Wednesday June 25 2014
Schizophrenia tends to run in families
“Study finds people predisposed to [schizophrenia] and drug users share common genes,” the Mail Online reports. A new study suggests that ‘schizophrenia’ genes are associated with cannabis use.
It has long been known that there is an association between cannabis use and schizophrenia – but the “direction of travel” has been hotly debated.
Does cannabis use trigger the onset of schizophrenia in vulnerable individuals? Or are people with a genetic predisposition to develop schizophrenia more likely to use cannabis than the population at large (possibly as a coping mechanism)?
This latest study suggests that the latter may be the case; at least in some people. The study involved 2,082 healthy adults whose genetic make-up was examined for risk factors for schizophrenia.
People with more genetic risk factors (carrying more of the DNA variants that have been associated with schizophrenia) were more likely to have reported ever using cannabis.
However, it is important to note that none of the people in the study actually had a diagnosis of schizophrenia. In addition, as this is a cross-sectional study (see below), it cannot definitively answer the question of cause and effect.
A person’s risk for schizophrenia, or for cannabis use, are likely to be influenced by a complex mixture of genetic factors (including those not identified or examined here), lifestyle and environmental factors.
Where did the story come from?
The study was carried out by researchers from the Institute of Psychiatry, King’s College London; Queensland Brain Institute and QIMR Berghofer Medical Research Institute, Australia; the Department of Developmental Psychology and EMGO Institute for Health and Care Research, Amsterdam; the Washington University School of Medicine.
It was funded by the UK Medical Research Council and National Institute for Health Research; the Australian National Health, Medical Research Council and Australian Research Council; the Centre for Research Excellence on Suicide Prevention (CRESP – Australia); and the Netherlands Organization for Health Research and Development.
The study was published in the peer-reviewed medical journal Molecular Psychiatry.
The Mail Online reported the story accurately and informatively.
What kind of research was this?
This was a cross-sectional study using data collected in a larger cohort study. It aimed to assess the association between cannabis use and the level of genetic predisposition for schizophrenia.
As it is a cross-sectional study it is only able to describe this association and cannot prove cause and effect. That is whether the genetic predisposition caused them to use cannabis or that conversely, cannabis would cause them to develop schizophrenia.
What did the research involve?
A group of 2,082 unrelated healthy adults were recruited from the large Australian Twin Registry studies.
The participants were asked questions over the telephone on their cannabis (marijuana) use, including:
- Did you ever use marijuana?
- How old were you the very first time you tried marijuana (not counting the times you took it as prescribed)?
- How many times in your life have you used marijuana (do not count times when you used a drug prescribed for you and took the prescribed dose)?
The genotype (each person’s genetic make-up) was obtained. These were compared with samples from a large Swedish study which has identified a number of single nucleotide polymorphisms (SNPs), DNA sequence variations, that are believed to increase the risk of developing schizophrenia.
The presence of more than one of these SNPs gives a “polygenic” (multiple gene variants) risk factor, and some SNPs are associated with a particularly higher risk (having the most significant associations with schizophrenia).
These risk scores were analysed in comparison with the answers to the cannabis questions to look for any associations.
In the second part of the study, the researchers looked at the polygenic risk scores of 990 twins (just over a third were identical twins).
They took the mean polygenic risk score from each pair of twins and used this to predict whether neither, one or both twins used cannabis.
What were the basic results?
Out of the 2,082 adults included in the study, 1,011 (48.6%) had ever used cannabis. The mean age of starting cannabis was 20.1 (95% Confidence Interval [CI] 19.7 to 20.5) and the mean number of times they’d used cannabis over their lifetime was 62.7 (95% CI 19.7 to 20.5).
The researchers found a significant association between a person’s extent of genetic predisposition for schizophrenia and their reported use of cannabis. People who had used cannabis had higher genetic risk scores for schizophrenia than those who had never used cannabis. The strongest associations were found between the higher risk SNPs and ever use of cannabis.
However, the results showed that the genetic risk factors they assessed only predicted a small amount of a person's risk of using cannabis. This meant that other factors have more of an influence on whether a person uses cannabis.
In the secondary analysis, twin pairs where both reported using cannabis had the greatest polygenic risk factors for schizophrenia.
Pairs where only one of them used cannabis had an intermediate level of risk factors, and the lowest burden was in those where neither used cannabis.
How did the researchers interpret the results?
The researchers say this study shows “that to some extent the association between cannabis and schizophrenia is due to a shared genetic aetiology [cause] across common variants. They suggest that individuals with an increased genetic predisposition to schizophrenia are both more likely to use cannabis and to use it in greater quantities.”
This study shows an association between genetic risk factors for schizophrenia and cannabis use. However, as it is a cross-sectional study, it cannot answer the often debated cause and effect question of whether cannabis use increases risk of schizophrenia, or whether there is a common genetic predisposition to both.
The study cannot prove that cannabis use is a risk factor for developing schizophrenia.
It also cannot prove that the genetic risk factors (SNPs – variations in the DNA sequence that have been associated with schizophrenia) also directly increase the risk of using cannabis. As the researchers’ results suggested, the genetic risk factors they assessed only predicted a small amount of a person's risk of using cannabis. There may be many other factors involved. A complex mixture of genetics (including DNA variations not examined here), lifestyle and environmental factors is likely to contribute to a person’s risk of developing schizophrenia, and to their risk of using cannabis.
It should also be noted that none of the participants in the study actually had a diagnosis of schizophrenia. Though the SNPs thought to increase the genetic risk of developing schizophrenia were identified in a large Swedish cohort study, the authors do point out that they may not be accurate.
They say that in this Swedish sample from which these SNPs were identified, use of cannabis may have been more common among the people who had schizophrenia than in the controls without schizophrenia.
They say this could mean that the SNPs actually increase risk of cannabis use rather than risk of schizophrenia.
A further limitation of the study is that cannabis use was self-reported which may give rise to inaccuracies in the estimated level of use. Also people may not have been willing to disclose any use of an illegal substance during a telephone interview.
Cannabis may not be as dangerous as other drugs (including legal drugs such as tobacco and alcohol) but it is certainly not safe. There are many negative effects of cannabis, including a risk of developing dependency, its tendency to reduce motivation and concentration, and the likelihood that it reduces male fertility.
Furthermore, the risks of the tobacco and nicotine which are usually consumed at the same time need to be taken seriously. Read more information about the health risks associated with cannabis.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.