Because aggressive behavior during early childhood has been related to negative developmental outcomes, a further understanding of the underlying mechanisms of aggression during the first years of... Show moreBecause aggressive behavior during early childhood has been related to negative developmental outcomes, a further understanding of the underlying mechanisms of aggression during the first years of life is essential. Although the factors prenatal risk, parenting behavior, temperament and cognitive functions have consistently been related to externalizing behavior during preschool and school age, research focusing on their interplay in relation to aggressive behavior earlier in life is scarce. The aim of the current dissertation was to gain more insight into these associations during infancy and toddlerhood. Our studies indicated that impairments in children’s early cognitive regulation abilities play a role in the development of aggressive behavior. It can also be concluded that both adverse pre- and postnatal environmental influences have an impact on child aggression: higher prenatal risk and adverse parenting behavior were directly or indirectly (via poor cognitive functioning) related to higher levels of aggression. In addition, it was found that poor cognitive skills increased the risk of aggression in case of high prenatal risk or a highly reactive temperament during early development. These results suggest that early intervention programs to prevent aggression should focus on prenatal risk, parenting behavior and cognitive development during the first years of life. Show less
Anxiety disorders are globally one of the most prevalent and disabling forms of psychopathology in adults and children. Having a parent with an anxiety disorder multiplies the risk of anxiety... Show moreAnxiety disorders are globally one of the most prevalent and disabling forms of psychopathology in adults and children. Having a parent with an anxiety disorder multiplies the risk of anxiety disorders in the ofspring, although the specifc mechanisms and processes that play a role in this intergenerational transmission remain largely unknown. According to information processing theories, threat-related biases in cognitive processing are a causal mechanism in the development and maintenance of anxiety. These theories propose that individuals with anxiety are more likely to cognitively process novel stimuli in their environment as threatening. Creswell and colleagues proposed a theoretical model that highlighted the role of these cognitive biases as a mechanism in the intergenerational transmission of anxiety (Creswell et al., in Hadwin, Field (eds) Information processing biases and anxiety: a developmental perspective, Wiley, pp 279–295, 2010). This model postulated signifcant associations between (1) parents’ and children’s threat-related cognitive biases (2) parents’ threatrelated cognitive biases in their own and their child’s environment, (3) parents’ threat-related cognitive biases and parenting behaviors that convey anxiety risk to the ofspring (e.g., modeling of fear, and verbal threat information transmission), and (4) parenting behaviors and child threat-related biases. This theoretical review collated the recent empirical work testing these four core hypotheses of the model. Building on the reviewed empirical work, an updated conceptual model focusing on threat-related attention and interpretation is proposed. This updated model incorporates the links between cognition and anxiety in parents and children and addresses the potential bidirectional nature of parent–child infuences. Show less
Objectives: To adequately monitor the course of cognitive functioning in persons with moderate to severe dementia, relevant cognitive tests for the advanced dementia stages are needed. We examined... Show moreObjectives: To adequately monitor the course of cognitive functioning in persons with moderate to severe dementia, relevant cognitive tests for the advanced dementia stages are needed. We examined the ability of a test developed for the advanced dementia stages, the Severe Impairment Battery Short version (SIB-S), to measure cognitive change over time. Second, we examined type of memory impairment measured with the SIB-S in different dementia stages. Methods: Participants were institutionalized persons with moderate to severe dementia (N = 217). The SIB-S was administered at 6-month intervals during a 2-year period. Dementia severity at baseline was classified according to Global Deterioration Scale criteria. We used mixed models to evaluate the course of SIB-S total and domain scores, and whether dementia stage at baseline affected these courses. Results: SIB-S total scores declined significantly over time, and the course of decline differed significantly between dementia stages at baseline. Persons with moderately severe dementia declined faster in mean SIB-S total scores than persons with moderate or severe dementia. Between persons with moderate and moderately severe dementia, there was only a difference in the rate of decline of semantic items, but not episodic and non-semantic items. Conclusions: Although modest floor and slight ceiling effects were noted in severe and milder cases, respectively, the SIB-S proved to be one of few available adequate measures of cognitive change in institutionalized persons with moderate to severe dementia. Show less
Koini, M.; Duering, M.; Gesierich, B.G.; Rombouts, S.A.R.B.; Ropele, S.; Wagner, F.; ... ; Schmidt, R. 2018
Loss of grey-matter volume with advancing age affects the entire cortex. It has been suggested that atrophy occurs in a network-dependent manner with advancing age rather than in independent brain... Show moreLoss of grey-matter volume with advancing age affects the entire cortex. It has been suggested that atrophy occurs in a network-dependent manner with advancing age rather than in independent brain areas. The relationship between networks of structural covariance (SCN) disintegration and cognitive functioning during normal aging is not fully explored. We, therefore, aimed to (1) identify networks that lose GM integrity with advancing age, (2) investigate if age-related impairment of integrity in GM networks associates with cognitive function and decreasing fine motor skills (FMS), and (3) examine if GM disintegration is a mediator between age and cognition and FMS. T1-weighted scans of n = 257 participants (age range: 20–87) were used to identify GM networks using independent component analysis. Random forest analysis was implemented to examine the importance of network integrity as predictors of memory, executive functions, and FMS. The associations between GM disintegration, age and cognitive performance, and FMS were assessed using mediation analyses. Advancing age was associated with decreasing cognitive performance and FMS. Fourteen of 20 GM networks showed integrity changes with advancing age. Next to age and education, eight networks (fronto-parietal, fronto-occipital, temporal, limbic, secondary somatosensory, cuneal, sensorimotor network, and a cerebellar network) showed an association with cognition and FMS (up to 15.08%). GM networks partially mediated the effect between age and cognition and age and FMS. We confirm an age-related decline in cognitive functioning and FMS in non-demented community-dwelling subjects and showed that aging selectively affects the integrity of GM networks. The negative effect of age on cognition and FMS is associated with distinct GM networks and is partly mediated by their disintegration. Show less
Children spend most of their days interacting with their social environment. Emotions form a large part of these interactions and vice versa social emotions become meaningful when interacting... Show moreChildren spend most of their days interacting with their social environment. Emotions form a large part of these interactions and vice versa social emotions become meaningful when interacting with others. Understanding the emotion processes that underlie successful social functioning is important, especially in children that experience difficulties in social-emotional functioning such as children with Autism Spectrum Disorders (ASD). These studies used a unique approach towards understanding the complex mechanisms that are involved in emotion processing, incorporating how emotions are perceived, experienced, regulated, and expressed. Sensitive and direct measures of emotion processing such as eyetracking and physiology revealed for the first time on a neurobiological level that children with ASD have difficulties emotionally resonating with others, use less efficient strategies to regulate their emotions, and provided evidence for a possible discordance between the expression and experience of emotions. The preschool years also presented with a possible window of opportunity; children with ASD do feel emotions when it comes to their own experiences and the development of social attention towards others might be prone to improvements during the preschool years. These findings are important to parents and professional and enhance the understanding of emotion processing during these very early years of life. Show less
The locus coeruleus (LC) is a nucleus in the brainstem, and projects widely to the forebrain where it releases norepinephrine (NE). Catecholamines such as NE do not have a unitary effect on their... Show moreThe locus coeruleus (LC) is a nucleus in the brainstem, and projects widely to the forebrain where it releases norepinephrine (NE). Catecholamines such as NE do not have a unitary effect on their target neurons, but instead influence the function of other neurotransmitters, a process that is known known as neuromodulation. By virtue of the LC’s wide projection profile and the neuromodulatory properties of NE, the LC-NE system profoundly influences neural firing characteristics and associated cognitive processes. The work presented in this thesis addresses the role of the LC-NE system in various aspects of human cognition, and the modulation of brain state. Show less
Zantinge, G.M.; Rijn, S. van; Stockmann, L.; Swaab, J.T. 2017
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
With increasing age the prevalence of hypertension rises. High blood pressure at midlife is associated with cognitive impairment. Nevertheless, in older persons a lower rather than a higher... Show more With increasing age the prevalence of hypertension rises. High blood pressure at midlife is associated with cognitive impairment. Nevertheless, in older persons a lower rather than a higher blood pressure is associated with incident dementia. The main purpose of the work in this thesis was to explore the role of blood pressure in relation to cerebral structure, neurocognitive functioning and hemodynamics of the brain in old age. Therefore, we sought to determine whether discontinuation of antihypertensive therapy in persons aged 75 years and over with mild cognitive deficits and using antihypertensive medication (the Discontinuation of ANtihypertensive Treatment in Elderly people [DANTE] population) would improve their cognitive and psychological functioning. The assumption was that the increase in blood pressure after the discontinuation of antihypertensives would lead to a direct increase in cerebral blood flow and, as a consequence, to an improvement in cerebral functioning. An additional objective was to investigate possible underlying mechanisms in the relation between blood pressure and neurocognitive functioning. To enable this, brain MRI was used to determine whether (lower) blood pressure was associated with (micro)structural damage, cerebral small vessel disease and blood flow in the brain, and also whether the presence of cerebral (micro)structural damage was related to neurocognitive functioning. 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
In conclusion, the results of the present studies show how schizotypal symptoms may develop following child psychiatric psychopathology and how these symptoms unfavorably influence a persons__... Show moreIn conclusion, the results of the present studies show how schizotypal symptoms may develop following child psychiatric psychopathology and how these symptoms unfavorably influence a persons__ quality of life. It is important for clinicians to be aware of the complex dynamics of psychopathology and the higher risk for adult schizotypal symptomatology following behavioral problems and psychiatric disorders at child and adolescent age. Show less
During early adolescence, there is no association between internalizing behaviour and cannabis use. There is an association between externalizing behaviour and cannabis use, where externalizing... Show moreDuring early adolescence, there is no association between internalizing behaviour and cannabis use. There is an association between externalizing behaviour and cannabis use, where externalizing behaviour precedes cannabis use rather than the other way around. Secondly, during adolescence, there is an association between psychosis vulnerability and cannabis use, where cannabis use predicts psychosis vulnerability and vice versa, suggesting a bi-directional cascading association. Thirdly, during early adolescence, the social skill “self-control” was (unexpectedly) unrelated to cannabis use. Cooperation and assertiveness are associated with cannabis use during this life phase, where higher levels of cooperation decrease the chance of using cannabis and higher levels of assertiveness increase the chance of using cannabis during early adolescence. Cooperation and assertiveness did not differentiate between early and late onset of cannabis use or predict frequency of use. In addition, compared to non-users, cannabis users experience problems only in motivational inhibitory control, not in cognitive inhibitory control. Also, cannabis users experience problems in behavioural impulsivity, which is related to motivational inhibitory control. Lastly, cannabis users have problems with social perception in comparison to non-using controls, particularly when these social perception skills involve emotion recognition. Also, heavy cannabis users experience significantly more psychological problems when they have relatively poor social perception skills. Future research must determine whether the behavioural and cognitive concepts and constructs examined in this thesis in relation to cannabis use should be incorporated in prevention and intervention programs. Show less
In this dissertation, we aimed to identify the influence of cortisol exposure and cognitive performance on the clinical course of bipolar disorder. Data regarding sociodemographics, disease... Show moreIn this dissertation, we aimed to identify the influence of cortisol exposure and cognitive performance on the clinical course of bipolar disorder. Data regarding sociodemographics, disease characteristics and genetic analysis of the cortisol receptors, were collected of 366 patients with bipolar disorder (BD). Part of this cohort participated in the longitudinal study, including the Test for Attentional Performance, prospectively registration of mood, and the collection of hair samples to assess long term cortisol. The main findings are as follows: 1) Several Glucocorticoid Receptor (GR) gene polymorphisms, in particular the 9β polymorphism (rs6198), relate with clinical characteristics of BD. The most important relations were with the number of (hypo)manic episodes, and second, with seasonal patterns of mood episodes, especially hypomania. 2) Higher long term cortisol exposure is associated with more psychiatric co morbidity in BD patients., and with an older age at onset, indicating a subgroup of patients. 3) Medication as potential confounder on cognitive performance, appeared to relate with the type (mainly antipsychotics) and the number of different types of medication used. Summarizing, cortisol exposure is associated with several clinically relevant phenomena defining course of BD and give insight in possible subgroups of patients with higher cortisol exposure. 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
Early dementias are difficult to distinguish from normal age-related memory decline. In the preclinical stages of Alzheimer’s disease and Huntington’s disease, brain functions are already changing... Show moreEarly dementias are difficult to distinguish from normal age-related memory decline. In the preclinical stages of Alzheimer’s disease and Huntington’s disease, brain functions are already changing, but this is not directly visible from the outside. Many research is aimed at discovering early disease markers. However, research using EEG registration during conventional eyes closed conditions revealed little additional information. The yield of EEG research can be improved by probing the weakest spot, which, in case of dementia, is memory. Karin van der Hiele introduced memory tests during EEG registration and found that early abnormalities in brain functioning can then be observed in Alzheimer’s disease and Huntington’s disease. An interesting finding came to light: the EEG in dementia displays a lot of muscle activity which is normally filtered out. However, the researchers decided not to throw this activity away but to measure it. Interestingly, they found that the amount of muscle activity was related to cognition and to the number of depressive complaints. It may pay to keep an open mind regarding the nature of the parameter to be measured. Show less
