BackgroundChronic migraine, a highly disabling migraine subtype, affects nearly 2% of the general population. Understanding migraine chronification is vital for developing better treatment and... Show moreBackgroundChronic migraine, a highly disabling migraine subtype, affects nearly 2% of the general population. Understanding migraine chronification is vital for developing better treatment and prevention strategies. An important factor in the chronification of migraine is the overuse of acute headache medication. However, the mechanisms behind the transformation of episodic migraine to chronic migraine and vice versa have not yet been elucidated. We performed a longitudinal epigenome-wide association study to identify DNA methylation (DNAm) changes associated with treatment response in patients with chronic migraine and medication overuse as part of the Chronification and Reversibility of Migraine clinical trial. Blood was taken from patients with chronic migraine (n = 98) at baseline and after a 12-week medication withdrawal period. Treatment responders, patients with ≥ 50% reduction in monthly headache days (MHD), were compared with non-responders to identify DNAm changes associated with treatment response. Similarly, patients with ≥ 50% versus < 50% reduction in monthly migraine days (MMD) were compared.ResultsAt the epigenome-wide significant level (p < 9.42 × 10–8), a longitudinal reduction in DNAm at an intronic CpG site (cg14377273) within the HDAC4 gene was associated with MHD response following the withdrawal of acute medication. HDAC4 is highly expressed in the brain, plays a major role in synaptic plasticity, and modulates the expression and release of several neuroinflammation markers which have been implicated in migraine pathophysiology. Investigating whether baseline DNAm associated with treatment response, we identified lower baseline DNAm at a CpG site (cg15205829) within MARK3 that was significantly associated with MMD response at 12 weeks.ConclusionsOur findings of a longitudinal reduction in HDAC4 DNAm status associated with treatment response and baseline MARK3 DNAm status as an early biomarker for treatment response, provide support for a role of pathways related to chromatin structure and synaptic plasticity in headache chronification and introduce HDAC4 and MARK3 as novel therapeutic targets. Show less
Introduction: Studies investigating the long-term effects of breast cancer treatment on cognition in older women with breast cancer are lacking, even though preserving cognition is highly valued by... Show moreIntroduction: Studies investigating the long-term effects of breast cancer treatment on cognition in older women with breast cancer are lacking, even though preserving cognition is highly valued by the older population. Specifically, concerns have been raised regarding the detrimental effects of endocrine therapy (ET) on cognition. Therefore, we investigated cogni-tive functioning over time and predictors for cognitive decline in older women treated for early breast cancer.Methods: We prospectively enrolled Dutch women aged >70 years with stage I-III breast can-cer in the observational CLIMB study. The Mini-Mental State Examination (MMSE) was performed before ET initiation and after 9, 15 and 27 months. Longitudinal MMSE scores were analysed and stratified for ET. Linear mixed models were used to identify possible pre-dictors of cognitive decline.Results: Among the 273 participants, the mean age was 76 years (standard deviation 5), and 48% received ET. The mean baseline MMSE score was 28.2 (standard deviation 1.9). Cogni-tion did not decline to clinically meaningful differences, irrespective of ET. MMSE scores of women with pre-treatment cognitive impairments slightly improved over time (significant interaction terms) in the entire cohort and in women receiving ET. High age, low educational level and impaired mobility were independently associated with declining MMSE scores over time, although the declines were not clinically meaningful.Conclusion: Cognition of older women with early breast cancer did not decline in the first two years after treatment initiation, irrespective of ET. Our findings suggest that the fear of declining cognition does not justify the de-escalation of breast cancer treatment in older women. 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Creating an optimal start during the first 1,000 days of children is an important focus for researchers and policy makers. Parents can positively influence child development through sensitive... Show moreCreating an optimal start during the first 1,000 days of children is an important focus for researchers and policy makers. Parents can positively influence child development through sensitive parenting, which is the ability to understand and promptly and adequately respond to a child’s signals. This thesis provides insight in the development of sensitive parenting from infancy to toddlerhood in primiparous mothers and fathers through longitudinal data from the Netherlands, United Kingdom, and United States. The results demonstrate that fathers and mothers respond more sensitively to their baby in more ecologically valid contexts, i.e. during situations more representative of their daily reality, than in less ecologically valid contexts. Therefore, we recommend to take context into account when parenting skills are studied and evaluated. Next, we made a first step towards clarity on the way parents reflect on the parent-child relationship during the transition to parenthood and in relation to parental sensitivity. We found weak evidence for the theorized link between this reflection and parental sensitivity. Finally, we found that mothers and fathers are equally sensitive across the first two years, and sensitivity levels during this period increase in both parents, indicating that mothers and fathers actually do become better in sensitive parenting. Show less
Background: Chronotype reflects an individual's optimal daily timing of sleep, activity, and cognitive performance. Previous, cross-sectional, studies have suggested an age effect on chronotype... Show moreBackground: Chronotype reflects an individual's optimal daily timing of sleep, activity, and cognitive performance. Previous, cross-sectional, studies have suggested an age effect on chronotype with later chronotypes in adolescents and earlier chronotypes in children and elderly. Additionally, later chronotypes have been associated with more depressive symptoms. Few studies have been able to study longitudinal associations between chronotype and age, while adjusting for depressive symptoms. Methods: Chronotype was assessed twice with the Munich Chronotype Questionnaire 7 years apart in the Netherlands Study of Depression and Anxiety (T1: N = 1842, mean age (SD): 42.63 years (12.66)) and T2: N = 1829, mean age (SD) 50.67 (13.11)). The longitudinal association between change in age and change in chronotype was tested using a generalized estimated equation analysis adjusted for covariates (including level of depressive symptoms). Using age-bins of 5 years (age at T2), change in chronotype between T1 and T2 was analyzed with Linear Mixed Models. Results: We found a change towards an earlier chronotype with higher age (B (95% CI): -0.011 (-0.014-0.008), p < 0.001). For the age-bins, the difference in chronotype was significant for the 25-29 years age-bin. Limitations: The sample did not include individuals younger than 19 years or older than 68 years. Conclusions: In the whole sample chronotype changed towards becoming more morning-type over a period of 7 years, but this change was only significant for those aged 25-29 years. The study was performed in a large naturalistic cohort study with a wide age-range, including patients with a diagnosis of depressive and anxiety disorder and healthy controls. Show less
This thesis investigated the development of emotional functioning in 2-to-6-year-old children with and without autism. Whereas autistic children experienced more challenges in the emotional domain,... Show moreThis thesis investigated the development of emotional functioning in 2-to-6-year-old children with and without autism. Whereas autistic children experienced more challenges in the emotional domain, their emotional abilities improved with age, and developed in similar ways as observed in non-autistic children. On the one hand, this thesis showed that autistic children might deal with emotions in a different way, and they might experience various difficulties when communicating emotions with non-autistic people. One the other hand, it is important to note that the difficulties could be bidirectional. As stated by the “double empathy problem”, non-autistic people may experience the same difficulties when communicating with autistic people. This could be a meaningful direction for future research, investigating emotional communication as a two-way interaction rather than focusing only on how people with autism react to people without autism. Furthermore, this thesis showed that autistic children had the potential to learn and to develop in the emotional domain. Again, this points to the importance of investigating how to create an inclusive social environment, which is not only nurturing for children without autism, but can also benefit the development of children with autism and with other special needs. Show less
A cross-sectional relationship between low-grade inflammation -characterized by increased blood levels of Creactive protein (CRP) and pro-inflammatory cytokines- and anxiety has been reported, but... Show moreA cross-sectional relationship between low-grade inflammation -characterized by increased blood levels of Creactive protein (CRP) and pro-inflammatory cytokines- and anxiety has been reported, but the potential longitudinal relationship has been less well studied. We aimed to examine whether basal and lipopolysaccharide (LPS-)induced levels of inflammatory markers are associated with anxiety symptom severity over the course of nine years. We tested the association between basal and LPS-induced inflammatory markers with anxiety symptoms (measured with the Beck's Anxiety Inventory; BAI, Fear Questionnaire; FQ and Penn's State Worry Questionnaire; PSWQ) at 5 assessment waves over a period up nine years. We used multivariate-adjusted mixed models in up to 2867 participants of the Netherlands Study of Depression and Anxiety (NESDA). At baseline, 43.6% of the participants had a current anxiety disorder, of which social phobia (18.5%) was most prevalent. Our results demonstrated that baseline inflammatory markers were significantly associated with several outcomes of anxiety at baseline over nine subsequent years. BAI subscale of somatic (arousal) symptoms of anxiety, and FQ subscale of agoraphobia demonstrated the strongest effects with standardized betacoefficients of up to 0.14. The associations were attenuated by 25%-30% after adjusting for the presence of (comorbid) major depressive disorder (MDD), but remained statistically significant. In conclusion, we found that participants with high levels of inflammatory markers have on average high levels of anxiety consisting of physical arousal and agoraphobia, which tended to persist over a period of nine years, albeit with small effect sizes. These associations were partly driven by co-morbid depression. Show less
Background Notwithstanding the firmly established cross-sectional association of happiness with psychiatric disorders and their symptom severity, little is known about their temporal relationships.... Show moreBackground Notwithstanding the firmly established cross-sectional association of happiness with psychiatric disorders and their symptom severity, little is known about their temporal relationships. The goal of the present study was to investigate whether happiness is predictive of subsequent psychiatric disorders and symptom severity (and vice versa). Moreover, it was examined whether changes in happiness co-occur with changes in psychiatric disorder status and symptom severity. Methods In the Netherlands Study of Depression and Anxiety (NESDA), happiness (SRH: Self-Rated Happiness scale), depressive and social anxiety disorder (CIDI: Composite Interview Diagnostic Instrument) and depressive and anxiety symptom severity (IDS: Inventory of Depressive Symptomatology; BAI: Beck Anxiety Inventory; and FQ: Fear Questionnaire) were measured in 1816 adults over a three-year period. Moreover, we focused on occurrence and remittance of 6-month recency Major Depressive Disorder (MDD) and Social Anxiety Disorders (SAD) as the two disorders most intertwined with subjective happiness. Results Interindividual differences in happiness were quite stable (ICC of .64). Higher levels of happiness predicted recovery from depression (OR = 1.41; 95% CI = 1.10-1.80), but not social anxiety disorder (OR = 1.31; 95%CI = .94-1.81), as well as non-occurrence of depression (OR = 2.41; 95%CI = 1.98-2.94) and SAD (OR = 2.93; 95%CI = 2.29-3.77) in participants without MDD, respectively SAD at baseline. Higher levels of happiness also predicted a reduction of IDS depression (sr = - 0.08; 95%CI = -0.10 - -0.04), and BAI (sr = - 0.09; 95%CI = -0.12 - -0.05) and FQ (sr = - 0.06; 95%CI = -0.09 - -0.04) anxiety symptom scores. Conversely, presence of affective disorders, as well as higher depression and anxiety symptom severity at baseline predicted a subsequent reduction of self-reported happiness (with marginal to small sr values varying between -.04 (presence of SAD) to -.17 (depression severity on the IDS)). Moreover, changes in happiness were associated with changes in psychiatric disorders and their symptom severity, in particular with depression severity on the IDS (sr = - 0.46; 95%CI = -.50 - -.42). Conclusions Results support the view of rather stable interindividual differences in subjective happiness, although level of happiness is inversely associated with changes in psychiatric disorders and their symptom severity, in particular depressive disorder and depression severity. Show less
Background: Depression has been associated with decreased regional grey matter volume, which might partly be explained by an unhealthier lifestyle in depressed individuals which has been ignored by... Show moreBackground: Depression has been associated with decreased regional grey matter volume, which might partly be explained by an unhealthier lifestyle in depressed individuals which has been ignored by most earlier studies. Also, the longitudinal nature of depression, lifestyle and brain structure associations is largely unknown. This study investigates the relationship of depression and lifestyle with brain structure cross-sectionally and longitudinally over up to 9 years.Methods: We used longitudinal structural MRI data of persons with depression and/or anxiety disorders and controls (N-unique participants = 347, N-observations = 609). Cortical thickness of medial orbitofrontal cortex (mOFC), rostral anterior cingulate cortex (rACC) and hippocampal volume were derived using FreeSurfer. Using Generalized Estimating Equations, we investigated associations of depression and lifestyle (Body mass index (BMI), smoking, alcohol consumption, physical activity and sleep duration) with brain structure and change in brain structure over 2 (n = 179) and 9 years (n = 82).Results: Depression status (B =-.053, p = .002) and severity (B =-.002, p = .002) were negatively associated with rACC thickness. mOFC thickness was negatively associated with BMI (B =-.004, p < .001) and positively with moderate alcohol consumption (B = .030, p = .009). All associations were independent of each other. No associations were observed between (change in) depression, disease burden or lifestyle factors with brain change over time.Conclusions: Depressive symptoms and diagnosis were independently associated with thinner rACC, BMI with thinner mOFC, and moderate alcohol consumption with thicker mOFC. No longitudinal associations were observed, suggesting that regional grey matter alterations are a long-term consequence or vulnerability indicator for depression but not dynamically or progressively related to depression course trajectory. Show less
Background and objectives: Comorbidity among anxiety and depression disorders and their symptoms is high. Rumination and worry have been found to mediate prospective cross-disorder relations... Show moreBackground and objectives: Comorbidity among anxiety and depression disorders and their symptoms is high. Rumination and worry have been found to mediate prospective cross-disorder relations between anxiety and depression disorders and their symptoms in adolescents and adults. We examined whether generic repetitive negative thinking (RNT), that is content- and disorder-independent, also mediates prospective cross-disorder associations between anxiety and depressions disorders and their symptoms.Methods: This was studied using a 5-year prospective cohort study. In a mixed sample of 1859 adults (persons with a prior history of or a current affective disorder and healthy individuals), we assessed DSM-IV affective disorders (Composite Interview Diagnostic Instrument), anxiety (Beck Anxiety Inventory) and depression symptoms (Inventory of Depressive Symptomatology) and RNT (Perseverative Thinking Questionnaire).Results: We found that baseline depression disorders and symptom severity have predictive value for anxiety disorders and symptom severity five years later (and vice versa) and that these associations were significantly mediated by level of RNT as assessed two years after baseline. The significant and rather large mediation effects seemed mainly due to the mental capacity captured by RNT, especially in the prospective relation of anxiety with future depression.Limitations: The mediation effects were greatly attenuated or even nullified after rigorously controlling for concomitant psychopathology at two years after baseline.Conclusions: From these results it can be concluded that repetitive negative thinking could be an important transdiagnostic factor, that may constitute a suitable target for treatment. Show less
Exposure to trauma strongly increases the risk to develop stress-related psychopathology, such as post-traumatic stress disorder (PTSD) or major depressive disorder (MDD). In addition, liability to... Show moreExposure to trauma strongly increases the risk to develop stress-related psychopathology, such as post-traumatic stress disorder (PTSD) or major depressive disorder (MDD). In addition, liability to develop these moderately heritable disorders is partly determined by common genetic variance, which is starting to be uncovered by genome-wide association studies (GWASs). However, it is currently unknown to what extent genetic vulnerability and trauma interact. We investigated whether genetic risk based on summary statistics of large GWASs for PTSD and MDD predisposed individuals to report an increase in MDD and PTSD symptoms in a prospective military cohort (N = 516) at five time points after deployment to Afghanistan: one month, six months and one, two and five years. Linear regression was used to analyze the contribution of polygenic risk scores (PRSs, at multiple p-value thresholds) and their interaction with deployment-related trauma to the development of PTSD-and depression-related symptoms. We found no main effects of PRSs nor evidence for interactions with trauma on the development of PTSD or depressive symptoms at any of the time points in the five years after military deployment. Our results based on a unique long-term follow-up of a deployed military cohort suggest limited validity of current PTSD and MDD polygenic risk scores, albeit in the presence of minimal severe psychopathology in the target cohort. Even though the predictive value of PRSs will likely benefit from larger sample sizes in discovery and target datasets, progress will probably also depend on (endo) phenotype refinement that in turn will reduce etiological heterogeneity. (c) 2018 Published by Elsevier B.V. Show less
Bogaerts, A.; Claes, L.; Schwartz, S.J.; Becht, A.I.; Verschueren, M.; Gandhi, A.; Luyckx, K. 2018
Developing a stable and coherent identity structure (i.e., a synthesized sense of self that can support self-directed decision making) represents a lifelong task. A person’s identity structure is... Show moreDeveloping a stable and coherent identity structure (i.e., a synthesized sense of self that can support self-directed decision making) represents a lifelong task. A person’s identity structure is continually revised through ongoing processes of identity exploration and commitment. However, longitudinal studies linking identity structure to identity processes are largely lacking. The present three-wave longitudinal study among 530 Flemish high school students [50.6% female; Mage = 15; SD = 1.85; age range = 11–19 years] examined the directionality of both between- and within-person associations linking identity synthesis and confusion to identity exploration and commitment processes. Between-person cross-lagged models indicated that adolescents who scored high on identity synthesis relative to their peers also scored high on proactive exploration and commitment processes, and low on ruminative exploration one year later, again relative to their peers. Adolescents who scored high on identity confusion relative to their peers also scored high on ruminative exploration one year later, again relative to their peers. With respect to effects of identity processes on identity structure, adolescents who scored high on identification with commitment relative to their peers also scored low on identity confusion one year later. Within-person cross-lagged models indicated that, when adolescents scored high on identity synthesis relative to their own average score, they reported increased proactive exploration processes one year later. In general, reaching a degree of identity synthesis appears to represent a prerequisite for proactive identity exploration at both the between- and within-person levels. Show less
Geel, M. van; Goemans, A.; Zwaanswijk, W.; Gini, G.; Vedder, P. 2018
In the current study two meta-analyses are performed on longitudinal studies on peer victimization and self-esteem. The goal of these meta-analyses was to analyze whether a low self-esteem predicts... Show moreIn the current study two meta-analyses are performed on longitudinal studies on peer victimization and self-esteem. The goal of these meta-analyses was to analyze whether a low self-esteem predicts future peer victimization, or whether peer victimization predicts future low self-esteem. The databases PsycINFO, MEDLINE, and ERIC were searched for relevant literature. Two authors independently went through the retrieved articles and found four doctoral dissertations and 14 peer reviewed articles eligible for inclusion in the meta-analysis. Articles were independently coded by two authors, with good interrater agreement. A total of 16,230 youth were included in the meta-analysis on peer victimization and self-esteem, and a total of 16,394 youth were included in the meta-analysis on self-esteem and peer victimization. Significant prospective pathways were found from peer victimization to self-esteem, and from self-esteem to peer victimization, which suggests that peer victimization and self-esteem are related in a transactional manner. Analyses suggested a negligible role of publication bias in the obtained results. Moderator analyses revealed that effect sizes were smaller for studies that used peer reports, and for studies that considered longer time-spans. The results of the current study suggest that peer victimization could have long lasting negative effects on self-esteem, but also point out that children may become victims because of low self-esteem. Show less
Children in foster care are often characterized by low academic outcomes which negatively impact their later lives. School engagement may be a key element to promote their academic and educational... Show moreChildren in foster care are often characterized by low academic outcomes which negatively impact their later lives. School engagement may be a key element to promote their academic and educational outcomes. However, little is known about the development of school engagement in foster children and longitudinal studies are lacking. The current study reports the findings of a three-wave longitudinal study wherein we examined the development of school engagement and analyzed which factors were predictive of school engagement in a sample of 363 Dutch foster children (age range 5–18 years, 46.6% girls). Multilevel analyses showed that characteristics related to demographics, school functioning, foster children, and foster families predicted levels of school engagement of children in foster care. Foster children's behavioral functioning and foster parents’ positive parenting appeared to be characteristics important to consider in screening and interventions. Based on the findings we suggest that teachers and foster care professionals should collaborate to ensure that school engagement and consequently school functioning becomes part of foster children's personal development plans. Show less
This dissertation focuses on the development of children in family foster care and examines which characteristics related to the foster child, the foster family, and the foster placement are... Show moreThis dissertation focuses on the development of children in family foster care and examines which characteristics related to the foster child, the foster family, and the foster placement are associated with foster children’s development. We used meta-analysis and longitudinal research to provide a better insight in foster children’s development. In sum, this dissertation clarifies that foster children vary greatly with respect to their developmental functioning. We found several characteristics related to foster children’s development. Although these characteristics partly explain foster children’s development and thereby provide useful insights, they cannot explain the total variance in foster children’s development. It is both this lack of an accurate model for foster children’s development and the heterogeneity of developmental trajectories that lend significance to screening and monitoring of foster children’s development. We advise foster care agencies to systematically implement screening and monitoring measures in order to capture foster children’s developmental diversity. This enables timely identification of those foster children who experience developmental difficulties and are therefore at risk for negative developmental trajectories and breakdown. Researchers and foster care professionals should establish collaborations in order to improve the validity as well as the feasibility of screening and monitoring children in foster care. Show less
This thesis describes a study on neuropsychiatric symptoms in Huntington’s Disease (HD). This cohort study was performed in HD mutation carriers (both pre-motor symptomatic and motor symptomatic),... Show moreThis thesis describes a study on neuropsychiatric symptoms in Huntington’s Disease (HD). This cohort study was performed in HD mutation carriers (both pre-motor symptomatic and motor symptomatic), and a control group of non-carriers that had an a-priori 50% risk for HD. The study started in may 2004 and a second measurement was performed 2 years later. The aim of this study was to study the presence and course of both formal psychiatric disorders and neuropsychiatric symptoms, and to find correlates and predictors associated with the psychiatric phenomena. This cohort study confirms that neuropsychiatric symptoms frequently occur in patients with HD. We expected a diminished insight in patients with a neuropsychiatric symptoms like irritability, but most patients were aware of their irritability. A strong relationship was found between the presence of psychopathology, cognitive functioning and global daily functioning. Irritability may be an early sign of the disease, but only apathy was closely related to the progression of HD indicating a relationship with the progressive neurodegenerative nature of the disease. However, we also found associations with apathy and irritability, and the use of psychotropic medications. Show less
