Attention-deficit hyperactivity disorder symptoms and brain morphology: Addressing potential selection bias with inverse probability weighting.

The goal of this study was to examine what happens to established associations between attention deficit hyperactivity disorder (ADHD) symptoms and cortical surface and thickness regions once we apply inverse probability of censoring weighting (IPCW) to address potential selection bias. Moreover, we illustrate how different factors that predict participation contribute to potential selection bias. Participants were 9- to 11-year-old children from the Generation R study (N = 2707). Cortical area and thickness were measured with magnetic resonance imaging (MRI) and ADHD symptoms with the Child Behavior Checklist. We examined how associations between ADHD symptoms and brain morphology change when we weight our sample back to either follow-up (ages 9-11), baseline (cohort at birth), or eligible (population of Rotterdam at time of recruitment). Weights were derived using IPCW or raking and missing predictors of participation used to estimate weights were imputed. Weighting analyses to baseline and eligible increased beta coefficients for the middle temporal gyrus surface area, as well as fusiform gyrus cortical thickness. Alternatively, the beta coefficient for the rostral anterior cingulate decreased. Removing one group of variables used for estimating weights resulted in the weighted regression coefficient moving closer to the unweighted regression coefficient. In addition, we found considerably different beta coefficients for most surface area regions and all thickness measures when we did not impute missing covariate data. Our findings highlight the importance of using inverse probability weighting (IPW) in the neuroimaging field, especially in the context of mental health-related research. We found that including all variables related to exposure-outcome in the IPW model and combining IPW with multiple imputations can help reduce bias. We encourage future psychiatric neuroimaging studies to define their target population, collect information on eligible but not included participants and use inverse probability of censoring weighting (IPCW) to reduce selection bias.

Examining longitudinal associations between prenatal exposure to infections and child brain morphology.

BACKGROUND: Maternal infection during pregnancy has been identified as a prenatal risk factor for the later development of psychopathology in exposed offspring. Neuroimaging data collected during childhood has suggested a link between prenatal exposure to maternal infection and child brain structure and function, potentially offering a neurobiological explanation for the emergence of psychopathology. Additionally, preclinical studies utilizing repeated measures of neuroimaging data suggest that effects of prenatal maternal infection on the offspring's brain may normalize over time (i.e., catch-up growth). However, it remains unclear whether exposure to prenatal maternal infection in humans is related to long-term differential neurodevelopmental trajectories. Hence, this study aimed to investigate the association between prenatal exposure to infections on child brain development over time using repeated measures MRI data. METHODS: We leveraged data from a population-based cohort, Generation R, in which we examined prospectively assessed self-reported infections at each trimester of pregnancy (N = 2,155). We further used three neuroimaging assessments (at mean ages 8, 10 and 14) to obtain cortical and subcortical measures of the offspring's brain morphology with MRI. Hereafter, we applied linear mixed-effects models, adjusting for several confounding factors, to estimate the association of prenatal maternal infection with child brain development over time. RESULTS: We found that prenatal exposure to infection in the third trimester was associated with a slower decrease in volumes of the pars orbitalis, rostral anterior cingulate and superior frontal gyrus, and a faster increase in the middle temporal gyrus. In the temporal pole we observed a divergent pattern, specifically showing an increase in volume in offspring exposed to more infections compared to a decrease in volume in offspring exposed to fewer infections. We further observed associations in other frontal and temporal lobe structures after exposure to infections in any trimester, though these did not survive multiple testing correction. CONCLUSIONS: Our results suggest that prenatal exposure to infections in the third trimester may be associated with slower age-related growth in the regions: pars orbitalis, rostral anterior cingulate and superior frontal gyrus, and faster age-related growth in the middle temporal gyrus across childhood, suggesting a potential sensitive period. Our results might be interpreted as an extension of longitudinal findings from preclinical studies, indicating that children exposed to prenatal infections could exhibit catch-up growth. However, given the lack of differences in brain volume between various infection groups at baseline, there may instead be either a longitudinal deviation or a subtle temporal deviation. Subsequent well-powered studies that extend into the period of full brain development (∼25 years) are needed to confirm whether the observed phenomenon is indeed catch-up growth, a longitudinal deviation, or a subtle temporal deviation.

Study Protocol on Cognitive Performance in Bulgaria, Croatia, and the Netherlands: The Normacog Brief Battery.

The Normacog Brief Battery (NBB) provides a comprehensive overview of an individual's cognitive functioning within a short amount of time. It was originally developed for the Spanish population in Spain. However, there is a considerable need for brief batteries in clinical neuropsychological assessment, especially in eastern European countries. Cultural background and other individual characteristics-such as age, level of education, and sex-are shown to influence both cognition and patients' performance on neuropsychological tests. Therefore, it is important to develop understanding of how and why culture impacts on cognitive testing and determine which sociodemographic variables affect cognitive performance. The current study aims to translate, adapt, and standardize the NBB in Bulgaria, Croatia, and the Netherlands, and to analyze the effect of sex, age, and education level on cognitive performance between these three countries. This brief battery assesses eleven cognitive domains, including those most currently relevant in cognition such as premorbid intelligence, attention, executive function, processing speed, and memory. The translation and adaptation of the battery for different cultures will be done using the back-translation process. After exclusion criteria, the current study will include a total sample of 300 participants (≥18 years old). The samples of 100 participants per country will be balanced through the consideration of their age and level of education. Effects of the sociodemographic variables (age, level of education, and sex) on cognitive performance are expected. Furthermore, this relationship is expected to differ across countries. A multivariate hierarchical linear regression will be used and exploratory analysis will be carried out to investigate further effects. The results will be particularly valuable for future research and assessment in cognitive performance. The growing demand for accurate and fast neuropsychological assessment shows the importance of creating a universal brief assessment tool for wider cross-cultural application.