The aim of this thesis was to assess the efficacy (part 1) and tolerability (part 2) of antiseizure medications (ASMs) in glioma patients with epilepsy. In addition, we aimed to get insight into... Show moreThe aim of this thesis was to assess the efficacy (part 1) and tolerability (part 2) of antiseizure medications (ASMs) in glioma patients with epilepsy. In addition, we aimed to get insight into the ASM prescription behavior and treatment policy in brain tumor-related epilepsy (part 3).First-line levetiracetam seems to be the most efficacious ASM in glioma patients, with favourable tolerability. This is demonstrated in multicenter retrospective observational cohort studies, a systematic review, and is the opinion among the vast majority of European neuro-oncology professionals. Enzyme-inducing AMSs should be avoided in glioma patients due to the high risk of adverse effects. ASM use was not independently associated with neuropsychiatric symptoms in glioma patients, but alternative factors seem to pose a greater risk for developing neuropsychiatric symptoms. If patients experience uncontrolled seizures on ASM monotherapy, levetiracetam combined with valproic acid has better efficacy than other ASM combinations in glioma patients, while toxicity is similar. Subsequently, potential add-on ASMs in glioma patients experiencing uncontrolled seizures on ASM dual therapy include clobazam, lamotrigine, and lacosamide. Show less
BackgroundAn important aspect of end-of-life decisions in dialysis patients is elective withdrawal from dialysis therapy. Several studies have shown that clinical factors, such as comorbidity, play... Show moreBackgroundAn important aspect of end-of-life decisions in dialysis patients is elective withdrawal from dialysis therapy. Several studies have shown that clinical factors, such as comorbidity, play a role in dialysis withdrawal. The role of symptoms of anxiety and depression is largely unknown. The.MethodsA prospective multi-center study has been set up to investigate anxiety and depressive symptoms longitudinally in dialysis patients. Anxiety and depressive symptoms were investigated using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) as baseline. Adverse events, including dialysis withdrawal and mortality were registered during follow-up. Multivariable cox proportional hazard models were used with anxiety and depression as the independent variable and dialysis withdrawal as the outcome variable. Models included age, sex, ethnicity and a set of clinical comorbidities.ResultsA total of 687 patients were included between 2012 and 2017, with a median follow-up of 3.2 years. A total of 48 patients (7%) withdrew from dialysis therapy, and subsequently deceased. Anxiety and depressive symptoms at baseline showed an association with dialysis withdrawal with hazard ratios of 2.31 (1.09-4.88) for anxiety and 2.56 (1.27-5.15) for depressive symptoms, independent of somatic comorbidities.DiscussionWithdrawal from dialysis therapy is associated with anxiety and depressive symptoms. Dialysis patients with more severe depressive and anxiety symptoms were more vulnerable for dialysis withdrawal. Insight in factors that play a role in dialysis withdrawal could aid patients and clinicians making an informed decision and develop clinical guidelines. Show less
Van der Ven, S.H.G.; Prast, E.J.; Van de Weijer-Bergsma, E. 2023
Individual variation in mathematical skills can be ascribed to differences in cognitive ability, but also to students’ emotional experiences of mathematics, such as enjoyment and anxiety. The... Show moreIndividual variation in mathematical skills can be ascribed to differences in cognitive ability, but also to students’ emotional experiences of mathematics, such as enjoyment and anxiety. The current study investigated how the interplay of working memory with math anxiety and enjoyment explains mathematical performance in primary school students. We also explored whether these relations differed with the type of math test and students’ age. Using mixed effect models, we reanalyzed data from 4471 Dutch primary school students (grades 2–6) who had completed two computerized working memory tasks, had filled out a questionnaire on math emotions, and had completed two math tests: story problems and speeded arithmetic. Findings showed that working memory, anxiety, and enjoyment were linear (but not curvilinear) predictors of performance on both tests, while some relations were stronger for the math (story)-problem-solving test. Higher math anxiety negatively impacted performance more strongly for students with stronger working memory skills, but only on the arithmetic test. No interaction between working memory and enjoyment was found. The relation between math anxiety and math performance increased with grade level, but no other age-related changes were found. Interpretations and recommendations focus on situated views on learning and emotion. Show less
Background:Up to 40% of patients suffering from anxiety disorders do not benefit from currently available pharmacological treatments. Overactivity of the orexin-1 receptor (OX1R) has been... Show moreBackground:Up to 40% of patients suffering from anxiety disorders do not benefit from currently available pharmacological treatments. Overactivity of the orexin-1 receptor (OX1R) has been implicated in anxiety- and panic-related states.Aim & methods:We investigated the pharmacokinetics and characterized the pharmacodynamic (PD) profile of the OX1R antagonist JNJ-61393215 using a battery of central nervous system assessments investigating relevant functional domains such as alertness, attention, (visuo)motor coordination, balance, subjective effects and resting-state electroencephalography in a single ascending dose placebo-controlled study in doses from 1 to 90 mg inclusive, assessing PD up to 10 h after dosing, safety and pharmacokinetic in 48 healthy male subjects.Results:Average time to maximal plasma concentration (Tmax) ranged between 1.0 and 2.25 h; average half-life ranged from 13.6 to 24.6 h and average maximum plasma concentration ranged from 1.4 to 136.8 ng/mL in the 1 and 90 mg groups, respectively. JNJ-61393215 did not demonstrate any statistically significant or clinically meaningful effects on any PD endpoint at any dose investigated at Tmax nor over the total period up to 10 h post-dose and was well tolerated. The reported somnolence rate was 16.7% (which was attributable to the cohorts receiving 6 mg and higher doses) compared to 12.5% in placebo.Conclusion:This observation is in line with our knowledge about the OX1R in preclinical studies, where only inconsistent and non-dose-dependent changes in electroencephalography or other behavioural measures were observed under non-challenged conditions, potentially exemplifying the need for a challenged subject. Show less
This thesis leads to empirical insights in the relationship between anger and aggression, on the one hand, and psychopathology, on the other hand, using robust study designs and a broad spectrum of... Show moreThis thesis leads to empirical insights in the relationship between anger and aggression, on the one hand, and psychopathology, on the other hand, using robust study designs and a broad spectrum of anger manifestations. It became clear that the occurrence of anger and aggression are common among both psychiatric outpatients, including individuals with depressive-, anxiety-, and bipolar disorders, and psychiatric inpatients, including individuals with psychotic- and personality disorders. Aggressive behaviour regularly leads to a referral to long-stay inpatient care. As supported by this thesis, the costs of aggression within long-stay wards are high. However, despite the increased awareness and efforts to reduce violence in clinical care among healthcare workers and policymakers, aggression incidents remain highly prevalent in psychiatric inpatient facilities. Research suggests diet to be a modifiable factor affecting mood and behaviour. Yet, the promising effects of nutritional supplementation on aggressive incidents found in previous studies were not replicated in psychiatric inpatients. These results strengthen the need for study of additional preventative and treatment options. Furthermore, our results underline the importance of including vulnerable populations, who are often underrepresented in RCTs, to provide evidence-based care for these groups. Show less
PurposeSiblings of probands with depressive and anxiety disorders are at increased risk for psychopathology, but little is known about how risk factors operate within families to increase... Show morePurposeSiblings of probands with depressive and anxiety disorders are at increased risk for psychopathology, but little is known about how risk factors operate within families to increase psychopathology for siblings. We examined the additional impact of psychosocial risk factors in probands—on top of or in combination with those in siblings—on depressive/anxious psychopathology in siblings.MethodsThe sample included 636 participants (Mage = 49.7; 62.4% female) from 256 families, each including a proband with lifetime depressive and/or anxiety disorders and their sibling(s) (N = 380 proband-sibling pairs). Sixteen psychosocial risk factors were tested. In siblings, depressive and anxiety disorders were determined with standardized psychiatric interviews; symptom severity was measured using self-report questionnaires. Analyses were performed with mixed-effects models accounting for familial structure.ResultsIn siblings, various psychosocial risk factors (female gender, low income, childhood trauma, poor parental bonding, being single, smoking, hazardous alcohol use) were associated with higher symptomatology and likelihood of disorder. The presence of the same risk factor in probands was independently associated (low income, being single) with higher symptomatology in siblings or moderated (low education, childhood trauma, hazardous alcohol use)—by reducing its strength—the association between the risk factor and symptomatology in siblings. There was no additional impact of risk factors in probands on likelihood of disorder in siblings.ConclusionOur findings demonstrate the importance of weighing psychosocial risk factors within a family context, as it may provide relevant information on the risk of affective psychopathology for individuals. Show less
This thesis examines questions related to the prevalence of anxiety symptomatology and disorders in older adults, and compares two brief low-threshold psychological interventions (blended... Show moreThis thesis examines questions related to the prevalence of anxiety symptomatology and disorders in older adults, and compares two brief low-threshold psychological interventions (blended Acceptance and Commitment Therapy versus face-to-face Cognitive Behavioral Therapy) for older adults with anxiety symptoms in primary care. Show less