What is schizophrenia?

Schizophrenia is a severe brain disease of neurodevelopmental origin and is characterized by chronic or relapsing episodes of psychosis.

Patient meeting

Approximately half a percent of the worldwide population is estimated to suffer from schizophrenia and the majority experience their first symptoms already in their late teens or in early adulthood. This makes schizophrenia one of the major public health challenges, and the estimated costs for the disease is estimated to be greater than those for all cancers combined. 

The clinical presentation shows considerable variability, but the core symptoms typically make a profound impact on thoughts, emotions, and behavior. The diagnosis is criteria based and the diagnostic assessment rely on repeated clinical interviews and mental status examinations. Despite the lack of objective biomarkers, a diagnosis of schizophrenia shows considerable stability over time.

Continuous antipsychotic medication is the mainstay of treatment for schizophrenia. However, disabling symptoms persist in many patients, and some suffer from unwanted side effects.

Genetic risk factors are the main cause of schizophrenia and unbiased large-scale genetic studies have identified a growing number of variations in the DNA sequence that associates with schizophrenia. Several environmental risk factors have also been identified. These include maternal immune activation as well as use of cannabis.

Large brain imaging studies and repeated investigations of brain tissue obtained from deceased individuals with schizophrenia have revealed indisputable structural brain abnormalities. Foremost, a reduction in frontal cortical thickness have been observed and can largely be explained by a loss of connections between the nerve cells, the so-called synapses. 

Asimenia Gkogka/Sellgren Lab. KaSP scientists discovered that an excess of synapses is eliminated in models of the developing human brain when using cells obtained from individuals with schizophrenia. This could largely be explained by genetic risk variations that leads to an increased expression of the CA4 gene, and follow-up studies revealed elevated C4A protein levels in cerebrospinal fluid obtained from individuals with schizophrenia that experienced their first psychotic episode. This is the first time a biological mechanism behind the disease has been described. This image shows the volumetric reconstruction of a microglial cell, crucial for maintaining brain’s health and functions, engulfing synaptic components within human brain organoids. The synaptic elements are statistically color-coded, based on their overlap with the microglia surface (from cyan = no overlap, to magenta = completely internalized by microglia). Photo: Asimenia Gkogka/Sellgren Lab

Large brain imaging studies and repeated investigations of brain tissue obtained from deceased individuals with schizophrenia have revealed indisputable structural brain abnormalities. Foremost, a reduction in frontal cortical thickness have been observed and can largely be explained by a loss of connections between the nerve cells, the so-called synapses. I

Investigations to understand how risk factors causes brain changes and symptoms in the patients are ongoing but much of the pathophysiology remains elusive. However, with such knowledge more precise and personalized drug targeting is possible. 

12-04-2024