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
Michelle Achterberg is a developmental neuroscientist with an interest in social emotional development. In her thesis, Michelle provides a comprehensive overview of the underlying mechanisms of... Show moreMichelle Achterberg is a developmental neuroscientist with an interest in social emotional development. In her thesis, Michelle provides a comprehensive overview of the underlying mechanisms of social emotion regulation in childhood. Her studies show that the brain is prone to signal for socially relevant information. She revealed that the network of social saliency is already present in childhood, indicating that this might be a core social mechanism.The thesis additionally shows that social rejection is often followed by behavioral aggression, and regulation of these retaliation emotions is related to control mechanisms of the dorsolateral prefrontal cortex. Moreover, the results show that the vast architecture of functional subcortical-prefrontal brain connectivity is already in place in middle childhood and suggest fine tuning of (social evaluation) brain networks across childhood. These findings highlighting the need to incorporate childhood into developmental models of social emotion regulation.Neuroimaging research, specifically neuroimaging in children is prone to challenges and several methodological considerations need to be taken into account when studying the childhood brain. In spite of these difficulties, studying childhood brain development has the potential to provide important insights into a unique developmental window of opportunity. 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
Goemans, A.; Geel, M. van; Wilderjans, T.F.; Ginkel, J.R. van; Vedder, P. 2018
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
Spinhoven, P.; Penninx, B.W.; Krempeniou, A.; Van Hemert, A.M.; Elzinga, B. 2015
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
We examined the development of international adoptees from infancy to young adulthood, and factors influencing developmental outcomes in middle childhood, adolescence and young adulthood. The... Show moreWe examined the development of international adoptees from infancy to young adulthood, and factors influencing developmental outcomes in middle childhood, adolescence and young adulthood. The results for cognitive development (Chapter 2) showed that early malnutrition influenced cognitive and health-related outcomes, but its consequences did not extend to socioeconomic success later in life. The human brain seems capable of adapting to changing environmental influences, but earlier placement in a positive family environment should be preferred (see also Chapter 1). The adoptees in the Leiden Longitudinal Adoption Study were exposed to few adversities due to their early adoptive placement, and the combination with the nurturing environment of a permanent adoptive family resulted in positive cognitive and socio-emotional outcomes (Chapters 2 and 3). Our results for longitudinal (sensitivity) and concurrent relations (reactivity to infant crying) with attachment representations in young adulthood (Chapters 3 and 4) clearly point to this role of the family environment in predicting social-emotional outcomes. High parenting quality is important, also in families where children do not share a common genetic basis with their parents. In sum, adoption can be seen as a positive intervention and the (adoptive) family environment matters for children growing up from infants to young adults. Show less
