New research has created a guide to show how the genes linked to higher risk of schizophrenia impact particular cells in the brain. This information is expected to help researchers in developing new and effective treatments for the disease. Schizophrenia is a complicated condition with different forms, making it difficult to understand the causes and find effective treatments. In a recent study published in Science on May 23, a team led by McLean Hospital researchers conducted thorough genetic and cellular analyses . The researchers have shed light on the complex molecular mechanisms behind schizophrenia. Their new study provides a map of how the genes linked to an increased risk of schizophrenia affect specific cells in the brain.
The lead and co-corresponding author, W. Brad Ruzicka MD, PhD, director of the Laboratory for Epigenomics in Human Psychopathology at McLean Hospital, explained, “We have identified which cell types express genes associated with schizophrenia risk differently, the biological functions that are impacted within those cells, and the transcription factors that are important for these changes.” This knowledge will be valuable for future research.to specific cell types in the brain. This suggests that tailored treatments for schizophrenia could be developed based on individual genetic and cellular characteristics. According to the World Health Organization, approximately 24 million people worldwide, or 1 in 300 people, are affected by schizophrenia. In a new study, a team of researchers from multiple centers conducted a thorough analysis of transcriptomic changes in the human prefrontal cortex at the single-cell level. They examined postmortem brain tissue from 140 individuals in two independent cohorts, analyzing over 468,000 cells. Their findings provide unprecedented insights into the cellular basis of schizophrenia, establishing a connection between genetic risk and specific brain cell types. This discovery opens the door to the development of personalized treatments for schizophrenia based on individual genetic and cellular factors.The researchers discovered that certain types of brain cells, known as excitatory neurons, were the most impacted by genetic risk factors for schizophrenia. This suggests that changes in these neurons may play a role in the development of the disorder. Additionally, they found that both rare and common genetic variants are involved in altering specific neuronal populations, underscoring the complexity of the genetic factors involved in schizophrenia. By analyzing the gene expression in individuals with schizophrenia, the researchers identified two distinct subgroups, characterized by the activity of specific excitatory and inhibitory neurons. This study sheds new light on the genetic and cellular mechanisms underlying schizophrenia.The study indicates possible connections between the pathology of schizophrenia and processes like neurodevelopment, synaptic signaling, and transcriptional regulation, highlighting important transcriptional regulators linked to both schizophrenia and neurodevelopmental disorders.
The researchers hope that the knowledge gained from this study could lead to specific interventions and personalized treatments for schizophrenia, potentially enhancing the clinical outcomes for people affected by this challenging and often crippling disorder.
The team is currently working on further exploring these findings by examining other areas of the brain.The research is focused on understanding the brain and molecular effects of psychiatric disorders like bipolar disorder. They are also studying the complexity of the system by looking at how specific genes are expressed in different types of cells and how these changes can lead to functional and potentially treatable changes in proteins.
“This study improves our understanding of schizophrenia at a more detailed level by looking at the various cells in the brain and the different experiences of individuals with this disease,” said Ruzicka, who is also an associate medical director at Harvard Brain Tissue Resource Center.n> “Our increased understanding of the mechanisms behind schizophrenia opens up opportunities for future research to uncover the genetic and environmental factors contributing to this complex disease, allowing us to better care for our patients.”
