A groundbreaking discovery at the Lieber Institute reveals secret genetic regulators that may hold the key to understanding schizophrenia
Think about the last time you learned something new, a name, a skill, a shortcut on your commute. Behind every one of those moments, a tiny protein in your brain called BDNF (Brain-Derived Neurotrophic Factor) was quietly doing its job. It helps brain cells grow, connect, and communicate. It supports memory. It fuels emotional resilience. In many ways, BDNF is one of the most important molecules your brain produces.
But here’s the thing about BDNF: too much of it is just as problematic as too little. Like the volume on a speaker, it needs to stay within the right range. Turn it up too high, and brain cells can become dangerously overexcited. Turn it down too low, and critical developmental processes stall. Scientists have long known that BDNF needs to be tightly controlled, but exactly how the brain manages that balance has remained one of neuroscience’s most compelling mysteries.
Now, researchers at the Lieber Institute for Brain Development in Baltimore have discovered something remarkable: hidden genes, previously unknown to science, that appear to act as volume controls for BDNF itself. Their findings, published in July 2025, could fundamentally change how we understand brain development, and disorders like schizophrenia.
What the Scientists Found
To understand the discovery, it helps to think of your DNA as a massive instruction manual for building and running your body. Most people are familiar with the idea that genes are the individual instructions in that manual. What’s less well known is that the spaces around those instructions are far from empty. They contain other types of genetic material, some of which appear to help regulate how loudly or quietly nearby genes are “read.”
The research team, led by Dr. Keri Martinowich and Dr. Gianluca Ursini, was analyzing genetic data from hundreds of postmortem human brain tissue samples when they noticed something unusual. Near the BDNF gene, there were signals, RNA molecules being produced, that didn’t match anything in the existing scientific record. These were uncharted transcripts, meaning pieces of genetic code being actively used by the brain, but never previously identified or named.
After extensive laboratory work, including experiments on both human and mouse brain cells, the team confirmed the existence of two entirely new genes. They named them BDNF-DT and BDNF-AS-DT.
What makes these genes especially fascinating is when and how they’re active:
- They switch on during critical brain development windows — including prenatal life, early childhood, and again during adolescence and young adulthood. These are precisely the periods when the human brain is most actively wiring itself.
- They respond to brain activity — when neurons were stimulated in the lab, both BDNF and these newly discovered genes became more active. Crucially, the new genes appeared to follow BDNF’s lead, suggesting they may help the brain pump the brakes after BDNF has done its job.
- Turning up BDNF turns up the new genes too — when researchers used a cutting-edge genetic tool called CRISPR to artificially increase BDNF production in human brain cells, the BDNF-DT gene also increased. This is a strong hint that these genes work together as part of a feedback system.
Why Should You Care?
You might be wondering: interesting science, but what does this have to do with my life?
The connection becomes clear when you consider schizophrenia ,a serious brain disorder that affects approximately 1 in 100 people worldwide. Schizophrenia typically emerges in late adolescence or early adulthood, causes profound disruptions to thinking and perception, and remains poorly understood at the biological level. Treatments exist, but they are far from perfect, and they don’t work for everyone.
Scientists have known for years that BDNF is somehow linked to schizophrenia risk. But the connection has been frustratingly difficult to pin down. This new research adds a crucial piece to that puzzle.
The team found that BDNF-DT is significantly more active in the brains of people diagnosed with schizophrenia compared to people without the disorder. Even more striking, a common genetic variant, a tiny DNA spelling difference called Val66Met that millions of people carry, appears to influence the activity of BDNF-AS-DT. People whose genetics predict lower activity of this gene show a higher risk for schizophrenia.
In other words, these newly discovered genes aren’t just biological curiosities. They may be active players in one of the most common and devastating psychiatric conditions in the world.
What Could This Lead To?
Discoveries like this one don’t produce new treatments overnight, but they plant seeds that can grow into medical breakthroughs over time.
By identifying these new genetic regulators, scientists now have fresh targets to investigate. Future research could explore whether medications or other interventions could influence how these genes behave, potentially offering more precise ways to restore BDNF balance in the brains of people with schizophrenia or other psychiatric conditions.
This discovery also raises broader questions that could reshape neuroscience. If hidden regulator genes exist near BDNF, they likely exist near other important brain genes too. The human genome may contain many more of these biological “volume controls” waiting to be found, each potentially relevant to a different aspect of brain health.
Additionally, understanding how these genes behave during adolescence, when schizophrenia risk is crystallizing, could eventually help identify individuals at elevated risk earlier, long before symptoms appear.
The Bottom Line
Science rarely delivers single, dramatic moments of discovery. More often, it advances through careful, painstaking work, analyzing thousands of brain samples, running experiments at odd hours, questioning results and running them again. This research is a perfect example of that process.
What began as an unexplained signal in a dataset has grown into the identification of two previously unknown human genes, genes that appear to help regulate one of the brain’s most vital proteins during its most critical developmental moments.
For millions of people living with schizophrenia, and for the families who love them, discoveries like this one represent something more than a scientific milestone. They represent progress, and progress, however incremental,
If you want to understand the research from a scientific perspective, we’ve prepared a more detailed summary that outlines our approach and key findings in greater depth.
Scientists study human brain tissue to uncover new targets, for therapies to develop therapies that could transform the lives of people with schizophrenia