Researchers at Karolinska Institutet collaborating in the large-scale Karolinska Schizophrenia Project are taking an integrative approach to unravel the disease mechanisms of schizophrenia.
The drugs currently available for schizophrenia are designed to alleviate the symptoms, but are only partly successful, as only 20 per cent of the patients become symptom-free. The Karolinska Schizophrenia Project (KaSP) brings together researchers from a number of different scientific disciplines to build up a comprehensive picture of the disease mechanisms and to discover new targets for drug therapy. Patients with an acute first-episode psychosis are recruited and undergo extensive tests and investigations. Cognitive function, genetic variation, biochemical anomalies as well as brain structure and function are analysed using the latest techniques and then compared with healthy peers.
In the very first results now presented in the scientific journal Molecular Psychiatry , the researchers show that patients with schizophrenia have lower levels of the vital neurotransmitter GABA as well as changes in the brain’s immune cells.
“Over the years, animal studies have suggested a link between decreased levels of GABA and schizophrenia,” says Professor Göran Engberg at Karolinska Institutet’s Department of Physiology and Pharmacology. “Our results are important because they clinically substantiate this hypothesis.”
The other study used the imaging technique of positron emission tomography (PET) to show that patients with untreated schizophrenia have lower levels of TSPO (translocator protein), which is expressed on immune cells such as microglia and astrocytes.
“Our interpretation of the results is an altered function of immune cells in the brain in early-stage schizophrenia,” says Senior lecturer Simon Cervenka at Karolinska Institutet’s Department of Clinical Neuroscience.
The results of the two studies provide new clues to the pathological mechanisms of schizophrenia, but it is unclear if the changes are the cause or the result of the disease. Follow-up studies are now underway to examine what causes the anomalies and how these biological processes can be influenced to change the progression of the disease.
KaSP is a collaboration between clinical and preclinical research groups at Karolinska Institutet and four psychiatric clinics under Stockholm County Council.
Simon Cervenka and Göran Engberg. Photo: Stefan Zimmerman