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iNature
A mental disorder is a disorder that causes dysfunction of the brain, in which an individual is severely disturbed
emotionally, cognitively, or behaviorally.
Mental illness is reported to be a serious public health problem
as a result of millions of people living with mental illness worldwide.
Psychiatric disorders are characterized by a range of physiological changes in the brain, including a number of heritable imaging-derived phenotypes (IDPs) that can be measured
non-invasively by MRI.
An association between brain imaging phenotype and psychiatric disorders has been reported, however, whether there is a causal relationship between these associations remains unclear
.
On October 10, 2022, Yang Tielin and Guo Yan of the Center for Biomedical Informatics and Genomics of Xi'an Jiaotong University published an online publication in Nature Neuroscience “Mendelian randomization analyses support causal relationships between brain imaging-derived phenotypes and risk of psychiatric disorders” This study demonstrates a causal relationship between brain imaging phenotypes and psychiatric disorders through bidirectional two-sample Mendelian randomization (MR) analysis, a finding that provides a potential strategy
for predicting and intervening in the risk of mental disorders at the brain imaging level.
For example, the thinner thickness of the insula and anterior cingulate cortex on the side of the snout is thought to be a brain marker of adolescent anxiety; The thickness of the temporal and parietal cortex was reduced in patients with schizophrenia compared to healthy people, while the thickness of the temporal and parietal cortex was increased in patients with autism spectrum disorder; Patients with bipolar disorder showed lower fractional anisotropy (FA) and higher mean diffusivity (MD) in retrothalamic irradiation; Reduction in hippocampal volume was found in adolescents with anorexia nervosa, older adults with depression, and twins with severe post-traumatic stress disorder; There is evidence that thalamic volume decreases in patients with attention deficit hyperactivity disorder and increases in patients with Tourette syndrome; Changes in brain structure in patients with OCD are mainly manifested by a decrease
in cortical surface area in several regions.
Although there is growing evidence that physiological changes in the brain are associated with mental disorders, the causal relationship between IDPs and mental disorders remains unclear
.
In addition, the results of traditional observational studies do not explain confounders
.
It is important to
explore the presumptive causal role of IDPs on mental disorders.
Mendelian randomization (MR) is a widely used epidemiological method that uses genetic variation as a tool to infer causal relationships
between phenotypes and outcomes.
Large-scale genome-wide association studies (GWASs) through MR systems provide an opportunity
to explore the underlying causal relationship between numerous IDPs and mental disorders.
In this study, the researchers performed a bidirectional two-sample Mendelian randomization (MR) analysis, based on 587 key brain magnetic resonance imaging (MRI) (N = 33,224 people) with 10 common psychiatric disorders (N = 9,725 to 161,405 people (including ADHD, anorexia nervosa, anxiety, autism, bipolar disorder, depression, obsessive-compulsive disorder, post-traumatic stress disorder, schizophrenia, tics).
The researchers demonstrated that there were 9 IDPs (including the FA value of the upper frontal occipital tract of the white matter fiber tract and the ICVF value of the superior radial crown, and the sagittal layer in the body of the callus MD value, volume of the third ventricle, etc.
) on risk factors
for schizophrenia, anorexia nervosa, and bipolar disorder.
MR analysis from brain image-driven phenotype to psychiatric disorders (Figure from Nature Neuroscience) further showed through reverse MR analysis that Only genes predicted that schizophrenia was positively correlated with two IDPs, the cortical surface area and the right orbital volume
.
This suggests that the occurrence of schizophrenia leads to an increase in
the surface area and volume of the inferior frontal gyrus orbit.
The researchers also created the BrainMR database ( lang="EN-US" style="font-family: Arial, sans-serif;" _istranslated="1">) to share the study's findings
.
In summary, the study performed a bidirectional two-sample MR analysis to systematically estimate the potential causal relationship
between neuroimaging phenotypes and mental disorders using large-scale GWAS data.
The findings reveal strong genetic evidence
of a causal relationship between neuroimaging phenotypes and psychiatric disorders.
These findings can guide early prevention, etiological diagnosis, and treatment
of mental illness at the brain imaging level.
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