Podcast: The curious link between vitamin D and schizophrenia

Schizophrenia is a debilitating mental illness that affects more than 21 million people worldwide. While genetics plays a part, several environmental factors can predispose someone to getting the condition. This episode of A Grey Matter features Professor John McGrath, a psychiatrist and schizophrenia researcher at the Queensland Brain Institute. He talks about smoking, vitamin D, and how common it actually is to experience hallucinations and delusions.  

Transcript

Donna Lu Hi, I’m Donna Lu, and you’re listening to A Grey Matter, the neuroscience podcast from the Queensland Brain Institute.

Just how common are hallucinations and delusions? What is schizophrenia, and what predisposes you to getting it?

In this week’s episode, I sat down with Professor John McGrath, a psychiatrist who researches here at QBI. We talked about marijuana, smoking, and vitamin D, all of which are linked to the risk of getting schizophrenia.

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Donna Lu These days, the words ‘psycho’ and ‘psychotic’ are frequently used in common conversation. People call each other ‘psycho’ as an insult, or describe someone as being  ‘psychotic with rage’. Actress and writer Mindy Kaling once even referred to the ‘psychotic ambitious side’ of herself in an interview.

But the real meaning of the word ‘psychotic’ is tied up with the neurological experience of psychosis. Here’s Professor McGrath:

Professor John McGrath Psychosis is a broad collection of different disorders that involve people losing touch with reality. They can see or hear things that are not there; they’ll have false beliefs out while keeping their cultural and religious backgrounds, et cetera.

Now to get a diagnosis of a psychotic disorder, you need to have a lot of symptoms and disability over a certain time period and you need to exclude various conditions as well. Within the group of disorders like psychosis, the main one is schizophrenia but there are other disorders that have psychotic features like bipolar disorder as well. So these terms, Donna, reflect the fact that we’re not very sure where the boundaries of psychotic illnesses are because we do make the diagnosis based on the surface level symptoms.  

Donna Lu In Australia, about 1 in 100 people develop schizophrenia, and it’s usually life-long. It costs the Australian community about $2.6 billion each year in both direct health costs and loss of productivity. It’s important to think of the disorder of schizophrenia as a collection of symptoms and signs that continue over time.

Professor John McGrath Ancient physicians used to think that fever was a disease, and there was this fever that occurred every 3 days and there was a fever that occurred every 4 days. And then people realized, ‘Well, wait on,’ fever is just a non-specific marker of other things, that could be infection, and those infections could be bacterial or viral, fevers can be associated with toxins, with autoimmune diseases. So science and medicine was eventually able to pull that one apart based on the surface level symptoms. Unfortunately, the brain is such a complex organ; we’re not really good at pulling apart what types of things cause delusions and hallucinations.

When I trained as a psychiatrist, we were told that if you heard voices, you probably had schizophrenia; if you had a delusion, you probably had schizophrenia. So there’s this kind of jumping to a conclusion that these symptoms were entirely linked to psychosis and the assumption was that they did not occur in the general population. However, if you look at other mental disorders, they do occur on a continuum. There is serious depression but we all get depressed; getting depressed is part of everyday life. If you lose someone you love, or have some bad news, you can get quite sad. And also being anxious is also a feature of everyday life that’s just completely understandable.

Donna Lu To determine whether psychotic symptoms also occur on a continuum, John and his colleagues looked at individual experiences of hallucinations and delusions.

Professor John McGrath We used very, very large international surveys where they interviewed tens of thousands of people in many countries, and everyone was asked, ‘Have you heard a voice when no one else could hear it, or there was no voice around or do you have these beliefs?’

Donna Lu What they found was the hallucinations and delusions are much more common than previously thought.

Professor John McGrath: So the first key finding, Donna, is that about 1 in 20 people have these experiences, and in particular, hallucinations were common. People reported that they had at one stage in their life heard voices or seen things. But the key new element of our research is we asked people, ‘Well, how many times did that occur?’ And it turns out that most people who had these experiences just had them once or twice or a handful of times. So that allows us to fractionate out that there’s a sub-group of the population where it’s very transient and sporadic. They’re not disabled, they don’t seek help, they don’t need to see a doctor, and we don’t need to treat them because they’re going to get better. On the other hand, we also confirmed that there’s a small sub-group in the general population, that seemed to be hearing voices continually and that makes us worry that they need help and it may well be that we need to think again about the linkages between these symptoms and psychotic disorders.

Donna Lu An unexpected result of the study was that hallucinations and delusions were more common in women.

Professor John McGrath I was surprised that women were more likely to have these experiences because when you look at the full clinical disorder of schizophrenia, that occurs in men more than women. Not a huge excess, say for every three men who have schizophrenia, usually about two women have it. Now that flips around the other way when you look at anxiety disorders and depression, which are more common in women than in men. So that’s an interesting dissociation between the isolated symptoms, which is our new study, versus the full clinical disorder.

Donna Lu In terms of the full clinical disorder, schizophrenia, John has spent many years researching about the non-genetic risk factors that can predispose people. Interestingly, not spending enough time in the sun might be one of them.

Professor John McGrath This is work that I’ve done with my colleagues here at the Queensland Brain Institute, Daryl Eyles and Tom Burne, and also colleagues in Denmark. So we had done a lot of epidemiology and the field had done a lot of epidemiology that showed that if you’re born in winter or spring, you have a slightly increased risk of schizophrenia. Now there’s a running gag that it could be a star sign – clearly that’s not true but clearly we’ve thought it could be due to prenatal infections maybe if you were born in winter your mother could have been exposed to prenatal infection, so we’re kind of thinking like rubella and German measles leading to altered brain development.

But it struck us that Vitamin D should be a candidate as well because that’s the sunshine hormone. Even in sunny Brisbane Vitamin D levels drop during winter and spring due to our behavior and due to lower ultraviolet radiation. So when we proposed this hypothesis many years ago there was absolutely no evidence that Vitamin D did anything at all to the brain. In the last decade, Daryl Eyles and Tom Burne have shown that that’s wrong. In fact, if you look at our models, you can disrupt brain development by taking out Vitamin D.

And what’s really fascinating, Donna, is that what we see in the rodent experiments is that it cross-links with what we se e in people with schizophrenia. Dopamine seems to be slightly altered; reaction to certain stressors and psychoactive substances tend to be different. So then we needed to actually test the hypothesis by measuring Vitamin D in stored bio-bank samples. Now schizophrenia comes on in the 20s, 20s and 30s, and we needed samples from birth. So we went to Denmark and they have kept neonatal blood spots, and we were able to measure Vitamin D in these tiny samples of filter paper. And we showed a few years ago, in 2010, that Vitamin D concentration at birth did link to schizophrenia and we’ve since replicated that, we haven’t published that finding yet, we’re feeling pretty upbeat that this is a signal that, at least in Denmark, that the babies, that are born with low Vitamin D have an increased risk of having schizophrenia. Now this is a profoundly important finding because you can treat Vitamin D deficiency, in fact, it’s really easy to treat: safe and publicly acceptable, and this is the Holy Grail for researchers, if we can reduce the instance of a disease like schizophrenia, then that’s a good outcome and that we’re following out these findings urgently and are doing a lot more work on trying to unravel the mechanisms. So we’re very excited about these discoveries.

Donna Lu Skin colour was actually a big signal about the potential importance of vitamin D. People with darker skin produce more of a pigment called melanin. Melanin protects the skin against too much UVB exposure, which also means that it reduces the amount of vitamin D that the skin can produce. 

Professor John McGrath In cold countries like the Netherlands, Denmark, Sweden, UK, the dark skinned migrants and the offspring of the dark skinned migrants were having really high risks of schizophrenia—tenfold. Now that’s a remarkable epidemic, essentially. And it could be due to other factors such as stress, it could be due to substance use, but it could well be that low Vitamin D just contributes to a subtle risk that causes psychosis. So in the Danish dry blood spot study we found that the offspring of migrants tend to have low Vitamin D, just as we expected.

We’ve got a lot more work to do before we can say low Vitamin D causes schizophrenia. This is the nature of science; you get an idea and then you try to reject it, you try to knock it down, and we haven’t been able to knock it down yet. But you know Donna even if low Vitamin D contributes to a small fraction of those with schizophrenia we think that this is a really important one to follow up. And even if it doesn’t help in every one, it can help with respect to schizophrenia, it can help their bones. We’re pretty confident about that. [Laughs]

Donna Lu While the link between marijuana smoking and schizophrenia is well established, what’s interesting is that there’s also a link with ordinary cigarette smoking.  

Professor John McGrath James Scott and I, and colleagues from the School of Public Health, published a study several years ago that linked age at first cannabis use to an increased risk of schizophrenia and these hallucinations and delusions as well. We did that on great study that Jake Najman and his colleagues have been running for many years – 30 years or so, it’s called the Mater University Study of Pregnancy and it follows a birth cohort, so many of your listeners may have seen documentaries like Seven Up where they follow kids every seven years. And Jake Najman and his team following up several thousand people for about 30 years. And we were able to ask them 'When did you first use cannabis?’ and we were able to look at their mental health through various phases of young adulthood. When we did that study, on cannabis, we did see some signals about tobacco and it’s very hard to pull apart because many people who had used cannabis also smoke tobacco, so it’s a bit of a perfect storm—not very easy to pull apart. Then some of my colleagues in the UK and Sweden started to worry that maybe tobacco could be a causal factor that could contribute independently to the risk of psychosis. Now that issue was kind of ignored for a while because we have a much, much bigger issue that once you get schizophrenia, then you tend to smoke, and it’s much harder to stop. So we know that schizophrenia and smoking are linked but we always thought that was downstream. Schizophrenia comes first, then you smoke, and then you’ve got a problem because you find it very hard to stop. So we did a study in Brisbane’s cohort where we excluded those that had use and just looked at how old were you when you first started to smoke tobacco and then was that associated with later psychotic experiences. Now, we found that it was associated with some isolated psychotic experiences. The study was a little bit underpowered; we couldn’t confidently say that it causes schizophrenia. So we published that and right about the same time there was a little cluster of studies from other countries, Sweden, for example, and the UK, that were saying the same thing. So we’re getting convergent evidence that maybe tobacco could contribute in a very small way, tipping someone over the edge into a psychotic illness.

We don’t need any more evidence to tell us that tobacco is bad, okay? Clearly tobacco is bad, it causes a lot of cancers and cardiovascular diseases—it’s just very, very bad. So we can now add, probably, mental illnesses to that list as well. Now, we can prevent tobacco smoking through public health measures, education, plain packaging taxes or sin taxes on these agents. In fact in Australia, the rates of tobacco smoking are falling in many demographic groups, not as fast as we’d like, in young women, unfortunately. So that’s a clue—but going back in the Queensland Brain Institute, that clue can now allow us to crosslink with the work that people like Brian Mowry and Naomi Wray are doing here at QBI, because they have already found links in variance in genes that are involved in cholinergic receptors and nicotinic receptors. So these are the receptors that tobacco works on. So there’s a nice crosslink between genetic vulnerability and our new epidemiological finding that makes these pathways of greater interests so we can—that’s like a foot in the door for scientists—they can say, ‘Well wait on, these candidate pathways need more scrutiny.’ And that’s what we’re following up now.

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Professor John McGrath I’m very upbeat that the work we’re doing here at the Queensland Brain Institute will contribute to unravelling serious mental disorders. It’s a great privilege to work here because we have so many smart people who know so much about the brain and I hope that as a psychiatrist and as an epidemiologist I can seed new ideas into the laboratories around this building here and I think that’s a great testament to Perry Bartlett, and our new director Pankaj Sah, whom I’m working with on some Vitamin D research now that we can make these cross links. I think this is like the fertile intersection of great science and, you know, you hear about the Large Hadron Collider that kind of discovers subatomic particles—well, I feel like is this is a collider of neuroscience ideas. Great ideas can collide and from some of those collisions we can come up with new discoveries about the brain. So it’s a great opportunity that we have here at the Queensland Brain Institute.

Donna Lu I’m Donna Lu, and that’s all for this episode. Let us know what you think or if you have any requests for future podcasts. We’re on Twitter @QldBrainInst and on Facebook, or you could give us a review on iTunes. Thanks for listening. 

This podcast features music from Incompetech and Bensound, available under a Creative Commons Attribution-Noncommercial license.

Music used:

Better Days – http://bit.ly/1KIUquE

Funky Hip Hop – http://bit.ly/1Ld4RVN

‘There It Is’ by Kevin McLeod – http://bit.ly/1nW96tY