Association of amygdala volume and autistic traits in monozygotic twins: Controlling for confounds

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Abstract Submission 

Neda Sadeghi¹, Tonya White¹

¹National Institute of Mental Health, Bethesda, MD

Neda Sadeghi  
National Institute of Mental Health
Bethesda, MD

Tonya White  
National Institute of Mental Health
Bethesda, MD

Autism is a complex neurodevelopmental disorder that is characterized by difficulties in social interaction and a pattern of restrictive and repetitive behaviors. There has been an increasing interest in studying the role of the amygdala in autism, especially given that it is a component structure of the "social brain" (Brothers, L. 1990; Baron-Cohen, S., et al., 2000; Zalla, T. et al., 2013; Sharp, T.H., et al., 2023). However, findings related to the amygdala have been mixed. This could be due to many reasons such as differences related to confounding factors, i.e., age, sex, race, etc. In addition, studies that utilize neuroimaging suffer from scanner induced variability.

To control for these potential biases, we used monozygotic (MZ) twin data from Adolescent Brain Cognitive Development (ABCD) study (Iacono, W.G., et al., 2018) to assess the relationship between autistic traits (scores on Social Responsiveness Scale (SRS); Constantino, J.N. et al., 2003) and amygdala volume. Using MZ twin data provides a unique opportunity to control for many confounds.

We analyzed data from 372 pairs of MZ twins ( Male: 191, Female: 181; age 9-10 years). Autistic traits were measured using the SRS short form. This measure assesses the severity of social difficulties across the spectrum of autistic symptoms, including children with ASD, subclinical symptoms, and typically developing (Constantino, J.N. et al., 2003). Higher SRS scores indicate greater autistic symptoms. For each twin pair, difference between SRS scores was calculated. Neuroimaging data were collected, processed, and quality checked by ABCD Data Analysis, Informatics & Resource Center (DAIRC). T1-weighted images were collected on 3-Tesla scanners (Casey, B.J., et al., 2018). FreeSurfer was used to extract subcortical and cortical regions of interests. We used the available volumetric measures for amygdala.

The difference between volumetric measures of left and right amygdala within each twin pair was calculated and normalized by their average score to create a relative difference in volume between twins. Linear regression was performed to assess the relationship between differences in SRS scores in relation to differences in amygdala volume in twin pairs.

Autistic traits as measured by SRS were negatively correlated with left amygdala volume (Beta=-3.39, 95%CI = -6.45, -0.35, p=0.029), however, there was no association between SRS and right amygdala volume (Beta=-2.34, 95% CI=-6.16, 1.48, p=0.23; Figure 1). We noticed two outliers in the SRS measure, we repeated the analysis after removing these outliers and the result was no longer significant for left amygdala (Beta=-2.42408 , 95% CI= -5.25, 0.40, p=0.093; Figure 2).

We found a negative association between SRS and volume of left amygdala, indicating an increased amygdala volume in a twin is associated with a lower SRS score. However, even though we found a significant association between SRS and relative size of left amygdala, the effect size is small, and after removing two outlier data points, the result was no longer significant. Since the ABCD study excluded subjects with moderate to severe autism, our study focused on those with mild or subclinical symptoms. Thus, our findings may not be true for those with more severe autistic symptoms. Our study provides a mechanism to control for potential cofounds and biases when evaluating neuroimaging correlates of autistic symptoms.

Neurodevelopmental/ Early Life (eg. ADHD, autism) ¹

Social Cognition ²

Autism

MRI

PEDIATRIC

Social Interactions

STRUCTURAL MRI

Structures

Sub-Cortical