Major research project provides new clues to schizophrenia

March 14, 2017, Karolinska Institutet
Functional magnetic resonance imaging (fMRI) and other brain imaging technologies allow for the study of differences in brain activity in people diagnosed with schizophrenia. The image shows two levels of the brain, with areas that were more active in healthy controls than in schizophrenia patients shown in orange, during an fMRI study of working memory. Credit: Kim J, Matthews NL, Park S./PLoS One.

Researchers at Karolinska Institutet collaborating in the large-scale Karolinska Schizophrenia Project are taking an integrative approach to unravel the disease mechanisms of schizophrenia. In the very first results now presented in the prestigious 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.

Schizophrenia is one of the most disabling psychiatric diseases and affects approximately one per cent of the population. It commonly onsets in late adolescence and is often a life-long condition with symptoms such as delusions, hallucinations, and anxiety. The disease mechanisms are largely unknown, which has hampered the development of new drugs. The drugs currently available 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 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.

The first results from the project are now presented in two studies published in the journal Molecular Psychiatry. One of the studies shows that patients with newly debuted schizophrenia have lower levels of the neurotransmitter GABA in their cerebrospinal fluid than healthy people and that the lower the concentration of GABA the more serious their symptoms are.

GABA is involved in most brain functions and along with glutamate it accounts for almost 90 per cent of all signal transmission. While glutamate stimulates brain activity, GABA inhibits it, and the two neurotransmitters interact with each other.

"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 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 , 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.

Explore further: Study uncovers clue to deciphering schizophrenia

More information: "CSF GABA is reduced in first-episode psychosis and associates to symptom severity". Orhan F, Fatouros-Bergman H, Goiny M, Malmqvist A, Piehl F, Karolinska Schizophrenia Project (KaSP) Consortium, Cervenka S, Collste K, Victorsson P, Sellgren CM, Flyckt L, Erhardt S, Engberg G. Molecular Psychiatry, online 14 March 2017. DOI: 10.1038/MP.2017.25

"Lower levels of the glial cell marker TSPO in drug-naive first-episode psychosis patients as measured using PET and [11C]PBR28". Collste K, Plavén-Sigray P, Fatouros-Bergman H, Victorsson P, Schain M, Forsberg A, Amini N, Aeinehband S, Karolinska Schizophrenia Project (KaSP) consortium, Erhardt S, Halldin C, Flyckt L, Farde L, Cervenka S. Molecular Psychiatry, online 14 February 2017. DOI: 10.1038/mp.2016.247

Related Stories

Study uncovers clue to deciphering schizophrenia

June 7, 2016
The brains of healthy relatives of people with schizophrenia may hold a clue to better understand - and ultimately treat - the devastating illness, finds new research led by a Michigan State University scientist.

Researchers find chemical switch that may decrease symptoms of schizophrenia

February 7, 2017
A new study by University of Maryland School of Medicine researchers has found that in mice, adjusting levels of a compound called kynurenic acid can have significant effects on schizophrenia-like behavior. The study appeared ...

Study finds no link between subcortical brain volumes and genetic risk for schizophrenia

February 1, 2016
Over the last decade, important contributions to our understanding of schizophrenia have come from two different types of studies.

Possible mechanism for specific symptoms in bipolar disorder discovered

December 15, 2015
Researchers at Karolinska Institutet, and the Sahlgrenska Academy at Gothenburg University in Sweden have identified a gene variant linked to psychotic symptoms and cognitive impairment in people with bipolar disorder. The ...

New gene variant may explain psychotic features in bipolar disorder

March 5, 2013
Researchers at Karolinska Institutet in Sweden have found an explanation for why the level of kynurenic acid (KYNA) is higher in the brains of people with schizophrenia or bipolar disease with psychosis. The study, which ...

Recommended for you

New research has revealed we are actually better at remembering names than faces

November 14, 2018
With the Christmas party season fast approaching, there will be plenty of opportunity to re-live the familiar, and excruciatingly-awkward, social situation of not being able to remember an acquaintance's name.

Brain changes found in self-injuring teen girls

November 13, 2018
The brains of teenage girls who engage in serious forms of self-harm, including cutting, show features similar to those seen in adults with borderline personality disorder, a severe and hard-to-treat mental illness, a new ...

The illusion of multitasking boosts performance

November 13, 2018
Our ability to do things well suffers when we try to complete several tasks at once, but a series of experiments suggests that merely believing that we're multitasking may boost our performance by making us more engaged in ...

Major traumatic injury increases risk of mental health diagnoses, suicide

November 12, 2018
People who experience major injuries requiring hospital admission, such as car crashes and falls, are at substantially increased risk of being admitted to hospital for mental health disorders, found a study in CMAJ (Canadian ...

Nearly one in ten Americans struggles to control sexual urges

November 9, 2018
(HealthDay)—The #MeToo movement has given many Americans a glimpse into an unfamiliar world that may have left many wondering, "What were they thinking?"

Brain activity pattern may be early sign of schizophrenia

November 8, 2018
Schizophrenia, a brain disorder that produces hallucinations, delusions, and cognitive impairments, usually strikes during adolescence or young adulthood. While some signs can suggest that a person is at high risk for developing ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.