Home Medizin Kyoto-Wissenschaftler kartieren Double-Whammy-Gencluster für Angststörungen

Kyoto-Wissenschaftler kartieren Double-Whammy-Gencluster für Angststörungen

von NFI Redaktion

Angststörungen (ADs) affect over 280 million people worldwide, ranking among the most common mental disorders. These disorders have a genetic basis, evident from the familial inheritance, and individuals with one AD subtype tend to have another, indicating a common genetic foundation. While the brain circuits involved in AD have been identified, their relationship with gene expression remains unclear. Researchers from the University of Kyoto in Japan sought to uncover this relationship and discovered two gene clusters expressed in the brain.

In previous studies, targeted gene sequencing and genome-wide association studies (GWAS) have identified common mutations in people with AD or anxiety-associated personality traits, linking these mutations to specific genes in the human genome. Additionally, brain imaging techniques such as functional MRI (fMRI) and PET scans have shown that activity in specific neural circuits can predict anxious temperament in rhesus macaques, and microstimulation techniques in these monkeys can reveal which neural circuits are involved in AD symptoms.

The researchers from the University of Kyoto, Ms. Karunakaran and Dr. Amemori, investigated whether AD-associated genes are expressed in the same neural circuits identified through imaging and microstimulation techniques. Specifically, they examined whether the regions where AD-associated genes are expressed could unveil the neurocircuitry of AD by analyzing spatial-temporal transcriptomic data of over 200 genes linked to four AD subtypes: generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder, and panic disorder, in over 200 brain regions of normal human brains, available in the Allen Brain Atlas.

Using statistical tests, the researchers found that AD-associated genes are strongly expressed in the brain nuclei, midbrain, and limbic system. Further analysis revealed two AD gene clusters with different spatial expression profiles—one strongly expressed in the limbic system and a specific set of forebrain nuclei, and the other in the midbrain and a different set of forebrain nuclei. Prior physiological studies showed that these brain structures are involved in regulating AD behavior. Additional analyses found that the two clusters were indeed associated with different behaviors and displayed different enrichment patterns for subtype-specific genes, establishing a clear link between each cluster and specific AD subtypes.

One cluster was involved in glutamatergic receptor signaling, while the other was associated with serotonergic and dopaminergic signaling, further supporting a dichotomy in the neurophysiology of ADs. Additionally, the two clusters were linked to different region-specific gene networks and cell types.

Finally, the researchers examined developmental transcriptomic data to track the expression patterns of AD genes during brain development and found that the two spatial clusters exhibit different and negatively correlated identities at specific developmental stages. One cluster is strongly expressed in late infancy and adulthood, while the other is prominent in late prenatal stages and early childhood. Therefore, mutations in AD-associated genes could disrupt the normal timing of their expression, potentially affecting the development of signaling pathways and neural circuits, leading to the symptoms associated with AD.

This research unveiled two AD-associated gene clusters in the human brain with distinct spatial and temporal expression patterns and functional profiles. Further investigations of these gene clusters could provide new insights into the underlying causes of AD.


Institut für fortgeschrittene Studien der Humanbiologie (ASHBI)


Karunakaran, KB, & Amemori, K. (2023). Raumzeitliche Expressionsmuster von mit Angststörungen assoziierten Genen. Translationale Psychiatrie. doi.org/10.1038/s41398-023-02693-y.

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