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Transdiagnostic and Diagnosis-specific ADHD/ASD Morphological Similarity Related Gene Transcription

Poster No:

2289

Submission Type:

Abstract Submission

Authors:

Fanyu Zhang¹, Lin Liu¹, Jinzhong Peng¹, Guobin Ding¹, Yilu Li¹, Pan Wang¹, Bharat Biswal²

Institutions:

¹University of Electronic Science and Technology of China, Chengdu, China, ²New Jersey Institute of Technology, Newark, NJ

First Author:

Fanyu Zhang
University of Electronic Science and Technology of China
Chengdu, China

Co-Author(s):

Lin Liu
University of Electronic Science and Technology of China
Chengdu, China

Jinzhong Peng
University of Electronic Science and Technology of China
Chengdu, China

Guobin Ding
University of Electronic Science and Technology of China
Chengdu, China

Yilu Li
University of Electronic Science and Technology of China
Chengdu, China

Pan Wang
University of Electronic Science and Technology of China
Chengdu, China

Bharat Biswal
New Jersey Institute of Technology
Newark, NJ

Introduction:

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are both highly heritable developmental psychiatric disorders with a high degree of comorbidity (Lord et al. 2018, Posner et al. 2020). The present study focuses on the neuroanatomical changes and their underlying gene transcriptional profile in ADHD and ASD.

Methods:

A total of 258 participants were obtained from publicly available 1000 Functional Connectomes Project (92 individuals with ADHD, 59 individuals with ASD, and 107 healthy controls). Morphological similarity networks (MSN) analysis was performed on the T1-weighted magnetic resonance imaging data to investigate the transdiagnostic and diagnosis-specific structural alterations between ADHD and ASD. Gene transcriptional profile analysis based on the partial least squares regression was performed to identify the MSN-related genes (Li et al. 2021). Enrichment analysis was further conducted on ADHD/ASD risk genes and MSN-related genes to investigate the cellular and genetic pathophysiological mechanisms.

Results:

MSN: ADHD primarily showed the MSN changes distributed in areas related to high-level cognitive functions, while ASD had MSN changes in low-level sensorimotor areas. ADHD and ASD exhibited the transdiagnostic abnormalities with concurrently increasing morphological similarity in the right middle temporal gyrus (one-way ANOVA analysis, false discovery rate correction, P < 0.05).
Figure 1. MSN Results. A, The distribution of mean morphological similarity values in three groups respectively. B, The distribution of morphological similarity differences between the three groups. C, Post-hoc results. SMG, supramarginal gyrus; PCUN, precuneus; MTG, middle temporal gyrus; DCG, median cingulate and paracingulate gyri; REC, gyrus rectus; ORBinf, orbital part of inferior frontal gyrus; STG, superior temporal gyrus; ADHD, attention-deficit/hyperactivity disorder; ASD, autism spectrum disorder; HC, healthy controls; MSN, morphological similarity network; L, left; R, right.
Gene transcriptional profile: The ADHD and ASD risk genes were enriched in more than ten synaptic transmission and regulation pathways, as well as processes related to neuronal development (false discovery rate correction, P < 0.05). Similar biological processes enriched in excitatory and inhibitory neurons suggest that the synaptic signaling transmission in excitatory and inhibitory neurons exhibit transdiagnostic abnormalities in ADHD and ASD.
Figure 2. Functional enrichment of gene transcription. A, Three gene lists, including ADHD and ASD risk genes, PLS1- (Z < -5) gene list, jointly participate in the gene transcription process. B, Expression of genes associated with MSN changes in seven specific cell types. FDR, false discovery rates; PLS1-, the first negative principal component of partial least squares related to MSN changes; MSN, morphological similarity network.

·Figure 1

·Figure 2

Conclusions:

Both ADHD and ASD exhibited diagnosis-specific morphological similarity changes in multiple brain networks involved in sensory-motor and high-level cognitive functions. ADHD and ASD showed a transdiagnostic morphological similarity increase in the right middle temporal gyrus, which is associated with motor disfunction (Lord et al. 2018, Posner et al. 2020). The expression of MSN-related genes may reflect potential alterations in excitatory and inhibitory neural pathways in ADHD and ASD (Morgan et al. 2010, Yokokura et al. 2021).

Brain Stimulation:

Non-invasive Magnetic/TMS

Disorders of the Nervous System:

Neurodevelopmental/ Early Life (eg. ADHD, autism)

Genetics:

Transcriptomics ²

Modeling and Analysis Methods:

Connectivity (eg. functional, effective, structural)

Novel Imaging Acquisition Methods:

Anatomical MRI ¹

Keywords:

MRI

Other - Attention-deficit/hyperactivity disorder

^1|2Indicates the priority used for review

Provide references using author date format

Lord, C. (2018). ‘Autism spectrum disorder’. The Lancet. vol. 392, no. 10146, pp. 508-520.
Posner, J. (2020). ‘Attention-deficit hyperactivity disorder’. The Lancet. vol. 395, no. 10222, pp. 450-462.
Li, J. (2021). ‘Cortical structural differences in major depressive disorder correlate with cell type-specific transcriptional signatures’. Nature Communications. vol. 12, no. 1, pp. 1647.
Morgan, J.T. (2010). ‘Microglial activation and increased microglial density observed in the dorsolateral prefrontal cortex in autism’. Biological Psychiatry. vol. 68, no. 4, pp. 368-376.
Yokokura, M. (2021). ‘In vivo imaging of dopamine D1 receptor and activated microglia in attention-deficit/hyperactivity disorder: a positron emission tomography study’. Molecular Psychiatry. vol. 26, no. 9, pp. 4958-4967.