The observation of enlarged brain ventricles in some individuals with schizophrenia is a long-standing finding in psychiatric research. This connection has prompted extensive investigation into its underlying causes, requiring a foundational knowledge of both the brain’s ventricular system and the complexities of schizophrenia as a neurobiological disorder.
The Brain’s Ventricular System
Deep within the brain is a network of four interconnected cavities known as the ventricular system. It includes two large lateral ventricles, a central third ventricle, and a fourth ventricle in the hindbrain. These ventricles are filled with cerebrospinal fluid (CSF), a clear liquid that is continuously produced and circulated.
Specialized tissue within the ventricles, called the choroid plexus, produces the CSF. The fluid moves from the lateral ventricles into the third ventricle, through the cerebral aqueduct into the fourth ventricle, and then exits into the space surrounding the brain and spinal cord before being reabsorbed into the bloodstream.
This circulation of CSF serves several purposes. It acts as a cushion to protect the brain from physical shock, removes metabolic waste, transports nutrients, and helps maintain stable pressure within the skull. The size of these ventricles can also naturally vary between individuals.
Understanding Schizophrenia
Schizophrenia is a persistent and complex brain disorder that alters how a person thinks, feels, and behaves. It affects fundamental mental functions, often leading to psychosis, where an individual may have difficulty distinguishing their own thoughts and perceptions from reality. The condition emerges in late adolescence or early adulthood and is influenced by a mix of genetic and environmental factors.
The symptoms are often categorized into three main groups. Positive symptoms represent experiences added to a person’s reality, such as hallucinations and delusions, and are often accompanied by disorganized thinking. Negative symptoms involve a reduction of normal functions, such as a lack of motivation, diminished emotional expression, and social withdrawal. Cognitive symptoms can impair functions like attention and memory, affecting a person’s ability to manage daily tasks.
Ventricular Enlargement in Schizophrenia
One of the most consistent findings in neuroimaging studies of schizophrenia is the presence of enlarged brain ventricles. As a group, individuals with the disorder tend to have larger lateral and third ventricles compared to people without the disorder. This finding is an average difference and does not apply to every individual, as not all people with schizophrenia have enlarged ventricles.
Some healthy individuals may also have ventricles that are larger than average. Consequently, ventricular size is not used as a diagnostic tool. The enlargement is considered a neuroanatomical biomarker, a measurable physical characteristic associated with the disease.
Studies have found this difference in people experiencing their first episode of psychosis, suggesting it is not solely a result of long-term illness or treatment. The presence of enlarged ventricles has been linked in some studies to poorer outcomes and more significant cognitive impairment.
Exploring Causes of Ventricular Changes in Schizophrenia
The leading theory for ventricular enlargement in schizophrenia is that the ventricles expand due to a reduction in the volume of adjacent brain matter. This loss of tissue is particularly noted in gray matter, which contains most of the brain’s neuronal cell bodies. Studies have documented reduced volume in regions near the ventricles, such as the thalamus and parts of the temporal cortex, suggesting the ventricular space expands to fill the area left by this reduction.
Evidence points to neurodevelopmental origins, with processes leading to enlargement beginning long before clinical symptoms appear. Birth complications, such as a lack of oxygen, are associated with increased risk for both psychosis and ventricular enlargement. Research also indicates these changes may be progressive, with ventricular volume increasing during the early stages of the illness.
Genetic factors also play a role. The rare condition 22q11.2 deletion syndrome, involving a missing piece of chromosome 22, increases the risk of developing schizophrenia. Individuals with this syndrome often show ventricular enlargement, providing a model to study the genetic basis of this brain alteration.
Research using mouse models of this syndrome has identified specific genes, like Dgcr8, which is involved in producing microRNAs that regulate gene expression. The deletion of Dgcr8 was found to reduce certain microRNAs, leading to an increase in a specific dopamine receptor on the surface of motile cilia.
Motile cilia are hair-like structures lining the ventricular walls that help circulate CSF. The altered microRNA levels caused these cilia to move more slowly, which was associated with ventricular enlargement in animal models. This suggests a cellular mechanism linking a genetic defect to impaired CSF dynamics.