Study Maps the Brain's Overlooked Histamine System

Researchers at King's College London and the University of Porto have built the first multiscale map of the histamine system in the brain, spanning genetics to behavior and related mental health conditions. Histamine—a molecule more commonly associated with allergies—also plays a separate but poorly understood role in brain function, and this new work could point toward new treatment strategies for histamine-related conditions such as depression, ADHD, and schizophrenia. The study was published in Nature Mental Health.

Histamine is a neurotransmitter, a molecule crucial for neurons to communicate with one another. Neuroscience research has classically focused on understanding other neurotransmitter systems such as dopamine and serotonin.

"This work provides a crucial foundation for future research. By integrating molecular biology, brain imaging, and computational analysis, it offers a new perspective on how neurotransmitter systems are organized across the human brain," said Daniel Martins, first author on the paper. "As neuroscience moves toward more integrated and personalized models of mental health, understanding systems like histamine may prove essential for unlocking new approaches to diagnosis and treatment."

To build the map, the team combined genetic and molecular data with physical maps of the brain, then linked those data with positron emission tomography imaging of histamine receptors in living individuals and functional neuroimaging databases that map brain regions to specific cognitive processes and mental health conditions. They found that different histamine receptors sit on brain cells that either turn activity up or down, suggesting histamine may help maintain the balance between excitation and inhibition, a fundamental property of healthy brain function.

Brain regions with higher histamine-related gene expression were consistently linked to emotional regulation, stress and fear responses, decision-making, impulsivity, reward, sleep, and memory. These regions also overlapped significantly with brain areas affected in attention-deficit/hyperactivity disorder, major depressive disorder, schizophrenia, and anorexia nervosa.

"Current psychiatric treatments largely target neurotransmitters such as serotonin and dopamine, yet histamine interacts closely with these systems and influences their activity," Martins said. "By providing a detailed map of histamine-related pathways, this work suggests new opportunities for developing treatments that target this system more directly, particularly for symptoms such as cognitive dysfunction, fatigue, and impaired motivation."