Schizophrenia is one of the most disabling psychiatric diseases and
affects approximately 1% of the population. It’s onset commonly takes place 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% of the patients
become symptom-free.

‘Schizophrenia patients have lower levels of the vital neurotransmitter GABA as well as changes in the brain’s immune cells.’

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.

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 analyzed 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% 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 Gran
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

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.

Source: Eurekalert

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