Data Blitz

December 12, 2020

Data Blitz

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00:00So let's get going one.
00:03Adjust to I'll introduce
00:05Doctor Block who will help us
00:08moderate this this session but.
00:10Thanks everyone for coming to the
00:134th of our Associates week ventures.
00:17And for this first hour,
00:19we're going to do what we call a datablitz,
00:23where you'll get to hear very succinct,
00:25very well presented.
00:27Tidbits of research and this is a
00:30format that we've used in a number of
00:33settings that Michael and Tom have,
00:36especially refined that was just
00:37gives you a sense of the excitement
00:40of the work and the succinctness
00:42of our communication skills.
00:44So I would love to turn this
00:46over to Doctor Michael Bloch,
00:48who will moderate this data blitz
00:51session and then we'll get back together
00:53shortly after 3:45 will begin our panel.
00:57Just one housekeeping please.
00:59If you're not speaking to mute.
01:02And if you have questions,
01:03Michael,
01:04you're going to take those at the end.
01:06Is that correct? Or I'll talk about in
01:09a second so it will have people take
01:12questions in the chat, so I'll let me.
01:15Let Michael do the pragmatics of questions,
01:17but again welcome and thanks to
01:19all of our associates for all
01:21of your support in joining us.
01:23So Doctor Michael block.
01:24Well, thank you for having
01:26us and thank you for joining.
01:28I'm gonna share my screen quickly.
01:30I'm greetings from the colon.
01:32Yeah, we all people can see my screen now.
01:37OK, right everyone can see my screen.
01:41Yep, OK, I said the big thing of
01:44the data blitz is really in a time
01:47efficient manner to highlight
01:49research and really the research
01:52coming up from the next generation
01:54of investigators and we were lucky
01:57enough to have a really talented group
02:00of up and coming stars in the field.
02:04Amanda Detmer, Cardic, Pipipi, Airmon,
02:06Emily Olson and Yongsun show and
02:09and really the data blitz looks.
02:12Uh, is really supposed to be in a time
02:14efficient way to really highlight this.
02:17Their science and their grades skills
02:19so that talks are going to that we're
02:21going to spend 10 minutes for each speaker.
02:24Essentially, they already produced
02:25a 7 minute video of their signs,
02:27which we're going to share.
02:29And then we're going to spend about
02:313 minutes worth there.
02:32Actually be here to answer questions.
02:34So the idea is that people place questions
02:37in the chat box, function of zoom,
02:39and then the then will pick out
02:42a couple of questions to answer.
02:44And then if the panel is don't have
02:45time to answer all the questions,
02:47so keep answering them in the chat
02:50afterwards.
02:50Anan I guess.
02:51I just really wanted to.
02:53I guess I was thinking about how to introduce
02:56the speakers and I'm not much for like.
02:59Uh.
02:59Sort of generic introductions,
03:02and while I was watching
03:04the NBA draft last night,
03:07I was kind of thinking about what to say,
03:11and I guess and think about our
03:14training programs and an R&R
03:16up incoming investigators here.
03:18I really like to think about
03:21our trainees is like Unicorn,
03:23so unicorns are not probably everyone's
03:26thinking about the mythical creature,
03:28but in the NBA draft.
03:30Their basketball players that are 7
03:33feet tall are able to handle the ball
03:37defendant block shots and then also
03:40have the shooting range to shoot out 2,
03:43three to three point line.
03:45So it's essentially a very rare
03:47skill set and I really consider
03:50each of these presenters unicorns,
03:53that they're not only great
03:55researchers that you'll hear about,
03:57but there are also outstanding clinicians
04:00and advocates and activists for.
04:02Children and families in the community
04:05and that I really think they're
04:07special talents or just in the soul.
04:10Net program,
04:10which is one of our various training
04:13programs for child and adult psychiatrist.
04:15We typically have 500 applicants
04:17and we take two people at every
04:20year and we interview 20 and I
04:22think the people presenting here
04:24are exceptional individuals,
04:26not just exceptional researchers.
04:27So I guess instead of introducing
04:30people with their title and everything
04:32else which you can read on line.
04:35I was really going to talk about why I
04:37thought all these people were unicorns
04:40before we share their presentation.
04:42So first up,
04:43we have Amanda Detmer,
04:44and I guess she's gonna talk really
04:47better out outstanding research that
04:49she's going to talk about in a second,
04:52but I I really think of her as a great
04:55communicator of science and also a
04:57fierce advocate for the community and
05:00the care of children in the community.
05:02I think that's something that
05:04makes her a Unicorn.
05:06Besides the outstanding research
05:07that Angie is going to play
05:10the video for in a second.
05:14Hi I'm doctor Amanda Detmer
05:17and I'm very excited to share
05:20with you today.
05:22A recent study from my lab examining
05:25how early secure attachments shape
05:29second generation health outcomes
05:31in rhesus monkey models of child health.
05:36So here at the Child study center,
05:40my lab's research focuses on
05:42identifying causal mechanisms.
05:44Linking early life adversity,
05:47or Conversely early secure attachments with
05:50later health outcomes across the life course.
05:53And when we say health outcomes,
05:56we are very interested in holistic health.
05:59We examine behavioral, cognitive,
06:01mental and physical health outcomes
06:03and one reason we primarily study
06:06MCAT models of child development is
06:08because although human studies have
06:10done a phenomenal job at linking,
06:13early life experiences was later health.
06:16For various reasons they have not
06:18been able to establish causality.
06:21Anne with rhesus monkeys.
06:23We can do that.
06:25One way
06:26major way that
06:27we conduct these
06:28studies is by relying on
06:30a longitudinal data set,
06:31which I have transferred from the
06:34National Institute of Child Health
06:36and Human Development to yell I
06:38was a senior postdoc in the Lamb
06:40of Doctor Steven Sumi until 2017,
06:42and when he retired in 2018,
06:44which is when I started here at Yale,
06:47I successfully transferred an archive
06:49of biospecimens and behavioral and
06:52health data spanning the 35 years of
06:54the labs history and across that time.
06:56The labs focus was on identifying genetic
07:00and environmental factors that shape
07:03individual developmental trajectories.
07:05As well as examining continuity
07:07and change across development,
07:09and that is what is the relative
07:11stability of individual
07:12differences throughout development.
07:15And of course,
07:16the degree of generalizability of our labs.
07:19Findings to both wild monkeys
07:20and in particular to humans,
07:22and so we're now leveraging this
07:24archival data set to begin to answer
07:27these causal questions of early
07:29life experience and later health and
07:32the way we can determine causality,
07:34is by randomly assigning infant
07:35monkeys to experience different
07:37early social experiences.
07:38So for the first 8 to 10 months
07:41of life each year that rhesus
07:43monkeys were born into our colony.
07:46Half of them were randomly assigned to
07:49the control condition to be mother Periord,
07:51meaning they are reared in large
07:53social groups with mothers,
07:54other adult animals,
07:55and other infants and the other
07:57half were assigned to be nursery.
08:00Weird reared for the first month
08:01of life by human caregivers,
08:03and then given daily pier exposure
08:06in one of two formats.
08:08After the first month of life
08:10being reared by human caregiver.
08:11With bottle feeding,
08:13an incubator monkeys were either exposed,
08:15appears 24 hours a day in the pure
08:18in condition or rear with a cloth
08:20covered surrogate and given pure
08:23exposure for a couple of hours a day.
08:25Importantly,
08:26both of these types of varying
08:28conditions were random.
08:29They lived in the same housing room
08:32and they continue to get pure exposure,
08:34but without the important exposure
08:37to adults or mothers or other
08:40caregivers to form a secure attachment.
08:42And in a recent study.
08:46Published in the working Paper series
08:48in the National Bureau of Economic Research,
08:51we found that these very early,
08:53secure attachments,
08:54those monkeys that were mother reared,
08:56had long lasting effects even
08:58into the second
08:59generation. So we studied
09:02three decades of data on 650 mother
09:05offspring pairs and what we found
09:07was that if an infant which we're
09:09calling generation was generation two,
09:12was reared with its mother,
09:14and its mother was also mother rear.
09:17So there were two generations of
09:20secure attachments that infant
09:21realized health advantages across
09:23the life course in infancy.
09:25Those infants had a higher rate of
09:29survival in the first month of life.
09:32As adolescents, they had a higher
09:34frequency of time in good health,
09:37meaning they did not require
09:39veterinary interventions,
09:40and in adulthood those infants
09:42achieved a higher social rank
09:44than any of the other infants not
09:47experiencing secure attachment or
09:49whose mothers did not experience secure
09:52attachment and similar to humans
09:54are higher social rank in rhesus
09:56monkeys is associated with multiple
09:59numerous beneficial health outcomes.
10:01In the future,
10:03we hope with additional funding
10:05to identify the biological
10:07mechanisms that are responsible for
10:10these intergenerational effects.
10:12So we're just beginning to start
10:14looking at DNA methylation across
10:17generations and across the lifespan
10:20at measures of inflammation.
10:22If you had perhaps seen my earlier post
10:26earlier this week on Lactational programming,
10:29that's another mechanism were probing as
10:32well as several other biological mechanisms,
10:35and we also hope to examine potential
10:38interventions for subset of these monkeys.
10:41They experienced enhanced
10:42social interactions,
10:43either naturalistically enhanced
10:45face to face interactions between
10:47caregiver and offspring,
10:48or experimentally controlled enhanced
10:50social interactions in the laboratory.
10:53Other monkeys experience later exposure
10:55to adults after nursery rearing,
10:57and we're also interested in seeing
10:59how other factors like the extent of
11:02an individual social network might
11:05shape it's later health outcomes.
11:07I want to thank you very much
11:10for your attention and I need to
11:12absolutely acknowledge all of the
11:14people who made this work possible,
11:16as well as the funding sources
11:18up until this point.
11:19Very happy to take your questions.
11:21Thank you so much.
11:23OK, thank you.
11:26I guess we'll.
11:28Is it anyone have a question or should I ask?
11:33Ask the first question? Going once.
11:39So I guess 1 one thing that the
11:41research brings up is I was curious what.
11:43What do you think the lessons are for?
11:46They they care of young children
11:48and in what society can do to sort
11:50of have the most bang for your Buck
11:53in helping young children.
11:54Based on the research you do?
11:56Yeah, that's a great
11:57question Michael.
11:58Thank you and I'm really delighted
12:00to be a part of this esteemed group.
12:02Thank you all for having me at one
12:04of the points we made in that paper
12:07in the NBR working series. Is that?
12:09These findings support previous work in
12:12humans that has emphasized investment
12:14in the first five years for children,
12:17but especially by looking at
12:19this model of causality,
12:20an or nonhuman primates,
12:22which were unable to do in children.
12:25We can even more definitively say that
12:27investment in the first five years,
12:30and I might even extend that to the first 6
12:34if we think of the first year prenatal E.
12:38Doing all that we can to encourage
12:41policymakers to provide supports
12:43for young children and their
12:45families and caregivers will enable
12:47children to form secure attachments,
12:49which obviously not only have health
12:52impacts across that individual lifespan,
12:54but potentially their grandchildren's
12:56as well. Though.
13:01I guess anyone else have another question?
13:05I'll ask a question, great talk,
13:07really interesting stuff.
13:08I was just wondering,
13:09you mentioned like the very what about
13:11the variability between macaques, right?
13:13You showed the overall?
13:14Did you notice a lot of variability
13:16where some just seem to naturally
13:18do better where others didn't? Or
13:20they pretty stereotyped
13:21across the board, right?
13:23Again, a great question.
13:24And just like with human children,
13:26there is a good amount of
13:27individual variability,
13:28and so within each type
13:30of random ring condition,
13:31you know we might see some
13:33mother reared infants who maybe.
13:35Do require more medical care in adolescence,
13:37or maybe have a little bit lower
13:39social rank and then seeing
13:41with nursery reared infants,
13:42they might not have as high of stress,
13:45responsivity,
13:45and so when I was talking about how
13:48with by securing future funding we
13:50hope to look at other mechanisms.
13:52Those are the kinds of things
13:54we want to look and see.
13:56If the interventions that we know
13:58have happened might be accounting
14:00for some of that variability.
14:01So there is some variability
14:03in some of the outcomes,
14:05but collectively the group
14:06differences are most striking.
14:07But we're very interested in
14:09individual trajectory's, thanks.
14:11So
14:12thank you very much for
14:14the great talking next.
14:16Next I get to introduce cardiac who
14:20get to talk about why he's a Unicorn.
14:24Besides being an avid sneaker enthusiast.
14:26Kartik is this Daniel here
14:28but his great research I.
14:30I think he's just a
14:32wonderfully gifted clinician,
14:33especially focusing on kids with
14:36developmental disabilities in the
14:37intersection with genetics that I've
14:39been unlucky enough to supervise
14:41him in the outpatient clinic.
14:43And it's wonderful, say,
14:44get to see him in action doing that and
14:48you're going to see what a wonderful
14:51scientific mind he is also so.
14:53Kartik is up.
14:57I am I think I'm a
14:59fifth year integrated fellow at the
15:00Child Study Center and I'm currently
15:02working in the laboratory of men
15:04incest and I'll present to talk today
15:06titled History System Schizophrenia,
15:08the role of in utero,
15:09disruption of prefrontal cortical dynamics
15:11circuitry in the etiology of schizophrenia,
15:13a term that I recently learned
15:15with hysteresis,
15:16which I think is very relevant to the
15:18work that we do with the Child study center.
15:21What hysteresis is defined as
15:23is the dependence of the current
15:25state of a system on its history.
15:27I think no study best represents
15:29that then the Asus study which
15:31showed that early life traumas abuse
15:33neglect and household dysfunction
15:35lead to later changes in behavior
15:38and physical and mental health.
15:40For example,
15:40early life trauma increases your
15:43chances of developing diabetes or
15:45heart disease much later in your life.
15:47I think this concept of history's
15:49is also very relevant to biological
15:52psychiatry as well,
15:53specifically schizophrenia.
15:54The neuro developmental theory
15:55of schizophrenia proposes that.
15:57Early life in utero.
15:58Disruption of brain development leads
16:00to the later symptoms of schizophrenia,
16:03which usually occur during early adolescence.
16:06Or, sorry,
16:07late adolescence or early adulthood.
16:09While the data supporting that
16:11was initially circumstantial,
16:13more recent genetic data has identified
16:15a disruption of schizophrenia.
16:17Disruption of schizophrenia alleles
16:18in the frontal cortex during
16:20mid fetal development,
16:22and so this begs the larger
16:24overarching question,
16:25how do neurodevelopmental events
16:27in the mid fetal frontal cortex
16:29lead to the complex symptoms of
16:31schizophrenia in adolescents and adults?
16:34To address this question,
16:36we were interested in what
16:38is uniquely going on.
16:39In the mid fetal frontal cortex
16:41to address this question,
16:43we used existing human transcriptomic
16:44data from the brain span in psych
16:47encode initiatives that were partially
16:49generated in the system lab and looked
16:51for jeans that were enriched in the
16:53frontal lobe or the frontal cortex
16:55compared to the other regions of the brain.
16:58But we identified is a lot of genes
17:00involved in circuit formation,
17:01synapse formation,
17:02Axon guidance,
17:03which was known.
17:04We know that circuits are developing
17:06during this period of development,
17:07but with something that was novel.
17:09As we identified it,
17:11enrichment of genes associated
17:12with retinoic acid signaling.
17:14Retinoic acid is a vitamin A
17:16derivative that's very important for
17:18various aspects of not just brain
17:20development but whole body development.
17:22This finding was significant and
17:24clinically because disruption of retinoic
17:26acid signaling has been associated
17:28with an increased risk of schizophrenia.
17:30Specifically,
17:31in cases with severe cognitive deficits.
17:34So then we asked our nest next question
17:37what is the role of retinoic acid
17:39signaling in mid fetal frontal cortex?
17:41What is retinoic acid doing and to
17:43study this we did various studies but
17:45I'll focus on one specific finding
17:48that we found in the early post
17:50Natal mouse which is very similar
17:52to mid fetal human development.
17:53What we looked at was connectivity
17:55between the front of the brain
17:57to other regions of the brain.
17:59We found a very selective deficit.
18:01We found a dramatic reduction of
18:03connectivity between the front of the brain.
18:05The prefrontal cortex and the thalamus on the
18:07left is the control of the wild type mouse.
18:10On the right is a mouse or we specifically
18:12reduce retinoic acid signaling just in
18:14the front of the brain and what you
18:16can see here is a dramatic reduction in
18:18the amount of connections between the
18:20front of the brain and the thalamus.
18:23And this is very interesting from a
18:25clinical perspective because reduce
18:27connections between the frontal cortex
18:29and the thalamus have been described in
18:31patients with schizophrenia both early onset.
18:33So patients within four weeks of
18:35diagnosis as well as patients with
18:38chronic schizophrenia as well in addition,
18:40work that was actually done here
18:42at Yale by Alan Tisha.
18:44Bitch showed that patients that later
18:46developed schizophrenia during their
18:48prodromal stage during their adolescence
18:50period showed reduced connectivity between
18:52the frontal cortex of the thalamus as well.
18:55And this circuit,
18:56the connection between the front
18:58of the brain in the thalamus,
19:00is deeply important for cognition and
19:03has been associated with IQ and is
19:06involved in working memory perspective
19:08clinical studies in kids found that
19:10patients that kids that later develop
19:13psychotic disorders showed a progressive
19:15decline in IQ starting as early somewhere
19:18between 818 months in four years.
19:20This is seen both in full scale
19:23IQ verbal IQ in non verbal IQ.
19:26So even though diagnosis of
19:27schizophrenia can occur much later,
19:29they are actually showing cognitive decline
19:32decades before there later diagnosis.
19:34So putting all this data together,
19:36what we propose is that disruption of
19:39genes associated with retinoic acid
19:41signaling lead to reduce connectivity
19:43between the front of the brain.
19:45The prefrontal cortex in the
19:47mediodorsal thalamus and this occurs
19:49during in utero development.
19:50Specifically during mid field
19:52development or the 2nd trimester.
19:54And this explains the early
19:56cognitive symptoms in schizophrenia,
19:57which manifest as early as
19:59one to two years of life.
20:01But we are interested in how this
20:03specific deficit can lead to later
20:05changes that underlie the positive and
20:08negative symptoms of schizophrenia.
20:10We propose is that this selective
20:12disruption of this circuit,
20:13that which is due to retinoic acid signaling,
20:16leads to secondary,
20:17can pensa Tori changes in the brain,
20:20and this has been previously described
20:21in other studies that show increased
20:24connectivity between the thalamus
20:25and other regions of the brain,
20:27and these can pensa Tori.
20:29Changes may underlie the later
20:31positive symptoms.
20:32Of schizophrenia,
20:32specifically hallucinations or delusions,
20:34but this is also very exciting.
20:36From an interventional perspective,
20:38the prodromal period of schizophrenia
20:40is historically been thought to be
20:43just a couple years before the onset of
20:46full positive symptoms and diagnosis.
20:48However,
20:48the prodromal period of schizophrenia
20:50now can be extended to in euro
20:53development and this gives us an
20:55extremely long period to try to
20:58intervene to prevent or mitigate the
21:00morbidity of schizophrenia specifically.
21:02If we can target this reduced
21:04connectivity between the thalamus
21:06in the prefrontal cortex,
21:07we can hopefully reduce the early
21:10cognitive symptoms of schizophrenia,
21:11as well as preventing the later secondary
21:14circuit changes and completely preventing
21:16the positive symptoms of schizophrenia.
21:18Currently, I think one approach that we
21:21can use to kind of target this early life.
21:25Disconnectivity and cognitive symptoms
21:26is brain training cognitive training.
21:28Try to work on cognitive
21:31skills in working memory.
21:32To try to strengthen this circuit,
21:34hopefully in the future using deep brain
21:36stimulation or pharmacological interventions,
21:37we can directly target and strengthen
21:39this circuit early in life,
21:41and this is something that I'm
21:43interested in pursuing in the future.
21:45So I'd like to acknowledge the large number
21:48of people are involved in this study,
21:50especially members of the test in lab as well
21:53as our collaborators and funding sources,
21:55and I'd like to specifically think this
21:58element program the Child Study Center,
22:00which was essential for the
22:02completion of this project,
22:03specifically Michael Block Northeast,
22:04to be tiny, Cologne and Doctor
22:06Linda Maze for their support.
22:08Thank you.
22:10Thank thank you
22:12for the excellent presentation.
22:15Will give a few seconds for people to.
22:20I guess we have a question
22:22from Tom Fernandez.
22:23You want to unmute yourself
22:25and ask the question. Not sure
22:28card. So now that retinoic
22:30acid is implicated, are you
22:31aware of any treatment studies
22:33plans that target this pathway?
22:35Or are you planning to
22:36stay? Yeah yeah, it's a
22:38great question.
22:38There are some groups in Australia
22:40there considering retinoic acid
22:42as a possible later intervention.
22:43They were building up a study that showed
22:46during the 2nd trimester of pregnancy
22:48and this was a perspective trial.
22:50That page like mothers at later had
22:52children with schizophrenia show
22:54to reduce level of retinoic acid.
22:55It wasn't significant this small study but.
22:58That trended that way,
22:59the issue is retinoic acid is involved in
23:01so many aspects of development, right?
23:03And so I didn't get go into
23:05the basic science of it.
23:07It's in my poster,
23:08but basically retinoic acid is
23:10exquisitely controlled by a set of
23:12like activating genes that produce it,
23:13and jeans that degrade it to get
23:16it really localized in one area.
23:17So to really to be able to target retinoic
23:20acid would have to do it during pregnancy,
23:22and that would be pretty difficult.
23:24We show in our paper that
23:26if you force like have.
23:28Extra expression of retinoic acid.
23:29You get extra connectivity and
23:31so it could be a possibility,
23:33but I think anytime you intervene with
23:35a child or during pregnancy you have
23:37to be really confident that you're
23:39going to make a be able to intervene.
23:42I'm hoping that you know that's why
23:44maybe later life intervention on
23:45that circuit instead of like just
23:47retinoic acid focus just strengthen.
23:49That circuit could be more
23:50effective strategy, but who knows?
23:52I think there is a possibility of early
23:54life like in Euro intervention to to
23:56kind of intervene on that circuit.
24:00Hartikainen question first of all, thank
24:02you. That was really, really fascinating.
24:04I'm really glad to see you
24:06focusing on schizophrenia. I think.
24:08I think it's an understudied area.
24:10Thank you. What do we know?
24:12What retinoic acid might interact with
24:14in the brain? What
24:15other components? Sure, sure,
24:16so the testing lab is.
24:18It's like a neurogenetics lab.
24:20Like we really interesting like
24:21signaling pathways downstream a bit.
24:23And so in our initial study,
24:25we actually identified a lot of jeans
24:27that weren't directly retinoic acid,
24:29like related proteins, but.
24:30Can be regulated by retinoic
24:32acid and so there's kind of two
24:35studies that we've we've submitted.
24:37One is looking at gene downstream,
24:39retinoic acid.
24:39That's important for
24:41Synapse formation directly,
24:42and actually shows a human
24:43specific expression.
24:44Human and chimpanzee specific expression
24:46that actually not present macaques and so,
24:48and it also seems to regulate certain
24:51other interesting genes including genes,
24:53plane, autism in jeans and schizophrenia.
24:55So I have a couple jeans that I cherry
24:58picked that I'm specifically interesting,
25:00interesting.
25:00Following up, yeah,
25:01we're still trying to kind
25:03of flesh out this network.
25:05What retinoic acid specifically
25:06regulating in the front of
25:08the brain at that period.
25:10And I guess he just above question
25:12is what are there any other
25:14sort of psychiatric disorders
25:16that retinoic acid and kind of
25:18fetal cortical development?
25:19Irrelevant for sure.
25:20I mean in this case frame line 22,
25:23Q 11 is
25:24thought to be a retinoic acid
25:26disregulation when they look at
25:28actually the heart abnormalities.
25:29So I hypothesize maybe that underlies
25:32their increased chance of schizophrenia,
25:33certain retinoic acid associated genes
25:35are also implicated in autism as well.
25:37I mean, there's so much similarity.
25:40I think both genetically as well as maybe.
25:42If you look at just like the
25:44social kind of symptoms,
25:46the apathy that you see in the
25:48negative symptoms schizophrenia.
25:49So there's definitely jeans
25:50related during the week.
25:51Acid there involved in that as
25:53well as early neural development.
25:54Microcephaly also seems to affect
25:56genes involved in a retinoic
25:57acid. Well thank thank you
26:00for the great presentation.
26:01Next up, we have your compatriot
26:04in this only program.
26:05Emily Olson, who's also a fifth
26:07year in the Soulmate Integrated
26:09Program and the I guess the thing
26:12that makes her a Unicorn is to me.
26:15He is. I've had the pleasure of
26:17working with her in that thread.
26:19So CD Clinic and specifically looking
26:22at treating kids with body focused
26:24repetitive behaviors and ADHD and not
26:26only is she going to give a first rate
26:29genetics presentation on the subject.
26:31But he's really interested and she's
26:33done a lot already to help make our
26:36care of those kids better in the clinic.
26:38So without further ado,
26:40here's Emily.
26:41So hello, my name is
26:43Doctor Emily Olson.
26:44I'm currently a fifth year
26:47resident in the child insults
26:49psychiatry training program here
26:51at the Yale Child Study Center.
26:56Today I'm delighted to have the
26:58opportunity to talk to you about a research
27:01project focused on two conditions,
27:03trichotillomania or hair pulling
27:05disorder and excoriation,
27:06or skin picking disorder.
27:08These are conditions that you may
27:11not have heard much about before,
27:13but they're actually relatively common,
27:15impacting at least 1% of
27:17the population there.
27:19Classified as OC D related disorders
27:21and individuals who have them
27:23often spend hours a day pulling
27:25or picking at their hair or skin,
27:28which leads to significant distress,
27:30functional impairment at
27:32school and social situations,
27:33and also medical complications.
27:36These conditions usually onset in early
27:38adolescence and if untreated can impact
27:41individuals throughout their lifetime.
27:43They predominantly occur in females and
27:45currently the really difficult to treat
27:48behavioral treatments have some effect,
27:50at least in the short term,
27:52but there are no first line
27:55pharmacological treatments,
27:56and no FDA approved medications.
27:59And so an important step when we
28:01think about developing new treatments
28:03for patients and families is to try
28:06and understand the biology more.
28:08And what we know from past research
28:11is that genetic factors are
28:13important in the development of
28:15these conditions and actually,
28:17some data suggests that similar
28:19genes contribute to both
28:20trichotillomania excoriation disorder,
28:22which is why I'm studying them here together.
28:25But something that's been
28:27harder for scientists.
28:29Has been finding specific risks,
28:31jeans and when you think about
28:33developing new treatments and
28:35identifying druggable targets.
28:37This is actually really important
28:39and one of the reasons for this
28:42gap is that there are no previous
28:44Lee published genome wide studies
28:46in either disorder and so really.
28:49My goal with this project was to bring
28:52state of the art genomic approaches
28:55to these understudy conditions of
28:57Trichotillomania Annex creation disorder.
28:59Then child psychiatry.
29:01One approach that's been especially fruitful
29:04is DNA sequencing of parent child trios.
29:08So because each of us in here at
29:11half of our DNA from our parents,
29:13this approach allows us to not
29:15only look at inherited mutations
29:17associated with the condition,
29:19but
29:19also new or de Novo
29:21mutations and all of us have about
29:2350 to 100 of these de Novo variants.
29:26An when they occur within genes that can
29:28actually impact the proteins that are formed.
29:31An impact brain function.
29:34And so this approach of DNA sequencing
29:36of parent child trios was first
29:38pioneered in the field of autism.
29:40In here I'm showing a recent study where they
29:43found over 100 high competence risk genes.
29:47In chronically, these jeans are
29:49already impacting patient care,
29:51and this is because for
29:53patients and families.
29:54You know, just knowing why they have
29:57a condition can be helpful clinically,
29:59if they're planning to have more
30:02kids understanding how that how the
30:04disorder is inherited is helpful.
30:06And then also specific genetic
30:09changes do have implications for
30:12specific medical treatments as well.
30:14And this approach that, as I said,
30:17was pioneered in autism more recently.
30:19It's been shown to find risk genes
30:21in both direct disorder and OC D and
30:24studies led by my mentor here at Yale, Dr.
30:27Fernandez.
30:29And so given the similarities
30:32between OC D Tourettes.
30:34With you know,
30:35trichotillomania Annex coordination disorder.
30:37In 2018 we started the tab study,
30:40so we started recruiting individuals with
30:42trichotillomania and excoriation disorder,
30:44as well as both their parents.
30:46We collected saliva for DNA sequencing
30:49and had them complete surveys about
30:51their symptoms and family history,
30:53and here I'm going to show you
30:56data from sequencing of the first
30:5965 parent child trios they had,
31:01where the child had a primary
31:03diagnosis of either trichotillomania,
31:05excoriation disorder, or both conditions.
31:07We compare this to 225 control trios
31:10that were previously sequenced,
31:12and, in our analysis,
31:13we focused on these rare de Novo
31:17variants that were thought to
31:19influence the coding regions of genes.
31:22And what we found is we found a
31:25higher rate of these likely damaging
31:27mutations in cases versus controls,
31:30so this was,
31:31you know,
31:31very reassuring that this approach
31:33was the right approach for finding
31:36risk genes and these likely damaging
31:38mutations are thought to alter
31:40the protein function either by
31:42causing a frameshift,
31:43introducing a new stop codon,
31:45or maybe just changing an amino
31:47acid that's predicted to be
31:50damaging to the protein function.
31:52And so we can also use these.
31:55Look at these jeans.
31:57They have these likely damaging mutations
32:00and see if they overlap for risk.
32:03Genes for other disorders and so
32:05we did that and what we found is
32:08that a few individuals did have
32:11likely damaging mutations that
32:13were risk genes for say autism.
32:16But these individuals don't have autism.
32:18They have excoriation disorder
32:20or trichotillomania.
32:21And this gets up this idea plea
32:24atropy the idea that similar genetic
32:26changes may have different clinical
32:28manifestations in different individuals,
32:30and this is something that we're continuing
32:33to explore. In addition,
32:35we can look at the jeans that have these
32:39likely damage invariants and see if
32:41they are enriched for certain pathways.
32:44And here are our top pathways were circadian
32:48entrainment and glutamatergic synapse.
32:50And this is really interesting because
32:52the glutamate system is actually already
32:54been implicated in the treatment of
32:57trichotillomania Nicks creations disorder.
32:59And so this is really getting at kind of
33:02the underlying biology of these conditions,
33:04and so at the beginning of this talk,
33:06I told you how sequencing a parent
33:09child trios, you know this approach
33:11was pioneered in autism,
33:12but had been shown to have a lot of discovery
33:15potential and several other conditions
33:17and studies led by my mentor and others.
33:20And then here today I showed you how
33:23this also has a discovery potential
33:26for two understudy conditions,
33:28trichotillomania and excoriation disorder.
33:30But we're not stopping there.
33:33You know, in the lab we're also
33:35looking at childhood anxiety disorders.
33:37Another poster here at the
33:38associates meeting focused on this,
33:40and I also have some really
33:42interesting data and ADHD.
33:44And it's likely that this approach
33:46will continue to be helpful for many
33:48childhood onset psychiatric conditions.
33:49And so for that app study,
33:52the next steps are we're going to continue
33:54recruiting and sequencing trios and our,
33:56you know,
33:57our hope is that once we get to a few 100
34:00will find the first kind of exome wide.
34:03High confidence risk genes
34:04for these disorders.
34:06And then you know my hope.
34:08And then my plan really is,
34:10you know,
34:10as a next step is then understanding
34:13how these risk genes and pathways,
34:15from a mechanistic standpoint,
34:16how they lead to development
34:18of these disorders,
34:19which I think is a critical next step
34:21in terms of treating these conditions.
34:24So with that I just want to thank
34:26you know all the individuals
34:28and families participated.
34:29It's A wonderful population to work with.
34:31I want to thank both my mentors,
34:33everyone in the lab and all of our funding.
34:38So thank you for the excellent talk. I
34:41guess I'll have two questions and you
34:44can choose which one you want to answer
34:47and skip the other one so the the first
34:49question you could ask is we we get a
34:52lot of these samples through the clinic,
34:55but it be worth talking about how you
34:57got in the majority of the body focused
35:00repetitive behaviors sample for this
35:02study and then the second question you
35:04can answer if you want more scientific
35:07one is really no one has done this.
35:10ADHD, like why it seems like such
35:12a common condition or anxiety.
35:16I'm I'll answer both questions.
35:19So the first question. We so, um,
35:23Michael knows the answer to this,
35:25but we started this project.
35:27We actually started in April 2018.
35:29An there's a foundation,
35:30the TLC Foundation for Body
35:32focused repetitive behaviors
35:33that spatial basically a
35:35patient centered conference
35:36that provides support
35:37and resources. And
35:38so we went out to San Francisco.
35:40Kind of not knowing what to expect,
35:43I was brand new to the field that
35:46we brought our saliva kits and
35:48our surveys on iPads, and it was.
35:51It was really amazing.
35:52Um, you know how many people
35:54signed up for this study an it was
35:57really kind of at this conference.
35:59My first day kind of recruiting
36:01it was are you know that I
36:03realized that this was
36:05such an important population because,
36:06you know, we're
36:07not paying these subjects anything.
36:09They're all signing up for
36:10this kind of voluntarily, and
36:12I think it's in part 'cause
36:14there is such limited research on
36:16these conditions. And it is so
36:18understudied in the treatments
36:19are often ineffective. So so, a
36:21lot of our samples have
36:23been through. We've been
36:24to the conference twice, unfortunately.
36:26In 2020, given Kovid and everything,
36:28we couldn't go this year,
36:30but we've the most of our recruitment really
36:33through through the TLC
36:35Foundation and what not.
36:36And it's been wonderful.
36:38The second question, you know it,
36:40it is impressive to me that this hasn't
36:43yet been done on a large scale in ADHD.
36:47There for some few smaller studies.
36:49Ann, I think the biggest
36:51study has just about 15 trios.
36:53That's published in 80 HD,
36:55but we do have some really
36:57exciting data. Lemon airy data.
36:59An I just started.
37:01I received the cleaning Steam
37:02Foundation grants and it just started
37:04this year and so we're hoping to increase
37:07and do a similar project in ADHD as well.
37:10And so we're working on that now and then.
37:13The data is really promising
37:14that will be able to find high
37:17confidence risk genes there as well.
37:19And again childhood anxiety.
37:20We have really exciting data,
37:22mainly recruited at the Child Space
37:24Center here with our anxieties program.
37:27Thank you I guess Next up for the
37:30sake of time, we should keep going.
37:32We have young son show and I guess
37:35she's a Unicorn. She probably has
37:37no idea what I'm talking here.
37:39You were here, I guess, but that's easy.
37:42Unicorn 'cause she's really a
37:44wonderful clinician and teacher.
37:45In addition to being a great researcher.
37:48And when the job opened up,
37:50tell kind of help from the Enter TV program,
37:54which is a sister program.
37:56Of this only program in the
37:58Adult Psychiatry Department,
37:59I thought she'd be created doing it
38:02'cause she's got a great eye for talent.
38:05But she's also great clinician,
38:07mentor and teacher.
38:09Without further ado.
38:17Thank you for your interest in our
38:20work. My name is young Sancho
38:22and I'm an assistant professor
38:24in the Young Child Study Center.
38:26This poster shows some work that
38:28examined how motivation effects
38:29the brain circuits that support
38:31working memory and overall,
38:33our results suggest that motivation
38:34improves working memory by
38:36shaping neural signals in the
38:38prefrontal and parietal cortex.
38:39We were interested in motivation and
38:41cognition together because they are both
38:43refined during childhood nettle essence,
38:45meaning they continue to develop,
38:47which suggests there dynamic
38:48but also vulnerable.
38:49Ann is
38:50a testament to
38:51this vulnerability. They
38:52are both disrupted in a number
38:54of psychiatric illnesses,
38:55but we still don't really
38:56know how the brain links,
38:58motivation and cognition to
38:59achieve goal directed behaviors,
39:01which then limits our ability to design
39:02meaningful psychiatric treatments.
39:04So to start to embark on this path,
39:07understanding how the brain links,
39:08motivation and cognition,
39:09we made a test to probe incentivized
39:12working memory that we called mid kog,
39:14which you can read about in the
39:16upper right corner and we focused
39:18on working memory which is.
39:20A key building block of cognition,
39:22which refers to the active maintenance
39:24of information in your mind and it's
39:26needed for other cognitive functions,
39:28such as abstractions or problem solving.
39:30And we use this task with fMRI in
39:33a group of healthy young adults,
39:35and we found that incentives or those
39:37things that motivate our behaviors,
39:39and in this case it's money,
39:41improve working memory,
39:42and that the neural signals are greater,
39:44and parietal and prefrontal regions
39:46when working memories incentivized.
39:48Then when working memory is not incentivized.
39:50And more specifically,
39:51the greater neural signal in
39:52these regions was associated with
39:54better working memory performance,
39:55so this work highlighted some key
39:57mechanisms that help us understand how
39:59the brain begins to link motivation,
40:01cognition,
40:01and in the future we hope to
40:04use or we will use this tech.
40:08Whoops,
40:12sorry I'm back
40:22so. I guess that was a young
40:26son was supposed to be.
40:29We have a full 8 seven
40:31minute talk that we had.
40:33We switched it with the poster
40:35session by accident,
40:36so I guess I'm just going to.
40:38Is it OK if I throw it out
40:40to you young son? Yeah, this
40:42is OK. Talk a little bit more
40:44about the work, I don't.
40:46I don't know what happened, but we're not
40:48gonna fix it for the
40:50sake of time, and I apologize, that's
40:52OK. It's a much more succinct presentation
40:54anyway, so I don't know if you want to talk
40:57a little bit more about the
40:58stuff you're presenting in
41:00the talk. I think it mostly
41:01covered the main points.
41:02Basically, we're trying to really
41:04understand how the brain coordinates
41:05motivation and cognitive processes,
41:07because these are two fundamental
41:08processes that are disrupted in a
41:10number of psychiatric illnesses.
41:11Of course they continue to develop
41:13as children and adolescents grow,
41:15and so we want to understand,
41:17sort of how the brain integrates
41:19these functions so that we can later
41:21understand how their vulnerable to
41:22development in psychiatric illness.
41:24So that's sort of the main idea of
41:27this study, and then first passes.
41:29This is to design a task for fMRI and
41:32to look at a group of healthy adults,
41:34and then the circuits that we
41:36identified are really frontal and
41:38parietal circuits that are really
41:40in the posterior regions of those.
41:42Areas and meaning through their
41:44sort of located in the back of
41:46the prefrontal cortex or the back
41:48of the parietal cortex and are
41:50also integrated with visual areas.
41:52So there's a lot of sensory and
41:54cognitive integration that happens
41:56as well as the emotional piece in.
41:58Refer motivational signals to sort
42:00of boost working memory and yield
42:02to improvements in working memory.
42:05And So what? I guess,
42:07what kind of disorders is this
42:10relevant to? The relevant alot of disorder?
42:12So schizophrenia is Kartik is mentioned.
42:15You know has clear cognitive
42:17disruptions in the working memory is
42:19it has been consistently reported as
42:21being disrupted in schizophrenia.
42:23There's also motivational disruptions.
42:25It happened there with the negative symptoms.
42:28Depression also comes with cognitive
42:30and motivational deficit, substance
42:32use disorders. ADHD all come with
42:34these sort of
42:35code. Disruptions of.
42:36Cognitive and motivational symptoms.
42:38So I think that's kind of
42:40interesting and understanding
42:41better how they're linked.
42:42Independent wanna meet one another
42:44in the brain is interesting.
42:47I I guess I wish the I guess the other thing.
42:50I just want to say before we finish
42:53up is we're kind of experimenting
42:55with the format is a way to kind of
42:58update people on the research that
43:00goes on at the Child study Center.
43:03So if any anyone who's in the
43:05audience has any ideas of how we
43:07can present the research better.
43:09Also we were thinking around
43:11sending out short videos of.
43:12Love of emerging research over the
43:14course of the year, featuring things
43:17that people do have a good sense, what?
43:19What could be the first video that we share?
43:22But but I guess I just wanted to thank all
43:27the panelists and just as we're in this,
43:30you know, emerging different world of
43:33presenting things in our research.
43:35Just thinking about ways that we can make
43:38things more accessible in the future,
43:41especially the young researcher
43:44emerging investigators.
43:46Thank you, thank you,
43:47thank you so much and thank you to to Emily
43:50and Karthik and Amanda Anne Youngson.
43:53Great that we can highlight this new way
43:56of trying to get the information out.
43:58And as Michael says,
43:59we're looking for we're looking for
44:02feedback on the format and also will.
44:04This has been recorded too,
44:05so we'll be able to circulate it.
44:08Now we're going to switch to the next.
44:10The next part of this afternoon's
44:12program with three panels want touching
44:15on Tele Health and what we've learned
44:17over this time with Tele Health.
44:19One touching on autism and related
44:22developmental disabilities and then then we
44:25will have 1/3 panel on maternal depression.
44:28The way will work.
44:30This is that will have the panels.
44:32The panelist in each of those areas present,
44:35and then we'll take questions at
44:37each of those times and I'll be
44:39moderating the questions the same.
44:41This will do the same that please
44:44put your questions either in the
44:46chat or just speak up an will.
44:48I'll be sure that your questions
44:50get to get to the proper channels.
44:53So let me just be sure that we have
44:56Pam Hoffman is here and I see famine,
44:59Dennis and fam.
45:00Dennis Anuar joined with Jan as well, right?
45:03Yes, so we have a wonderful first
45:05panel on Tele Health.
45:07Ann.
45:07As you've heard me say.
45:09And several of these days,
45:11the Child study center transition
45:12to Tele Health really very quickly,
45:15but calls with the pandemic.
45:16And when Pam joined our faculty,
45:18we had the plan pan that it would
45:21be over an 18 month period.
45:23It basically was over a two week
45:25period and then we've been refining
45:28that subsequently to follow
45:29Michaels example live.
45:30With that you can go on the web and see
45:34see about each
45:35of these individuals,
45:36but I would just like to just introduce
45:39them by the things that that the
45:42many things in ways they stand out.
45:44So one you just heard is Pam's ability
45:47to make something happen really quickly.
45:50Her enormous interest and capacity
45:52to bridge clinical trial psychiatry
45:54and complex issues of information
45:56technology and leading informatics.
45:57And then what you might not see from
46:01her CV is she has a deep interest in
46:04literature and how literature in various
46:07forms of literature and music and art
46:09inform our ways of working with children.
46:12Dennis Sadosky you've met on other other
46:15associates meetings and I'm just so glad
46:18that you get a chance to meet Dennis now.
46:21Dennis is the most upbeat person I know
46:24and had the chance to convert his lab
46:27really quickly to doing assessments over
46:29Tele format and just did it without any.
46:33Maybe Dennis,
46:33you didn't show your anxieties and
46:36worries but but my sense it was
46:38just smooth and you were always
46:41being creative and thinking of new
46:43ways to help children and families.
46:45And then Jan Ponson is our medical director,
46:48outpatient services.
46:49Jan is the most unflappable person
46:51in the clinical setting I.
46:53Absolutely no,
46:54and he has an ability to hold complexity
46:57in mind and just just go with it
47:00and at the same time has a great
47:03sensibility about children and families.
47:05So let me.
47:083 colonies fam Dennison young.
47:12Thank you
47:12and I'm so excited to be talking a
47:15little bit about what we've done.
47:17I'm really mostly excited about talking
47:19bout what more fun we have in store,
47:22and so I'd like to give a little bit of
47:25a short presentation on which is some
47:28numbers so that we can see a little bit of
47:32what child study center has done so far.
47:34So as thank you for introducing me,
47:37it's very nice. I I hold a lot of
47:40different hats in the health system.
47:42My favorite one obviously biased.
47:44Yes, is that I'm here.
47:46The Child study center.
47:47I also spend a lot of my time at why CMI,
47:51which is Yale Center for Medical Informatics,
47:54where I Amoco training director for
47:56the Health Informatics Masters degree
47:58students an I run an teach their
48:00fall in spring capstone courses,
48:02so we're looking forward to the
48:04end of that semester in two weeks
48:07and as she described.
48:08I'm also medical director
48:10for Tele Health at Yale,
48:12New Haven Health Systems, and.
48:14Yellow medicine,
48:14so all of that integrates really nicely
48:17into what the Child study Center has
48:19done with respect to Tele health so far.
48:22So allow me to just shock
48:24you all with some numbers.
48:26We have almost done a half
48:29a million video visits.
48:30I have a feeling given that we we
48:33started out before the pandemic doing
48:36between 30 and 40 video visits a day.
48:39There were mainly pilot programs,
48:41Tele, ICU, Tele stroke.
48:43We had Tele neuro.
48:44We were talking about a business
48:47plan for telepsychiatry knowing that
48:49telepsychiatry is beautiful and easy
48:51way of integrating Tele health.
48:53Into general practice,
48:54especially given other limitations and
48:56physical examinations and things like that.
48:58So everybody knew that Tele Psych was
49:01going to be a nice fit for Tele medicine,
49:04but I can tell you,
49:06after the public health emergency hit,
49:08as you can see, in March,
49:11we jumped to end up seeing between
49:132400 and we're having now.
49:15Around 4000 video visits a day
49:18for the health system,
49:19and this is across all ambulatory
49:22programs in YM.
49:23Any MTR outpatient services?
49:24Why NHHS services.
49:25Another delivery network locations.
49:27What I really want to focus your
49:29attention on is this other number.
49:31We don't look at it as often and I
49:34really believe we should 289 thousand
49:37phone consoles now we know that a
49:40lot of these are our patients and
49:42we know that because a lot of our
49:45patients don't have the access to
49:47the technology or the broadband
49:49or the access to be able to have
49:52a successful video visit.
49:53So right now we are completing over
49:55half a million video or telephone
49:57console so far and we need to be
49:59thinking about the two of them
50:01and how they interact together.
50:03So I also really wanted to tout
50:05the amazing options that have been
50:08possible because of the child study center.
50:11We are truly Trail Blazers and Tele health,
50:15mainly because because different
50:16departments and different services
50:18in different
50:19teams have found gaps where
50:21patients wanted to continue.
50:22For example, to have their group
50:25therapy and so we could set up a
50:28pilot for proof of concept to allow
50:30specific therapies happening on zoom.
50:33Even though it wasn't our preferred video
50:35client and then to have it actually
50:37transfer into our preferred video client.
50:39So it was really incredible to be
50:41able to work with clinicians an
50:43operations leads and the entire child
50:46study center to be able to say there
50:48needs to be more that can be done.
50:50We know it's possible.
50:51Let's show that it can get
50:53that it can happen,
50:54and so there's been a lot of really
50:57good work back and forth between
50:59IT and between the child study
51:01center to be able to make all of
51:03these different projects possible.
51:04We started out.
51:05Let's see if we can use an
51:07alternative platform.
51:08Let's see if we can use something
51:10special that can last for hours and
51:12hours for neuro psychological testing.
51:14Let's see if we can use a new
51:16software that was coming out.
51:18Our video visits 2.0 as we called it,
51:21which was using a different type
51:23of the software that would have
51:24had to be integrated into epic.
51:26Our electronic health record as it
51:28upgraded in September and the Child
51:30Study Center were were Trail Blazers.
51:32In being able to test out in pilot.
51:35That that new software I will also say
51:37that the child consultation liaison
51:40service were actually champions that
51:42they used as reason for an entire
51:45pilot to be started on the pediatric
51:48inpatient service that would allow for
51:50consoles across three different units
51:52in the Pediatrics inpatient world.
51:54They thought that because we were
51:57able to do it when no one else was,
52:00it means that others could use this,
52:03and so so far they've used the.
52:06Experience of our amazing CL psychiatry
52:08staff to then build and transform
52:10inpatient consoles for the Pediatrics teams.
52:13We also are now attempting
52:15to pivot and change again.
52:17What kind of software you're using
52:20because we are constantly responding
52:22to feedback and suggestions and so
52:24there is another special pilot to try
52:27to see if zoom should be our primary
52:30instead of an art alternative software
52:32platform and child study center again
52:35stepped up to the plate and agreed to do.
52:38Pilots for that.
52:39So the other the next part is,
52:42you know,
52:42our journey is just beginning.
52:44We need to continue to be champions.
52:46We're going to continue to be
52:47early adopters and we're looking
52:49not just at patient satisfaction,
52:50but we're looking at outcomes improvement.
52:52It's not just about that our patients
52:54want this, we know they want this.
52:56It's that they're going to
52:57do better because of it.
52:58That's really the idea.
53:00How can we best care for them?
53:02How can we reach them where they're at,
53:04and how can we make sure
53:05that they are staying well,
53:07it's not just that we can't
53:08just help our patients.
53:10We can't just help our families.
53:12To expand that,
53:13reach to our community and beyond.
53:15So how are we rethinking where
53:17remote patient monitoring goes?
53:19Are we looking this as a
53:21form of digital checkins?
53:22Are we considering rating scales
53:24both in between and during sessions
53:26to be done remotely so that you
53:28can get additional andmore,
53:30andmore comprehensive data?
53:31Are we thinking about mobile health apps?
53:34Are we collaborating?
53:35We are.
53:36I'm working with a with a
53:38postdoctoral fellow in Informatics
53:40who has a special interest in.
53:42Um, in the mental health of black
53:45women she was able to do her.
53:47Her PhD research was on how they have
53:51limited resources and they don't go
53:53through getting resources in the same way.
53:56So she's developed several mobile
53:58health apps in order to increase
54:00engagement and in treatment for
54:02for patients who really need it
54:04and then continuing to collaborate
54:07within the Community Schools,
54:08churches everywhere where our families are,
54:11we need to continue that collaboration.
54:13And then of course,
54:14it's not just our community,
54:16it's working for making the changes
54:18that made this possible stick.
54:20So we talked about telephone visits.
54:22They need to keep going at least
54:25for some subset of our population.
54:27We still need to talk about parity right now.
54:30It's not just parity from mental
54:32health to physical health,
54:34it's parity for treatment for Tele health,
54:36for mental health care,
54:38and Tele health,
54:39for for physical health care really
54:41becomes that much more impressive
54:42when people start questioning parity.
54:44For care for the patients,
54:46because we can truly show that 100% of
54:49the shares the same virtually is in person,
54:52and yet the reimbursements do
54:54not end up reflecting that.
54:56And then of course,
54:58it's access to care.
54:59And I think this is really an
55:02amazing opportunity.
55:03We're looking at federal and
55:04different organizational grants
55:06to look at broadband access,
55:07increased access and devices
55:09while continuing to remember that
55:11privacy needs to be where we're
55:13thinking for each of our patients,
55:15wherever we.
55:16Access them that we need to be
55:18thinking about their privacy
55:20because oftentimes they are not.
55:22So this is where I think our
55:25our journey is going and.
55:27To enclose the future of Tele
55:29Health was yesterday.
55:30We are now in a whole new world where
55:33Tele health is going to just be yet
55:36another modality of care for our patients.
55:38And I am so pleased to say that our
55:41clinicians here have stepped up to the plate.
55:44They've really made this part of
55:46their of their care signature,
55:48and they've made this part of
55:50the treatment that they give
55:51for our patients and families,
55:53and it's really wonderful to see that.
55:56So that is a general overview of.
55:58Of Tele health here,
55:59and I'm happy to answer any questions.
56:01I'm happy to give additional data if
56:03you'd like to know from a global or
56:06from the Health Center standpoint,
56:08and I'm happy just to talk about
56:10Donald all all day if you want.
56:13Thank you Pam. Why don't we
56:15go to dentist and then we'll
56:17take questions at the end of
56:19the panel as well. So Dennis.
56:26So I learned to unmute myself, so
56:29thank you and I know I also
56:31have a couple of slides.
56:34Will they pop up or should I?
56:38Share my screen.
56:39Kyle, can you give Dennis sharing privileges?
56:43You should have sharing privileges.
56:46Now there you go and thank you again
56:50for inviting me to comment about
56:53it will work and transition
56:56on this work to Tele Health.
56:59My lab does clinical trials on
57:03behavioral therapy and of course,
57:05this therapy has been historically
57:08conducted as one one face to
57:11face psychotherapy with children.
57:14We will spend quite a bit of effort
57:17trying to engage children with autism
57:19spectrum disorder in one on ones
57:22like a therapy which is in itself
57:25is quite a challenge and we've been
57:27running a study of behavioral therapy
57:30for anxiety in children with autism.
57:33Have them as you can imagine,
57:35with the onset of the pandemic
57:38in with social isolation,
57:39having both orders and anxiety
57:41was was really hard for children.
57:44With their families so that and I will work,
57:49we did what we could to do help
57:52children remain in the study and
57:55to stay engaged and to benefit as
57:59much as possible from the treatment
58:02that we have to offer.
58:05This is a study that was funded
58:08by NCH D and as a researcher.
58:11I'm very concerned was doing things
58:14by the protocol because things need to
58:17be structured and done by the book,
58:19and of course with the closures and
58:22was transitioned to Tele Health.
58:24We really needed to change everything
58:27and the studies for children in
58:30the age range from 8 to 14.
58:32They have to meet criteria
58:34for both order on anxiety.
58:37They participate in blinded ratings
58:38conducted by a clinician who is
58:41not involved in in the treatment.
58:43Everybody is randomized hand on top
58:45of all that children need to complete
58:47FMR right before and after treatment.
58:49So there is a lot.
58:52So with the beginning of kovit we
58:56transitioned to online Tele health delivery.
59:01On this treatment we.
59:03Were surprised how committed children and
59:06families were to remain in this study,
59:10but with what was equally surprising
59:12is how much the symptoms of anxiety
59:15change so that kids who were in the
59:19study requestor of fears of birds
59:22and high places and going to school.
59:25So essentially they can go outside
59:28and they didn't have to go to school.
59:31But new fears emerged, of course.
59:34And the treatment approaches that we had,
59:37such as exposure in response prevention,
59:39where you take a child in a community
59:42and you slowly expose them to things
59:45that they are reluctant to participate
59:48are we couldn't do it either.
59:50So we needed to re calibrate our
59:53treatment targets and our treatment
59:55techniques in addition to the
59:57delivery method.
59:58So this is the result from a
01:00:01children who started the treatment
01:00:03before the pandemic and continued
01:00:06and we collected their outcome
01:00:09assessments after the pandemic,
01:00:12so the blue lines are children
01:00:15who received our targeted CBG.
01:00:17An red lines that children who
01:00:20receive supportive psychotherapy.
01:00:22There was a control condition so
01:00:25strikingly everybody participated
01:00:26in all outcome assessments and.
01:00:29Children who were in active treatment
01:00:32and whose assessments were collected
01:00:34at around the time of the pandemic.
01:00:37They didn't show as much improvement as.
01:00:40As we would have predicted,
01:00:42but Fortunately from March through
01:00:44August we we started to see improvement
01:00:47in systems in symptoms an we've learned
01:00:51from kids how to make our treatment
01:00:54enjoyable and exciting for that.
01:00:56The other area of research in the Sadosky
01:00:59lab is disruptive behavior and irritability,
01:01:03so that we were really
01:01:05worried that was quarantine.
01:01:07As lockdowns there was lack of
01:01:10access to enjoyable activities,
01:01:11kids would deteriorate with
01:01:13respect to behavioral problems,
01:01:15so we track very carefully
01:01:17disruptive behaviors.
01:01:18Only one kid really had hard time,
01:01:21and because he used to go to McDonald's
01:01:25pretty often for his favorite meals.
01:01:28Don't do it anymore so that it
01:01:31really created a lot of hardships
01:01:33with the family in terms of being
01:01:36able to help this boy to to find
01:01:40other things to enjoy and do.
01:01:42And we were able to kind of guide this
01:01:45family through the study of CBD for anxiety,
01:01:49and Fortunately for us,
01:01:51we're also starting a new studies
01:01:53that will be targeted on CBT for
01:01:56irritability and disruptive behaviors so.
01:01:59For this particular project that
01:02:01were also designed for face to face
01:02:04or face to face and delivering so
01:02:06we are developing Tele health tools
01:02:08that we are ready to deploy and I'm
01:02:12happy to report that yesterday were
01:02:14included our first participant.
01:02:16So we will start this study by Tele
01:02:19Health and hope that it will be useful
01:02:22for the kids and that we can carry it
01:02:26out with sufficient research rigor.
01:02:28Thank you so much.
01:02:32Thank you, thank you Dennis.
01:02:36Yeah take it over. So I think
01:02:39what what, what I'll talk about
01:02:41briefly is just an overview and I
01:02:44don't have slides to put up is as as
01:02:46Pam Doctor Hoffman was mentioning.
01:02:48We had a huge conversion.
01:02:51The Tele health very fast,
01:02:52and it reminds me of a little of evolution.
01:02:55Sometimes evolution is slow and meandering,
01:02:57and other times they are wrapped is more
01:03:00rapid evolution because of Seminole events.
01:03:02I think we were.
01:03:04We were moving along towards
01:03:06Tele Health and this forced it
01:03:08upon US code essentially. The
01:03:11conversion was was a bit
01:03:13frightening because these
01:03:14decisions were made in the
01:03:16context of people feeling unsafe.
01:03:18Wanting to continue to provide care,
01:03:20but concerned about their safety.
01:03:22So needing to think creatively
01:03:23under the context of stress,
01:03:25I think, was was difficult.
01:03:27The the outpatient clinic
01:03:29certainly converted many,
01:03:30many to Tele Health,
01:03:31and that's been the primary delivery
01:03:33and there's many people in front of the
01:03:36scenes behind the scenes who are involved.
01:03:38And I'm just a person speaking
01:03:40about it in the Children's Day
01:03:42Hospital where we have kids 6 to 12,
01:03:45which is a group based format.
01:03:48This is a little bit more complicated
01:03:50because younger children don't
01:03:52tend to do as well for extended
01:03:54periods of time on on Tele health.
01:03:56And we were converting.
01:03:57We converted our program to Tele Health.
01:04:00Which had not been done.
01:04:02I wasn't aware of any intensive
01:04:04group based program.
01:04:05This is a 3 hour a day,
01:04:07four days a week program and so
01:04:09we converted to to Tele Health.
01:04:11And then we're not able to
01:04:13do the full program,
01:04:14so we reduced the kid time and
01:04:17spent more family and parent time.
01:04:19And the lessons that we learned our
01:04:21that we were doing things not so
01:04:23well before covid in some areas and
01:04:25doing them better with Tele health.
01:04:27So so some of the learning that we
01:04:29were all doing together now and further
01:04:32is where is Tele health useful?
01:04:34Where is it not useful?
01:04:36Which families and kids benefit
01:04:38from Tele help?
01:04:39Which kids don't younger kids older kids?
01:04:41Who are the kids that should be
01:04:43identified for in person visits
01:04:45versus telehealth visits?
01:04:46This is a struggle for developmental
01:04:48assessments where we need to
01:04:50see the kids in person.
01:04:51But how do we keep each other safe?
01:04:54And in the future,
01:04:56how do we Blend Blend Blend the two?
01:04:58So I think the story hasn't been
01:05:01hasn't hasn't been finished the way Dr.
01:05:03Hoffman described,
01:05:04but but we're moving in the right direction.
01:05:07So next steps for us would include,
01:05:09for example,
01:05:10which we've gone back to is
01:05:12giving live groups to kids.
01:05:14But parents and family sessions are
01:05:16all virtual intakes or virtual.
01:05:18We were talking about having
01:05:20parents joined a group rather than
01:05:22coming in person by video help.
01:05:23So it's a way to have a group
01:05:25session with all the kids in Group
01:05:27with all the parents of the kids
01:05:30in Group joining together without
01:05:32all the safety concerns but also
01:05:34the work and life concerns.
01:05:35Even post covid about being
01:05:37able to all make it together.
01:05:39So I think that's the next step,
01:05:41and then creativity is how we
01:05:43can take what's the best of Tele
01:05:46health and incorporated into
01:05:47our into our regular practices.
01:05:50And I think
01:05:51I'll stop there.
01:05:51Yeah, thank you very much.
01:05:53So we're now open for we have a few
01:05:56minutes for questions for this panel.
01:05:58Pam, I see you've already
01:05:59answered one question in the chat.
01:06:01I've got video fatigue.
01:06:02Do we have other questions
01:06:04for our panelists?
01:06:08I think the video 15 question is 1
01:06:11where a perfect example of
01:06:13theirs Tele health during Covid.
01:06:14And then there's a use of
01:06:17Tele health post covid.
01:06:18So when a child and family at work
01:06:21all day rather than on zoom all day,
01:06:24that Tele health session is going
01:06:26to feel very different than then.
01:06:28Then then it would otherwise.
01:06:30So I think the question is, is context.
01:06:32Operating right now I would
01:06:35also add you
01:06:35know I I don't know if any of the
01:06:38providers here could I think most
01:06:40of the providers here would say
01:06:42exactly what I'm saying and that it
01:06:44is a different level of intensity
01:06:45for the same amount of time when
01:06:47you're seeing someone were over.
01:06:49Video is when you're seeing them in
01:06:51the room and people have described
01:06:52this that the half hour doesn't feel
01:06:54like 1/2 hour because frequently
01:06:56we found with patients psychiatric
01:06:58and otherwise is they come prepared
01:07:00with questions a little more there a
01:07:02bit more concrete about their time.
01:07:03They spend a little less time on small talk.
01:07:06Because they know they have a limited
01:07:08time over video with their provider,
01:07:10and they're actually much more
01:07:12engaged in very real and specific way.
01:07:14So it is a more intensive time and
01:07:17so some of the changes that need to
01:07:19happen from a provider standpoint
01:07:21is to be mindful of that level of
01:07:24intensity that you're going to be
01:07:26feeling all day and prepare around it.
01:07:28We didn't properly prepare our
01:07:30clinicians for that Ann,
01:07:31and that was my mistake and we will
01:07:34continue to try to educate and.
01:07:36Help support so that when when
01:07:38clinicians are pulled into this
01:07:40it's not the exact same thing.
01:07:42It is different how we're looking
01:07:44at patients,
01:07:45has to be different how we're
01:07:47treating patients and how we treat
01:07:49ourselves as providers have changed.
01:07:51I think in the last six months.
01:07:53So I do believe that as we go on,
01:07:56it's it's going to be seen that.
01:07:59When people were allowed out of their homes,
01:08:01everybody wanted an in person appointment,
01:08:03not from behavioral health,
01:08:04but everybody wanted to see their
01:08:06doctors because I just can't stay
01:08:07at home with my family anymore.
01:08:09Doc, please let me go see you.
01:08:11And so we're going to see that.
01:08:13And we started to see a little re balance.
01:08:16Now with the search and I think at some
01:08:19point we're going to end in a nice place.
01:08:21The health system is looking
01:08:23at a 33% video visit average,
01:08:24so that's what we're looking at
01:08:26as our optimal goal.
01:08:27Child Study Center has been around.
01:08:2990 or so.
01:08:30So we're above average,
01:08:31but I I do believe that that will
01:08:34shift depending on Department.
01:08:35I think
01:08:36we have time for one more question for
01:08:38this panel so question in the chat,
01:08:41it's about the reimbursement
01:08:42for telehealth. I mean,
01:08:43I think I could answer that in him.
01:08:46You can chime in.
01:08:47I think this is still a work in progress.
01:08:50There's been, yes,
01:08:51lots of bypass right now.
01:08:52There was some insurance companies
01:08:54planning to eliminate this in September,
01:08:56and they've learned that this
01:08:57was poor timing on their part.
01:08:59This question is going to be
01:09:02through a number of stakeholders.
01:09:05Insurance companies have customers.
01:09:07Those customers are going to
01:09:09start increasingly expect,
01:09:11especially millennials too.
01:09:13Have to have Tele health access.
01:09:16There's some data coming out that
01:09:18Tele Health one large data set
01:09:20of millions showed that that that
01:09:23scores for physician for liking your
01:09:25physician the chance of referring
01:09:27your hospital referring your clinic
01:09:29increases through Tele Health.
01:09:31There's better customer care service,
01:09:33patient service through Tele health.
01:09:35So I think all these all these factors
01:09:37will come together and providing
01:09:39access providing medical access,
01:09:41which is a Medicaid interest as well,
01:09:44Medicare?
01:09:44So I think the book is not written yet.
01:09:47I think companies will try to
01:09:49move back in order to prevent to
01:09:51make that a lower height and the
01:09:52threshold for access to care,
01:09:54because there are obviously incentives to
01:09:55deny care in some respects in our system.
01:09:58But there are many stakeholders who
01:09:59have an interest in Tele Health as well.
01:10:01I think it remains to be written.
01:10:03I would also
01:10:04add that I'm working specifically with
01:10:06contract ING and payers for their neck.
01:10:08Text contracts to ensure that whether
01:10:10or not our government decides to
01:10:12make it at parity, that we're
01:10:14trying to put it in our government.
01:10:17Our contracts with commercial payers
01:10:18that they see this as a service that is
01:10:21provided at the same quality as in person.
01:10:24And to answer the second one,
01:10:26would you have research that shows
01:10:28that the same quality for diagnostic
01:10:30for treatment and for clinical
01:10:32outcomes have been shown both for
01:10:34for in person an video visits and
01:10:36that's for adults and children.
01:10:37Adolescents and I can give
01:10:39you references if you want.
01:10:41Next email,
01:10:42thank you very much.
01:10:44So let's let's move to our second panel.
01:10:48This is our autism colleagues,
01:10:50Doctor, Mccartin, Doctor,
01:10:51Barska and Doctor Ventola.
01:10:53Are autism team is so familiar
01:10:55to many of our associates but
01:10:58just to say that as you know,
01:11:00Doctor Mcpartland is not only a
01:11:02remarkable communicator but has a
01:11:04great vision for how to do studies
01:11:07that are collaborative and bring so
01:11:09many people together around autism,
01:11:11autism not Ripper Harsco has an
01:11:13enormous sense of playfulness.
01:11:15You may not know as much about
01:11:17her puppet work in her ability to
01:11:20integrate normal developmental ideas
01:11:21into her work with autism in infants.
01:11:24And she will introduce her
01:11:26colleague Suzanne Mcquarrie,
01:11:27and Doctor Ventola brings a focus
01:11:30on on young adults with autism.
01:11:33And how we help those individuals
01:11:35continue to live full lives and get
01:11:38the best services we can provide in
01:11:41addition to her real interest in
01:11:44training people internationally.
01:11:46So Jamie,
01:11:47may
01:11:47I turn it over to you,
01:11:50that sounds great man.
01:11:52Let me share my screen.
01:11:54It is so nice to see so many
01:11:58familiar faces and I look
01:12:00forward to the time when I can.
01:12:03See them not on a computer screen
01:12:05and share a meal and maybe a
01:12:08glass of wine with you and so.
01:12:10How does one sum up progress
01:12:12in 2020 in three minutes?
01:12:14And so I'm going to talk a little
01:12:16bit about a topic we've heard about
01:12:18it from a little bit of a different
01:12:21perspective and and the how we
01:12:23responded to the pandemic in in many ways,
01:12:26how we've reinvented a lot of the
01:12:28work that we do both in the clinic
01:12:30and in the in our research program,
01:12:33we heard a lot about Tele medicine.
01:12:35We've adopted Tele medicine,
01:12:36and in many ways in the clinic,
01:12:39many of the parent interviews.
01:12:40That we do, we now do.
01:12:43Using Tele health.
01:12:44However,
01:12:44there are some of the things that are
01:12:47so critical to understand about autism.
01:12:50The interpersonal human connection,
01:12:51the nonverbal signals,
01:12:52the facial expressions that are
01:12:54so hard to do via Tele health,
01:12:57and are frankly so hard to
01:12:59do even with a mask.
01:13:01And when the pandemic hit an many families.
01:13:05Experienced really an incredible crisis
01:13:07and people who rely on specialized
01:13:09services who rely on routine.
01:13:11Many clinicians around the
01:13:13world truly around the world,
01:13:15thought, felt at a loss to help,
01:13:18and went back to the drawing
01:13:21board and clinicians.
01:13:23Around the world got together formed
01:13:24this group called the International
01:13:26Collaboration for Diagnostic Evaluation
01:13:27of Autism and Really Reinvented Things.
01:13:30New diagnostic tools that didn't exist.
01:13:32Two months new approaches,
01:13:33you see here.
01:13:34Images from the clinic,
01:13:36simple things,
01:13:37some very simple,
01:13:38like sneeze guards that make it
01:13:40safe for two people to be in a
01:13:42room and engage with one another.
01:13:45iPads to let us minimize the amount of
01:13:47materials that were handing back and forth,
01:13:50but then also really clever
01:13:52things like using a window.
01:13:53To have a face to face interaction
01:13:55with a person unmasked while
01:13:57both parties are safe.
01:13:59If that doesn't work,
01:14:00it's hard to do that with young children.
01:14:03We could use one of our observation
01:14:05mayors to have a child interact
01:14:07with the apparent without masks
01:14:09with us behind the mirror.
01:14:11And so with a really rapid
01:14:13and steep learning curve,
01:14:14we're up and running where working
01:14:16with families at our usual pace,
01:14:18two per week and and since the pandemic,
01:14:21we've seen 21 families in the clinic and.
01:14:23It's incredibly satisfying to be
01:14:25able to help again at a time when
01:14:29help is so desperately need it.
01:14:31The lab is really a different
01:14:33set of challenges and trying to
01:14:35get running again and here we put
01:14:37together a different team that the
01:14:40consortium that I directly Autism
01:14:42Biomarkers Consortium for clinical
01:14:43trials work together to develop
01:14:45a new set of protocols for really
01:14:47collecting neuroscience data safely.
01:14:49Here involved a lot of building,
01:14:51so our labs look different than they used to.
01:14:54We now have partitions so that experimentals
01:14:57are nowhere near the participants.
01:14:59All the sensitive equipment
01:15:00that we have is encased in.
01:15:02Taxi glass so that we can clean
01:15:05it thoroughly afterwards.
01:15:07Then standard things like PPE.
01:15:08The good news is that we're up we're running.
01:15:11We've seen 23 participants.
01:15:13We actually we wondered if people would be
01:15:16interested in coming in during a pandemic.
01:15:18And as context we have 12 families that are
01:15:21scheduled to come in in the next month.
01:15:24They're very interested.
01:15:25They are very eager,
01:15:26and the data work.
01:15:28I'll say one of the things that I didn't
01:15:31anticipate is how some of the doors
01:15:33that would open in terms of research,
01:15:36so domic Trevisan.
01:15:37Who is actually a Hillebrand poster
01:15:39postdoctoral fellow in the lab,
01:15:41has moved his research online,
01:15:42and it's been a boon.
01:15:44He has seen 327.
01:15:45He's able to do 327 research visits
01:15:47on line because the constraints
01:15:49just aren't there anymore,
01:15:51and so it's been a challenge.
01:15:53We've learned so much,
01:15:54and I want to echo a sentiment that I
01:15:57think Pam made earlier is that none of us.
01:16:00None of us are glad that this happened.
01:16:03None of us would have wished for
01:16:05this opportunity for learning.
01:16:07But it's an opportunity for
01:16:09learning nonetheless,
01:16:09and when we come out of this clinical
01:16:12service and clinical research in autism
01:16:15will be better than it ever has been,
01:16:18and more accessible than it ever has been.
01:16:21Because of this crisis.
01:16:22And I'll stop there and share.
01:16:25Unshare my screen so my colleagues can go.
01:16:30And I just want to acknowledge
01:16:32all the people we really,
01:16:33really, really, really fast.
01:16:38Thank you.
01:16:40Thank you so much Jamie.
01:16:41It's really great, but thank you Kasha.
01:16:44May I turn to you to introduce Suzanne?
01:16:47Yes, it will be my pleasure.
01:16:49Suzanne Mccurry is
01:16:51the governmental scientists
01:16:52and research scientists here.
01:16:54The Child study center.
01:16:56She corrects with me the
01:16:58social effort in affective
01:17:00neuroscience about design program,
01:17:02and it's went up there.
01:17:04She's one of
01:17:05the pillars of our autism Center of
01:17:08Excellence and international baby
01:17:10Sibling Research Consortium, so he
01:17:13said he's going to talk about some
01:17:16of the. Work that
01:17:18we've done to exceed pandemic
01:17:19and ways in which we adapted.
01:17:26Thank you kasha.
01:17:29That's my screen. Can everyone see
01:17:31it? Looks great, OK, thank
01:17:34you. Thank you for the opportunity
01:17:36to speak with you all today.
01:17:38On behalf of coffee in the lab.
01:17:41So like everyone else,
01:17:43we have definitely experienced challenges,
01:17:45but also some opportunities during
01:17:47the pandemic we discovered a lot
01:17:50of things that can be done without
01:17:52necessarily being all together in person.
01:17:55We submitted to grants.
01:17:57We published three papers.
01:17:58We have several others in the works and
01:18:02continue training our new research fellows.
01:18:05During the pandemic,
01:18:06we also quickly converted our
01:18:08lab visits into virtual visits,
01:18:10but as soon as that it was
01:18:12permitted in September,
01:18:14we began inviting participants and
01:18:15patience and since then we have
01:18:18seen over 35 families in person.
01:18:20You know this is important
01:18:22because all the things we do,
01:18:24whether it's clinically to help
01:18:26families or to conduct studies,
01:18:28we can't do everything in a virtual format.
01:18:31We really do have to see them on the
01:18:34precision of diagnosis, you know.
01:18:36Depends a lot on the ability to
01:18:38interact directly with children,
01:18:40and the way that we can
01:18:43better understand emotional,
01:18:44functioning,
01:18:44attentional functioning also depends
01:18:46on us being able to study them
01:18:48in very controlled environments,
01:18:50so this was really an tremendous
01:18:52achievement of our team to be able
01:18:54to carry these visits out safely.
01:18:57So on that note,
01:18:58one very important thing that
01:19:00we were able to do during this
01:19:03time that answer is one of the
01:19:05biggest questions in the field.
01:19:07Not only here at the center,
01:19:09but it's really in the whole field
01:19:12of autism is how do you mask affect
01:19:15children's perception and behavior
01:19:16during face to face interactions.
01:19:18And Fortunately we were able to conduct
01:19:20sort of this natural experiment.
01:19:22We had been using lie by tracking,
01:19:25which is a way of studying attention
01:19:27during face to face interactions in
01:19:29toddlers with and without autism.
01:19:31And we started this work before Covid
01:19:33and we continued it during the pandemic,
01:19:36at which point we added a plexiglass.
01:19:39Divider shown here and masks and
01:19:41the question was will the kids
01:19:44be really upset when having to
01:19:46interact with someone wearing a mask?
01:19:48Maybe they don't want to.
01:19:50Maybe they will not pay attention
01:19:53to someone who looks so strange,
01:19:55but our results showed something
01:19:57really different.
01:19:58They suggested that emotionally
01:20:00children are responding quite
01:20:01normally in the presence of masks.
01:20:04We didn't see any changes from
01:20:06pre covid to now kids are.
01:20:09Typically pretty neutral during
01:20:10this kind of engagement,
01:20:11and they remain so,
01:20:13and if anything they tended to
01:20:15look more at the person who's
01:20:17interacting with them,
01:20:18which may have been caused by
01:20:20the novelty of the mask, but.
01:20:22It might also be that they're
01:20:24working a little bit harder to try
01:20:27to decode communication cues from
01:20:29the person who's speaking to them,
01:20:31so this is all fantastic work and we
01:20:34just submitted it to to our major conference,
01:20:37the International Society
01:20:39for Autism Research.
01:20:41OK,
01:20:41so a crisis like covid an existential
01:20:44crisis really pushes us all to
01:20:47really rethink our priorities.
01:20:49So we've thought much more about
01:20:51not only what's happening now,
01:20:53but what will happen when
01:20:56things stabilize again.
01:20:57What have we been learning and how
01:21:00can we take things to the next level?
01:21:03So in terms of our current priorities,
01:21:06diagnostics are something
01:21:07we're known very well.
01:21:09For we're continuing to
01:21:11expand the these services,
01:21:13so we just hired an excellent
01:21:15clinician who is bilingual Mariana
01:21:18Torres be so who will help us
01:21:21augment our diagnostic work?
01:21:23Um, we've committed to studying Co
01:21:25occurring conditions like emotional
01:21:27and behavioral problems and autism,
01:21:29which are highly debilitating
01:21:30and trying to understand their
01:21:33roots in infancy and toddlerhood.
01:21:35And we've always done a lot of
01:21:37work in supporting parents who
01:21:39are receiving a first diagnosis
01:21:41of autism through individual
01:21:43support or through parent groups.
01:21:45After Kelly Powell has been
01:21:47running a parent support group
01:21:49for a number of years now,
01:21:51and we've added some more
01:21:53targeted messaging for parents.
01:21:55Thanks to Meghan Lions and Amy Jugar Carney
01:21:58that answers more specific questions.
01:22:00Really,
01:22:00timely questions taking care of yourself
01:22:03during the pandemic transitioning
01:22:04to this very unusual school year.
01:22:07And so forth,
01:22:08but I think the most important new
01:22:11and exciting direction that we're
01:22:13taking now is to start to translate
01:22:15what we've learned from our basic
01:22:18research into things that can improve
01:22:20intervention for children with autism.
01:22:22One Direction and we won't have
01:22:24time to go into these in any detail
01:22:27and we will have an opportunity.
01:22:29I think in January to do this,
01:22:32but one of them has to do with
01:22:34improving a core symptom of autism.
01:22:378 typical social attention and
01:22:38based on some of the work we've done
01:22:41that's been funded by the associates,
01:22:44we've developed a protocol that
01:22:45may help us address some of these
01:22:48deficits are very early in life,
01:22:50even as early as infancy.
01:22:52And there's a second area,
01:22:55although there are some very well
01:22:57designed an empirically validated
01:22:59interventions like Jasper which is
01:23:01joint attention, symbolic play,
01:23:04engagement and regulation.
01:23:05Children respond to these interventions very,
01:23:08very differently.
01:23:09Some children respond immediately,
01:23:10some don't.
01:23:11Some need a lot of hours of intervention,
01:23:14some need less,
01:23:16and we want to better understand
01:23:18what the predictors are early on.
01:23:20Who will respond to this intervention?
01:23:23How do we need to adjust the intervention
01:23:26for those who don't respond in order
01:23:29to make it more most effective?
01:23:32OK so I will stop here.
01:23:37And I'm trying to get to my next slide.
01:23:40Once there we are just to give thanks
01:23:43to the entire team without whom this
01:23:46work would really not be possible.
01:23:49We have a totally amazing stellar
01:23:51clinical team who are in the trenches
01:23:54with our families who are so incredibly
01:23:57dedicated to seeing the families
01:23:59during the pandemic of research team.
01:24:02Of course an are wonderful fellows
01:24:04also so dedicated to seeing our
01:24:07kids and our staff and thank
01:24:09you also to our funders.
01:24:11And thank you all for your attention.
01:24:14Then thank you very much and I should
01:24:17just say before I turn it over to Pam.
01:24:20Suzanne's mentioning in January because we
01:24:22have this wonderful new virtual technology.
01:24:24We will be actually having some
01:24:27special sessions in December and
01:24:29January to highlight in greater depth
01:24:31on the work of our autism team.
01:24:33So stay tuned for announcements about that.
01:24:35So now let me turn it over to
01:24:39Doctor Ventola Pam. Thank you.
01:24:42Here. Great.
01:24:53Down. Right, looks like there are
01:24:57excellent fantastic. Well thank you
01:25:00all for for coming in and listening
01:25:04to the the work that we're doing so
01:25:08my work has is all about clinical
01:25:11trials and both running clinical
01:25:13trials in autism and in supporting
01:25:16international clinical trials that are
01:25:19done after my industry sponsors their
01:25:22large scale academic groups and in.
01:25:25Prior meetings and meetings
01:25:27with the associates in toxic.
01:25:29Focused on what we've done in our
01:25:31lab with behavioral treatments.
01:25:33An that's still going on.
01:25:34And as you've heard from my my colleagues,
01:25:37alot of this move to Tele medicine
01:25:40and our work has as well we're doing
01:25:43a lot of video consultations and
01:25:45parent training with young children
01:25:47have autism and that is going very,
01:25:49very well.
01:25:50But we also are doing a lot of
01:25:52work right now with the pandemic
01:25:55in supporting international.
01:25:56Industry sponsored or pharmaceutical trials.
01:25:59And that's a big focus of my lab as well,
01:26:03and that's been growing and
01:26:06just really exciting and new.
01:26:08And I wanted to to share that piece
01:26:12of things with you
01:26:14today. So when the pandemic hit,
01:26:16there's lots of clinical trials that are
01:26:20ongoing and that are planned in this
01:26:23space of developmental disabilities,
01:26:25rare diseases, genetic conditions.
01:26:27That are absolutely debilitating and
01:26:29for many of these conditions there's the
01:26:32children are very impaired or shortened.
01:26:35Life expectancies and the families are
01:26:37really desperate for treatment options,
01:26:40and there are often no no
01:26:42effective treatments, so you know,
01:26:45even in the face of covid,
01:26:47these trials needed continue both for safety,
01:26:50because these children were already on
01:26:53drugs or starting different therapies,
01:26:55but also because the need is just so great.
01:26:59So our lab was leaned on quite a
01:27:03bit to help come up with solutions,
01:27:06so lot of which you've heard already,
01:27:09but on a large scale.
01:27:11So things trials that are
01:27:13going internationally.
01:27:14So how can you continue a trial?
01:27:17Not just it?
01:27:18Major academic Medical Center in the US,
01:27:21but trials that are on going
01:27:24around the world.
01:27:25So we had to figure out how to move.
01:27:29These visits,
01:27:30when their their families
01:27:32and children came to clinic,
01:27:34how traditionally to assess their,
01:27:36you know their outcome,
01:27:37how their development was progressing,
01:27:39language motor skills and how to
01:27:41take that and do that remotely.
01:27:44And that's what we have spent
01:27:46tremendous effort.
01:27:47We have do it very quickly,
01:27:50so we had to pivot.
01:27:52Help these trials pivot very quickly,
01:27:54so in one way that we worked a lot on
01:27:57doing this is developing creative means.
01:28:00So as Jamie was describing what
01:28:03we did and clinic,
01:28:05we're doing very similar things
01:28:07just on a very large scale.
01:28:09So how to creatively assess?
01:28:12Children who might be very,
01:28:14very impaired and talk with their
01:28:16families and how to get that data
01:28:19about their their skills in their
01:28:21functioning in a remote context.
01:28:23So things like sharing your screen so
01:28:26to having a video conference having
01:28:28lots of zoom meetings or meetings over
01:28:31you know different video platforms
01:28:33an sharing your screen and being
01:28:35able to ask them a lot of questions,
01:28:38but the parents could also see
01:28:40them through this screen share.
01:28:42We're doing video visits where you're
01:28:45showing them things able to observe
01:28:48the children through video and
01:28:50just to you, it sounds so simple and
01:28:54in a way it is.
01:28:56But we're implementing
01:28:57this in not only in the US,
01:29:01in North America and Europe,
01:29:03but in South America and in
01:29:06Asian countries like China,
01:29:07where there's different access and
01:29:10different broadband capacities and
01:29:12different kinds of devices and rules around.
01:29:15Privacy, so there was a
01:29:17lot to figure out that we,
01:29:20but we've done it successfully there.
01:29:22These trials are keeping are still going.
01:29:25We're also validating,
01:29:27so I have many collaborative papers
01:29:29that are going to be coming out soon.
01:29:32Looking at the validation of different
01:29:35assessment measures done in person
01:29:37versus on video or over the phone.
01:29:40'cause that's an important question.
01:29:42When I say if I'm doing this measure.
01:29:46I'm doing this in trivial.
01:29:48Are we sure it's the same if it's
01:29:51in person or over a video platform,
01:29:54we think it is,
01:29:55but we need data and we need
01:29:58to be able to show if it is the
01:30:01same or how it's different.
01:30:03As an example,
01:30:05families may feel more comfortable
01:30:07endorsing symptoms when it's just on paper.
01:30:09You know they might feel shy or quiet
01:30:12about telling their clinician about that,
01:30:15but feel more comfortable.
01:30:17Writing it,
01:30:17or vice versa when they
01:30:19get their clinician on the line
01:30:21and feel like they can talk more.
01:30:24Do they endorse more and are their response
01:30:27is different and that's just important
01:30:29information for us to know as we move
01:30:33into this new world of more virtual.
01:30:35Collect your virtual clinical trials.
01:30:37More virtual clinical visits.
01:30:39I'm also developing is also
01:30:42Jamie alluded to different tools,
01:30:44but tools that can be used and
01:30:47there are designed to be used to
01:30:50measure skills completely,
01:30:52remotely, completely,
01:30:52virtually through structured observations
01:30:54and interviews with parents,
01:30:56we can gain really granular information
01:30:58about the child symptoms development,
01:31:01functioning without actually
01:31:02being in the room with the child.
01:31:06And Lastly, towards this end of just,
01:31:09you know, this remote visits and assessing
01:31:12symptoms and functioning remotely,
01:31:14doing a lot of work.
01:31:16Also on implementing web based cognitive
01:31:19assessments with new populations.
01:31:21So in certain areas that are
01:31:24not diseases that I work in,
01:31:26it's not not typically in autism
01:31:29or developmental disorders.
01:31:30These cognitive tests are used
01:31:32a lot in dementia research and
01:31:35and psychiatric research.
01:31:37Other indications
01:31:38it's really knew this isn't
01:31:40something that we've done in autism
01:31:42or developmental disabilities,
01:31:43but now we're starting to where
01:31:45someone can log into a website and
01:31:48launch an app to that will collect
01:31:51really high quality and sensitive data
01:31:54about their cognitive functioning.
01:31:56So we're piloting that with a lot of
01:31:59different kinds of disorders now as well,
01:32:02and this work is just so exciting
01:32:05and it's really meaningful for me.
01:32:07Because you know,
01:32:09I see these families with both
01:32:11with autism and other kinds of
01:32:13disabilities and their struggling
01:32:15and they they need treatments,
01:32:17but it's hard so it's hard getting to.
01:32:21The clinic is hard.
01:32:22Bringing your child who can't
01:32:24walk or who can't talk.
01:32:26You know who's 12 years old
01:32:29and is functioning very,
01:32:30very low.
01:32:31It's hard to get to these the
01:32:34doctor's office and sometimes it's a
01:32:37far distance there traveling there.
01:32:39In parts of the world that don't
01:32:41have major academic medical
01:32:43centers so they can get care,
01:32:45so being able to offer these
01:32:47services and these opportunities,
01:32:49being families at a level they
01:32:51can access much more easily,
01:32:53I think is huge.
01:32:54So I think this was it's amazing and
01:32:57he started because of the pandemic,
01:33:00but because of that I think the
01:33:02world of clinical trials is
01:33:04absolutely shifting and we're going
01:33:06to be able to see greater access.
01:33:09To these opportunities that for the
01:33:11families who are interested in them,
01:33:14even beyond the pandemic.
01:33:17Thank you Pam. Very much
01:33:19so we have time for just
01:33:21a few questions. Anybody want to ask
01:33:25questions into the chat or speak them out?
01:33:32No questions.
01:33:43Well, I'm just very grateful to all the work.
01:33:46I think you can see the creativity of
01:33:48our autism team and how they have adapted
01:33:51in these very challenging circumstances.
01:33:54They've adapted to continue their research
01:33:56and continue their clinical care,
01:33:58and so we're very proud of that.
01:34:00And please do stay tuned for for the
01:34:03more in depth sessions that will
01:34:05have one in December 1 in January.
01:34:08I'm about this work.
01:34:11I want to turn them an if you
01:34:13have quite you think of questions,
01:34:15put them in the chat and I would
01:34:17ask that Jamie Anne Pam and Susanna
01:34:20Kasha just monitor the Shannon
01:34:22and answer questions even then.
01:34:24So let me turn them to our third
01:34:27panelist and this is on maternal
01:34:30depression at the Child Study Center,
01:34:32we take a two and three generation
01:34:35perspective and think about what
01:34:37happens in utero and what happens in
01:34:40parenting environment as direct effects
01:34:42on children in child development.
01:34:44And so for this last session,
01:34:47and it's my pleasure to have Jenny Dwyer,
01:34:50221 faculty member, who joined us last year.
01:34:53Danny Dwyer and a second faculty
01:34:56member who just joined us,
01:34:57secure and O'Donnell.
01:34:58And what I would say about Jenny
01:35:01is remarkably creative,
01:35:02as she will hear.
01:35:04But Jennie is also in her own maternal
01:35:06transition time,
01:35:07so I'm just very glad that she could join us
01:35:10in person and will want to hear about that,
01:35:13Jenny.
01:35:14And then Kieran,
01:35:15who has as I said,
01:35:17just recently joined us,
01:35:19certainly had a dramatic effect
01:35:21of the pandemic on his ability to
01:35:23actually get to American embassies
01:35:25and be able to get into the country.
01:35:28So he has already remarkable persistence
01:35:30before he even came to New Haven.
01:35:33So Jennifer, we first play your video.
01:35:37Sure, that's fine.
01:35:38OK, well Kyle,
01:35:40can you put the video up for me?
01:35:46Resume do we still have Kyle with us?
01:35:56Let me locate him.
01:36:00Jenny D. Message I have a copy of it also so
01:36:06I don't know. Do you want
01:36:08me to go first or Kiran? Did you want
01:36:11to? Do you have a copy?
01:36:12I'll tell you what I will.
01:36:14I will give you screen
01:36:16sharing privileges so okey
01:36:17Dokey. Alright look at us adapting. I think
01:36:20that's the theme today. OK, should
01:36:22be able to screen share. Folks, let
01:36:28me know if you
01:36:31can't hear. Hopefully
01:36:34the audio should play.
01:36:39Hi everybody is talking to
01:36:41the 2020 associates meeting.
01:36:43I'm setting fire and excited
01:36:44to talk to you about our
01:36:47depression program for today.
01:36:48You might notice that this
01:36:50is a recording. Jenny,
01:36:52can you turn it up a bit volume
01:36:58wise? This is a picture of our son.
01:37:01This is Jules Michael Dwyer,
01:37:03three weeks old today and I am
01:37:05hopeful that he will cooperate with
01:37:07an app around the time that will be
01:37:09doing the panel discussion and I'll
01:37:11be able to talk more with you then,
01:37:14but I'm going to tell you right now,
01:37:17but my other baby from this year,
01:37:19which is the pediatric treatment
01:37:21resistant depression program.
01:37:22You might notice from combining Doctor
01:37:24O'donnell's work with my own that we're
01:37:26really trying to take the lifespan
01:37:28perspective on depression treatment.
01:37:29Maternal depression is a huge risk
01:37:32factor for teenage depression,
01:37:33nearly doubling the risk depression is
01:37:36already pretty common in adolescents.
01:37:38So up to one in five teens
01:37:41experiencing depression.
01:37:42And we know that this can be deadly,
01:37:45so increasing the risk of suicide by 30
01:37:47fold the depression diagnosis and suicides.
01:37:50Now the second leading cause
01:37:52of death in young people.
01:37:54Treatment is so important and we have
01:37:57medications and psychotherapy that can
01:37:59be quite effective for many patients,
01:38:01but up to 20% will have depression
01:38:05symptoms that are treatment resistant.
01:38:08And so our real goal of the last
01:38:10year since I've joined the faculty,
01:38:13is trying to establish child study center
01:38:15as a world leader in pediatric depression,
01:38:18clinical treatment and
01:38:19translational research.
01:38:19And so I'm going to tell you about some
01:38:22of the progress and areas for growth.
01:38:25Program.
01:38:25So the first is the clinical program
01:38:28that we've started to build the
01:38:30subspecialty service pediatric
01:38:32patients with TRD or underserved.
01:38:34So there's already a shortage of
01:38:37child psychiatrists and these kinds
01:38:39of cases that are complicated
01:38:41and keep people up at night.
01:38:43It's even harder to find a specialist
01:38:45with both the bandwidth and the expertise
01:38:48to take on these types of presentations.
01:38:51So we started the pediatric treatment
01:38:53resistant Depression Service,
01:38:54which opened a year ago in.
01:38:57Number of 2019 I Co direct the service
01:39:00with Michael Block and we provide
01:39:03comprehensive assessment of complex patients.
01:39:05At the end of our half Day interview,
01:39:09instead of assessments,
01:39:10we give a diagnostic formulation
01:39:12and treatment recommendations,
01:39:13and in the cases where it's appropriate,
01:39:16we also help facilitate access to
01:39:19interventional psychiatry approaches
01:39:20such as our TMS Academy or ECT.
01:39:23And that's really a unique feature of
01:39:25the environment here at Yale and our
01:39:28partnerships both within the Department
01:39:30and across the Department of Psychiatry.
01:39:33We,
01:39:34like everyone else.
01:39:35I've had significant covid challenges,
01:39:37but I think also some
01:39:40opportunities embedded therein,
01:39:41similar to let Doctor Cegelski
01:39:43talked about with Tele medicine.
01:39:45Being able to really bring
01:39:47treatments and assessments in a
01:39:50way that has enhanced access.
01:39:52We've adapted our assessment virtually,
01:39:54and I think this can be really
01:39:57helpful in terms of equity,
01:39:59so we get requests from all over the
01:40:02country for these types of assessments.
01:40:05But not everyone is able to
01:40:07travel to New Haven,
01:40:08and so we hope that Tele medicine
01:40:10is something that's here to stay
01:40:12so that we can reach more people.
01:40:14This is an area of rapid growth.
01:40:17We're hoping that will have the
01:40:19resources to hire some additional staff
01:40:21and personnel so that we're able to
01:40:24bring this subspecialty care to more
01:40:26kids over the coming months and years.
01:40:30So the secondary I'm going to talk about
01:40:33is some of our translational research
01:40:35about novel pediatric treatments,
01:40:37so you can see here on the left looking
01:40:39at the number of FDA approved anti
01:40:42depressant medications in adults,
01:40:44there's like 30 Medecins to choose
01:40:46from and Pediatrics.
01:40:47Maybe you can't even see this tiny
01:40:50speck that represents the two
01:40:52medications that are FDA approved.
01:40:53The results of this is that many
01:40:56medications are prescribed off label.
01:40:58And even if kids get evidence based
01:41:01treatment, which many do not together,
01:41:04you know 20% that will have
01:41:06resistance symptoms.
01:41:07So we really need new treatments.
01:41:11Industry has had some questionable
01:41:13clinical trials in the past and
01:41:16for a variety of reasons,
01:41:17many major players in industry have largely
01:41:20left the pediatric mental health space.
01:41:23Which leads us to rely on federal funding,
01:41:26which is actually not been much more helpful.
01:41:29They haven't funded a pediatric TRD
01:41:32clinical trials and tortilla was funded,
01:41:34which started back in 2001.
01:41:37So we're really looking at this treatment
01:41:40wastelands for pediatric patients in
01:41:41pediatric patients deserve evidence
01:41:43based medicine just like everyone else,
01:41:45and so we've been working to try to
01:41:48sort of create an Oasis in the desert
01:41:51here with our clinical trial work.
01:41:53So I showed this figure two years ago.
01:41:56I think from our initial CADA
01:41:58mean randomized control trial.
01:41:59We were the first group to ever do
01:42:02in RCT of CADA mean in this group,
01:42:05and this is showing a significant
01:42:07reduction of depression.
01:42:08Symptoms in kids with TRD after a
01:42:11single dose of cada mean lasting
01:42:13all the way out to two weeks.
01:42:16Based on this data,
01:42:17we started the second clinical
01:42:19trial called the Sad Kids trial
01:42:22severe adolescent depression.
01:42:23Cada mean intermediate duration study.
01:42:26And this is a repeat dosing trial,
01:42:28so looking at 6 doses of CADA mean
01:42:31versus 6 doses of an active control and
01:42:34then following kids over six months to
01:42:36look at both safety and effectiveness.
01:42:39The study was initially funded
01:42:41by the Clean Steam Foundation,
01:42:43which we're very grateful for,
01:42:45and we're hopeful that these
01:42:48studies will resume very soon once
01:42:51kovid is under better control.
01:42:54And the last piece I'm going to talk about,
01:42:57which I'm really excited about,
01:42:58is integrating this idea of brain
01:43:01based personalized medicine
01:43:02into some of our research.
01:43:04So we know that we need new treatments,
01:43:06but it's not just.
01:43:07Is there a treatment available but
01:43:09which treatment for which patients?
01:43:11And right now the current state
01:43:13of antidepressant prescribing
01:43:14is pretty pathetic.
01:43:16It is trial and error medicine
01:43:18where we try a medicine.
01:43:20We wait 6 to 8 weeks.
01:43:22It doesn't work.
01:43:24We try something else and we waste so much
01:43:27developmental time playing a guessing game.
01:43:30And so the gold standard is really to be able
01:43:34to have a biologically based,
01:43:37reproducible brain based measure
01:43:39that helps predict what treatment
01:43:41will work for which patients.
01:43:43As you try to move towards that goal,
01:43:46we've partnered with Todd Constable in
01:43:49the Department of Radiology to utilized
01:43:52this MRI based predictive modeling.
01:43:54So we put our participants in a magnet and
01:43:57have them do a series of tasks and rest
01:44:00conditions while scanning their brain.
01:44:03Sort of make this analogous
01:44:05to a cardiac stress test,
01:44:07acceptance of brain stress test.
01:44:09So we're going to stretch the
01:44:11brain across multiple domains,
01:44:13so cognitive domains affect if
01:44:15domain social domains and then we
01:44:17can aggregate all of that data and
01:44:20turn it into an individual brain
01:44:22fingerprint or connect own fingerprints.
01:44:25And use that for prediction.
01:44:28So you can complete this task
01:44:30in under an hour.
01:44:31We've run some kids through this protocol.
01:44:33They tolerate it well.
01:44:35And this has been a successful
01:44:37predictive strategy.
01:44:38It's mostly been used to predict symptoms,
01:44:42so it's successfully predicted the
01:44:44degree of inattention in ADHD sample
01:44:47that has also successfully predicted
01:44:50autism symptom scores and mixed
01:44:53sample of kids with ADHD and autism.
01:44:55But I'm really keen on this idea of
01:44:58using it not just to predict symptoms,
01:45:01but to predict treatment and
01:45:03in adults this work has started
01:45:05to really bear some fruit,
01:45:07so being able to predict treatment
01:45:09outcomes in adult substance use disorders.
01:45:11So we've decided to integrate this
01:45:13into our clinical trial model and
01:45:16I'm really excited to share with
01:45:18you that we just got a big grant,
01:45:20almost a $2,000,000 grant from
01:45:22the NIH for a project called
01:45:24reducing adolescent suicide risk.
01:45:26Safety,
01:45:26efficacy,
01:45:27and connection phenotypes of
01:45:29intravenous Academy.
01:45:29So really marrying Academy clinical
01:45:32trial work with some of the brain
01:45:35based personalized medicine work.
01:45:37So this is a four year trial that's
01:45:39going to incorporate neuroimaging
01:45:41based predictive modeling,
01:45:43and it's the first NIH funding
01:45:45for an adolescent depression
01:45:47trial in nearly two decades.
01:45:48And so we're really excited that NIH
01:45:51appreciates that this is an area of great
01:45:55need and potentially great innovation.
01:45:57So I hope that I've convinced you that
01:45:59we are well on our way to building
01:46:02a real flagship program in terms of
01:46:05clinical and translational excellence
01:46:06in pediatric depression care.
01:46:08We have clinical trial work going on
01:46:11this personalized medicine approach
01:46:12going on and then really integrating
01:46:15that into our clinical programs
01:46:17so that we can bring cutting edge
01:46:19care to as many kids as possible.
01:46:22So I really appreciate you all
01:46:24taking the time to listen,
01:46:26and I'm hopeful that we'll be
01:46:28able to chat a little bit.
01:46:30More.
01:46:32Thank you very much.
01:46:35Any really thank you great.
01:46:38So here in my turn to you and then
01:46:40will have questions, I'm at the end.
01:46:45Thank you so much Linda,
01:46:47and what a privilege.
01:46:48But also such a challenge to follow
01:46:50the fantastic talks that we've
01:46:52heard not just this afternoon,
01:46:55but from our colleagues across this week.
01:46:57It's really been such an interesting
01:46:59associates week and my name is Kieran
01:47:02O'Donnell and as Linda mentioned,
01:47:04I am a recent addition to the
01:47:06Child Study Center virtually since
01:47:08July 1st and then in person since
01:47:11the end of September and I lead
01:47:13the health omics and perinatal.
01:47:15Epidemiology research group here at the
01:47:18Child Study Center and within my group,
01:47:21we capitalize on our ability to describe
01:47:24and characterize complex biological
01:47:26systems an in greater depth and breath
01:47:29than has ever been previously possible.
01:47:32And then the goal is to mobilize this
01:47:35new knowledge to inform the care of
01:47:38pregnant women and their children.
01:47:40Now, one biological system that my group
01:47:43spends a lot of time characterizing.
01:47:46Is the epigenome now epigenetics?
01:47:48Quite simply means on top of genetics
01:47:52and there is a series of chemical marks
01:47:56or modifications that sit on or close
01:47:59to the DNA that can change its function.
01:48:02But I like to think of the epigenome
01:48:05as essentially a translator as an
01:48:07interpreter that allows the environment
01:48:09to communicate with the genome.
01:48:12Changing the genomes function in response
01:48:14to changes in the environment with
01:48:17potentially the lasting effects on the
01:48:19phenotype of the of the mother or the child.
01:48:22And now,
01:48:24of course the question are there.
01:48:26When I started my presentation,
01:48:27I mentioned that we try to mobilize
01:48:29these data to improve health outcomes.
01:48:32So the question is,
01:48:33what is the health outcome that I focus on?
01:48:36Well,
01:48:37for those of you that have heard
01:48:39me speak before,
01:48:40you know that I obsess about a
01:48:43series of numbers and those numbers
01:48:45are 414 and 4414 and 40.
01:48:47So what do these numbers represent?
01:48:49Well, these numbers represent one in four.
01:48:51That is, the number of women.
01:48:53Number of pregnant women that we may
01:48:56struggle with their mental health,
01:48:58most commonly anxiety or depression.
01:48:59One in four,
01:49:00and we know that many of these women
01:49:03will not even be assessed for their
01:49:06mental health needs in pregnancy
01:49:07and those that are assessed may not
01:49:10receive the adequate treatment.
01:49:12So that's one in four.
01:49:14Now,
01:49:15what about those other numbers that
01:49:17I mentioned? The 14 and the 40?
01:49:21Well,
01:49:21those numbers represent the costs
01:49:24associated with untreated perinatal
01:49:26mental health problems in the
01:49:28United States per year.
01:49:30And most probably even more shockingly,
01:49:32the 40% that cost is derived from the
01:49:34adverse effects of perinatal mental
01:49:36health problems on child outcomes,
01:49:38and those costs are only calculated
01:49:40from birth to four years of age.
01:49:43So you can imagine as we go from 5 to
01:49:4610 to 15 to 20 years post pregnancy,
01:49:49how those costs are likely to add up.
01:49:52So you might ask,
01:49:53what are the costs associated with?
01:49:55Well,
01:49:56my own research in a large cord
01:49:58from the United Kingdom.
01:50:00Assume that children born to women
01:50:02who experience high levels of
01:50:04anxiety or depression in pregnancy
01:50:05have double the risk for adverse
01:50:07mental health outcomes themselves.
01:50:09These effects are evident in early childhood
01:50:12and they persist until at least early.
01:50:14Adult hood. Now, of course,
01:50:16the question then becomes
01:50:17what can we do about this?
01:50:19So within my group we are trying to
01:50:22build better next generation screening
01:50:23tools to identify women that are
01:50:26likely to struggle with their mental
01:50:28health in and around pregnancy.
01:50:30So we're building a molecular
01:50:32screening tool based on hormone
01:50:34sensitivity in pregnancy,
01:50:35so implementing a molecular
01:50:37screen in first trimester,
01:50:38pregnant women and using gene network
01:50:41analysis to identify genes that are
01:50:43sensitive to hormones of pregnancy and
01:50:46that predict risk of postpartum depression.
01:50:48Because we know that there's at
01:50:50least a subgroup of women that
01:50:53you'll heighten sensitivity,
01:50:54the hormones of pregnancy,
01:50:56and when those levels dropped
01:50:58precipitously in the postpartum,
01:50:59those women.
01:51:00Are rendered more more susceptible
01:51:02to postpartum depression.
01:51:03The second tool that we're developing is
01:51:06sitting in most of your back pockets,
01:51:09or hopefully not your hands at the moment.
01:51:12That's a smart phone,
01:51:13so we're using passive data capture,
01:51:15so that's background data capture
01:51:17from smartphones to create a digital
01:51:19index of social support because we
01:51:22know that social support plays a
01:51:24profound role in influencing risk
01:51:26for perinatal mental health problems.
01:51:28So there are two of the examples
01:51:31in my group that I'm.
01:51:32Research projects that I'm
01:51:33expanding here at Yale,
01:51:35but turning out to the child were also
01:51:37harnessing the information contained
01:51:39in individuals biology to better
01:51:41understand which children are at risk.
01:51:43You will remember that I mentioned the
01:51:45children children born to women who
01:51:47struggle with anxiety or depression
01:51:49and pregnancy have twice the risk
01:51:51for emotional behavioral problems.
01:51:53But the important message is that
01:51:55not all children are affected,
01:51:56and those children that are affected
01:51:59can be affected in very different
01:52:01ways and we just don't.
01:52:02Understand what is the biological
01:52:05basis in the biological contribution
01:52:07to such individual differences.
01:52:09So we've been developing biomarkers,
01:52:11particularly epigenetic biomarkers,
01:52:13to better understand the biological
01:52:15embedding of the early environment,
01:52:18and this is 1 example of those biomarkers.
01:52:21An epigenetic Clock that allows us
01:52:24to calculate a child epigenetic age,
01:52:27and we find that children who are
01:52:31epigenetically older and show a greater rate.
01:52:34Of an autism spectrum disorder
01:52:36and most recently in our study in
01:52:39Singapore and in the Netherlands,
01:52:41we find that maternal prenatal anxiety
01:52:43is associated with accelerated
01:52:45epigenetic aging,
01:52:46and the question that we then ask
01:52:48ourselves is how can we use this
01:52:52information to inform interventions.
01:52:53I think a theme that we've heard
01:52:56from Doctor Dwars talk.
01:52:58I've also doctor Makaris talk and
01:53:01really throughout this week is
01:53:03trying to promote.
01:53:04Personalized care how can we
01:53:06integrate measures of biology to
01:53:08better understand why some children
01:53:09do better and some children don't
01:53:12respond to early interventions.
01:53:14Some very excited to partner
01:53:15with Doctor Megan Smith who
01:53:17you heard from yesterday,
01:53:19is developing really a phenomenal
01:53:21intervention in Bridgeport, CT,
01:53:23where women vulnerable women will
01:53:25be supported through pregnancy
01:53:27in terms of their mental half,
01:53:28their ability to parent and multiple
01:53:31aspects of child development,
01:53:32and we hoped it.
01:53:34Integrates these epigenetic
01:53:35biomarkers to better understand
01:53:36individual differences in treatment
01:53:38response to early intervention,
01:53:40so putting it all together,
01:53:41we're really trying to harness the
01:53:44information contained within the genome
01:53:45within biology to better understand
01:53:47the impact of the early environment,
01:53:50and I think this can be summed up
01:53:52beautifully in this image taken from
01:53:54the WHL nurturing care framework,
01:53:57which says that if we can change
01:53:59the beginning of the story,
01:54:01we can change the whole story.
01:54:03I truly believe that.
01:54:05With every woman we can,
01:54:07we should promote and optimize
01:54:08pregnancy well.
01:54:09Being and in doing so we stand to
01:54:12promote and optimize child development.
01:54:14Thank you,
01:54:15thank you
01:54:16so much, Karen. And thank you for
01:54:19bringing us to a message of hope.
01:54:22And the virtual floor is open for
01:54:25questions for Jenny and procuring.
01:54:30And Jenny the best way we can see that your
01:54:33live is the sunset that was behind you.
01:54:36Become Twilight, yes. So any questions?
01:54:40Thank you for sharing a picture of your son
01:54:43to that. That's him when he is quiet
01:54:45and end jellick, I figured that was
01:54:48the right one to show.
01:54:51If you would like, you can just speak out
01:54:53the questions or put them in the chat.
01:55:02I guess I have a
01:55:04question about Kieran's work.
01:55:06When you were talking about the
01:55:08molecular screen in the first trimester.
01:55:11For women that seem really
01:55:13sensitive to hormonal changes,
01:55:14does that have any implications for
01:55:17the new postpartum depression treatment
01:55:19that was FDA approved BREXANOLONE,
01:55:21which is supposed to help sort
01:55:23of create a smoother landing pad?
01:55:26I guess for the declining levels
01:55:28of pregnancy hormones exactly
01:55:30yeah, so this is, as you know,
01:55:32really interesting
01:55:33development in the treatment.
01:55:35Of postpartum depression.
01:55:38One of the challenges without treatment
01:55:41is that it's incredibly expensive,
01:55:43so costs over $35,000 for treatment
01:55:45with Solaris or Brown, Lexile, Ann,
01:55:47and what's interesting about it is
01:55:50essentially replenishing and naturally
01:55:51occurring metabolite of progesterone.
01:55:53So we would really like to determine
01:55:56if we can identify which women are
01:55:59likely to respond to that treatment.
01:56:01So there's not this huge cost for
01:56:04potentially ineffective treatment,
01:56:05so within that molecular screening
01:56:07tool assessment.
01:56:08We're also including and allopregnanolone
01:56:10arm to the study to try and determine
01:56:13sensitivity to Al pregnenolone,
01:56:15so we will have separate arms determining
01:56:18sensitivity to dexamethasone so it
01:56:20looks like corticoid and to Easter
01:56:22Dylann to allopregnanolone so great.
01:56:25Great question,
01:56:25so hopefully we can get closer
01:56:28to that precision medicine.
01:56:30Very cool.
01:56:32Thank you. Any other questions?
01:56:37I have a question. Please so it
01:56:44might not necessarily fit in,
01:56:46but it's kind of thinking of a lot
01:56:49of the adolescents that we see in
01:56:52the in the Depressione clinic.
01:56:54Alot of them are driven there.
01:56:56Hormones drive a lot of
01:56:58their depressive episodes.
01:57:00Current do do you know if there's any
01:57:03studies done about hormones and if
01:57:05any of these markers might tell you
01:57:08which women are more prone to have
01:57:11depression because of these changes in there?
01:57:14Here, in their hormonal
01:57:16patterns prior to being.
01:57:18Pregnant. Yeah,
01:57:20that you know,
01:57:21and so that's a great question.
01:57:23And there has actually been a
01:57:25lot of research focusing around
01:57:27menopause and showing certain women
01:57:29being particularly sensitive to
01:57:30manifolds in terms of precipitating
01:57:32and depressive like symptoms and
01:57:34then showing that if you do make
01:57:36experimental manipulation of Easter
01:57:38dial levels that you can again
01:57:40precipitate increased symptoms
01:57:41of depression and would there is
01:57:43not a whole lot of literature on
01:57:46that in the context of puberty.
01:57:48So it's a very interesting
01:57:50research perspective.
01:57:51One of our colleagues in Copenhagen
01:57:53actually has an experimental approach
01:57:55where they use subcutaneous implants
01:57:57to push and pull Easter dial levels,
01:58:00and she does show that in some
01:58:03women they can precipitate and
01:58:05kind of depressive
01:58:06symptoms. 'cause we we've
01:58:08seen a subset in the in this just
01:58:11taking it back to some of the other
01:58:14pathologies that we we study.
01:58:17A specific subset of women,
01:58:19for example with Tourettes syndrome.
01:58:21That during during the hormonal changes.
01:58:24That drastically changes that
01:58:26the way or the patterns in which
01:58:29they are there ticks manifest.
01:58:32Of course women with Tourette's
01:58:34are a minority,
01:58:35so it's difficult to kind of follow them,
01:58:39but it almost seems like the the hormones
01:58:42are uniquely driving the the the
01:58:45sequence of the ticks that are happening.
01:58:48So I'm just interested in maybe seeing
01:58:51or using some of this molecular.
01:58:54Biomarkers and maybe using it for
01:58:56other not just in pregnant women,
01:58:59but maybe for other you know,
01:59:01focusing specifically on women's
01:59:02mental health.
01:59:04I think you know
01:59:05it's trying to identify those
01:59:07subgroups. Trying to understand that
01:59:09heterogeneity, so I think that's that's
01:59:11fantastic engineer experience
01:59:13with adolescent girls.
01:59:14In puberty, in the clinic,
01:59:16sure, yeah. I mean, the gender
01:59:18difference in depressione
01:59:19incidents comes out at puberty,
01:59:21so we know that there is a significant
01:59:24impact of hormones on the brain.
01:59:26And so we certainly see that just in
01:59:29terms of the ages is when people say,
01:59:32like you know, really starting to get bad
01:59:35right around the time that puberty happened.
01:59:38I think the literature on hormone
01:59:40manipulation adolescence is a tricky one.
01:59:42I mean, there's actually
01:59:44some big observation.
01:59:45ULL studies that suggest that oral
01:59:47contraceptives can actually lead
01:59:49to worst mental health outcomes.
01:59:50You know where you would think?
01:59:52Maybe if we're regulating cycles that you
01:59:55would get better mental health outcomes.
01:59:57So it is a really complicated system that
02:00:00has a lot of complex biofeedback built in.
02:00:03So anytime you take her with
02:00:05something over here, you get a can
02:00:08pensa Tori change somewhere else.
02:00:09But it's something that we
02:00:11certainly pay attention to,
02:00:12and actually,
02:00:13in preparing for this meeting
02:00:15we talked about.
02:00:16Maybe we should be measuring
02:00:17hormone levels in some
02:00:19of our clinical trials,
02:00:20so I think
02:00:21it's a really important important
02:00:23area to be thinking about.
02:00:25Well, I want to be sensitive to everyone's
02:00:28time and thank you so much for joining us.
02:00:32Just so you know, we have recorded
02:00:34these sessions so that will make
02:00:36them available over the next week.
02:00:39They'll be available for if you want to
02:00:41listen to them either again or share them.
02:00:45I will also we would also welcome any
02:00:47questions that you might have issue,
02:00:49think about what you've heard.
02:00:51And we would be very grateful
02:00:53for feedback on this format.
02:00:54It's allowed us to have you
02:00:56with us over a week.
02:00:59It's also allowed us to have more people
02:01:02to talk and to present more of our science
02:01:04and to present it in different ways.
02:01:07So so we'd be very,
02:01:08very grateful for your feedback
02:01:10on on the format.
02:01:12And just want to thank you again
02:01:14for joining us and hope to see you
02:01:16online and hopefully in person
02:01:18in the not too distant future.
02:01:19Thank you very much.
02:01:21May I comment?
02:01:23May I just
02:01:24say I would just like to thank
02:01:27you Linda and support staff and
02:01:30researchers and clinicians for the
02:01:33incredibly impressive transition you
02:01:35made this year with the pandemic.
02:01:38How quickly, with new hires an all the
02:01:42present people in place you moved from
02:01:45the regular format to this format,
02:01:48which I think is spectacular
02:01:51considering the circumstances.
02:01:52And we're fortunate enough to
02:01:54have technology on our site.
02:01:5620 years ago. It would have happened.
02:01:59The work itself is extremely impressive.
02:02:01There wasn't one.
02:02:03One presentation today that would
02:02:05not have passed what Edward
02:02:08for used to refer to as the.
02:02:10So what test they all did Anne
02:02:13Anne beautifully executed.
02:02:15I have loads of questions that will
02:02:18come up as as time goes on 'cause the
02:02:22research is so intricate and this is really.
02:02:25The tip of the iceberg,
02:02:27but I'm very,
02:02:28very grateful for the incredible
02:02:30capacity displayed today in the way
02:02:32that that it was shared with us,
02:02:34and I'm very grateful to be apart of
02:02:37this. Alright, we're very grateful
02:02:39to have you be a part of it,
02:02:41so thank you so much.
02:02:43Very very thank you and I
02:02:45love your background, thanks.
02:02:48So again thanks everyone,
02:02:50and we'll see you online soon again
02:02:53and the posters will remain up.
02:02:55So please, if you have time to see them,
02:02:58the posters are spectacular too.
02:03:00Thank you. Thank you.
02:03:01Thanks everybody.