Schizophrenia

Aetiology

As schizophrenia is a complex brain disorder, it likely results from the interplay of genetic, behavioural, developmental and other factors. The exact cause of this group of illnesses is not known but stress, trauma and viral infection at an early age are factors thought to be involved.

Schizophrenia can run in families and it is likely that the disease has a genetic component – if one twin of an identical pair has schizophrenia, there is a 46% chance that the other twin will also suffer from a schizophrenic disorder. It is not known how many genes are involved or how the genetic predisposition is transmitted. In addition, recent evidence suggests that schizophrenia may result when neurons  in the brain form inappropriate connections during foetal development. It may be that an intrauterine starvation or infection causes such inappropriate connections to form and these may lie dormant until puberty when substantial neuron reorganisation occurs in the brain. Identification of specific genes involved in the development of schizophrenia will provide important clues as to what goes wrong in the brains of people with the disease and this will guide the development of improved treatments.

Stress imposed by life events or family circumstances appears to be an important external event associated with schizophrenia. The onset of illness is often associated with a distressful period in life and it may be that stress can trigger the onset of illness in those people with a genetic predisposition to the disease.

An imbalance in the concentrations of dopaminergic and glutamatergic systems in the brain is also thought to play a role in the development of schizophrenia. The dopamine hypothesis states that the behavioural patterns typical of schizophrenia are a result of overactivity of dopamine in certain regions of the brain. Serotonin is also important in schizophrenia and it may be that the serotonin system interacts with the dopamine system to modify the way in which it operates. The serotonin receptors which are important in the treatment of schizophrenia are 5-HT1, 5-HT2 and 5-HT3.

What Happens in the Brain?

The areas of the brain implicated in schizophrenia are the forebrain , hindbrain  and limbic system .

It is thought that schizophrenia may be caused by a disruption in some of the functional circuits in the brain, rather than a single abnormality in one part of the brain. Although the brain areas involved in this circuit have not been defined, the frontal lobe, temporal lobe, limbic system,(specifically the cingulate gyrus , the amygdala  and the hippocampus ) and the thalamus  are thought to be involved. The cerebellum , which forms part of the hindbrain, also appears to be affected in people with schizophrenia.

neurotransmitters  are implicated in the development of schizophrenia. The dopamine hypothesis of schizophrenia postulates that schizophrenia is caused by an overactive dopamine system in the brain; excessive dopamine and reduced striatal activity can disrupt all aspects of motor, cognitive and emotional functioning and can result in an acute schizophrenic psychosis. An excessive dopamine concentration in the brain of people with a schizophrenic disorder was originally thought to be associated with increased activity of the D2 class of dopamine receptors in the prefrontal cortex . Recent studies indicate that reduced numbers of the D1 class of dopamine receptors may contribute to the rise in dopamine concentration. Other neurotransmitters, including serotonin, glutamate, gamma aminobutyric acid and acetylcholine may also be involved in the pathogenesis of schizophrenia. It may be that due to the careful orchestration between neurotransmitter systems, an imbalance in one neurotransmitter affects others which are not causally involved in the pathogenesis of disease.

Several structural changes are found in the brains of people with schizophrenia, most of which occur in the forebrain. Reductions in the volume of grey matter  in the frontal lobe, and decreased brain volume and activity, have been repeatedly noted among people with a schizophrenic disorder. The ventricles  are commonly found to be larger than normal, as are the basal nuclei , while the hippocampus and amygdala are often smaller. The disease is also associated with alterations in blood flow to certain areas of the brain.