Two studies carried out on behalf of the Karolinska Schizophrenia Project, at the Karolinska Institutet in Stockholm, Sweden, have revealed that a deficiency of the neurotransmitter GABA in the cerebrospinal fluid and abnormal markers of the nervous Immune Cells are associated with schizophrenia. The two studies were published in Molecular Psychiatry, one of the most prestigious psychiatry journals of the Nature publishing group.

GABA: a key neurotransmitter

The acronym GABA stands for gamma-aminobutyric acid and names one of the most important neurotransmitters within brain neural circuits.

Its main function is to inhibit the electrical activity of neurons in the cerebral cortex. Not surprisingly, a reduced or insufficient activity of the circuits that use GABA is the basis of epilepsy, a neurological disorder hallmarked by out of control electrical activity.

A growing body of scientific evidence indicates that GABA plays a crucial role in the normal functioning and development of neural circuits in the cerebral cortex. For example, abnormalities of GABA circuits have been linked to autism. Furthermore, it has been hypothesized that GABA circuits are also involved in schizophrenia disorder.

Low levels of GABA in schizophrenia

"To test this hypothesis" says Professor Göran Engberg of Karolinska Institutet's Department of Physiology and Pharmacology, and one of the lead authors of the research "we measured the concentration of GABA in the cerebrospinal fluid and we correlated it with clinical indices of mental impairment typical of schizophrenia".

The researchers observed that the levels of GABA in the cerebrospinal fluid are lower in people with schizophrenia compared with that measured in healthy people. Notably, for the first time they showed that the lower the levels of GABA and the worst are the psychotic symptoms of schizophrenic patients.

In the second study, neuroscientists from the Karolinska Schizophrenia Project have used positron emission tomography, a neuroimaging technique known as PET to dose the protein called TSPO.

and that distinguishes the immune cells of the nervous tissue as microglia and astrocytes, shows lower levels than normal of TSPO in early schizophrenic patients. These results suggest that schizophrenia is associated with an imbalance of the nervous immune system at the earliest stages of the disease.

Future studies will tell whether the reduction of GABA and immune system deficiency are caused by or follow schizophrenic symptoms and if the new indices can be used to monitor clinical evolution and suggest new therapeutic approaches.