Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Brain Morphology and Physical Symptoms: A Population-Neuroimaging Study in 13,250 Pre-Adolescents

Version 1 : Received: 12 May 2021 / Approved: 14 May 2021 / Online: 14 May 2021 (11:31:23 CEST)

How to cite: Estévez-López, F.; Kim, H.H.; López-Vicente, M.; Legerstee, J.S.; Hillegers, M.H.J.; Tiemeier, H.; Muetzel, R. Brain Morphology and Physical Symptoms: A Population-Neuroimaging Study in 13,250 Pre-Adolescents. Preprints 2021, 2021050324 (doi: 10.20944/preprints202105.0324.v1). Estévez-López, F.; Kim, H.H.; López-Vicente, M.; Legerstee, J.S.; Hillegers, M.H.J.; Tiemeier, H.; Muetzel, R. Brain Morphology and Physical Symptoms: A Population-Neuroimaging Study in 13,250 Pre-Adolescents. Preprints 2021, 2021050324 (doi: 10.20944/preprints202105.0324.v1).

Abstract

Physical symptoms are defined as symptoms for which adequate examination does not reveal a sufficient underlying root cause, e.g., pain and fatigue. The extant literature of the neurobiological underpinnings of physical symptoms has been largely inconsistent and primarily consists of (clinical) case-control studies with relatively small samples sizes. Therefore, we studied the association of brain morphology with physical symptoms in pre-adolescents from two independent and population-based cohorts. This study included 2,683 individuals from the Generation R Study (51% girls, 10.1 ± 0.6 years old) and 10,567 pre-adolescents from the ABCD Study (48% girls, 9.9 ± 0.6 years old). High- resolution structural magnetic resonance imaging (MRI) was collected using 3-Tesla MRI systems. Physical symptoms were evaluated using the somatic complaints syndrome scale from the parent-reported school-age version of the Child Behavior Checklist. Linear regression models were fitted for global brain metrics (i.e., cortical and subcortical grey matter volume and total white matter volume) as well as surface-based vertex-wise measures (surface area and cortical thickness). Analyses were initially conducted separately in each cohort and later meta-analysed. No associations were observed in either cohort separately. In the combined vertex-wise meta-analysis of both cohorts; the right hemisphere surface area, most notably the rostral middle frontal gyrus, superior frontal gyrus and anterior cingulate cortex, were related to physical symptoms after correcting for multiple comparisons (cluster area = 1,882 mm2). The present study, which is the most representative and well-powered to date, suggests that surface area, but not other measures of brain morphology, are modestly related to physical symptoms in pre- adolescents. While these effects are subtle, future longitudinal research is warranted to elucidate whether such associations indicate a cause or a consequence of the physical symptoms.

Keywords

Cohort studies; Epidemiology; Gray matter; Neuroimaging; Paediatrics; Psychiatric symptoms; QDECR; Vertex-wise analysis.

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