Elsevier

NeuroImage

Volume 201, 1 November 2019, 116006
NeuroImage

Brain structural differences in monozygotic twins discordant for body mass index

https://doi.org/10.1016/j.neuroimage.2019.07.019Get rights and content

Highlights

  • Differences of regional gray matter volume (GMV) in BMIdiscordant monozygotic twins

  • Reduced GMV in heavier vs. leaner twin siblings

  • •GMV reductions within brain regions implicated in reward and valuation processes

Abstract

Background

Substantial efforts have been made to investigate the neurobiological underpinnings of human obesity with a number of studies indicating a profound influence of increased body weight on brain structure. Although body weight is known to be highly heritable, uncertainty remains regarding the respective contribution of genetic and environmental influences.

Methods

In this study we used structural magnetic resonance imaging (MRI) data from the Human Connectome Project (HCP). Voxel-based morphometry (VBM) was applied to study BMI-associated differences in gray matter volume (GMV) within monozygotic (MZ) twin pairs discordant for BMI (ΔBMI ​> ​2.5 ​kg*m−2, n = 68 pairs). In addition, we investigated the relationship of ΔBMI (entire range) with GMV differences within the entire sample of MZ twin pairs (n = 153 pairs).

Results

Analyses of BMI discordant twin pairs yielded less GMV in heavier twin siblings (p < 0.05 FWETFCE; paired t-Test) within the occipital and cerebellar cortex, the prefrontal cortex and the bilateral striatum including the nucleus accumbens. A highly converging pattern was found in regression analyses across the entire sample of MZ twin pairs, with ΔBMI being associated with less GMV in heavier MZ twins.

Conclusion

While MZ twins share the same genetic background, our findings indicate that non-genetic influences and the mere presence of a higher BMI constitute relevant factors in the context of body weight related structural brain alterations.

Introduction

Overweight and obesity remain a worldwide health concern, particularly in industrialized countries (Abarca-Gómez et al., 2017).This obesity epidemic can be largely ascribed to an obesogenic environment that promotes a behavioral phenotype characterized by unhealthy eating patterns and a sedentary lifestyle (Cecchini et al., 2010; Chaput et al., 2011). With behavior being the driving force behind the development of adiposity, increasing efforts have been made to enhance our understanding of associated neurobiological mechanisms. Considerable evidence indicates altered function of mesolimbic and mesocortical dopaminergic reward pathways as a potential mechanisms which - on a behavioral level – results in compensatory increases in reward-related behavior (e.g. eating palatable foods; Berridge et al., 2010; Kenny, 2011; Volkow et al., 2013). Evidence exists that the neurobiological underpinnings that underlie body weight homeostasis and associated behavioral phenotypes are somewhat genetically determined (e.g. Heni et al., 2014; Ho et al., 2010; Vainik et al., 2018; Weise et al., 2017), yet a number of intervention studies point to a dynamic interaction of potential mechanisms (e.g. Dunn et al., 2010; Karlsson et al., 2016; Prehn et al., 2016; Rullmann et al., 2018; Tuulari et al., 2016). In the past decade numerous studies investigated body weight related brain morphological changes, mostly showing reduced gray matter volume (GMV) of distinct brain regions in overweight and obese but also underweight individuals (e.g. Horstmann et al., 2011; Kurth et al., 2013; Pannacciulli et al., 2006; Taki et al., 2008; Walther et al., 2010; Titova et al., 2013). However, the cross-sectional design of the majority of these studies does not allow drawing any conclusions regarding the origin of these changes. We previously showed that brain regions associated with adiposity underlie varying degrees of heritability, indicating that some of these regions might constitute risk factors for obesity in the sense of a predisposing endophenotype (Weise et al., 2017). Nevertheless, due to the descriptive nature of these observations, a cautious interpretation is required, as this approach does not have the potential to establish causality. In contrast, studies of MZ twins discordant for a specific trait have the potential to identify environmental effects in the absence of genetically determined differences.

Therefore, we sought to follow up on our previous study by investigating brain structural differences in MZ twins discordant for body mass index. However, this approach implies the analyses of sibling pairs where both individuals may share – according to BMI criteria - a similar weight status. Therefore, our findings primarily reflect brain structural differences in relation to BMI differences - independently of genetic predispositions - but not structural differences between lean and obese siblings in the narrower sense. Here, we hypothesized that heavier MZ siblings – compared to their leaner counterparts - would exhibit reduced gray matter volume of brain regions within mesocorticolimbic pathways involved in eating and reward related behavior. To do so, we analyzed data from the Human Connectome Project, a large-scale study of twin and non-twin individuals with the goal to identify genetic and environmental influences on the central representation of behavioral aspects by applying multimodal neuroimaging methods (Van Essen et al., 2013).

Section snippets

Study population

For this study, we analyzed data from the publicly available Human Connectome Project (HCP) database (www.humanconnectome.org). The HCP sample is composed of a total of n = 1206 healthy young to middle-aged adults and contains data from non-twin siblings, monozygotic (identical) and dizygotic (fraternal) twins. For a detailed description of eligibility criteria and study protocols, we refer to previously published work (Van Essen et al., 2012, 2013). Complete structural MRI and BMI data of each

Results

From 153 pairs of MZ twins we identified 68 pairs with a BMI difference >2.5 ​kg*m−2. Table 1 lists basic subject characteristics for weight discordant MZ twins and the entire sample of MZ twins. Expectedly, BMI was significantly different in weight discordant MZ twins (p < 0.0001) but no significant differences were observed for education, measures of fluid intelligence and measures of endurance (all p ≥ 0.49).

Paired t-tests of weight discordant MZ twin pairs showed reduced GMV of several

Discussion

One prevailing question in obesity research is to which extent the obese phenotype is driven by heritable as compared to environmental influences. In order to address this question, we investigated differences in brain structure of 68 pairs of MZ twins discordant for BMI. Here, heavier MZ twins compared to their leaner siblings presented reduced GMV within brain regions involved in valuation and reward processes – important cognitive mechanisms required to control food choices and eating

Acknowledgments

Data were provided [in part] by the Human Connectome Project, WU-Minn Consortium (Principal Investigators: David Van Essen and Kamil Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and Centers that support the NIH Blueprint for Neuroscience Research; and by the McDonnell Center for Systems Neuroscience at Washington University. This study was supported by the IFB AdiposityDiseases, Federal Ministry of Education and Research, Germany, FKZ: 01E01001 (http://www.bmbf.de), the BMBF nutriCARD

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