Program: Immunotherapy could treat some psychiatric syndromes

Preeya Alexander: The next story is on immunotherapy, but not in the space that we usually think of, this is mental health.

Norman Swan: Yeah, and it's not the same immunotherapy drugs that are used in cancer, which we talk about all the time. And the person I'm about speak to, Associate Professor Elizabeth Scott at the University of Sydney, has spent most of her career looking after young people with very complex mental health issues, and what she's found over the years is that there's a solid biological reason for some of these young people to have these complex mental health issues, and in fact it's the immune system causing it. This has just been published, and it's a small series, 43 young people, starting at the age of 12, who had complex mental health issues, but in fact what was going wrong with them was their immune system and they had an autoimmune disease, and when they found that out, they were able to treat it. And so this has been an obsession but also a strong research interest of Liz Scott, who works at the Brain and Mind Centre at the University of Sydney.

Elizabeth Scott: They present with very severe mood disorders, complicated sometimes by syndromes like OCD. They have psychotic type symptoms that come and go, so they don't have sustained psychosis.

Norman Swan: And just to decode some of that, when you say mood disorders, so they've got really quite profound depression.

Elizabeth Scott: Yes, they have quite severe depression or unstable mood, bipolar type syndromes where they go from having very kind of elevated, activated mood, not always very happy mood, often it can be kind of irritable or agitated with a lot of energy, changes in impulsivity, often a lot of self-destructive behaviours or suicidal ideation, or very low mood and low energy states where people can't get out of bed, they want to hibernate, they don't want to socialise with people, again can be very irritable. And these syndromes can be extremely difficult, not only for the young person but also for their families. They're very hard to understand and can be quite changeable over time, so can present initially with OCD type symptoms or anxiety, then develop more severe depression, have psychotic type episodes, and also have quite significant cognitive impairment. So one of the real characteristics of these syndromes are the deterioration in their cognitive function, capacity to think, capacity to attend to things, to sustain attention, concentration, short-term memory. So it's a deterioration in people's capacity to kind of think and engage with the world often.

Norman Swan: And dominantly women. 

Elizabeth Scott: Yeah, so interestingly in our series it's a very high proportion of females, and that relates to the health bias where young women are more likely to see care. It also reflects the fact that autoimmune and immune conditions are much commoner in young women than they are in young men.

Norman Swan: And the youngest in your series was age 12.

Elizabeth Scott: Yes, we do see quite early onset in some cases of young people who've experienced a kind of autoimmune syndrome earlier in life, or Tourette's type syndrome with OCD symptoms and tics, motor tics, that then go on to develop these atypical mood or psychotic disorders as they grow up through adolescence.

Norman Swan: These people have been around forever, you would assume, so what are the labels that they're getting and parents being told that's wrong with their child?

Elizabeth Scott: To some extent those people who are labelled as treatment resistant then become reclassified as having personality disorders, or they are told that they have a somatisation disorder, that it's really about the physical expression of psychological distress, or the increasing kind of trend to label people as having functional neurological disorders with neurological symptoms where there isn't an obvious neurological cause, so people get sent off for psychotherapy, which is not particularly helpful and often causes a lot of distress and delay in treatment.

Norman Swan: Now, you say they're rare, but there's been this whole thing which has grown through the years, that even schizophrenia and regular depression has got an immune story in the brain.

Elizabeth Scott: Correct. Increasingly people are aware of the underpinning, the immune or inflammatory processes that underpin brain development in adolescence. So you change your brain by activating your immune system and turning on your genes of the immune response.

Norman Swan: Now, you've used the word 'autoimmune', meaning the immune system's turning against the body, but I remember years ago we did a documentary on…it was predominantly women who got it, it looked like an extreme version of schizophrenia, they had cognitive decline, and they had a tumour, and when it was removed that cured them.

Elizabeth Scott: That's right. The syndrome that was originally described, thought to be extremely rare, was anti-NMDA antibody syndrome, where you make antibodies to these particular receptors in the brain, and that occurs when people have ovarian tumours, for instance, and that immune system gets activated and makes antibodies to these brain receptors, causing this very acute florid brain-on-fire type syndrome. We know that's not the only cause of anti-NMDA encephalitis, because young men can get it too.

Norman Swan: And what I remember from that one is that it had to be detected early because you could get permanent damage.

Elizabeth Scott: That is correct. So in all autoimmune conditions, whether they affect your joints or they affect your thyroid or they affect your brain like MS, detection and early intervention are key to prevent the damage associated with these immune processes, and that is absolutely true in these types of conditions in young people; if we don't detect them early, if we don't treat them early, then people are likely to go on to have long-term damage and the disability associated with that.

Norman Swan: Okay, so you've got these unusual symptoms which go together, which should now trigger a warning sign that the immune system might be majorly involved. But are there tests that are going to reveal this?

Elizabeth Scott: We used a set of clinical criteria based around what we've discussed, this kind of very severe atypical mood disorders or psychotic symptoms, or OCD type symptoms that don't respond to conventional treatments, or conventional treatments actually make you worse, that have this kind of deteriorating cause, deteriorating cognitive function, and associated with particular sets of family history and laboratory markers to define who we thought was at risk and then who needed to go on to further, more detailed assessment, and then planning for more specialised immunotherapy treatment.

Norman Swan: Just give us a sense of how you decided what you were going to use. And this is not the immunotherapy used in cancer, this is immunotherapy used largely in autoimmune disease.

Elizabeth Scott: That's correct. So the decision for treatment was based on a panel decision with an immunologist, a neurologist and a psychiatrist. We involved the young people and their families. So these were really collaborative decisions, and they were brought about by consensus. 

Norman Swan: This wasn't a randomised trial, you were just observing what happened to these people. In a sense they were their own controls, because they had a pattern up to that point. You then instituted immunotherapy, and you got a result. What were the results?

Elizabeth Scott: We found that there was a significant response rate to people having immunotherapy, and these were young people who were really not doing well. They'd had repeated periods of hospitalisation, very aggressive psychiatric treatment, including things like ECT, a high proportion of them were not in education or employment, and their level of functioning was poor. So, comparatively, after treatment they were all doing very well. So we got about an 88% response rate in terms of improvement in symptoms and improvement in function, which is pretty remarkable. 

Norman Swan: So their cognitive capacity came back.

Elizabeth Scott: Their cognitive capacity improved, it did not come back to pre-disease levels in all people, but it certainly improved significantly, enough for a very high proportion of young people to get back into education, training and employment and to have a substantial improvement in their level of function. 

Norman Swan: What about side effects? Because these are not harmless drugs.

Elizabeth Scott: About 20% of people, a bit over 20% had moderate to severe side effects associated with therapies, including things like recurrent skin cancers in some cases. So they're certainly significant, and they certainly need to be monitored.

Norman Swan: So somebody who's listening to this conversation and they realise that they themselves or they have a child with this pattern, what is a person to do in the current health system to get this sort of care? 

Elizabeth Scott: Really it's about raising awareness. The people that have gotten to care often have parents that have advocated for their treatment and assessment, have really not accepted poor treatment or deteriorating function or disability. We're trying to raise awareness in the medical profession, we would like to establish specialised clinics in all states where people could be properly evaluated and assessed, and more importantly we can collect the data that is required to both make sure that these treatments are safe and that they're effective, but also to drive research. We screen all of our patients presenting to our psychiatric services early, so we look at their immune, inflammatory and metabolic markers, and we've published the data on this. So I think as we get better at understanding some of the early changes that you see around these kind of immune inflammatory processes, we'll be able to pick people up earlier, make sure that we put them into the appropriate treatment streams where these things are monitored, so that we can pick up changes quickly.

Norman Swan: Associate Professor Elizabeth Scott, who's principal research lead in Youth Mental Health at the Brain and Mind Centre in Sydney. So there may well be people listening whose child or the young adult in their family has exactly these symptoms, and it can unlock diagnosis and treatment. Important story.

Preeya Alexander: You're with the Health Report on ABC Radio National.