Inside the Brain
The underlying mechanisms of schizophrenia are extremely complex and not properly understood. The effect that schizophrenia has on normal brain structure and function continues to be the focus of intense medical research around the world. Particular attention has been paid to the activity of the neurotransmitter dopamine within specific areas of the brain. An elevated response to dopamine within the mesolimbic pathway, the pathway that normally controls our behavioural response to reward, has been thought to contribute to some of the possible positive symtoms of the disease. Changes in the activity of glutamate signalling has also formed the basis of more recent research after postmortem studies on schizophrenic patients showed a much lower than normal number of glutamate receptors in the brain.
Strong evidence suggests that schizophrenia targets areas of the frontal, parietal and temporal lobes along with the hippocampus. These areas are known to be responsible for short and long-term memory tasks, planning, attention, auditory perception and spatial navigation. Abnormalities in these areas have profound effects on the cognition and memory of sufferers.
The image above is from a study by Thompson et. al. (2001) showing the extent of the loss of grey matter (neuronal cell bodies; in contrast to white matter that is made of the myelinated axons that extend from the cell body) in the outer surfaces of the brain in patients with schizophrenia compared to normal controls. Areas in pink and red show the greatest levels of degradation.
Deep within the brain it becomes clear that the loss of neural mass is not only confined to the cerebral cortex. MRI scans comparing the brains of sufferers with people who are unaffected show that the lateral ventricles (the large fluid-filled cavaties within the brain that act as the site of cerebrospinal fluid formation) can become enlarged in patients with schizophrenia. The image below is of two MRI scans from twins, the one on the left is the unaffected twin, the one on the right is the twin with schizophrenia. The extent of damage is clearly seen in the schizophrenic brain deep within the cerebral hemispheres. This finding is also common in other neurodegenerative diseases such as bipolar disorder and Alzheimer's.
A study published in 1998 suggests that a protein known as reelin (encoded by the RELN gene on chromosome 7) may be involved in the loss of grey matter seen in patients with schizophrenia. Reelin has a number of important functions in the developing embyro and the adult brain. In development it helps to regulate the migration of neurons to their target locations; in adults it modulates synaptic plasticity important for memory and learning; and it helps to regulate the migration of neuroblasts from subventricular regions during neurogenesis, the process where adult stem cells within the brain divide and differentiate to produce new neurons. The study found that areas of the frontal lobe, temporal lobe, hippocampus and basal ganglia had a near 50% reduction in RELN expression.