Background: Questionnaires are the current hallmark for quantifying social functioning in human clinical research. In this study, we compared self- and proxy-rated (caregiver and researcher)... Show moreBackground: Questionnaires are the current hallmark for quantifying social functioning in human clinical research. In this study, we compared self- and proxy-rated (caregiver and researcher) assessments of social functioning in Schizophrenia (SZ) and Alzheimer's disease (AD) patients and evaluated if the discrepancy between the two assessments is mediated by disease-related factors such as symptom severity.Methods: We selected five items from the WHO Disability Assessment Schedule 2.0 (WHODAS) to assess social functioning in 53 AD and 61 SZ patients. Caregiver- and researcher-rated assessments of social functioning were used to calculate the discrepancies between self-rated and proxy-rated assessments. Furthermore, we used the number of communication events via smartphones to compare the questionnaire outcomes with an objective measure of social behaviour.Results: WHODAS results revealed that both AD (p < 0.001) and SZ (p < 0.004) patients significantly overestimate their social functioning relative to the assessment of their caregivers and/or researchers. This overestimation is mediated by the severity of cognitive impairments (MMSE; p = 0.019) in AD, and negative symptoms (PANSS; p = 0.028) in SZ. Subsequently, we showed that the proxy scores correlated more strongly with the smartphone communication events of the patient when compared to the patient-rated questionnaire scores (self; p = 0.076, caregiver; p < 0.001, researcher-rated; p = 0.046).Conclusion: Here we show that the observed overestimation of WHODAS social functioning scores in AD and SZ patients is partly driven by disease-related biases such as cognitive impairments and negative symptoms, respectively. Therefore, we postulate the development and implementation of objective measures of social functioning that may be less susceptible to such biases. Show less
The use of smartphone-based location data to quantify behavior longitudinally and passively is rapidly gaining traction in neuropsychiatric research. However, a standardized and validated... Show moreThe use of smartphone-based location data to quantify behavior longitudinally and passively is rapidly gaining traction in neuropsychiatric research. However, a standardized and validated preprocessing framework for deriving behavioral phenotypes from smartphone-based location data is currently lacking. Here, we present a preprocessing framework consisting of methods that are validated in the context of geospatial data. This framework aims to generate context-enriched location data by identifying stationary, non-stationary, and recurrent stationary states in movement patterns. Subsequently, this context-enriched data is used to derive a series of behavioral phenotypes that are related to movement. By using smartphone-based location data collected from 245 subjects, including patients with schizophrenia, we show that the proposed framework is effective and accurate in generating context-enriched location data. This data was subsequently used to derive behavioral readouts that were sensitive in detecting behavioral nuances related to schizophrenia and aging, such as the time spent at home and the number of unique places visited. Overall, our results indicate that the proposed framework reliably preprocesses raw smartphone-based location data in such a manner that relevant behavioral phenotypes of interest can be derived. Show less
Eijk, R.P.A. van; Eijkemans, M.J.C.; Nikolakopoulos, S.; Jansen, M.D.; Westeneng, H.J.; Eijk, K.R. van; ... ; Es, M.A. van 2020
Genetic mutations related to amyotrophic lateral sclerosis (ALS) act through distinct pathophysiological pathways, which may lead to varying treatment responses. Here we assess the genetic... Show moreGenetic mutations related to amyotrophic lateral sclerosis (ALS) act through distinct pathophysiological pathways, which may lead to varying treatment responses. Here we assess the genetic interaction between C9orf72, UNC13A, and MOBP with creatine and valproic acid treatment in two clinical trials. Genotypic data was available for 309 of the 338 participants (91.4%). The UNC13A genotype affected mortality (p = 0.012), whereas C9orf72 repeat-expansion carriers exhibited a faster rate of decline in overall (p = 0.051) and bulbar functioning (p = 0.005). A dose-response pharmacogenetic interaction was identified between creatine and the A allele of the MOBP genotype (p = 0.027), suggesting a qualitative interaction in a recessive model (HR 3.96, p = 0.015). Not taking genetic information into account may mask evidence of response to treatment or be an unrecognized source of bias. Incorporating genetic data could help investigators to identify critical treatment clues in patients with ALS. Show less
ObjectiveWomen with premature ovarian insufficiency (POI) enter menopause before age 40. Early menopause was associated with increased risk for coronary artery disease (CAD), death from... Show moreObjectiveWomen with premature ovarian insufficiency (POI) enter menopause before age 40. Early menopause was associated with increased risk for coronary artery disease (CAD), death from cardiovascular disease and all-cause mortality. We compared the prevalence of CAD between middle-aged women on average 10years following the initial POI diagnosis, with a population-based cohort.DesignCross-sectional case-control study.ParticipantsWomen from two Dutch University Medical Centers above 45years of age previously diagnosed with POI (n=98) were selected and compared with age- and race-matched controls from the Multi-Ethnic Study of Atherosclerosis (MESA).MeasurementsThe primary outcome was detectable coronary artery calcium (CAC) determined by coronary computed tomography (CCT).ResultsWomen with POI had significantly higher blood pressure, cholesterol and glucose, despite lower BMI compared to controls. Similar proportions of detectable CAC (CAC score >0 Agatston Units) were observed in women with POI and controls (POI n=16 (16%), controls n=52 (18%), P=0.40 and P-adj=0.93). In women with POI separately, we were not able to identify associations between CVD risk factors and CAC. The following CVD risk factors in controls were positively associated with CAC: age, diabetes mellitus, hypertension and LDL cholesterol. HRT use was negatively associated with CAC in controls.ConclusionsThe presence of CAC did not differ significantly in women with POI around 50years of age, compared to an age- and race-matched control group. We observe no increased calcified coronary disease in POI patients, despite the presence of unfavourable cardiovascular risk factors in these women. Show less
Jong, V.M.T. de; Eijkemans, M.J.C.; Calster, B. van; Timmerman, D.; Moons, K.G.M.; Steyerberg, E.W.; Smeden, M. van 2019
