Depression Patients Say Even Tanghulu Isn't Sweet to Them...

Dr. Gu Ja-wook of Korea Brain Research Institute and Prof. Kang Hyo-jung of Chung-Ang University Joint Research Team Identify Gene Causing Anhedonia in Depression Patients

The reason why people with depression cannot feel pleasure has been confirmed by domestic researchers. This is expected to contribute to the development of treatments for depression patients experiencing anhedonia.

The Korea Brain Research Institute (Director Seo Pan-gil) announced on the 14th that a joint research team led by Principal Researcher Gu Ja-wook of the Affective Cognitive Disorder Research Group and Professor Kang Hyo-jung of the Department of Life Sciences at Chung-Ang University has identified that anhedonia caused by prolonged mental stress occurs through molecular mechanisms involving specific brain regions and genes.

Although many depression patients experience anhedonia and chronic stress is known as the main cause, information about the related brain regions and genes has remained largely unknown.

The joint research team from the Korea Brain Research Institute and Chung-Ang University confirmed through experiments using a ‘Chronic Unpredictable Stress (CUS) animal model,’ which well represents anhedonia, that the activity of the prefrontal cortex in the brain is particularly important in anhedonia caused by prolonged mental stress.

Using optogenetic techniques to activate the prefrontal cortex of animals with anhedonia, individuals that previously showed no interest in sugar water began to prefer it more than before, indicating that the prefrontal cortex has a significant influence. Transcriptome network analysis of the prefrontal cortex in animals exposed to the same stress but showing or not showing anhedonia revealed a group of genes with increased expression in animals exhibiting anhedonia, with the gene Syt4 (Synaptotagmin-4) at the center.

The joint research team overexpressed the Syt4 gene in the prefrontal cortex of experimental animals and subjected them to stress for seven days. These animals exhibited severe anhedonia. Conversely, suppressing the expression of this gene during prolonged stress prevented the appearance of anhedonia and depressive symptoms.

The Syt4 gene is known to mediate the secretion and transport of various neurotrophic factors and neuropeptides in the brain, regulating synaptic and circuit functions. The research team confirmed that overexpression of this gene inhibits the release of brain-derived neurotrophic factor (BDNF) in the brain, revealing that the ‘Syt4-BDNF regulatory mechanism’ plays a crucial role in the development of anhedonia.

Professor Kang Hyo-jung of Chung-Ang University and Principal Researcher Gu Ja-wook stated, “This study significantly enhances the understanding of anhedonia by revealing that the prefrontal cortex and specific genes play an important role in the onset of anhedonia caused by long-term stress,” and added, “The Syt4 gene and brain circuitry discovered in this study are expected to be utilized in the development of new treatments for depression.”

Researchers Kim Jeong-seop from the Korea Brain Research Institute and Seol Si-hwan from Chung-Ang University participated as first authors in this study, which was published in the latest issue of ‘Experimental & Molecular Medicine (IF:12.8),’ a sister journal of Nature.

This content was produced with the assistance of AI translation services.