In this podcast we talk to postdoctoral research fellow Gail Alvares, of the Telethon Kids Institute, Perth, Australia. Gail begins by discussing her recent JCPP paper ‘Investigating associations between birth order and autism diagnostic phenotypes’. There is also a video abstract on this paper.
She then talks about her upcoming research projects including the intolerance of uncertainty for individuals on the spectrum, and why it is so important to follow research with clinical practice.
Gail’s research has primarily involved coordination of Australia’s first national biobank for autism (the Australian Autism Biobank), currently the largest detailed biological and clinical repository of information about autism in Australia. She has also developed and tested an attention training game for children with autism. In 2016, Gail was named a “Top 5 Under 40” scientist by ABC’s Radio National.
Interviewer: Hello, welcome to the In Conversation podcast series for the Association for Child & Adolescent Mental Health, or ACAMH for short. I’m Jo Carlowe, a freelance journalist, with a specialism in psychology. Today I’m interviewing Dr. Gail Alvares, a Postdoctoral Research Fellow of the Telethon Kids Institute, the University of Western Australia, in Perth. Gail recently co-authored a paper in the Journal of Child Psychology & Psychiatry investigating associations between birth order and autism diagnostic phenotypes. If you’re a fan of our In Conversation series, please subscribe on iTunes, or your preferred streaming platform. Let us know how we did with a rating, or review, and do share with friends, and colleagues. Gail, thank you for joining me. Can you start by introducing yourself?
Gail Alvares: Oh, thank you so much for having me. So, as you mentioned, my name is Gail Alvares. I’m a scientist that specialises in autism research. I work in Perth, which is in the West Coast of Australia.
So I just want to acknowledge [inaudible 00:01:31] past and present, and emerging, for their generosity, and wisdom, in the research we conduct at Telethon Kids. And just to extend my respect to any Aboriginal or Torres Strait Islander people who might be listening to this.
And also, just as a quick note, that as we talk about autism research, I might use my language interchangeably between person first and identity first language. So, I might say “Individual on the autism spectrum”, or I might say “Autistic person” or “Autistic adult.” And just to acknowledge that people have different perspectives about language used about autism and that there isn’t really a preferred term for everyone. But just to be upfront that that’s the language I’ll use. But thank you very much for having me.
Interviewer: And how did you become interested in child, and adolescent, mental health and, in particular, autism research?
Gail Alvares: Yes. So I did my PhD in mental health research or in psychiatry at the University of Sydney a little while ago. And I was really focusing on social anxiety disorder research in young people, particularly the biological mechanisms that contribute to the development of mental health conditions. And, in the last, kind of, five to six years in my post-doctoral research, really interested in understanding treatments as well as the mechanisms that contribute to autism. And now, in my more recent work, specifically, treatments, or new therapies, that can help identify mental health problems for children on the autism spectrum.
Interviewer: Gail. As mentioned in the intro, you recently co-authored a paper in the JCPP, investigating birth order, and autism, and this was published in November 2020. Can you tell us how you carried out this important work, and, also, something about the findings?
Gail Alvares: Yeah, absolutely. I find it a fascinating study. Because there has been a lot of research in, kind of, the broader general population about these links between the order in which someone is born, and, actually, a wide range of characteristics of those individuals. So, for example, one of the most heavily investigated areas are pretty well established links between birth order, and intelligence, or educational attainment. And also, some evidence of differences in sexual orientation by birth order. So it’s really fascinating research.
There’s really, over the last decade, or so, kind of, an emerging body of evidence that showed that there was links between increasing birth order and the likelihood of getting a diagnosis of autism, so that there were increased odds of getting a diagnosis for autism in firstborn children, or in later born children. And this was potentially reflecting differences in, for example, the reproductive histories of families, or family decision making, around having children. So what was really interesting to us is not so much the likelihood of whether, or not, an individual has a diagnosis of autism, but really the clinical presentation for individuals who already have a diagnosis. Because, of course, we understand that for any individual on the autism spectrum, there is a wide variety of abilities, and challenges, that can present in anyone, at any one time.
From a clinical perspective, it’s really important to understand what are the mechanisms that contribute to that variability? Because that helps us understand what supports we need to design, to help that individual, kind of, achieve their goals, and their potential. So, from our perspective, we wanted to know whether there was a link between birth order, and differences in the phenotype, or the clinical characteristics, for individuals on the autism spectrum. And there was a little bit of research already done in this area, but in, kind of, smaller clinical samples.
So we wanted to look at it in a very large sample. And, luckily, in Western Australia, we actually hold a very large resource called a Diagnostic Registry. So, it’s called the Western Australian Autism Diagnostic Registry. And it was established in 1999, so, actually, quite some time ago. And, for a proportion of time, it was capturing data of every single person diagnosed with autism, in the entire state. So, as of this year, it has records of more than 6000 individuals. So what we were able to do was to capture data through this registry, and look at birth order, so, the reported siblings, for individuals, at the time they were diagnosed, and then look at then that individual’s diagnostic information.
So not just whether, or not, they had a diagnosis, but, actually, the clinical features of that diagnosis. So their intelligence levels, their functional abilities, any other co-occurring symptoms. And so, using this, we were able to do a series of statistical models to look at what was the differences in later born children relative to first born children. And we actually found this really interesting association that compared to children who were born first in the family, that later born children actually had increasing functional difficulties, and decreasing IQ, and increasing likelihood of intellectual disability.
And this was also the case for children who didn’t have siblings. So children who were the first born in their family, but didn’t have any other siblings at the time that were diagnosed. So the really interesting findings, and the later you were born, in a family, the more significant that difference in functional abilities was. So by the time we were getting to the third, and the fourth, born children, we were seeing differences in sort of three, to four, points, on this adaptive functioning scale measure, which is what we would consider a clinically significant difference.
Interviewer: What are the implications of this then? What does it mean for clinicians? What does it mean for families?
Gail Alvares: Absolutely. I mean, this is the most important question we have to ask with some of these research studies is what does this actually clinically mean? And so, there’s a couple of different implications we have from this study. So, for clinicians, it might imply that understanding the birth order, of an individual, and their family size, might be really important, when doing a diagnosis of an individual, or considering a diagnostic evaluation, for a child. And then, it might also be important, particularly for clinicians, to be doing really detailed functional assessments, for those individuals, at the time of diagnosis, because this helps us understand the supports that that individual might need.
The other implication is that this research might actually provide some evidence for the factors that might influence family decision making. So, for example, there was evidence in this study that children without siblings had poorer IQs and a greater likelihood of intellectual disability compared to first born children with siblings. So this might indicate that children with greater functional challenges may then have an impact on family decision making around having further children. Or they might delay having further children to provide greater support for that child.
So this might have some implications for things like providing supports for families at the time of diagnosis, or increased supports. What this research does show for families is that there is an incredible variety, or variability, in clinical symptoms, and functional abilities, at the time of diagnosis. So the assumption is that when you get a diagnosis that you have very significant delays in lots of different areas. But, actually, even in this very large cohort of five and a half thousand children in this sample, there was a huge variety of intellectual abilities, and of functional abilities, across a number of different domains, like communication or daily living skills.
And so this study really just provides one mechanism that explains some of this variability, but it also highlights that there is an incredible amount of variability for individuals on the spectrum.
Interviewer: So given that amount of variability, would you say that findings, of this sort should include families, in terms of decision making, around family planning, or is it too broad?
Gail Alvares: No. I mean, I think, it just provides evidence that we should be doing more detailed assessments of ability levels so that the measure we used, for example, in this study was a very broad interview or questionnaire that can be done. It’s a very widely used measure. Other research in our team has shown that really we should be doing more strengths based functional assessments that not only identify the difficulties that someone has, but, also, what are their relative strengths?
How can we then help design supports, and strategies, that help highlight those strengths, while also providing supports for those things that somebody might find challenging? So, this is one study of a range of studies we’ve been using from this registry. All of them really imply that we should be doing really detailed functional assessments for individuals, at diagnosis. So it’s not as important what criteria someone meets, to meet a diagnosis, but, actually, what are the challenges that they’re exhibiting, and how can we provide them best supports to help them achieve their potential?
Interviewer: That’s very interesting. And are you planning any follow up research to the birth order study?
Gail Alvares: Yeah, absolutely. So while this was an amazing, and very large, resource, we were limited in the types of information we had available based on what was collected using this registry. And, in parallel work, I’ve been really heavily involved in a very large biobank that we’ve established. So we’ve called this the Australian Autism Biobank. And this is a really large study of children on the autism spectrum and their families. And, within that study, we’ve done very detailed, clinical, interviews, and assessments, alongside also recruiting siblings not on the autism spectrum.
So we have, sort of, data from more than 1100 children on the spectrum, plus siblings, and children from the general population. So, from this resource, we might be able to, actually, follow up this study, and look, and see, if there are any further associations, or more nuanced effects of birth order, on clinical phenotypes, in kids on the autism spectrum.
Interviewer: In other research, you’ve looked at novel treatments, including, investigating the effects of intranasal oxytocin to treat social impairments in psychiatric disorders, including youth with autism. Can you tell us more about this work?
Gail Alvares: Yeah, absolutely. So this is, sort of, the area of research in which I, sort of, cut my teeth on, when I first started working in research. And it’s really around the potential effects of oxytocin in modulating human social behavior. So, I mean, oxytocin is something that, I think, probably, a lot of people have heard of, or, at least, anecdotally, might have heard about it, mainly because it’s the hormone that’s responsible for contractions during childbirth. And it’s also responsible for lactation, so the milk reflex when you’re breastfeeding.
And, because of this, it was actually developed, synthetically, as a compound, to assist with lactation for people who were struggling with that. So we know there’s actually decades of research that we know that giving this synthetic oxytocin is actually quite safe. And, in parallel, there was all this really interesting animal work that was happening, showing that oxytocin wasn’t just the hormone responsible for these physiological functions. It actually seemed to have a really important role in attachment, and social behaviours, specifically things like mother infant bonding, or pair bonding, or sexual attraction. And, also, how we understand, and interpret, social behaviours, so something called social cognition in humans.
So there was a series of studies in, sort of, the early 2000s that, sort of, indicated that oxytocin, when given to healthy volunteers, seemed to modulate, or change, aspects of social behaviour. So the lab that I did my PhD in was one of the first groups in the world to really then make the next link to go “Well, then, potentially, would this represent a novel treatment for people who have symptoms, or conditions, that have characteristics, social difficulties, as part of their phenotype?”
And so, in our group, we were embarking across a range of different clinical trials, both in very acute short term administration, and then longer repeat administration, to see whether oxytocin could increase, or change, or improve aspects of social cognition, and social behaviour, in a range of conditions like schizophrenia and autism. I was involved in coordinating an autism clinical trial, so, for adolescents with a diagnosis of autism. And we were also doing some studies in younger children, so, sort of, more preschool age children.
The summary of that evidence seems to indicate that it’s really complicated, or it’s quite mixed. So some of the clinical trials have shown some really interesting positive benefits in administration of oxytocin, in changing parent ratings of social behaviours in children on the autism spectrum. But then the trial that I was involved in showed a very, very, strong placebo effect. So parents who thought their child had been receiving oxytocin, in a double blind study, were actually the ones who were reporting the most significant benefits in the trials.
So it seems to be, you know, a bit of a complicated story. I mean this research is still very much underway, and there definitely seems to be much more nuanced studies coming out that are showing complicated effects of how it may be working. But it’s still a fascinating area, and there’s still lots, and lots, of trials still underway at the moment.
Interviewer: Yes, it’s really fascinating. Are you involved with any other novel treatments, or research, or novel approaches to assessment?
Gail Alvares: Yeah. So a few years ago, I was working with some colleagues at the University of Western Australia, and we actually developed a game as a potential novel approach for targeting social attention difficulties for children on the autism spectrum. So we started with the premise that some children with autism have difficulties attending to social information, so particularly faces. And this might underlie why they might find it difficult to understand what other people might be thinking, or feeling. So we wanted just to test a hypothesis whether we could design an interactive game that was interesting to kids on the spectrum, that would actually reinforce paying attention to faces, so these avatars that we had created.
So it was, sort of, an interesting effect that doing this in a really short term, kind of, 15 minute gameplay was enough to modulate eye contact, when we were measuring this through eye tracking, that when we gave the game for kids to play at home, for a week, that it didn’t really seem to do anything. Again, it comes from a…I guess a line of research that I’m interested in is around what are the mechanisms that we think that contribute to difficulties for children on the autism spectrum, then can we target, or design, interventions that might then address those mechanisms?
Interviewer: What other research areas are coming up for you?
Gail Alvares: Well, so I’ve just been awarded a grant to work on an anxiety type intervention for very young children, on the autism spectrum. Again, this is, sort of, a very mechanistic study, but it works on the premise that we know that for many young children, or children on the autism spectrum, they have difficulties with tolerating uncertainty. Certainty is something that I think everyone has had to learn how to deal with, in the last 12 months. Absolutely, the unknown, and uncertain, environments, that we’re all having to live through, at the moment.
And, for some individuals, not just individuals on the spectrum, uncertainty is a really challenging thing to deal with. And it’s, kind of, a mechanism called intolerance of uncertainty. So, where uncertainty can be perceived as very stressful and causes quite significant distress and worry. And we think that for individuals on the spectrum, that this intolerance of uncertainty is actually one of the key mechanisms that lead to anxiety, later in life. We know that individuals on the spectrum have incredibly high rates of mental health conditions, across their lifetime.
So the premise of this new grant that I’m working on is whether we can evaluate therapy that might help to tackle this mechanism really early. So we’re looking at really young kids aged four to seven who are starting to show these symptoms, they’re just emerging, they’re not quite at clinically significant levels yet, but they are causing concern, or distress. And instead of working with children, the novel aspect of this therapy is that it’s parent mediated, which means we actually work with parents, not with children.
And we empower parents to learn strategies to help support their child so that when they are faced with uncertain environmental situations, they can help manage, and support, that child to help deal with that anxiety. And the premise of this intervention is actually about working with children early in development so that we may be able to help not just reduce their anxiety symptoms, or worries, now, but, actually, potentially, prevent later disability, later in life, by helping not just support them now, but, also, empower their parents to help support them, over the course of their childhood.
Interviewer: Any interim findings, or is it too early?
Gail Alvares: Oh, we’ve just started, so we just…so, literally, started this week. But the research is actually based on a therapy that was actually developed in the UK by our collaborators at the University of Newcastle. So this intervention does have preliminary evidence for children on the spectrum, age six, and above, and in adolescence, and some emerging evidence in young adults. But this is the first time that we’re actually developing it for a really younger age of children, and really focusing on how do we empower, and support, parents at this really early developmental stage to then support the later development.So there’s some really good, strong, emerging evidence, that this might, actually, be really beneficial in not just supporting intolerance of uncertainty in children, but, also, in parents. Because we also know that parents struggle with this as well. And so we might be able to have a sort of a bidirectional effect in supporting both parents, and children’s, mental health.
Interviewer: That’s excellent. Gail, we’ve talked about your research, which you carry out as part of CliniKids, which is Telethon Kids Institute’s first team investigating world class research, with clinical services. How do you, and the team, go about translating your findings into practice?
Gail Alvares: So CliniKids is, actually, a really new model for our institute. And it really came about because the head of our research group, Professor Andrew Whitehouse, you know, a couple of years ago, we were, sort of, talking about how we were doing all this really great clinical research, but that there was this really well known, and substantial, gap between publishing research data, and disseminating it. And when it, actually, gets into actual real clinical practice for benefitting families, and children, which is what we are doing this research for.
You know, this really large gap was just not good enough. Because, of course, we work with children and, by that point, those children are already adults. And it’s just not good enough for us to be developing these new therapies, talking about them to families, and then not be able to offer them. So we decided to, I guess, involve our research group to not just be a clinical research group, but to, actually, develop a clinic, where we could offer these new evidence based interventions, to our clinical community, here in Perth, but, really importantly, to train clinicians both here in Perth and nationally.
So we do our training over Zoom, as well, so that families are able to benefit from evidence based interventions, as soon as we have evidence that they are going to be effective for some children. So the other part of our model is, as we’re discovering new evidence, or we’re investigating new projects, we are able to offer it to our families coming through our clinics as part of their routine clinical care. So when families come through, who are presenting with different clinical concerns, that we can offer them a range of different clinical trials, for them to be part of, as part of their usual best practice care.
And this is something that’s quite new. I mean, it’s something that you see a lot in clinical research, in other fields of medicine. But it’s something that you don’t really see a lot of in autism or, just generally, in psychological research. And, it’s a shame, because it means that families might be reading about new evidence, or new research, but have no way of accessing it. So we really hope that this model of integrating our research into clinic, and, also, providing a mechanism to train other people, as soon as we know that there’s evidence to support those interventions, will then mean that not just families in our local area can benefit from our research, but everyone who’s able to access that training can then have access to that intervention.
And we know in Australia, in particular, we have huge disparities between access to health care in our regional and remote areas. We’re a huge country. So by designing our clinic to be able to provide training, and clinical services, both through telehealth, and through virtual training, we’re then enabling more families to get access to the most evidence based health care.
Interviewer: Right. That sounds so important. Is it something happening globally, would you say?
Gail Alvares: I mean, we’re certainly seeing more of these research integrated clinics being established, at least in the field of autism, across the world. But these are areas of privilege, or big cities. And part of what we understand, here in Australia, is that there’s huge disparities in access to health care. And so, we hope that this will be a model that people will see and hopefully try and consider how these models could be adapted in other settings around the world. And we also know that the evidence for autism interventions is actually still really early. I mean, we’ve recently published a really big policy document, so, an umbrella review, for our government, around the current state of autism intervention evidence. And, actually, the majority of it is still really, like, early, or mixed, evidence for its actual efficacy, in supporting developmental gains, across a range of different domains like language, and cognitive, and functional. So we need more of these larger integrated research clinics that are collaborative, across a range of cities, to actually push the state of evidence, or the state of science further. Because we’re really at an unacceptable stage.
I mean, the majority of evidence, at this stage, still comes from things like behavioural interventions, like ABA or applied behaviour analysis. And we know that the state of evidence for that is actually quite poor, but it’s the largest body of evidence that we have so far. So we really need more of these types of clinics to start evaluating with some science and a higher level of evidence.
Interviewer: Right. So it’s not just about clinical translation, it’s also about influencing policy and change?
Gail Alvares: Yeah, absolutely. I mean, there’s…part of our research group is not just thinking about how we influence clinical practice, but it’s really important about advocating for policy change of our government. So we have very strong links with national disability provider, in our government, here in Australia. But it’s around trying to change how disability services are funded, and supported, because we need to tackle service delivery, and improvement, across multiple different areas. So, not just at our local level, but at a government level, and at national, international, level.
Interviewer: Are you optimistic that that type of change will happen?
Gail Alvares: So I’ve been here in Perth now for six years. This change that I’ve witnessed in the field has been staggering, like, we’re exponentially increasing the numbers of trials that people are proposing, and working on. The quality of those trials are getting better. We’re definitely making huge progress. It doesn’t mean that there isn’t still enormous room for improvement, in our field. But the last decade has witnessed a really transformative shift in the way that we conduct science, in this field.
Interviewer: That’s great to hear. Gail, is there anything else, in the pipeline, that you’d like to mention?
Gail Alvares: I guess the only other thing that we’re really committed to, in our research group, is dissemination to the community. Because, too often, I guess, our research sits within the scientific domain. And we have a really core mission around dissemination, really short videos, which we call second science. And so there are videos that we do where we try and explain a recent autism paper that either we published, or, mostly, it’s other people’s work, and explain that in language that we think that the autism community can understand, and that can ask questions, or provide feedback of studies that they wish us to review, and provide feedback on.
So if anyone’s really interested in the research that we do, or interested in understanding more about autism science, I’d encourage them to, kind of, find those videos by looking up, Telethon Kids Autism Research on YouTube, or Facebook. The best way to find it is through Facebook. So we’re called CliniKids Autism Research, and we also have a Twitter handle, which is CliniKids AU.
Interviewer: Finally, what is your takeaway message, for those listening to our conversation?
Gail Alvares: So my takeaway message from this research that we started talking about at the beginning of this conversation is around birth order, and family size, and that these are, you know, one of many different factors that can contribute to the enormous variability in clinical presentations, for children on the autism spectrum. And so, this research doesn’t tell us anything about, I guess, the individual, in a family, but it does provide clues at a population, or general, level about one potential mechanism that might underlie these differences.
And, again, it really underscores the importance of us understanding the functional abilities that individuals can present with so that we can provide them the appropriate supports that they need, to achieve their potential.
Interviewer: And that was published in the JCPP in November 2020, wasn’t it?
Gail Alvares: That’s right.
Interviewer: Gail, thank you ever so much. For more details on Dr. Gail Lavares, please visit the ACAMH website, www.acamh.org and Twitter at ACAMH. ACAMH is spelt ACAMH. And don’t forget to follow us on iTunes, or your preferred streaming platform, let us know if you enjoyed the podcast with a rating, or review, and do share with friends, and colleagues.