Study links social isolation to brain iron buildup, anxiety

A team of Chinese scientists has identified a possible biological link between prolonged social isolation (SI) and anxiety that offers new insight into how loneliness may affect the brain.

The study, published recently in the journal Cell Metabolism, suggests that extended social isolation in mice can lead to abnormal iron buildup in a brain region involved in emotional regulation.

The work was led by Wang Zhuo, an associate professor at the School of Medicine at South China University of Technology, in collaboration with Zhejiang University and Southern Medical University in Guangzhou, Guangdong province.

Using a mouse model designed to mimic long-term solitary living, the team found that isolated mice developed abnormally elevated iron levels in the ventral hippocampus, a part of the brain associated with emotional responses. According to Wang, excess iron appeared to activate a protein called α-synuclein, triggering unusually high neuronal activity linked to anxiety.

Wang compared the process to a faulty electrical signal, saying that the excess iron acts like an electrical short circuit that persistently sends anxiety-related signals.

The team refers to this mechanism as "ferroplasticity", which they define as a form of neuroplasticity influenced by iron metabolism and experience. While iron is typically considered essential for brain health, the study suggests that under certain stress conditions, it may contribute to harmful changes in neural signaling.

The researchers also explored whether targeting this pathway could reduce anxiety-like behavior in mice.

By delivering compounds that affect iron levels or α-synuclein through the nasal cavity, they observed reduced anxiety behaviors and more stable neuronal activity within about two weeks.

Wang said the team plans to focus next on safety testing, dosage studies, and non-invasive imaging methods to detect iron accumulation in the brain, with the long-term goal of conducting clinical trials.

Social isolation has drawn increasing attention as a public health concern. The World Health Organization has identified it as a growing global risk, and official statistics show that single-person households continue to rise in China.

According to the 2025 China Statistical Yearbook released by the National Bureau of Statistics, single-person households represented approximately 19.5 percent of total households in the country in 2024, with Guangdong showing a higher proportion at 28.1 percent.