Schizophrenia affects millions of people around the world and remains one of the most challenging mental health disorders to understand.
The illness can cause hallucinations, confused thinking, difficulties with emotions, and problems carrying out everyday activities. Many people with schizophrenia require long-term medical care and support.
Scientists have spent many years trying to understand why some people develop schizophrenia while others do not. One of the strongest clues comes from family history. The condition tends to run in families, indicating that genes play an important role. However, researchers have struggled to identify all the genetic factors involved.
Part of the difficulty comes from the extraordinary complexity of the human genome. The genome contains thousands of genes that interact in complicated ways. In schizophrenia, risk appears to be spread across many genetic variants rather than concentrated in a single gene.
A major new study published in Nature Genetics suggests that scientists may have been overlooking important parts of this puzzle. The research was carried out by investigators at the Lieber Institute for Brain Development together with collaborators from the University of Bari in Italy and more than 60 psychiatric hospitals around the world.
The researchers analyzed genetic data from more than 102,000 people and studied brain tissue samples from hundreds of donors. They focused on six different regions of the brain to better understand how genes influence brain function.
Traditional genetic studies usually investigate DNA changes located close to a gene. These nearby variants are easier to study and have produced many important discoveries. However, scientists now know that genes can also be influenced by regions of DNA located far away.
The researchers developed sophisticated computer models to track these long-distance interactions. They compared the process to a social network. In society, people do not interact only with their neighbors.
They also communicate with friends, family members, and colleagues who live far away. The same idea applies to genes inside the brain. A gene’s activity may be influenced by distant parts of the genome through complex regulatory networks.
By examining these broader networks, the researchers uncovered 641 previously unknown genes associated with schizophrenia. These genes had not been identified using older approaches.
The study also revealed that many of the newly identified genes participate in important biological pathways. Some are involved in glutamate signaling, a system that allows brain cells to send messages to one another. Others are linked to communication between brain cells, immune functions, and the processes that guide brain development.
These findings support the view that schizophrenia develops through disruptions in large networks of genes rather than isolated genetic errors. The condition may emerge when many biological systems interact in unusual ways during brain development and throughout life.
The results also reinforce growing evidence that the immune system may contribute to psychiatric disorders. Scientists increasingly recognize that the brain and immune system are closely connected and may influence each other more than previously believed.
The researchers say their findings bring science closer to precision psychiatry. In the future, doctors may be able to classify patients according to the specific biological pathways involved in their illness and choose treatments that are better suited to each person’s unique genetic profile.
However, the study does not mean that a genetic test for schizophrenia is immediately available. Schizophrenia remains a highly complex condition influenced by both genes and environmental factors. Stress, early life experiences, and other biological processes also likely contribute to risk.
The findings are significant because they provide a much richer understanding of the genetic landscape of schizophrenia. By expanding their search beyond nearby genes and investigating how distant genetic regions communicate, scientists have uncovered hundreds of new clues about the biology of the disorder.
Although more research is needed, this work may eventually lead to new ways of diagnosing, preventing, and treating one of the most burdensome mental illnesses.
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Source: Lieber Institute for Brain Development.
