/3 carriers may be more prone to distress, and may also be more sensitive to (pharmacological) changes which may counteract or sustain their vulnerability. Consistently, we observed subtle markers of depressogenic side-effects of OC only in MR-haplotype 1/3 carriers. Our findings regarding the MR-haplotypes 2 carriers are generally in line with earlier observations. We observed that MR-haplotype 2 carriers – especially homozygotes – are the less susceptible, more optimistic and more rational individuals, also in ‘unstressed’ conditions. However, stress-related psychopathology is very heterogeneous by nature and proteins from multiple genes are likely to interact in the stress-susceptibility phenotype. Last but not least, we should not ignore that the increased vulnerability of women to mood disorders is the result of a plethora of biological, psychological and sociological factors.OC-users had lower affect variability and reduced sensitivity to interpersonal emotional cues. This may be experienced as either a stabilizing or a blunting effect of OC, perhaps depending on the individual’s appraisal. The lower depression scores of OC-users in our longitudinal study suggests a protective effect of monophasic OC on symptoms of reproductive depression. Future studies should investigate (former) OC-users in larger cohorts including novel users, satisfied users and ‘brand-switchers’ in order to control for the survivor effect. Show less
This dissertation contains the results of an RCT into the effectiveness of an online self-help intervention for people living with HIV (PLWH) and depressive symptoms. Many PLWH suffer from... Show moreThis dissertation contains the results of an RCT into the effectiveness of an online self-help intervention for people living with HIV (PLWH) and depressive symptoms. Many PLWH suffer from depressive symptoms. Online interventions to treat depression may have benefits, such as less perceived stigma, a large reach and high accessibility. The online self-help intervention that we investigated is based on cognitive behavioral therapy and contains 4 components: stimulating activities, relaxation exercises, changing negative thoughts and goal attainment. Two meta-analyses were conducted and the results point to the effectiveness of psychosocial interventions for PLWH to improve depressive symptoms, anxiety symptoms, quality of life, psychological well-being, and medication adherence. The most important result of the RCT was that the intervention together with telephone coaching is effective in reducing depressive symptoms, compared to an attention-only control group. It was also found that the intervention may be effective for all PLWH, regardless of certain baseline characteristics. Furthermore, behavioral activation and goal reengagement were found to be mediators of the intervention effect. Also, the intervention is likely to be cost-effective compared to attention only. As eHealth interventions have benefits compared to face-to-face interventions, they should be more widely implemented in the mental healthcare for PLWH. Show less
The overriding aim of my thesis was to study the relationship between blood pressure (BP) and cognitive and psychological functioning in older persons. Observational studies indicate that lower BP... Show moreThe overriding aim of my thesis was to study the relationship between blood pressure (BP) and cognitive and psychological functioning in older persons. Observational studies indicate that lower BP increases risk for cognitive decline in older persons. Older persons are at risk for impaired cerebral autoregulation, and lowering their BP may compromise cerebral blood flow and cognitive function. Contradictory to our hypothesis, the Discontinuation of Antihypertensive Treatment in Elderly people (DANTE) Study Leiden, a community-based randomized clinical trial in older persons (aged ≥75 years) with mild cognitive deficits, did not show that discontinuation of antihypertensive treatment improves cognitive functioning. The lack of the effect of this trial may be due to the unintentional inclusion of persons with a relatively intact cerebral autoregulation. Furthermore, we demonstrated that older persons with mild cognitive deficits and with orthostatic hypotension, who discontinued all their antihypertensive medication had an increased probability of being free from orthostatic hypotension 4 months later, compared to persons who continued their medication. Finally, in the DANTE MRI sub study, the relationship between BP and both conventional features of small vessel disease (SVD) and microstructural damage was explored, as well as the relation between microstructural damage and cognitive and psychological dysfunction. Show less
One of the main findings of the current thesis is the fact that psychosocial factors such as life events and low social support are not primarily predictors of subsequent mood symptoms, but also... Show moreOne of the main findings of the current thesis is the fact that psychosocial factors such as life events and low social support are not primarily predictors of subsequent mood symptoms, but also seem to occur as a result of mood symptoms . Over the last decades longitudinal studies have proven their great value for research in BD. These studies provided ample knowledge about the bipolar disease course and its associated factors. The current study contributed to this knowledge by adding different research approaches to analyse and interpret these complex longitudinal associations. These results implicate that it is difficult, and maybe not even very useful, to determine cause and effect when studying the ongoing interaction between the course of bipolar disorder and psychosocial factors. Consequently, models in which strict monocausal directions of causality are abandoned might lead to a closer approximation of the reality of the disorder and its complex interactions with the environment. The network approach may turn out to be a suitable statistical method to analyse and understand such complex associations. Show less
In this thesis the epidemiology of suicidal ideation and suicide attempts (together referred to as 'suicidality') in Huntington's disease (HD) is investigated and coping styles and support... Show moreIn this thesis the epidemiology of suicidal ideation and suicide attempts (together referred to as 'suicidality') in Huntington's disease (HD) is investigated and coping styles and support strategies that may serve to help suicidal HD mutation carriers are explored. Suicidality frequently occurs in HD, with a 1-month prevalence of up to 20%. Mutation carriers who were most likely to currently experience suicidal ideation or suicidality had a shorter disease duration, were anxious, aggressive, previously attempted suicide, used antidepressants, and had a depressed mood. The presence of a depressed mood and use of benzodiazepines were the only significant independent predictors of incident suicidal ideation or suicidality. Biological parameters, in particular functioning of the immune system and the hypothalamus-pituitary-adrenal axis were not found to be associated with suicidality in HD. In a qualitative study it was shown that suicidal HD mutation carriers generally used four strategies to cope with suicidality: talking about suicidality, employing self-management activities, using medication, and discussing end-of-life wishes. Lastly, in a meta-analysis, we examined whether the expression of suicidal ideation predicted subsequent completed suicide. Effect estimates differed substantially among different populations, but none of the included studies investigated this association in HD. Show less
In this thesis Marcelo Gerona and Silvana Sosa undertake an analysis of the Great Depression (1928-1934) in a sample of three highly interconnected South American countries: Argentina, Brazil and... Show moreIn this thesis Marcelo Gerona and Silvana Sosa undertake an analysis of the Great Depression (1928-1934) in a sample of three highly interconnected South American countries: Argentina, Brazil and Uruguay (ABU). The problem tackled in this work is the relative vulnerabilities of ABU, which contributed to the strong impact of the Great Depression, as well as the nature of the policy responses to the economic emergency. In this context, the hypothesis is that ABU were highly vulnerable to the Great Depression, and among them the smallest country, Uruguay, was the most vulnerable of all. This research is original not only for having assessed jointly these three scarcely analysed countries from a historical-comparative perspective during this uneasy period of time, but also because of the introduction of a new eclectic conception of ‘complex vulnerability’ that involves many paradigms and points of view. Furthermore, the historic research along with a comparative reference to the Financial Crisis of 2008 helps the reader to understand the role of the semi-periphery, in an effort that is appealing for both historians and policymakers worldwide. Show less
This thesis aimed to investigate the neurobiological mechanisms of adolescent onset depression and anxiety disorders. A longitudinal fMRI study design was used that included both task related brain... Show moreThis thesis aimed to investigate the neurobiological mechanisms of adolescent onset depression and anxiety disorders. A longitudinal fMRI study design was used that included both task related brain activation and resting state functional connectivity. All participants were scanned three times in a six-month period. In between scan sessions the adolescents from the clinical group received treatment as usual. Adolescents from the control group were scanned within the same time interval but did not receive treatment. During a scan session several MRI parameters were collected including task based fMRI (emotional face processing task) and resting state fMRI. We also administered several questionnaires about derpession and anxiety symptomatology. It was demonstrated that adolescents with depressive and anxiety disorders show differentiating patterns of amygdala reactivity and connectivity compared to a healthy control group. Furthermore, using a dimensional approach and taking individual differences in self-reported depression and anxiety symptoms into account highlighted the role of self-reported anxiety symptoms in amygdala reactivity during emotional faces processing. These findings indicate that the amygdala indeed is an important region involved in emotional face processing and that focusing on this region can provide further insights in the development and persistence of depressive and anxiety disorders in adolescents. Show less
Depressie en angststoornissen, zoals major depressive disorder, paniekstoornis, sociale angststoornis en gegeneraliseerde angststoornis, vallen onder de meest voorkomende psychiatrische... Show moreDepressie en angststoornissen, zoals major depressive disorder, paniekstoornis, sociale angststoornis en gegeneraliseerde angststoornis, vallen onder de meest voorkomende psychiatrische ziektebeelden. Door middel van neuroimaging onderzoek zoals structurele en functionele MRI (fMRI) is het mogelijk om op een non-invasieve manier de onderliggende neurobiologie van deze stoornissen in kaart te brengen. Op basis van dergelijk onderzoek werden ruim 15 jaar geleden enkele neurobiologische modellen opgesteld waarin werd voorgesteld dat het goed of juist niet goed hersengebieden een belangrijke bijdrage leverde aan het ontstaan en/of instandhouden van depressie en angst. In de loop der jaren zijn nieuwe MRI technieken ontwikkeld. Met behulp van structurele MRI en resting-state fMRI, waarmee connectiviteit tussen hersengebieden onderzocht kan worden, heb ik gekeken naar anatomische en functionele hersenafwijkingen bij volwassenen en jongeren met depressie en/of angststoornissen. Doel was te bepalen of de reeds bestaande neurobiologische modellen bevestigd danwel aangepast of aangevuld zouden kunnen worden met recent ontwikkelde onderzoeksmethoden. De resultaten van mijn studies bevestigden grotendeels de betrokkenheid van de hersengebieden in de modellen, maar wezen tevens op een rol voor uitgebreidere netwerken van hersengebieden dan in de modellen werd verondersteld. Show less
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
