Schizophrenia and substance use disorder have genetic link

A new paper, published in the Journal science has performed an investigation into schizophrenia, specifically the relationship and genetic risk factors behind this mental health condition and substance use disorders. Those with schizophrenia are, on average, much more likely to have substance use disorders, and so the relationship between schizophrenia and use of substances such as cannabis, is a complex one. Indeed, in the papers own words, the role of cannabis use as a risk factor for Schizophrenia and first episode psychosis onset remains a classical “chicken or egg” problem in psychiatry. But that is something that this paper is attempting to unpick.

Shivani - There's been a long standing discussion about whether having schizophrenia increases one's propensity to engage in substance use disorders, or is it the other way around or in many times in genetics is there just a very complex interplay? So in the medical sphere and in psychiatry itself, we know that cannabis use specifically really does increase the statistical risk that someone will develop schizophrenia. Last year they had a huge study. There were 7 million health records taken out and they found that 30% of men could have prevented developing schizophrenia had they not engaged in cannabis use.

Will - And so with such a complex thing to unpick then what was the genetic study they carried out to try and look into this?

Shivani - They take a big population of people whose DNA has been sequenced and they try to correlate people with substance use. So in this case it was cannabis use disorder and regular smokers and then people with an established diagnosis of schizophrenia. And what they found was substance use disorder is correlated with the genetic increase in schizophrenia. And that was more so with cannabis than smoking. But they also found bidirectionality, which means that people with schizophrenia are more likely to have genes that cause them to engage in substance use disorder.

Will - The paper does seem to conclude that the reason for such a strong interlinking of these two disorders isn't so much because one affects the other, but they exist as cross trait loci, as genes that code for more than one thing. And unfortunately in this instance, it seems to be a greater risk for schizophrenia does also code for a greater risk for substance use disorder. It's perhaps not so much chicken or egg, as chicken and egg.

Shivani - They found one of those genes was linked to an acetylcholine receptor. So acetylcholine is one of the many neurotransmitters found in the brain. And so it's not surprising that a lot of substance use disorders are linked with neural networks of positive reinforcement. You get a kick out of the result, you want to go back to it. And schizophrenia, likewise, is a result of a different imbalance of neurotransmitters. So for one to be linked with the other is not wholly unsurprising. And actually it was important to find this out through the study because there are established drugs which act on receptors like this used for other diseases. So potentially we can look at using drugs like this to help people who have both kind of genetic predispositions.

Will - I've known people with, not necessarily schizophrenia, but chronic physical and mental illnesses that use stuff like cannabis as a means of abating symptoms. And do you think the relief element of substances has to be factored in as to why so many people with schizophrenia may have substance use disorders?

Shivani - I definitely think so. I mean, it's a very classic association, for example, between depression and alcohol intake. Unfortunately, when people aren't supported with their mental health, it can lead to them using substances to help with symptoms and schizophrenia is a very scary disease and people may feel like they have to rely on another kind of crutch in that sense. And it's very unfortunate. And I think the study's super important because as cannabis becomes legalised in more and more countries we might then see an increased rate of schizophrenia being diagnosed. And likewise potentially people who have a family history of schizophrenia, if you have a first degree relative with schizophrenia, you are eight times more likely to develop it yourself. And so people who are already high risk, I think a study like this is really important to kind of inform whatever life choices they want to make.

Will - And I suppose one of the useful things to come out of this paper may well be, it could highlight how we can better treat schizophrenia and substance use disorders or perhaps even both.

Shivani - Yeah, absolutely. And I don't think there's any established medical guidelines of using, for example, acetylcholine receptor inhibitors for people with substance use. So by finding out which neurotransmitters are involved, we can kind of look at prevention rather than management. And in medicine that always yields the optimal outcomes. We want to prevent people from developing or going down such a bad path and ultimately it leads to better quality of life, longer lifespans, et cetera.