Meta-Analysis Revises Current Research Opinion on Schizophrenia
The results of a meta-analysis conducted by JARA-BRAIN scientist Prof. Dr. Thomas Nickl-Jockschat and Dr. Claudia Eickhoff show: A COMT gene variant does not necessarily influence brain performance in people with schizophrenia. Past imaging studies indicated a correlation between this gene defect and brain activity patterns.
“In up to 85 % of schizophrenia cases, the genes are the decisive factor determining whether the illness actually breaks out,” explains Thomas Nickl-Jockschat. The COMT gene plays a role in this psychiatric disorder, since it codes an enzyme which regulates the neurotransmitter dopamine in the brain. The dopamine levels in schizophrenic patients, in turn, are usually unbalanced.
Against this backdrop, several years ago researchers conducted a study which received great attention: after placing them in a magnetic resonance tomograph, the researchers had asked test subjects who had a certain variant of the gene – called COMT Val158Met polymorphism – to perform tasks which tested specifically the working memory. In this gene variant, only a single base of the genetic code is modified, but this leads to a different activity of the COMT enzyme.
In the study, the scientists recorded the brain activities to determine whether the blood circulation in the frontal lobe of people with the risk variant changed in comparison to a control group without the risk variant.
This theory was confirmed, so that for some years the focus of schizophrenia research shifted to studies which examined the consequences of risk variants on brain activity by means of functional imaging. This branch of research is therefore also known as imaging genetics.
Researchers process data from 995 test subjects
Thomas Nickl-Jockschat, who is senior physician at University Hospital Aachen’s Department of Psychiatry, Psychotherapy and Psychosomatics and conducts research at the Institute of Neuroscience and Medicine, has now critically questioned this approach. Together with Prof. Dr. Simon Eickhoff from Heinrich Heine University Düsseldorf, the psychiatrist used the outstanding computing infrastructure at Forschungszentrum Jülich and fed a total of 995 test subject data sets from 14 similarly structured studies into the high-performance computers. The result: a comparison of the data from the studies showed that there is no overall spatial connection in the brain.
“Meta-analysis has once again shown that we require much larger cohorts in order to make scientifically founded statements,” explains Thomas Nickl-Jockschat.
He adds that the theory that gene effects can be better represented by means of functional magnetic resonance tomography than through behavioural observations should be questioned. The research findings were recently published in Biological Psychiatry.