Summary: Researchers have made a major breakthrough in understanding the genetic basis of anxiety disorders (AD), which affect more than 280 million people worldwide.
By analyzing spatiotemporal transcriptomic data of AD-related genes in the human brain, they identified two distinct gene clusters with specific expression patterns in the brain nuclei, midbrain, and limbic system (regions previously associated with AD behavior) . These clusters correspond to glutamatergic and serotonergic/dopaminergic signaling, respectively, and their unique expression at different developmental stages suggests that they play a role in the development of AD symptoms.
This study provides important insights into the genetic and neurophysiological basis of AD and its subtypes, opening up avenues for targeted therapies.
Key facts:
- Anxiety disorders affect more than 280 million people worldwide.
- Research from Kyoto University discovered two gene clusters with different spatial and temporal expression patterns related to AD.
- These gene clusters correspond to different signaling pathways and developmental stages and are shown to play a role in the development of AD symptoms.
source: ashby
Anxiety disorders (AD) affect more than 280 million people worldwide, making them one of the most common mental health conditions. From a family perspective, AD has a genetic basis, and people with one subtype of AD tend to have another subtype, suggesting a common genetic basis. Although brain circuits associated with AD have been identified, their association with gene expression remains unclear.
Two researchers from Kyoto University in Japan set out to uncover this connection and discovered two gene clusters expressed in the brain.
In previous studies, targeted gene sequencing and genome-wide association studies (GWAS) revealed mutations that occur frequently in people with AD or anxiety-related personality traits. These mutations have been mapped to specific genes in the human genome.
Meanwhile, neuroimaging techniques such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) have shown that the activity of specific neural circuits predicts anxious temperament in rhesus monkeys, and microstimulation techniques in these monkeys can demonstrate which neural circuits are associated with AD symptoms.
Kyoto University researchers Ms. Karunakaran and Dr. Amemori et al. investigated whether AD-related genes are expressed in the same neural circuits identified through imaging and microstimulation techniques.
Specifically, they analyzed the four AD subtypes (generalized anxiety disorder, social anxiety disorder, and obsessive-compulsive disorder), and the Allen Brain Atlas showed the presence of phobias and panic disorders in more than 200 normal human brain regions.
Through statistical tests, the researchers found that AD-related genes are highly expressed in the brain nuclei, midbrain, and limbic system.
Further analysis of these regions by hierarchical clustering revealed that two AD gene clusters have distinct spatial expression profiles, one highly expressed in the limbic system and a specific set of brain nuclei, and the other in the midbrain and a distinct set of brain nuclei. Highly expressed in brain nuclei; previous physiological studies have shown that these brain structures are involved in regulating AD behavior.
Additional analyzes showed that the two clusters were indeed associated with different behaviors. The two clusters also showed different enrichment patterns of subtype-specific genes, establishing a clear link between each cluster and specific AD subtypes.
One cluster involves glutamatergic receptor signaling, while the other cluster is associated with serotonergic and dopaminergic signaling, further supporting the dichotomy of AD neurophysiology. Furthermore, these two clusters are associated with different region-specific gene networks and cell types.
Finally, the researchers examined developmental transcriptome data to track expression patterns of AD genes during brain development and found that these two spatial clusters have unique and negatively correlated identities at specific developmental stages.
One cluster is highly expressed in late infancy and adulthood, whereas the other cluster is expressed in late prenatal and early childhood. Therefore, mutations in AD-related genes may disrupt the normal timing of their manifestations, potentially affecting the development of signaling pathways and neural circuits, thereby producing AD-related symptoms.
In this study, scientists discovered two AD-related gene clusters with distinct spatial and temporal expression patterns and functional characteristics in the human brain. Further study of these gene clusters may provide new insights into the underlying causes of AD.
News about genetics and anxiety research
author: Hiromi Inoue
source: ashby
touch: Hiromi Inoue – ASHBI
image: Image via Neuroscience News
Original research: Open Access.
“Spatial and Temporal Expression Patterns of Anxiety Disorder-Related Genes” Author: Kalyani B. Karunakaran and Ken-ichi Amemori. translational psychiatry
Abstract
Spatiotemporal expression patterns of anxiety disorder-related genes
Anxiety disorders (AD) are the most common form of mental disorder, affecting millions of people worldwide. Although physiological studies have revealed neural circuits related to AD symptoms, the spatiotemporal expression pattern of AD-related genes in the human brain remains unclear.
In this study, we combine genome-wide association studies of four human AD subtypes (generalized anxiety disorder, social anxiety disorder, panic disorder, and obsessive-compulsive disorder) with spatial gene expression patterns.
Our study uncovered a novel delineation among AD-related genes characterized by significant and unique expression enrichment in nuclear, limbic, and midbrain regions.
Each gene cluster is associated with specific anxiety-related behaviors, signaling pathways, region-specific gene networks, and cell types. Notably, we observed significant negative correlations in the temporal expression patterns of these gene clusters at different developmental stages.
Furthermore, the specific brain regions enriched in each genome were consistent with neural circuits previously associated with negative decision-making and anxious temperament. These results suggest that these two distinct gene clusters may underlie distinct neural systems involved in anxiety.
Therefore, our findings bridge the gap between genes and neural circuits and reveal underlying mechanisms of AD-related behaviors.
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Image Source : neurosciencenews.com