Anxiety-related experience-dependent white matter structural differences in adolescence: A monozygotic twin difference approach

Abstract

Anxiety is linked to deficits in structural and functional connectivity between limbic structures and pre-frontal cortices. We employed a monozygotic (MZ) twin difference design to examine the relationship between structural characteristics of the uncinate fasciculus (UF) measured by Diffusion Tensor Imaging (DTI) and anxiety symptoms in a sample of N = 100 monozygotic (genetically identical), adolescent twins. The MZ difference design allowed us focus on environmental factors that vary within twin pairs while controlling for genetic and environmental factors shared by twin pairs. Twins aged 13–18 years reported on symptoms of generalized anxiety and social phobia prior to participating in a neuroimaging visit. Regions of interest from the JHU ICBM atlas, including uncinate fasciculus and sagittal stratum as a control tract, were registered to the study template. We incorporated multiple diffusion tensor measures to characterize the white matter differences. Within twin pairs, the more anxious twin exhibited decreased fractional anisotropy (t = −2.22, p = 0.032) and axial diffusivity (t = −2.38, p = 0.022) in the left UF compared to the less anxious twin, controlling for age and gender. This study demonstrated the feasibility and advantages of adopting the MZ twin design for DTI measures in neuroimaging research.

Longitudinal Research at the Interface of Affective Neuroscience, Developmental Psychopathology, Health and Behavioral Genetics: Findings from the Wisconsin Twin Project

“…Another example of our neuroimaging research uses the MZ difference design. In DTI analyses, we again focus on the uncinate fasciculus (Adluru et al, 2017). MZ co-twins are similar for FA values in the left and right uncinate fasciculus (ICCs = .66 and .75, respectively).…”

“…With the ability to choose the scale of the network under investigation, we demonstrated that the heritability of white matter structural connectivity patterns was robust and consistent across multiple network scales (including after five iterations that subdivided the whole brain into 3712 parcellations). Note: This figure depicts the white matter pathway uncinate fasciculus reconstructed using 100 MZ twins' DTI data described in Adluru et al (2017). The color spectrum indicates levels of similarities of underlying WM microstructure (FA) across the whole uncinate fasciculus structure.…”

White Matter Plasticity in Anxiety: Disruption of Neural Network Synchronization During Threat-Safety Discrimination

“…exposed to socioemotional deprivation (Eluvathingal et al, 2006). Decreased FA and radial diffusivity were also detected in the left uncinate fasciculus of affected monozygotic adolescent twins with anxiety disorders compared to unaffected siblings (Adluru et al, 2017), collectively suggesting compromised communication between PFC and amygdala in such individuals (Yavas et al, 2019).…”

Wisconsin Twin Project Overview: Temperament and Affective Neuroscience

“…a Co-twin ratings also collected. our early neuroimaging and epigenetic studies use the MZ difference design (Adluru et al, 2017;Alisch et al, 2017;Burghy et al, 2016). The twin neuroimaging data were also used to illustrate novel computational MRI methods (Chung, Luo, Adluru et al, 2018;Chung, Luo, Leow et al, 2018;Huang et al, 2019).…”

“…Many studies incorporate observational behavior and laboratory temperament assessments that were partially developed in our lab (Buss & Goldsmith, 2000;Gagne et al, 2011;Goldsmith et al, 2010;Planalp et al, 2017). Several of our neuroimaging studies incorporate the monozygotic (MZ) difference design (Adluru et al, 2017;Alisch et al, 2017;Burghy et al, 2016;Carroll et al, 2019). Recent empirical results from more than 30 papers are summarized in Schmidt et al (2019).…”