Researchers from the Karolinska Institutet have found that having fewer connections between nerve cells could be one of the key causes of schizophrenia.
The researchers believe that genetic risk variants, which lead to an excessive elimination of nerve cell connections by the brain’s immune cells could be one of the causes of schizophrenia. The research team have reported that the levels of protein from the relevant risk gene are elevated in the patient’s first schizophrenic episode and the inflammation caused by this can further increase the expression of this gene.
What is Schizophrenia?
Schizophrenia is a form of psychosis; people with the condition may find it difficult to distinguish their own thoughts and ideas from reality. Symptoms of schizophrenia can include hallucinations, delusions, a lack of interest in personal hygiene and a desire to avoid other people. The exact causes of schizophrenia are unknown.
During late adolescence, an elimination of less desirable connections between nerve cells takes place in the brain. The clearing of these connections, called synapses, is of vital importance to the development of functional networks in the brain. People who suffer from the condition are known to have fewer of these synapses, suggesting that this could be one of the causes of schizophrenia.
Previous research from the Karolinska Institutet has shown, through an experimental model, that the elimination of synapses is increased in people with schizophrenia. This can be linked to the gene coding for the complement component 4A (C4A), a protein involved in immune signalling.
The same group of researchers have now developed a method to measure C4A levels in cerebrospinal fluid. Cerebrospinal fluid is a clear liquid found within the tissue that surrounds the brain and spinal cord.
The researchers analysed elevated C4A levels in two independent cohorts of first-episode psychosis patients. All patients that were analysed in the study went on to develop schizophrenia in the following years.
“After checking for genetic risk variants, we still observed elevated levels of C4A,” said Jessica Gracias Lekander, a doctoral student at the Department of Physiology and Pharmacology, Karolinska Institutet, and first author of the study.
Researchers have already established the pro-inflammatory cytokines IL-1beta and IL-6 can be elevated in people with schizophrenia. For this study, the researchers performed several new experiments which revealed that these cytokines stimulate the expression of the C4A gene.
Patients with high C4A levels also displayed high levels of IL-1beta in cerebrospinal fluid. A link between C4A levels and markers of synapse density was also observed by the researchers.
Identifying the causes of schizophrenia can help improve care
“This indicates that the effect we see in the laboratory is also relevant in the brain,” said Sellgren Majkowitz, senior author Carl at the Department of Physiology and Pharmacology, Karolinska Institutet, and Psykiatri Nordväst, Region Stockholm.
The researchers believe that understanding the causes of schizophrenia can lead to more effective, personalised treatment strategies and be part of the emerging precision psychiatry approach to treatment.
“Existing treatments are non-personalised and focus on reducing psychotic symptoms in patients that have developed the disorder,” concluded Sellgren Majkowitz.
