New research from King’s College London and the University of Porto has mapped the histamine system in the brain. Histamine, a molecule more commonly associated with allergies, plays a distinct but poorly understood role in brain function. This study addresses this gap and builds the first multiscale map of the histamine system, from genetics to behavior to related mental health conditions.
The findings provide a new framework for understanding how this often overlooked chemical system contributes to brain function and may point to new treatment strategies for histamine-related disorders such as depression, ADHD, and schizophrenia. This research natural mental health Funded by the National Institute for Health Research (NIHR) Maudsley Biomedical Research Center.
Histamine is a neurotransmitter, an essential molecule that allows neurons to communicate with each other. Neuroscience research has traditionally focused on understanding other neurotransmitter systems, such as dopamine and serotonin.
This study provides an important foundation for future research. By integrating molecular biology, brain imaging, and computational analysis, we provide a new perspective on how neurotransmitter systems are organized throughout the human brain. As neuroscience moves toward more integrated and individualized models of mental health, understanding systems like histamine may prove essential to unlocking new approaches to diagnosis and treatment. ”
Dr Daniel Martins, Visiting Senior Research Fellow, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, and first author of the paper
Histamine molecules are captured by proteins called receptors, which determine how the signal affects the receiving neuron. There are several types of receptors that capture histamine, and they can have different effects on neuron activity.
By mapping the histamine system, researchers discovered that there are different histamine receptors on brain cells that either increase (excite) or decrease (inhibit) activity. This suggests that histamine may be important in maintaining the balance between excitation and inhibition, a fundamental property of healthy brain function.
To build a comprehensive map of how histamine acts in the brain, the researchers first combined genetic and molecular data with a physical map of the brain. This revealed which areas of the brain receive more input from the brain’s histamine system and which parts are better able to respond to histamine. These molecular data were correlated with positron emission tomography imaging of histamine receptors in living individuals and with functional neuroimaging databases that map brain regions to specific cognitive processes and mental health states. This type of scan shows how different parts of the brain are working by tracking tiny amounts of radioactive tracers in real time.
Brain regions with high expression of histamine-related genes were consistently associated with processes such as emotional regulation, stress and fear responses, decision-making, impulsivity, reward, sleep, and memory.
Additionally, the parts of the brain where histamine-related genes were most active overlapped significantly with brain regions known to be affected by several psychiatric disorders, including attention-deficit hyperactivity disorder, major depressive disorder, schizophrenia, and anorexia nervosa. This is consistent with previous hypotheses linking histamine to these diseases.
Dr Daniel Martins said: “Current psychiatric treatments primarily target neurotransmitters such as serotonin and dopamine, but histamine closely interacts with these systems and influences their activity. This study provides a detailed map of histamine-related pathways. “This suggests new opportunities to develop treatments that more directly target this system, particularly for symptoms such as cognitive impairment, fatigue, and motivational impairment. Although these findings do not establish a direct causal relationship, they do suggest that histamine is involved.” This signaling may contribute to localized vulnerabilities in these diseases, consistent with the psychiatric view that mental health conditions result from disruptions of entire interacting brain systems, rather than imbalances in a single chemical. ”
This new map paints a neuro-picture of molecules that have so far been little studied. This paves the way for future research to examine what exactly histamine does in different types of cells and parts of the brain.
“We would like to emphasize that these findings are hypothesis-generating and based on large datasets that capture patterns rather than direct mechanisms,” commented Professor Steve Williams, Professor of Neuroimaging at IoPPN King’s College London and senior author of the paper.
Future research will focus on testing how histamine signaling changes in living individuals, for example through pharmacological interventions or long-term imaging approaches.
Dr Daniel van Wameren, IoPPN Clinical Senior Lecturer in Neuroscience at King’s College London and one of the paper’s authors, said: ‘This type of research is already being done at King’s College London, for example with the iMarkHD project. The project is using positron emission tomography scans to study a particular histamine receptor (called H3) in people with Huntington’s disease, a genetic disease that affects the brain.The goal is to see how. Histamine activity changes in different parts of the brain over time, and we study how these changes relate to symptoms such as apathy, depression, and anxiety. ”
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Reference magazines:
Martins, D. others. (2026). Mapping the human brain histamine pathway network across cognitive and psychiatric disorders. Natural mental health. DOI: 10.1038/s44220-026-00637-1. https://www.nature.com/articles/s44220-026-00637-1
