Research conducted on mice provides new insights into how thyroid hormone influences brain wiring. The findings suggest that thyroid hormone aligns brain and bodily functions, promoting exploratory behavior. This research may pave the way for innovative treatments for specific psychiatric disorders.
Thyroid hormone is crucial for managing various bodily functions such as metabolism, body temperature, heart rate, and growth. It achieves these effects by interacting with nearly every organ system in the body. Despite extensive research into its impact on different organs, the way thyroid hormone affects the brain—arguably the most vital organ—has not been fully understood.
Recent studies by scientists at Harvard Medical School have illuminated the effects of thyroid hormone on the brain. Their research, published on August 22 in Cell, demonstrates that this hormone modifies the neural wiring in the brain, which in turn encourages animals to explore their surroundings.
The researchers discovered that by simultaneously adjusting brain wiring and metabolic rate, thyroid hormone orchestrates a connection between the brain and body. This coordination facilitates exploratory behavior during critical times, such as when animals need to seek mates or gather resources.
“Thyroid hormone is known to influence metabolism, and we’ve now shown that it also affects exploratory behavior through direct actions in the brain,” stated lead author Daniel Hochbaum, a research fellow in neurobiology at the Blavatnik Institute at HMS.
These findings highlight how insufficient levels of thyroid hormone may lead to depressive states, resulting in decreased interest in exploration, while excessive levels can trigger manic states characterized by a heightened drive to explore. The researchers view this as a significant step toward understanding how abnormal thyroid hormone levels could be linked to certain psychiatric disorders.
A Personal Motivation
Hochbaum’s interest in thyroid hormones stems from a personal experience: his wife was diagnosed with hyperthyroidism, which caused sudden and significant changes in her behavior and metabolism. While her symptoms improved with treatment, Hochbaum became curious about the hormone’s impact on the brain.
“I was truly surprised to discover the large psychiatric implications of thyroid hormone,” Hochbaum commented.
He learned that insufficient thyroid hormone can decrease metabolism and lead to depressive symptoms, whereas excess hormone can accelerate metabolism, resulting in mania. However, he struggled to find a clear scientific explanation for these effects.
During an unexpected discussion with Bernardo Sabatini, the Alice and Rodman W. Moorhead III Professor of Neurobiology at HMS, Hochbaum realized they shared a mutual interest in the subject.
“The reasons behind thyroid hormone’s influence on behavior puzzled me since medical school,” said Sabatini, also the director of the Kempner Institute for the Study of Natural and Artificial Intelligence at Harvard University, and senior author of the new study. “It was unclear why this hormone should even enter the brain.”
This sparked a project aimed at exploring the role of thyroid hormone in brain function.
Connecting Brain, Body, and Behavior
Thyroid hormone flows through the bloodstream, reaching nearly every cell in the body. Its levels are regulated by a complex interaction between the thyroid gland, the pituitary gland at the brain’s base, and the hypothalamus, which is located just above the pituitary gland.
Remarkably, the thyroid hormone receptor is found in cells throughout the brain, including areas of the cortex responsible for advanced cognitive functions like planning and decision-making.
<p”What is striking is that in the mature brain, the thyroid hormone receptor is present not just in the hypothalamus but essentially everywhere,” Hochbaum stated.
To explore this further, Hochbaum, Sabatini, and their research team conducted genetic sequencing on individual cortical cells in mice. They discovered that the hormone operates on neural circuits in the cortex by activating various genes, effectively modifying the connections between brain cells.
Furthermore, when the researchers increased thyroid hormone levels in the cortex, the mice exhibited greater willingness to explore their surroundings and take risks.
In contrast, when the hormone’s action was blocked in the cortex, the animals no longer altered their exploratory behavior based on thyroid hormone levels.
“This indicated that thyroid hormone plays a crucial role directly in the cortex,” Hochbaum explained.
However, this raised a new question: Why would a hormone that regulates metabolism also change brain circuits affecting behavior?
To investigate this, the researchers referred to earlier field studies that tracked behavior in natural settings, measuring thyroid hormone levels in lemurs, squirrel monkeys, and other mammals. The findings showed that thyroid hormone levels, and consequently metabolic rates, were generally higher in warm seasons when food and resources were plentiful—coinciding with increased exploration among animals during those times.
This research, combined with the recent findings, provides an important link between thyroid hormone’s impact on brain and body function.
“We believe that thyroid hormone directly influences brain circuits to align exploratory behavior with metabolic rates,” he continued. “It synchronizes your brain and body according to the environment.”
In Sabatini’s words, “It appears that thyroid hormone encourages the body to signal the brain to explore and gather resources.”
Future Directions
The manner in which thyroid hormone controls physiological processes is highly conserved across humans and other mammals, the researchers noted, suggesting that a similar brain-body connection exists in humans.
An upcoming 2024 study by the same team has linked elevated levels of thyroid hormone in U.S. adults to higher employment rates and more hours of work.
The researchers are currently examining this relationship among individuals in Indonesia who experienced the 2004 tsunami. They are interested in whether the psychological trauma from the disaster has resulted in long-lasting changes in thyroid hormone levels.
The team also aims to explore the fundamental biology of the exploratory brain circuits activated by increased thyroid hormone. They hope their research could highlight brain circuits relevant to psychiatric conditions like depression and bipolar disorder.
The belief is that these disorders also influence exploratory behavior, suggesting that modifying thyroid hormone could help alter brain circuits, identifying potential treatment avenues,” Hochbaum concluded.
