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My guest today is Dr. Kristen Lyall.

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Dr. Kristen Lyall is an associate professor in the Modifiable Risk Factors Program at

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the A.J. Drexel Autism Institute at Drexel University.

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She earned her doctorate in epidemiology from the Harvard School of Public Health, followed

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by postdoctoral training at the UC Davis Mind Institute.

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Subsequently, she served as a research scientist in the Environmental Health Investigations

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Branch of the California Department of Public Health.

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Her research is dedicated to exploring the modifiable factors that influence autism development.

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Dr. Lyall's work focuses on understanding how parental factors, prenatal exposure to

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environmental chemicals and maternal dietary elements interact and correlate with autism

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and other neurodevelopmental outcomes.

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She also employs continuous quantitative measures to explore traits related to neurodevelopmental

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diagnosis.

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Offering a nuanced view of the autism phenotype.

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Dr. Lyall plays a pivotal role in leading and participating in large-scale collaborative

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epidemiological studies.

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These studies aim to uncover insights into autism and various child health outcomes, leveraging

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her expertise to shape the field's understanding and approach to these conditions.

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With specialties in psychiatric, reproductive, and nutritional epidemiology, her research

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delves into broad spectrum of risk factors for autism, including exposure to air pollution,

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maternal prenatal, hormone, and protein levels, gestational diabetes, infertility treatments,

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and maternal, autoimmune, or other medical conditions.

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And now, my conversation with Dr. Kristen Lyall.

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Dr. Lyall, I would just love to understand about your medical journey or your education

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journey, and could you take me through that and just touch on the different stops you

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had and different interests?

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Sure.

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Well, first, I'll also start off by saying thank you for inviting me to your podcast.

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So yeah, I did my undergraduate degree at Middlebury College up in Vermont, and new going

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in, I was interested in science and really started out as a biology major.

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I was very interested in human genetics and kind of patterns of genetics, I guess, but

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wasn't someone that necessarily wanted to be in the lab.

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And then in the latter years of my undergraduate, I got really interested in psychology.

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And I also started working as a part-time job, as a behavioral aid for a family who had

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a child with autism.

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And that was really my introduction to autism and getting to know that family, and also

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the counselor who worked with that family.

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And then after school, I worked for several years as a research assistant at Massive Chuset's

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General Hospital in a very research active group with great people.

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And I think that's kind of a theme across my career is just getting to work with wonderful

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people.

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And again, got the opportunity to learn more about autism and to directly work with families.

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And I was administering various different assessments and tests.

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And so that was really interesting.

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And it also was my first introduction to epidemiology.

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So I had never even, I don't know that I'd heard the word epidemiology until my experience

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in that research group where one of the investigators was an epidemiologist.

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And the more that I learned about that field, the more it really kind of spoke to me and

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seemed like it could be a fit for my interests and kind of bringing together the different

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substantive areas that I was interested in, but applying the methods and the research

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design and the statistics.

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And so that was when I applied to a couple of epidemiology programs to get a doctorate

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or PhD and ended up going to Harvard School of Public Health.

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And there I got really interested in.

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So I was in the psychiatric epidemiology track.

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I also got interested in there are all these other subfields of epidemiology.

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It's not just infectious diseases.

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It's not just cancer epidemiology.

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And it's really kind of using those methods to study a whole range of different things

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from a kind of population perspective.

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And so I got interested in nutrition as well there.

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And then following my time in graduate school, I did a postdoc at UC Davis Mine Institute.

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And by that time, I had done quite a bit of work.

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My dissertation was focused on autism.

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Again, working with really great mentors, I was given the opportunity to help kind of

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lead a study while in graduate school.

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And so had learned so much about autism, done a lot of research kind of as a student.

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But the MIND Institute was a really wonderful postdoc experience because it had a much kind

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of broader training across areas that I didn't really previously have training in.

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So things like immunology, neurology, neuroimaging, all these other aspects, and then also the

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clinical exposure because I wasn't trained in kind of clinical assessments.

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I'd done some different measures, but hadn't been trained in diagnosing autism.

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And so there was really that kind of well-rounded training.

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And then from there, actually went to work as an epidemiologist at the California Department

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of Public Health, again, working with great people in an environmental group.

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And then after about a year there, I switched to my current role, which is at the A.J.

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Drexel Autism Institute of Drexel University.

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And I'm currently an associate professor.

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And I've been at Drexel for about eight years now.

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Yeah.

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What took you to Drexel?

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Well, it was wonderful living in California, I will say that.

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But most of my family is on the East Coast.

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And then I was also, so there was the family and the personal component, but there were

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really great people at the Autism Institute at Drexel.

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And I was really excited about the opportunity to work with them.

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And I think also I've kind of always been drawn to the academic environment where you're

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doing the research, but you also get to work with students and mentor students.

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And so those were some big reasons, but it definitely wasn't easy to leave California.

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Yeah.

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Tell me about the role of an epidemiologist with autism, because it doesn't, one, I just

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should say that I love this because it adds a little bit of diversity into the research,

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which I think anytime that happens in science is a huge bonus.

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But it's not something that you often hear about or see.

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Yeah.

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So there are different kind of aspects to epidemiology.

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So one, that I would say plays a big role in autism is kind of the descriptive epidemiology

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side.

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And that might sound kind of very basic.

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We're basically counting numbers, how many people have a given condition.

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And for autism, a huge factor, of course, is that the prevalence has increased so much

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over the past several decades.

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So when I began in the early 2000s, autism was still considered a very rare condition.

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The prevalence had been increasing since about the early 1990s, but was really on a

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very sharp upward trajectory that has continued.

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And epidemiology is the reason why we have those numbers.

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It's the methods that go into the counting and obtaining accurate estimates of autism.

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And so those surveillance efforts are kind of one side of the autism epidemiology piece.

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And of course, when we know that the prevalence has been increasing so much, that can also

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help to stimulate research into kind of what I would consider the other side of epidemiology

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or another portion of it is trying to figure out why a given outcome or condition is occurring.

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Are there people who are more susceptible to given conditions or what are the risk factors

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or contributing causes to a given condition?

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And so that's the other kind of portion of where epidemiology comes in is trying to understand

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causes of a condition, where and why and how it's occurring.

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And the last thing I would say is that, and as you mentioned, science is really better

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when we bring people together from different fields.

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And so while I'm an epidemiologist and I work with a lot of other epidemiologists, I've

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always working also with people from other fields too.

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And I think that's what keeps the work moving forward and helps make sure that, okay, I'm

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not an expert in immunology.

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I've had a little bit of training on it, but I'm going to work with this person over here

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that is an expert so that we can help try and learn more.

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Yeah, that's wonderful.

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In science, we have that silo.

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We often hear about the silo, which is a good thing because for that specific subject, we're

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increasing our knowledge and data set about that.

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But something especially as so broad as autism, it's good to have expanded edges outward and

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upward, I think.

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Yeah, for sure.

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We always try and work in interdisciplinary teams so that we're not looking at things

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from only one perspective.

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Yeah.

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Tell me about modifiable risk factors.

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Sure.

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So, you know, I mentioned having an early interest in human genetics.

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And so we know, of course, autism is something with a very high genetic contribution to it.

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There's a high heritability to autism.

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But we also know that that heritability and genetic background is very complex.

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And I spent some time working in some laboratories and doing some lab work.

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I think learning more about nutrition and environmental chemicals and sort of all these

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things in the environment that we're exposed to, I get really interested in, okay, what

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are the pieces of this puzzle that we have some control over or that can be modified

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or that, you know, shift different aspects of, you know, how outcomes present or co-occurrence

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of outcomes.

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And so I think it's, to some extent, it's that idea of being able to change and modify

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things.

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So, when we talk about modifiable risk factors, I think more on the environmental side, things

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that we have control over to change.

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It doesn't always mean that there are easy changes, you know, when we look at various

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environmental toxicants, oftentimes those require policy and regulation to change.

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So we're not always talking easy modification, but that's kind of one component there to

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thinking about factors that are possible to change.

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And then I'm also growing increasingly interested in kind of interactions across different factors.

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So, you know, are there dietary components that mitigate the effects of some of these

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environmental chemicals that we're exposed to?

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And there is some growing evidence that that's occurring.

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So, you know, maybe we can't really control our air pollution levels, but we can take

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a prenatal vitamin that might help mitigate some of the effects of some of those air pollutants.

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Okay.

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That's something that I'm curious about.

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If whatever it is that we have in our biology that is used to kind of fight off of these

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environmental risk factors.

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Is it that we're declining in our ability to fight off disease or these risk factors?

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Or are they these risk factors just increasing?

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In other words, I guess, is it we're lacking what we used to before the 1930s?

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Or is it just an overwhelming amounts of the environmental risk factors?

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I don't know the answer to that, but it is very fascinating to me.

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Yeah, it is.

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I mean, it's a good question.

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I don't know the answer necessarily, but I do know, you know, there were exposed to

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tens of thousands of chemicals in the environment, many of which are not very well regulated.

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And oftentimes when we do find evidence that a given chemical or class of chemicals does

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have adverse effects on health, you know, not just neurodevelopmental outcomes, but

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kind of broadly hormone disruption and all these other different impacts on health.

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Oftentimes those chemicals are replaced with other chemicals, even if that one class or

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chemical is banned.

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And so this is a situation that's called regrettable substitutions.

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So it's a little bit of an ongoing challenge in trying to make sure that, you know, all

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the different things that we are exposed to in our environment are actually safe for health

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and regulated.

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Yeah.

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But for sure, you know, the number of things that we've been exposed to in our environment

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with increasing industrialization, use of plastics has certainly increased exposures

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that have the potential to adversely impact health.

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Yeah.

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That's exactly what I was wondering or think about is the industrialization because it

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fits the timelines.

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And I mean, everything about it just makes sense.

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But I don't have data on it.

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But there are some things that you mentioned that I've already listed out for some questions.

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And I would, one of them, the most pressing one is since you mentioned diet, but maybe

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other prenatal vitamins and such, are there certain diets that can mitigate the risk of

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autism?

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I guess what I'm trying to say is or ask is, is there like an approach or preparation

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that families can take to kind of reduce the risk going into pregnancy?

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Yeah.

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So that's a really good question.

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I think my first response is to remember how complex autism is.

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And so I always get a little bit worried when we focus on one risk factor in trying to pitch

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it as something that is going to be the one factor that is going to be going to reduce

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risk for a given individual.

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But that said, there are over a dozen studies, at least now, that have found an inverse association

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between taking a prenatal folic acid supplement, a prenatal vitamin that is rich in folic

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acid, especially in that early part of pregnancy.

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There are a number of studies that have examined other dietary factors.

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And you mentioned a specific diet, right?

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And so that brings to my mind what we call dietary patterns.

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So these are routine ways of eating across a whole series of foods and nutrients.

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And so there have been a handful of studies that have looked at these kind of broader

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patterns of eating during pregnancy.

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And we haven't really found very strong associations there.

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We've done a couple of studies where we've looked at specific foods and in particular

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fish intake.

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Now fish are interesting because they're the primary source of polyunsaturated fatty acids.

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And there's a particular PUFA or polyunsaturated fatty acid that is of real interest for brain

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development and that's DHA.

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It's the most abundant fatty acid, omega-3 fatty acid in the brain.

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And it's really important in all of these ongoing neurodevelopmental processes that are occurring

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while the baby is growing inside the womb.

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And so we found in a couple studies that the more fish you eat or that eating fish at all

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in pregnancy has been associated with a reduced risk or likelihood of having a child with

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autism.

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That's not to say that's the only factor that's important.

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But it could be one contributing cause in some cases.

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So fish in pregnancy and reducing odds.

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And that may be because that fish is a good source of these brain healthy facts.

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The other thing, I guess I should take a step back and mention because I've been talking

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about mom diet or prenatal diet during pregnancy.

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And the reason why I've been talking more about the prenatal or pregnancy period is

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because we know one that's a really critical sensitive time period of the baby's development.

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It's also when the brain structures and early neurodevelopment is being set up.

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And then lastly, when we look to our experts in other fields, we've seen evidence that

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that's when some of the pathways to develop autism really begin early in gestation or

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during gestation.

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And that's not to say that autism can be diagnosed prenatally or at birth.

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But it's to say that some of the differences that we see in the brain are beginning during

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pregnancy.

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And so when we think about likelihood of developing autism, we're all often studying prenatal

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factors.

241
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And that's not at all to suggest that what happens after pregnancy doesn't matter for

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child development.

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It very much does.

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There's a ton of great research to show that early interventions really make huge impacts

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on children and their outcomes.

246
00:22:04,500 --> 00:22:09,740
But often when we're talking about risk factors or factors that are involved in etiology,

247
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we tend to be focusing on the very early periods of gestation.

248
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Okay.

249
00:22:15,100 --> 00:22:22,780
It's a very, it's a big region of interest, especially for my curiosity is that that time

250
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frame that you just described there.

251
00:22:26,380 --> 00:22:27,380
Yeah.

252
00:22:27,380 --> 00:22:36,500
Tell me a little bit about and correct me, as I say this about some of those, I don't

253
00:22:36,500 --> 00:22:43,460
want to call them biomarkers, but I'm going to have to about how you kind of quantify

254
00:22:43,460 --> 00:22:50,220
these and kind of establish the risk about each one.

255
00:22:50,220 --> 00:22:51,220
Sure.

256
00:22:51,220 --> 00:22:59,860
So I'll follow through with kind of the fish example as one exposure of interest.

257
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And so when we're doing these studies, there's lots of different ways that you can try and

258
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you know, say, is this exposure associated with autism?

259
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So we could collect a sample of families who have a child with autism and then try and

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collect a sample of comparison families who have a child who does not have a diagnosis

261
00:23:24,980 --> 00:23:29,900
of autism and then say, what did you eat during pregnancy?

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And that was, you know, five years ago.

263
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And then we could compare.

264
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That's called the case control study.

265
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And there's some concerns with, you know, one remembering back, well, what did I eat

266
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during pregnancy?

267
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Or what were the different things that I was exposed to?

268
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That's not to say that that study design isn't useful for some questions.

269
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But that's a concern with that.

270
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So another type of study design is enrolling women when they're pregnant and asking them

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about, okay, what are you eating in pregnancy?

272
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What products are you using?

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And collecting biospecimens from them.

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So can you give us a urine sample?

275
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Can you give us a blood sample?

276
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And then waiting over time to see how their child develops.

277
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And that's called a cohort study.

278
00:24:25,620 --> 00:24:32,620
And so that they introduced a couple of different study designs, but also to kind of note that

279
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there are, in addition to different ways we can collect information from people and group

280
00:24:37,500 --> 00:24:43,620
people, there are different ways that we can get information about exposure histories.

281
00:24:43,620 --> 00:24:51,300
And so when we collect urine samples or blood samples, we can measure all sorts of things

282
00:24:51,300 --> 00:24:55,780
in these biospecimens or samples that are provided.

283
00:24:55,780 --> 00:25:01,540
And so again, to get back to fish so we can collect those, those questionnaires asking

284
00:25:01,540 --> 00:25:08,580
about dietary intake, we can also measure those fats that I mentioned, the omega-3 fatty

285
00:25:08,580 --> 00:25:11,700
acids in people's blood.

286
00:25:11,700 --> 00:25:17,340
And that is another way that we can say, oh, well, this person has really high DHA levels

287
00:25:17,340 --> 00:25:18,820
in their blood.

288
00:25:18,820 --> 00:25:23,820
How does that relate to these outcomes of the child?

289
00:25:23,820 --> 00:25:32,100
And it's a nice, subjective way to compare to the reported data and get an actual biological

290
00:25:32,100 --> 00:25:40,500
assessment that is associated or not with the outcome that we're studying of interest.

291
00:25:40,500 --> 00:25:47,100
And so we've done some studies where we've measured these different fats in samples collected

292
00:25:47,100 --> 00:25:56,420
from moms and also from newborn heel sticks and measured these fats in the blood spots

293
00:25:56,420 --> 00:26:04,980
that are collected routinely from babies for neonatal screening processes and tried to see

294
00:26:04,980 --> 00:26:11,340
are these different levels of these fatty acids associated with autism.

295
00:26:11,340 --> 00:26:18,060
And like for most things with neurodevelopment, the answer is a little complicated.

296
00:26:18,060 --> 00:26:25,660
We haven't seen very clear patterns of associations, but we did find some evidence that, well,

297
00:26:25,660 --> 00:26:33,100
maybe there are certain levels that are associated, maybe very low levels are associated with

298
00:26:33,100 --> 00:26:40,380
a certain subtype of autism with co-occurring intellectual disability, but that's a sort

299
00:26:40,380 --> 00:26:44,820
of preliminary finding that needs a follow up.

300
00:26:44,820 --> 00:26:51,420
But those biomarkers can be really useful in different research studies that we're doing

301
00:26:51,420 --> 00:26:55,780
to try and get that objective measure of exposure.

302
00:26:55,780 --> 00:26:56,780
Okay.

303
00:26:56,780 --> 00:27:00,820
It's like whenever I hear you describe that.

304
00:27:00,820 --> 00:27:07,740
It's like putting, I don't want to say percentages, but I'm going to have to, I think, just because

305
00:27:07,740 --> 00:27:13,780
my inability to really explain what I'm thinking, but like certain percentages of risk associated

306
00:27:13,780 --> 00:27:19,900
with this item or in a combination of these items, is that accurate?

307
00:27:19,900 --> 00:27:20,900
Yes.

308
00:27:20,900 --> 00:27:21,900
Yeah.

309
00:27:21,900 --> 00:27:25,300
And actually, I would say that's a pretty good summary.

310
00:27:25,300 --> 00:27:34,540
So we have different ways of trying to assign risk associated with a given factor that we're

311
00:27:34,540 --> 00:27:35,540
studying.

312
00:27:35,540 --> 00:27:40,220
So one way we can think about it is attributable risk.

313
00:27:40,220 --> 00:27:48,020
So what are the, if we've removed this risk factor from the population, what would be

314
00:27:48,020 --> 00:27:53,060
the corresponding reduction in cases associated with that?

315
00:27:53,060 --> 00:27:59,380
And there are a lot of assumptions that go along with making those, determining those

316
00:27:59,380 --> 00:28:00,380
statistics.

317
00:28:00,380 --> 00:28:09,900
But essentially, yes, you're trying to determine, okay, like how much of the case load is this

318
00:28:09,900 --> 00:28:13,180
one factor contributing?

319
00:28:13,180 --> 00:28:19,700
Is this factor contributing to the rise in autism prevalence?

320
00:28:19,700 --> 00:28:23,940
And so those are different things that we try and tease out.

321
00:28:23,940 --> 00:28:30,180
And when we're doing these estimates and trying to look for associations between one factor,

322
00:28:30,180 --> 00:28:33,620
so I mentioned, we know it's never just one factor, right?

323
00:28:33,620 --> 00:28:35,340
Autism is so complex.

324
00:28:35,340 --> 00:28:43,940
And in addition to having multiple causes or risk factors within any one individual, it's

325
00:28:43,940 --> 00:28:52,260
also highly likely that we have different kind of sets of factors, so different combinations

326
00:28:52,260 --> 00:28:58,380
of factors going in to different cases.

327
00:28:58,380 --> 00:29:05,940
But when we're looking at any one individual factor at a time, we also try and say, okay,

328
00:29:05,940 --> 00:29:13,420
well, what else do I need to account for when I'm looking at this association and this outcome?

329
00:29:13,420 --> 00:29:22,700
Even if it's like a so-called weak association, if you have multiple weak associations, it

330
00:29:22,700 --> 00:29:30,140
kind of like builds up and strengthens the ability to maybe have actionable steps into

331
00:29:30,140 --> 00:29:31,740
reducing the risk.

332
00:29:31,740 --> 00:29:32,740
Yeah.

333
00:29:32,740 --> 00:29:41,140
So what you mentioned is kind of thinking about the multiple hits or combinations of

334
00:29:41,140 --> 00:29:42,140
risk factors.

335
00:29:42,140 --> 00:29:51,420
So we can think about, are there two risk factors that act on the same pathway that then increase

336
00:29:51,420 --> 00:29:53,780
susceptibility to this outcome?

337
00:29:53,780 --> 00:30:01,660
Or is there one factor that exacerbates the effect of another factor?

338
00:30:01,660 --> 00:30:03,180
I like to think about factor.

339
00:30:03,180 --> 00:30:09,900
What are other factors that mitigate the effects of risk factors?

340
00:30:09,900 --> 00:30:21,020
And so we're trying, more people now that we have more large-scale studies and databases

341
00:30:21,020 --> 00:30:27,740
with autism information, I think we're kind of in the era now where we're going to see

342
00:30:27,740 --> 00:30:33,220
more consideration of combinations of risk factors.

343
00:30:33,220 --> 00:30:40,460
In the past, we've been kind of limited by smaller sample sizes often, not always, but

344
00:30:40,460 --> 00:30:46,220
it can be hard to look at combinations of risk factors together when you have a small

345
00:30:46,220 --> 00:30:50,540
sample because then it gets to statistical power.

346
00:30:50,540 --> 00:30:55,580
And do you have enough people in each category to be able to do what you were talking about?

347
00:30:55,580 --> 00:31:02,020
Like, what's the percentage increase or decrease associated with this factor?

348
00:31:02,020 --> 00:31:09,300
So that's where a lot of these research efforts that are bringing together participants from

349
00:31:09,300 --> 00:31:14,020
all around the country have been really helpful.

350
00:31:14,020 --> 00:31:19,300
So I'm involved, for example, in one study that's a national consortium.

351
00:31:19,300 --> 00:31:25,780
It's called the Environmental Influences on Child Health Outcomes or ECHO study program.

352
00:31:25,780 --> 00:31:33,540
And it has brought together existing studies across the country and it has pooled data

353
00:31:33,540 --> 00:31:38,260
and is now collecting new data all under the same common measure.

354
00:31:38,260 --> 00:31:45,740
But what that has done has been, it's allowed us to have much larger sample sizes than have

355
00:31:45,740 --> 00:31:52,780
typically been seen in any one study of autism.

356
00:31:52,780 --> 00:31:57,340
It's like you're evolving a biomarker, in my opinion.

357
00:31:57,340 --> 00:32:05,020
We can take a biomarker from a test, lab test, whatever, however the method, but you're

358
00:32:05,020 --> 00:32:15,100
evolving it and a little bit of making it a step farther in for understanding, I think.

359
00:32:15,100 --> 00:32:16,820
And I just love that so much.

360
00:32:16,820 --> 00:32:27,820
And I hope more will get on to this because I think this is a very promising outcomes.

361
00:32:27,820 --> 00:32:29,300
It seems to me.

362
00:32:29,300 --> 00:32:37,900
I was reviewing your paper, I just love this paper, annual reviews of public health where

363
00:32:37,900 --> 00:32:43,460
there's many items listed and parsed out.

364
00:32:43,460 --> 00:32:52,340
Can you tell me a little bit about, maybe I'll start with immune factors or hormone and protein

365
00:32:52,340 --> 00:32:53,340
factors?

366
00:32:53,340 --> 00:32:54,340
Sure.

367
00:32:54,340 --> 00:33:02,060
Well, so I should note that as with all work I do, that paper was definitely a team effort.

368
00:33:02,060 --> 00:33:07,420
And I've mentioned how grateful I am to all the mentors I've had, but also to all the

369
00:33:07,420 --> 00:33:09,820
collaborators that I get to work with.

370
00:33:09,820 --> 00:33:14,860
And these are people who are experts in their own fields.

371
00:33:14,860 --> 00:33:24,420
And so the immune piece of autism and immunology in itself is very interesting.

372
00:33:24,420 --> 00:33:31,420
And so one thing that I've learned a lot along the way is actually during gestation,

373
00:33:31,420 --> 00:33:38,940
the immune system really has a lot of cross talk with neurodevelopment, which is something

374
00:33:38,940 --> 00:33:42,220
that I didn't know before I was a postdoc.

375
00:33:42,220 --> 00:33:49,980
And so there have been a lot of studies that have shown various maternal immune activation

376
00:33:49,980 --> 00:33:50,980
factors.

377
00:33:50,980 --> 00:34:00,820
So autoimmune diseases, fever during pregnancy, infection during pregnancy, and related those

378
00:34:00,820 --> 00:34:07,140
different factors to an increased risk of autism or likelihood of the child developing

379
00:34:07,140 --> 00:34:09,060
autism.

380
00:34:09,060 --> 00:34:16,100
There have also been some studies that have made use of biomarkers and looked at patterns

381
00:34:16,100 --> 00:34:23,460
of cytokines or pro-inflammatory markers and different immune markers and found some

382
00:34:23,460 --> 00:34:25,260
specific associations.

383
00:34:25,260 --> 00:34:33,660
And I've been lucky to get to work with some colleagues in California who've led a population

384
00:34:33,660 --> 00:34:40,180
based case control study that have really focused on a lot of immune markers and autism

385
00:34:40,180 --> 00:34:45,980
and learned a lot about how those relate to autism.

386
00:34:45,980 --> 00:34:50,340
And one interesting finding there is that there did seem to be kind of a general pattern

387
00:34:50,340 --> 00:34:55,540
of associations with some of these immune markers, specifically for autism with co-occurring

388
00:34:55,540 --> 00:34:58,220
intellectual disability.

389
00:34:58,220 --> 00:35:06,300
And I think that's sort of an example of we know how complex and diverse autism is.

390
00:35:06,300 --> 00:35:15,540
We have this one diagnostic label for what really represents a very broad phenotype and

391
00:35:15,540 --> 00:35:20,940
diversity of strengths and challenges.

392
00:35:20,940 --> 00:35:28,420
And I think it is interesting when we can pull apart factors that might put a child

393
00:35:28,420 --> 00:35:38,340
or an individual on a pathway to one kind of subgroup of that broader category because

394
00:35:38,340 --> 00:35:45,820
it helps us learn a little bit more about kind of the underlying biological pathways.

395
00:35:45,820 --> 00:35:51,740
Another thing you mentioned, so hormone influences in autism.

396
00:35:51,740 --> 00:35:55,580
And so there's been a lot of interest in thyroid hormones.

397
00:35:55,580 --> 00:36:00,620
So we know thyroid hormones are so important in neurodevelopment.

398
00:36:00,620 --> 00:36:06,940
All babies are screened and moms during pregnancy for their thyroid hormone levels.

399
00:36:06,940 --> 00:36:13,060
And so there have been a number of studies that have looked at both mom thyroid hormone

400
00:36:13,060 --> 00:36:17,580
levels and there are a couple different ones that are measured during pregnancy as well

401
00:36:17,580 --> 00:36:25,060
as baby in those newborn heel stick and other biospecimens and examined associations with

402
00:36:25,060 --> 00:36:26,940
those.

403
00:36:26,940 --> 00:36:31,660
And the results have been a little bit inconsistent.

404
00:36:31,660 --> 00:36:36,860
So I don't think we have necessarily a clear picture there.

405
00:36:36,860 --> 00:36:44,660
But I have a student who is using some different statistical methodologies and there seem to

406
00:36:44,660 --> 00:36:50,900
be some differences kind of across levels of autism traits.

407
00:36:50,900 --> 00:36:58,180
So it may be important to consider again kind of what are those subgroups or sub phenotypes

408
00:36:58,180 --> 00:36:59,460
within autism.

409
00:36:59,460 --> 00:37:11,180
Do we get a clearer picture of how this biomarker, this exposure might be related to this outcome?

410
00:37:11,180 --> 00:37:14,580
Thyroid is a region of interest.

411
00:37:14,580 --> 00:37:17,860
And you're right, it is across data.

412
00:37:17,860 --> 00:37:18,860
Yeah.

413
00:37:18,860 --> 00:37:26,460
And that's been one reason why there's a lot of interest in a class of chemicals called

414
00:37:26,460 --> 00:37:28,740
endocrine disrupting chemicals.

415
00:37:28,740 --> 00:37:36,220
And these are EDCs because we know that they, as the name implies, disrupt hormone levels.

416
00:37:36,220 --> 00:37:42,060
And so there's been a lot of interest in those chemicals and whether they relate to autism

417
00:37:42,060 --> 00:37:51,700
specifically and also neurodevelopment more broadly and evidence that these are important

418
00:37:51,700 --> 00:37:55,060
chemicals to be considering and regulating.

419
00:37:55,060 --> 00:37:58,060
Yeah.

420
00:37:58,060 --> 00:38:07,700
The tyrosine, synthesizing it from tyrosine is a very fascinating story, I think, because

421
00:38:07,700 --> 00:38:09,420
it's an aromatic amino acid.

422
00:38:09,420 --> 00:38:14,380
It's a very strange or rare special type of amino acid.

423
00:38:14,380 --> 00:38:18,740
And yeah, there's only three of them.

424
00:38:18,740 --> 00:38:22,980
And how they're synthesized is very unique.

425
00:38:22,980 --> 00:38:29,660
And we can see that there's a lot of people that's on thyroid medicine now that have disrupted

426
00:38:29,660 --> 00:38:37,700
thyroid, which is very problematic and goes back to the environmental risk factors that

427
00:38:37,700 --> 00:38:38,700
we're talking about.

428
00:38:38,700 --> 00:38:45,900
It's very much in line with this modern life, I think.

429
00:38:45,900 --> 00:38:50,860
Something I was wanting to talk to you about is you mentioned something as simple as a

430
00:38:50,860 --> 00:39:00,100
fever or something that's really even acute within pregnancy might increase the risk of

431
00:39:00,100 --> 00:39:06,660
this neurodevelopment at this time frame that really disrupts the progression or the process

432
00:39:06,660 --> 00:39:11,100
of the neurodevelopment, being a typical development.

433
00:39:11,100 --> 00:39:19,660
Is something so brief like that known to play a factor in maybe this child will now develop

434
00:39:19,660 --> 00:39:20,660
autism?

435
00:39:20,660 --> 00:39:23,380
Yeah, so it's a great question.

436
00:39:23,380 --> 00:39:25,780
I think there are a couple of different threads in there.

437
00:39:25,780 --> 00:39:30,980
And so one is the piece of critical windows.

438
00:39:30,980 --> 00:39:33,780
When is this specific factor happening?

439
00:39:33,780 --> 00:39:41,380
And can something so acute actually have such a big impact on development?

440
00:39:41,380 --> 00:39:47,620
And so we take, for example, folic acid and neural tube defects.

441
00:39:47,620 --> 00:39:55,820
So if you're really low deficient in folic acid, if that's occurring in what we call

442
00:39:55,820 --> 00:40:03,060
the periconceptional window when the neural tube is forming, then the baby can end up

443
00:40:03,060 --> 00:40:07,980
with these neural tube defects, which are catastrophic.

444
00:40:07,980 --> 00:40:14,420
And so that's the reason why we fortify and we recommend folic acid supplementation in

445
00:40:14,420 --> 00:40:17,060
the early part of pregnancy.

446
00:40:17,060 --> 00:40:19,460
And so that's the critical window aspect.

447
00:40:19,460 --> 00:40:24,380
And so we do have evidence, yes, that certain exposures that timing really matters.

448
00:40:24,380 --> 00:40:25,980
They have a much stronger effect.

449
00:40:25,980 --> 00:40:30,300
And that's because of the neurodevelopmental processes that are happening.

450
00:40:30,300 --> 00:40:37,700
It's lining up the exposure just at the right or wrong window of when these developmental

451
00:40:37,700 --> 00:40:42,340
processes are happening and when they're most susceptible to some sort of environmental

452
00:40:42,340 --> 00:40:43,340
insult.

453
00:40:43,340 --> 00:40:51,780
Now, the other piece can fever once during pregnancy actually cause autism.

454
00:40:51,780 --> 00:40:55,460
And that's kind of a loaded question.

455
00:40:55,460 --> 00:41:01,900
And so I think the other piece that's important to remember there is there's the genetic background.

456
00:41:01,900 --> 00:41:09,180
And so not everyone who gets fever during pregnancy develops a child, their child goes

457
00:41:09,180 --> 00:41:11,620
on to develop autism.

458
00:41:11,620 --> 00:41:16,940
And so we have to remember maybe it's fever combined with something else or maybe it's

459
00:41:16,940 --> 00:41:22,300
fever combined with a genetic background plus three other factors.

460
00:41:22,300 --> 00:41:28,100
And so it's this whole kind of interaction.

461
00:41:28,100 --> 00:41:31,060
And we call them causal pie as an epidemiology.

462
00:41:31,060 --> 00:41:33,740
It's all the different pieces that come together.

463
00:41:33,740 --> 00:41:40,580
But interestingly for both infection and fever, there have been suggestions that when we look

464
00:41:40,580 --> 00:41:45,860
at fever in the, I think it's the third trimester, I might be saying that wrong.

465
00:41:45,860 --> 00:41:49,340
I can't remember it's the first or third.

466
00:41:49,340 --> 00:41:56,100
But there have been stronger signals or evidence for an association and a specific trimester

467
00:41:56,100 --> 00:41:57,100
with those.

468
00:41:57,100 --> 00:42:00,260
So that's kind of another component there.

469
00:42:00,260 --> 00:42:08,260
And then there's also, we have to consider, the mom's health matters too, right?

470
00:42:08,260 --> 00:42:12,660
So mitigating the effects of that fever, it's important to get the fever under control.

471
00:42:12,660 --> 00:42:19,260
So anytime we're looking at a medical condition, of course, you have to consider, you know,

472
00:42:19,260 --> 00:42:21,900
what's the impact on the mom's health too?

473
00:42:21,900 --> 00:42:26,780
And is the mother taking some sort of medication for that condition?

474
00:42:26,780 --> 00:42:36,700
And then we get into questions about, well, is the medication causing any sort of impacts?

475
00:42:36,700 --> 00:42:41,540
And then there's this kind of balancing of risks and benefits.

476
00:42:41,540 --> 00:42:47,940
And I think we're still learning more about, you know, all these different components.

477
00:42:47,940 --> 00:42:53,100
But certainly evidence that when a mother does have a fever, it's important to, you know,

478
00:42:53,100 --> 00:42:54,100
address that.

479
00:42:54,100 --> 00:42:55,100
Wow.

480
00:42:55,100 --> 00:42:57,100
It could be so sensitive.

481
00:42:57,100 --> 00:43:05,660
I had a doctor, a surgeon on from Duke, who's now doing umbilical cord sim cells on autistics.

482
00:43:05,660 --> 00:43:07,460
And he done it on his son.

483
00:43:07,460 --> 00:43:10,940
And his son was almost nonverbal.

484
00:43:10,940 --> 00:43:17,220
And the way he describes it is about two weeks later, two, three weeks later, I mean, now

485
00:43:17,220 --> 00:43:19,940
he's completely, he lives independent.

486
00:43:19,940 --> 00:43:21,580
You know, he has like a girlfriend.

487
00:43:21,580 --> 00:43:23,340
It just like helped him so much.

488
00:43:23,340 --> 00:43:31,580
And I'm thinking as I hear more about this, it's like that umbilical cord is rescuing

489
00:43:31,580 --> 00:43:38,420
whatever insults from the placenta to womb that probably occurred during pregnancy.

490
00:43:38,420 --> 00:43:44,340
I'm not super familiar with that research.

491
00:43:44,340 --> 00:43:47,500
Um, yeah, I mean, it's certainly interesting.

492
00:43:47,500 --> 00:43:52,780
And I know there's a lot of interest in stem cells.

493
00:43:52,780 --> 00:43:58,540
I think for, you know, when we're looking at things in epidemiology studies, we're trying

494
00:43:58,540 --> 00:44:01,860
to get those population level effects.

495
00:44:01,860 --> 00:44:07,580
So, rather than, you know, is this something that has impacted one person?

496
00:44:07,580 --> 00:44:16,100
It's more looking at large groups of people and trying to glean and determine what at

497
00:44:16,100 --> 00:44:20,860
the population level are contributors to this outcome.

498
00:44:20,860 --> 00:44:26,420
Yeah, it's like what we mentioned earlier about maybe this thing is weak, but as you

499
00:44:26,420 --> 00:44:36,020
build up, it kind of just strengthens whatever it is, the topic of interest there.

500
00:44:36,020 --> 00:44:37,420
That's incredible.

501
00:44:37,420 --> 00:44:41,020
Air pollution is something that's heavily researched.

502
00:44:41,020 --> 00:44:50,340
There's been an explosion of air pollution studies over the past decade, one to two decades.

503
00:44:50,340 --> 00:44:57,100
I think the first paper looking at air pollution and autism, I think was 2012.

504
00:44:57,100 --> 00:45:00,660
So not that long ago.

505
00:45:00,660 --> 00:45:06,900
And I think, you know, the reason why there's a lot of interest in air pollution is everyone's

506
00:45:06,900 --> 00:45:08,220
exposed to it, right?

507
00:45:08,220 --> 00:45:17,340
So even if the effects are small, you know, or the only impacts for certain individuals,

508
00:45:17,340 --> 00:45:25,980
whatever the case may be, it is this ubiquitous factor that is really everywhere.

509
00:45:25,980 --> 00:45:35,780
And we know that there are certain pollutants in the air that do have impacts on development,

510
00:45:35,780 --> 00:45:43,740
neurodevelopment, all kinds of outcomes, asthma and airways, overall health.

511
00:45:43,740 --> 00:45:50,300
So it's certainly an exposure that people have been paying a lot of attention to.

512
00:45:50,300 --> 00:45:58,460
And I believe there's some emerging and ongoing animal studies that have demonstrated some

513
00:45:58,460 --> 00:46:06,580
biologic pathways that actually help to support the association, things like oxidative stress,

514
00:46:06,580 --> 00:46:07,580
inflammation.

515
00:46:07,580 --> 00:46:08,580
Oxidative stress.

516
00:46:08,580 --> 00:46:09,580
Yeah.

517
00:46:09,580 --> 00:46:14,460
Oxidative stress is definitely a question.

518
00:46:14,460 --> 00:46:18,340
And that's related, of course, also to input.

519
00:46:18,340 --> 00:46:21,940
Those are two kind of interlinked pathways.

520
00:46:21,940 --> 00:46:30,020
And so we did a study actually trying to measure biomarkers of oxidative stress and mothers.

521
00:46:30,020 --> 00:46:34,380
And this was in a relatively small study.

522
00:46:34,380 --> 00:46:42,700
But some colleagues of mine developed this study where families who already had a child

523
00:46:42,700 --> 00:46:50,020
with autism were contacted and asked if they were going to be getting pregnant again.

524
00:46:50,020 --> 00:46:55,620
And so then those families were followed through their next pregnancy to allow for that kind

525
00:46:55,620 --> 00:47:03,460
of cohort model and prospective follow-up from pregnancy through early development.

526
00:47:03,460 --> 00:47:10,300
And just wonderful participation in these studies that really help drive the research.

527
00:47:10,300 --> 00:47:15,100
And the mothers provided biological specimens.

528
00:47:15,100 --> 00:47:20,220
And we've been able to measure all sorts of different things in these samples.

529
00:47:20,220 --> 00:47:28,180
And so we measured isoprostanes and other markers of kind of generalized oxidative stress

530
00:47:28,180 --> 00:47:35,700
to try and see are these biomarkers during pregnancy that are indicators of increased

531
00:47:35,700 --> 00:47:36,900
oxidative stress?

532
00:47:36,900 --> 00:47:42,700
Are they related to later outcomes of autism?

533
00:47:42,700 --> 00:47:54,100
And again, didn't see very strong associations, but some potential kind of signals for different

534
00:47:54,100 --> 00:47:55,180
patterns.

535
00:47:55,180 --> 00:48:01,860
So something that I think could be expanded upon in larger studies and trying to tease

536
00:48:01,860 --> 00:48:10,700
apart, do we see different associations with different subgroups?

537
00:48:10,700 --> 00:48:14,260
What is something recently that you're most excited about?

538
00:48:14,260 --> 00:48:17,180
Well, I'm really excited.

539
00:48:17,180 --> 00:48:21,020
I mentioned the ECHO program, that large consortium.

540
00:48:21,020 --> 00:48:26,980
I'm really excited about getting to participate in that network.

541
00:48:26,980 --> 00:48:34,260
One because it allows for things that we haven't always been able to do yet in autism research

542
00:48:34,260 --> 00:48:40,700
with the larger numbers, at least for the type of work that I do, focus on nutrition

543
00:48:40,700 --> 00:48:43,100
and environmental chemicals.

544
00:48:43,100 --> 00:48:48,820
And then I'm really excited about looking at interactions and thinking about not just

545
00:48:48,820 --> 00:48:56,300
one factor at a time, but can we get a little bit more of a holistic picture about how all

546
00:48:56,300 --> 00:48:59,300
these puzzle pieces fit together?

547
00:48:59,300 --> 00:49:04,540
Not just one at a time, but what's the effect of this one and this one?

548
00:49:04,540 --> 00:49:11,180
Especially if we have some kind of pathway that we think they're both acting on or one

549
00:49:11,180 --> 00:49:17,660
is going to resolve the impacts of this factor on another pathway.

550
00:49:17,660 --> 00:49:25,500
And so we have a study now that is looking at does prenatal diet modify the effects of

551
00:49:25,500 --> 00:49:27,660
air pollution exposure on autism?

552
00:49:27,660 --> 00:49:32,380
And that's a study funded by NIEHS.

553
00:49:32,380 --> 00:49:36,940
And so we're delving into those results now.

554
00:49:36,940 --> 00:49:44,180
But I'm really interested in kind of expanding that line of work and then also trying to

555
00:49:44,180 --> 00:49:48,220
learn more about all the good and bad things in diet.

556
00:49:48,220 --> 00:49:54,260
So we've got these beneficial nutrients, but we also have highly packaged and processed

557
00:49:54,260 --> 00:49:58,420
foods that it can be a source of chemical exposures.

558
00:49:58,420 --> 00:50:05,220
What can we learn about their intake in children and how that's impacting child health?

559
00:50:05,220 --> 00:50:11,700
So I've focused mainly on prenatal diet, but what about the child diet side and how does

560
00:50:11,700 --> 00:50:12,700
that modify?

561
00:50:12,700 --> 00:50:20,300
We know that children with autism and individuals with autism can often have food sensitivities

562
00:50:20,300 --> 00:50:23,900
and highly restricted diets.

563
00:50:23,900 --> 00:50:28,500
And that presents all sorts of challenges in its own right.

564
00:50:28,500 --> 00:50:34,420
I think any parent can tell you that it can be hard to get their kid to eat vegetables

565
00:50:34,420 --> 00:50:36,420
and to eat a healthy diet.

566
00:50:36,420 --> 00:50:43,980
I think when you're working within the realm of autism, that whole kind of landscape changes

567
00:50:43,980 --> 00:50:44,980
even further.

568
00:50:44,980 --> 00:50:53,300
And so what can we do to help support the lives of these families and individuals in

569
00:50:53,300 --> 00:50:57,980
a way that improves supports and outcomes?

570
00:50:57,980 --> 00:51:04,820
And so I'm excited to learn more about kind of the ongoing child pieces and how that may

571
00:51:04,820 --> 00:51:12,820
kind of modify different outcomes within autism.

572
00:51:12,820 --> 00:51:20,260
And we've also kind of been expanding in different ways to think about learning more about kind

573
00:51:20,260 --> 00:51:30,260
of the health and well-being of the family unit and supporting mom health.

574
00:51:30,260 --> 00:51:37,820
When you've been in autism research for a long time, you really get a lot of great interaction

575
00:51:37,820 --> 00:51:44,420
with families and really are grateful for the research participation and for hearing

576
00:51:44,420 --> 00:51:46,980
back from families.

577
00:51:46,980 --> 00:51:52,340
And so I think it's important to think about ways that we can give back and help support

578
00:51:52,340 --> 00:51:53,340
as well.

579
00:51:53,340 --> 00:51:54,340
So Pam?

580
00:51:54,340 --> 00:52:02,220
Autism is a very pressing topic for many people and for good reason.

581
00:52:02,220 --> 00:52:09,900
Yeah, I'm glad that people are like that and participating.

582
00:52:09,900 --> 00:52:11,220
It's just so pressing.

583
00:52:11,220 --> 00:52:15,580
The rates are pressing.

584
00:52:15,580 --> 00:52:21,420
But the food sensitivity, it's like there's so many autism and XYZ conditions always.

585
00:52:21,420 --> 00:52:27,980
There's so many comorbids and GI problems is one that's really high and like the food

586
00:52:27,980 --> 00:52:31,860
sensitivity and so forth.

587
00:52:31,860 --> 00:52:40,620
It's like finding out how to fix this is incredible.

588
00:52:40,620 --> 00:52:44,940
And I'm so looking forward to the data that you just described.

589
00:52:44,940 --> 00:52:52,540
Is there a place that we can look for your research and this data in the future?

590
00:52:52,540 --> 00:52:53,540
That's a great question.

591
00:52:53,540 --> 00:52:57,860
Yeah, so again, I'm going to shout out the ECHO Network again.

592
00:52:57,860 --> 00:53:01,100
I think they do a really nice job of providing research.

593
00:53:01,100 --> 00:53:02,260
This is not just my work.

594
00:53:02,260 --> 00:53:06,780
There's a whole list of wonderful collaborators.

595
00:53:06,780 --> 00:53:14,900
But there's a large focus on, okay, let's not make science so hard to access and understand.

596
00:53:14,900 --> 00:53:15,900
Right?

597
00:53:15,900 --> 00:53:23,380
And so there's a whole page that summarizes research study across everything that ECHO

598
00:53:23,380 --> 00:53:25,180
is looking at.

599
00:53:25,180 --> 00:53:28,500
And so that's a site that I would direct people to.

600
00:53:28,500 --> 00:53:31,020
It's echochildren.org.

601
00:53:31,020 --> 00:53:37,580
And it provides one-liner summaries of research summary studies that have been recently published

602
00:53:37,580 --> 00:53:41,020
as well as longer summaries.

603
00:53:41,020 --> 00:53:43,220
And so that's one place.

604
00:53:43,220 --> 00:53:54,460
The more maybe scientific or technical side of things PubMed is searching on there, but

605
00:53:54,460 --> 00:54:02,820
those are often kind of more directed at the researcher side or scientist side audience.

606
00:54:02,820 --> 00:54:08,140
And although I will say some journals do a really nice job of making sure that there's

607
00:54:08,140 --> 00:54:15,580
a lay summary that we're not just directing results and findings to one audience only,

608
00:54:15,580 --> 00:54:21,460
but really trying to make sure that they're accessible and reachable and understandable

609
00:54:21,460 --> 00:54:24,420
to anyone who wants to access that information.

610
00:54:24,420 --> 00:54:25,420
Yeah.

611
00:54:25,420 --> 00:54:29,020
I mean, individual studies.

612
00:54:29,020 --> 00:54:36,140
So I mentioned that one cohort, the early study has its own website.

613
00:54:36,140 --> 00:54:42,780
And I'm sure I'm forgetting other different resources to find these things, but those

614
00:54:42,780 --> 00:54:45,740
are kind of some of the major ones.

615
00:54:45,740 --> 00:54:52,980
And the NIH also lists summaries, which also includes lay summaries of different projects

616
00:54:52,980 --> 00:54:53,980
that they're funding.

617
00:54:53,980 --> 00:54:59,860
And that can be another resource to find out about what are some ongoing projects that

618
00:54:59,860 --> 00:55:03,820
are going on in autism addressing these topics as well as others.

619
00:55:03,820 --> 00:55:09,820
Yeah, I just appreciate your actionable tools that you're providing for families.

620
00:55:09,820 --> 00:55:11,460
I think it's very incredible.

621
00:55:11,460 --> 00:55:17,620
And a lot more work to do, that's for sure.

622
00:55:17,620 --> 00:55:24,940
And yeah, hoping that we can provide some information that can be useful to people.

623
00:55:24,940 --> 00:55:25,940
Yeah.

624
00:55:25,940 --> 00:55:36,260
I'm hoping for the day that we can have this preparation, like preparing, going into pregnancy,

625
00:55:36,260 --> 00:55:43,780
and it will just do great wonders to the risk or the rates, I should say.

626
00:55:43,780 --> 00:55:45,180
I can't thank you enough.

627
00:55:45,180 --> 00:55:51,140
I'm very excited about your role, the epidemiology aspect of this.

628
00:55:51,140 --> 00:55:53,980
And I think this is just incredible information.

629
00:55:53,980 --> 00:56:00,340
Well, thank you so much, and I'm always happy to answer questions and again, really appreciate

630
00:56:00,340 --> 00:56:05,300
the invitation to come and spend time with you and talk about my work a little bit.

631
00:56:05,300 --> 00:56:07,860
Yeah, it's very valuable information.

632
00:56:07,860 --> 00:56:15,060
So I'll put some links in the show notes and promote it on social media, the little social

633
00:56:15,060 --> 00:56:16,060
media that I'm on.

634
00:56:16,060 --> 00:56:19,340
But yeah, I just want to get your message out.

635
00:56:19,340 --> 00:56:20,340
Great.

636
00:56:20,340 --> 00:56:21,340
Well, thank you so much.

637
00:56:21,340 --> 00:56:22,940
It's been so nice to get to talk to you.

638
00:56:22,940 --> 00:56:28,060
Yeah, I appreciate you interacting with me.

639
00:56:28,060 --> 00:56:32,780
If you're listening to the podcast or listening to the episode, please feel free to leave

640
00:56:32,780 --> 00:56:35,580
a review or ratings.

641
00:56:35,580 --> 00:56:42,940
In podcasting, review and ratings are crucial, and I very much appreciate your feedback.

642
00:56:42,940 --> 00:56:52,420
You can contact me on X at RPS, 47586, or click on the hop link so you can have links

643
00:56:52,420 --> 00:56:56,780
to all the show platforms and contact information.

644
00:56:56,780 --> 00:57:05,500
You can email me info.fromthespectrum at gmail.com.

645
00:57:05,500 --> 00:57:23,260
And thank you for listening to From the Spectrum podcast.

