Causal interactions between schizophrenia and gray matter: A Mendelian Randomization Study
Poster No:
525
Submission Type:
Abstract Submission
Authors:
Xuefei Wang1
Institutions:
1Fudan University, Shanghai, Shanghai
First Author:
Introduction:
Schizophrenia is a severe disease caused by various etiologies that impair brain function, leading to significant disruption of social functioning in affected individuals (Goldman, 2020). Schizophrenia imposes a huge burden on patients, families and society (Charlson, 2019). Research indicates that schizophrenia is frequently associated with structural changes in the brain, often manifested as alterations in cortical thickness and surface area (Karlsgodt, 2010). Previous studies (Goula, 2024, Stauffer, 2023) have conducted causal analysis between schizophrenia and brain structures, but no significant associations were found in the expected brain regions. Our study offers a more effective approach to uncovering the causal relationships between schizophrenia and brain structure.
Methods:
The study sample consisted of the IMAGEN dataset, which included individuals at 19 years (n=1051) and 23 years (n=773) who underwent 3T magnetic resonance imaging (MRI) data collection, along with assessments using the Community Assessment of Psychic Experiences (CAPE) scale. The Psychiatric Genomics Consortium and ENIGMA were used to obtain genome-wide association study (GWAS) results on schizophrenia, cortical thickness, and surface area. Modified Mendelian randomization (MR) was employed to analyze the causal interactions between schizophrenia and brain gray matter, followed by sensitivity analysis. This new MR approach utilized polygenic risk scores (PRS) as instrumental variables, incorporating contributions from multiple genetic variations while considering pleiotropic single nucleotide polymorphisms (SNPs).
Results:
The cortical surface area of para hippocampal (r=0.062, p=0.034), pars triangularis (r=0.072, p=0.012), rostral anterior cingulate (r=0.065, p=0.028), and temporal pole (r=-0.072, p=0.018) showed significant correlations with positive psychotic symptoms at age 19. The cortical thickness of transverse temporal (r=0.062, p=0.033) was also significantly correlated with positive psychotic symptoms at age 19. Schizophrenia was significantly associated with longitudinal changes in the surface area of the left insula (r=0.086, p=0.019) and right bankssts (r=0.08, p=0.036). Longitudinal changes in cortical thickness of the left insula (r=-0.11, p=0.006) and left pars orbitalis (r=-0.123, p=0.005) were significantly correlated with schizophrenia.
·Figure 1. Bidirectional Causal Relationships between Cortical Surface Area, Thickness and Schizophrenia as Revealed by Modified Mendelian Randomization Analysis
Conclusions:
Our study reveals a bidirectional causal relationship between schizophrenia and brain structure, contributing to a better understanding and interpretation of the relationship between schizophrenia and brain gray matter. This enhances the rationale for intervention research aimed at improving brain health.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Genetics:
Genetic Association Studies
Lifespan Development:
Early life, Adolescence, Aging
Novel Imaging Acquisition Methods:
BOLD fMRI 2
Keywords:
Cortex
MRI
Psychiatric Disorders
Schizophrenia
1|2Indicates the priority used for review
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Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.
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Provide references using APA citation style.
Goula, A. (2024). Dissecting causal relationships between cortical morphology and neuropsychiatric disorders. Neuroscience Applied, Volume 3, Supplement 1, 103960.
Goldman, ML. (2020). Schizophrenia. New England Journal of Medicine, 382(6), 583-584.
Karlsgodt, K.H. (2010). Structural and Functional Brain Abnormalities in Schizophrenia. Current Directions in Psychological Science, 19(4), 226-231.
Stauffer, EM. (2023). The genetic relationships between brain structure and schizophrenia. Nature Communication, 14, 7820.