From genes to evidence-based treatments: Translational research in trichotillomania and excoriation disorder

Transcript

• 00:01I am so delighted to,
• 00:03have the opportunity to to
• 00:05introduce
• 00:06our speaker today,
• 00:08someone who is very well
• 00:09known to many of us,
• 00:10but, will be new to
• 00:11some of you, Emily Olsen.
• 00:14So
• 00:15Emily, who is now in
• 00:16her third year as an
• 00:18assistant professor with us here
• 00:20at the Child Study Center,
• 00:23is really one of ours
• 00:24because she trained as part
• 00:26of the Solnit Integrated
• 00:28program.
• 00:29And in some ways is,
• 00:31a poster child
• 00:33as is her brother who
• 00:34is here,
• 00:35brother of sorts,
• 00:37different mother,
• 00:39but they're both are,
• 00:41Kartik and Emily, are really
• 00:43poster children for,
• 00:46clinician scientists.
• 00:48And it's been over thirty
• 00:50years at least that, the
• 00:52field of medicine has lamented
• 00:54the paucity of clinician scientists.
• 00:57And we've seen the numbers
• 00:58of clinician scientists,
• 01:00physician scientists,
• 01:03flatten or decrease over time
• 01:05because it's a very difficult
• 01:07field. And this is even
• 01:08before the challenges that we're
• 01:10facing today.
• 01:11So just to make it
• 01:12is remarkable,
• 01:14and to make it with
• 01:15the kind of science that
• 01:16we're gonna be seeing today
• 01:17and sometime soon from Kartik
• 01:18as well
• 01:20is is wonderful.
• 01:22Emily came to us before,
• 01:24being here. She was at,
• 01:26Saint Louis,
• 01:28Washington University in Saint Louis,
• 01:30where she got her MD
• 01:31PhD,
• 01:32and that's where she started
• 01:33her trajectory studying genes,
• 01:36mostly in adult disorders,
• 01:38boo, and now she is
• 01:40dedicating her incredible talents to
• 01:43childhood
• 01:44disorders.
• 01:45And,
• 01:46I think that many of
• 01:47us have heard of trichotillomania,
• 01:49Tourette syndrome,
• 01:50but fewer of us have
• 01:51heard of excoriation
• 01:53disorder and thought of it
• 01:54as a disorder.
• 01:55And Emily has not only
• 01:56done this, but has started
• 01:58paving the way to understanding
• 01:59some of the genetic and
• 02:01under underlying mechanisms involved and
• 02:03some of the treatments. So
• 02:04she really
• 02:05embodies the physician scientist in
• 02:07the the best way,
• 02:09and, and she's also a
• 02:10lovely person. I mean, I
• 02:12I hate people like that.
• 02:13It's like they're they're she's
• 02:14amazing, and she's, like, the
• 02:15loveliest person. So, Emily, come
• 02:17on up.
• 02:26So thank you,
• 02:27for that really kind introduction,
• 02:30and,
• 02:30thank you very much,
• 02:32for the invitation
• 02:33to talk with you today
• 02:34and share kinda some of
• 02:35our work on trichotillomania
• 02:37excretion disorder.
• 02:40I don't have any disclosures.
• 02:42I do have some research
• 02:43funding,
• 02:44listed here.
• 02:46And I wanna start with
• 02:47a video.
• 02:48I know this is a
• 02:49clinical department, and I think
• 02:51it's important that we're grounded
• 02:52in kind of the patients
• 02:53that we see.
• 02:58Hi, everybody.
• 02:59My name's Catherine. I'm from
• 03:01New York. I'm eighteen years
• 03:02old.
• 03:04I started pulling at the
• 03:05age of twelve, like many
• 03:07people here,
• 03:08from my scalp.
• 03:09The first time I pulled
• 03:11was right after I had
• 03:12my hair styled with bangs
• 03:13for the first time, and
• 03:14I noticed that one of
• 03:16the hairs in my bangs
• 03:17was longer than all the
• 03:18others. So I looked in
• 03:19the mirror and I flucked
• 03:20it out and I thought
• 03:21nothing of it. And now
• 03:22I think back to how
• 03:23nonchalantly I did that and
• 03:25I laughed to myself because
• 03:26I thought everyone pulled their
• 03:28out of place hairs.
• 03:30My trick got bad pretty
• 03:31fast. By the time I
• 03:32was thirteen, I was completely
• 03:34bald.
• 03:36I did my best to
• 03:37cover up and hide my
• 03:38condition from everyone.
• 03:40Like many others suffering from
• 03:42Trich and derm,
• 03:43I was bullied for my
• 03:44actions and for the lack
• 03:45of my hair.
• 03:47I was dragged from therapist
• 03:48to therapist, put on every
• 03:50medication you can think of,
• 03:52and it wasn't until the
• 03:54end of, middle school that
• 03:56my mom actually discovered TLC
• 03:57online because she became obsessed
• 03:59with my obsession and started
• 04:01researching everything she could.
• 04:03And that's when I started
• 04:04educating myself about the condition
• 04:06and really learning about what
• 04:07I was doing.
• 04:09Things were rough still for
• 04:10a long time,
• 04:12between family problems, other conditions
• 04:14popping up like depression and
• 04:16anxiety,
• 04:17and starting to do poorly
• 04:18in school. I felt like
• 04:19a failure.
• 04:20I felt like my life
• 04:21was spiraling out of control,
• 04:23and the only future I
• 04:24could picture was one where
• 04:25I was bald and depressed.
• 04:30So, I just wanted to
• 04:31start with that. I chose
• 04:33this. I just, you know,
• 04:34found it, online.
• 04:36I find her very compelling,
• 04:38but I think there are
• 04:39also elements of it that
• 04:40are common to a lot
• 04:42of the patients we see
• 04:43who have, Trich and skin
• 04:45picking.
• 04:46And so as I talk
• 04:47about some of the research
• 04:48today, I want you guys
• 04:50to keep Catherine in mind
• 04:51or maybe another patient you've
• 04:53seen in clinic who has
• 04:54one of these conditions.
• 04:56And I'm gonna present kinda
• 04:57some data we've been working
• 04:58on, but I wanna start
• 05:00by emphasizing these are really
• 05:01understudied conditions, and we really
• 05:03need more research on them.
• 05:06And at the end, I
• 05:06have time for questions. And
• 05:08if there's any feedback from
• 05:09it's kind of a opportunity
• 05:11for me to hear about
• 05:12kind of other directions of
• 05:13this work, that we can
• 05:15take it in in the
• 05:15future. I really would welcome
• 05:17that, other ideas you guys
• 05:18might have.
• 05:20And you may, you know,
• 05:21have,
• 05:22friends or family members impacted
• 05:24by these as well, and
• 05:25so keeping those in mind
• 05:26as well.
• 05:32Okay. So I'm gonna start
• 05:34with some background because as
• 05:36Andreas said, you may have
• 05:37heard of trichotillomania.
• 05:39Excoriation disorder is a little
• 05:41less well known. They're both
• 05:42kinda characterized
• 05:43as obsessive and compulsive related
• 05:45disorders in DSM five.
• 05:48Trichotillomania was kinda reclassified
• 05:50from the impulse control disorders,
• 05:52and excoriation disorder was added
• 05:54to the DSM five. So
• 05:55it hasn't been kind of
• 05:56formally studied,
• 05:58for that long.
• 06:00They're often both sub characterized
• 06:02together as these, body focused
• 06:04repetitive behavior disorders,
• 06:07and they have very similar
• 06:08definitions. Right? So they're characterized
• 06:10by persistent, recurrent pulling of
• 06:13the hair or picking of
• 06:14the skin
• 06:15leading to hair loss or
• 06:17skin lesions
• 06:18despite attempts to stop and,
• 06:19like, everything in the DSM,
• 06:21they're associated with kinda significant
• 06:22impairment and distress.
• 06:25Traditionally, they're thought to impact
• 06:27females predominantly more than males.
• 06:29I'm gonna share some data
• 06:30that it might not be
• 06:31quite as extreme as previously
• 06:33thought. I'm it used to
• 06:34be kind of quoted in
• 06:35the literature as it's almost
• 06:37four to one females to
• 06:38males, but we think it
• 06:39might be a little more
• 06:40gender even now.
• 06:42And they tend to onset
• 06:43adolescence. So this is really
• 06:45kind of, these are pediatric
• 06:47conditions, that really is in
• 06:48kind of that domain of
• 06:49kind of, child mental health.
• 06:52And they tend to have
• 06:54a waxing and waning course,
• 06:55and they're often chronic.
• 06:57So identifying them, treating them,
• 06:59providing psychoeducation is really important.
• 07:03And that's because they have
• 07:04a lot of consequences. And,
• 07:05I think Catherine kinda nicely
• 07:07highlighted that they're associated with
• 07:08shame, embarrassment, low self esteem.
• 07:10They lead to,
• 07:12impaired functioning in a variety
• 07:14of settings.
• 07:15They can also lead to
• 07:16a lot of financial losses.
• 07:17People spend a lot of
• 07:18time trying to hide their
• 07:19bald spots or, hide their
• 07:21skin lesions.
• 07:23And they also lead to
• 07:24kind of avoidance of activities.
• 07:26You know, right now, as
• 07:27we had our first kind
• 07:28of warm weekend last weekend,
• 07:29you think of swimming, and
• 07:30that's often really hard for
• 07:32them, because they spend a
• 07:33lot of time kind of
• 07:34styling their hair and and
• 07:35whatnot in the exposure.
• 07:37They also can have, medical,
• 07:41consequences.
• 07:41I mean, the classic kind
• 07:42of med school thing is,
• 07:44that, you know, a proportion
• 07:46of these individuals maybe kind
• 07:47of a fourth to a
• 07:48third
• 07:49will,
• 07:50consume their hair and that
• 07:51can lead to these, trichobezo
• 07:53words, which can lead to
• 07:55gastrointestinal
• 07:56complications and also kind of
• 07:57the skin picking can lead
• 07:58to infections.
• 08:01They're really high rates of
• 08:02comorbidity, and Catherine also talked
• 08:04about this. So high rates
• 08:05of depression, anxiety, OCD,
• 08:08and other disorders as well.
• 08:10So one of the first
• 08:11questions we kinda got interested
• 08:13in, which seems like an
• 08:14obvious one, is how common
• 08:15are these disorders? But, you
• 08:17know, they're not,
• 08:18really listed in kind of
• 08:20classic structured interviews. So there's
• 08:22really a limit in terms
• 08:23of kind of large epidemiologic
• 08:25studies of these conditions. And
• 08:27so
• 08:28with the help of kind
• 08:29of Michael Bloch and then,
• 08:31Luis Farhat, who's a researcher,
• 08:33in Brazil,
• 08:34we decided to do a
• 08:36meta analysis, looking at all
• 08:38these studies, and most of
• 08:39them are small, convenient samples
• 08:41to try and understand what
• 08:42is kind of the overall
• 08:43prevalence.
• 08:44And we found that there
• 08:45have about a prevalence trichotillomania.
• 08:47First, we did trichotillomania
• 08:49about one percent of the
• 08:50population. So this is a
• 08:51relatively common disorder.
• 08:54We then also looked at
• 08:56kind of the gender, balance,
• 08:58to see kinda looking at
• 09:00these studies,
• 09:01what is the ratio of,
• 09:03females to males affected. And,
• 09:06you can see here,
• 09:07it's an estimate odd ratio
• 09:08of almost one point three.
• 09:11This is females to males.
• 09:13It's not actually statistically significant
• 09:16in this group. That's in
• 09:17part driven by kind of
• 09:18a large study that was
• 09:19done by John Grant in
• 09:21two thousand.
• 09:22For those who aren't I
• 09:23guess I should have said
• 09:24this on the last slide.
• 09:25For those who aren't used
• 09:26to looking at these plots,
• 09:27because I have quite a
• 09:27few of these throughout the
• 09:28presentation,
• 09:30these forest plots, you can
• 09:31see the black,
• 09:33squares are the individual studies,
• 09:34individual effects, and then those,
• 09:37red diamonds give you kind
• 09:38of the overall estimates.
• 09:41So then we did this
• 09:42kind of again,
• 09:43with the help,
• 09:45Louise Farhat worked on this
• 09:46as well as Madison Reed,
• 09:47who was actually one of
• 09:48my summer, students from Sewanee
• 09:50who came here two years
• 09:51in a row,
• 09:52worked on this. And she,
• 09:54and we found that actually
• 09:56excoriation disorder tends to impact
• 09:58three point five percent of
• 09:59the population, so even more
• 10:01common.
• 10:02And the gender ratio, the
• 10:04estimate we got was a
• 10:05little bit higher. This one
• 10:06was statistically significant,
• 10:08one point four five kind
• 10:10of females to males,
• 10:13but not quite as high
• 10:14as kind of traditionally thought
• 10:15in the literature. And part
• 10:16of that might be kind
• 10:17of recruitment methods and kind
• 10:19of who seeks care in
• 10:20terms of clinical trials and
• 10:22things like that.
• 10:25There are obviously a lot
• 10:26of limitations of this. You
• 10:27know, these, employed generally small
• 10:29convenient samples. There was a
• 10:31lot of heterogeneity
• 10:32in terms of them. Few
• 10:34of them used kind of
• 10:35the true DSM five criteria.
• 10:38And really a major problem
• 10:39kind of across research in
• 10:41general is there's really a
• 10:42limited of diversity in these
• 10:44samples.
• 10:45But I think the take
• 10:46home point is that these
• 10:47conditions are relatively common.
• 10:49And this is important, for
• 10:50the field because this allows
• 10:52us to really advocate that
• 10:53we need more research. We
• 10:54need more dedication, kinda clinical
• 10:56care on these conditions because
• 10:57these are really impacting a
• 10:59large proportion
• 11:01of individuals.
• 11:02And they may impact, we
• 11:03think, women more than men,
• 11:05though maybe not as high
• 11:06as previously thought.
• 11:08So you may be asking,
• 11:09okay. You're talking about these
• 11:11conditions together. Are they actually
• 11:13similar? Their definitions are similar,
• 11:15but do they actually have
• 11:15similar characteristics?
• 11:17And so this was a
• 11:18study done by Ashley,
• 11:21who was a
• 11:22undergrad working with me at
• 11:24Yale,
• 11:25with Louise.
• 11:27She's now a med student.
• 11:28And we basically took the
• 11:30samples that we had collected
• 11:31here, and we compared the
• 11:32individuals who had trick,
• 11:35skin picking, and both conditions.
• 11:37And we looked at kind
• 11:39of do they have similar
• 11:40kinda clinical profiles. And one
• 11:42thing you'll see is they
• 11:43have, in our sample at
• 11:44least, had really high rates
• 11:46of co occurring disorders, like,
• 11:48especially,
• 11:49anxiety, sixty three to eighty
• 11:51two percent in these three
• 11:53different groups,
• 11:54high rates of depression, OCD.
• 11:57And there were essentially
• 11:58no statistical differences between the
• 12:01groups. They were all kinda
• 12:02similarly high. These were all
• 12:03very kinda similar profiles between
• 12:05them.
• 12:06We also because we have
• 12:07this large group of fifty
• 12:08individuals who have both trich
• 12:10and skin picking, we could
• 12:11look at that and compare
• 12:13their trich in these individuals
• 12:15to their skin picking symptoms.
• 12:16And we do find that
• 12:18within those individuals with both
• 12:19conditions, we see similar, we
• 12:22see this kind of positive
• 12:23correlation between the severity of
• 12:25hair pulling and skin picking
• 12:26symptoms,
• 12:27and we also see this
• 12:28correlation between their style of
• 12:31picking. So it looks like
• 12:32the individuals,
• 12:33who have both conditions tend
• 12:35to pull or pick in
• 12:36a similar style,
• 12:38to each other. And I'll
• 12:39describe the styles in a
• 12:40second, because that may sound
• 12:42those who aren't used to
• 12:43thinking about those, that may
• 12:46you may be
• 12:47questioning that.
• 12:50So as part of that,
• 12:51I'm gonna ask you you
• 12:52may be asking, okay. Well,
• 12:53what's the clinical course? I
• 12:54have a patient who presents
• 12:55to me. I can tell
• 12:56them this is relatively common,
• 12:57that these disorders
• 12:58commonly co occur with each
• 13:00other.
• 13:02But
• 13:02what can I tell them
• 13:03about kinda long term their
• 13:05prognosis?
• 13:08And we know,
• 13:09that both of these conditions
• 13:11tend to onset in adolescence.
• 13:13So Emily Ricketts, out at
• 13:15UCLA did these nice, latent
• 13:17factor analyses
• 13:18where she showed that the
• 13:19majority of individuals for both
• 13:21disorders kinda fall in these
• 13:23groups,
• 13:24that have this adolescent
• 13:26onset with a mean age
• 13:27of about twelve for trick
• 13:29and, thirteen for skin picking.
• 13:31And there are is a
• 13:32minority of individuals,
• 13:33that have kind of later
• 13:34adult onset.
• 13:36Of course, these can onset
• 13:37at any time, but this
• 13:39is just what is kind
• 13:40of most common as we're
• 13:41seeing this onset kinda right
• 13:42around puberty.
• 13:47Many patients,
• 13:48report being kind of fully,
• 13:50not being fully aware of
• 13:51it, and this is something
• 13:52we call automatic peeling. So
• 13:54this is what I meant
• 13:55by subtype. So people often
• 13:56describe that they'll be pulling
• 13:58and they're not even aware
• 13:59of
• 13:59of it. They might be
• 14:00watching TV, and then all
• 14:01of a sudden they've pulled
• 14:02like a a bald spot.
• 14:04There's also something called focus,
• 14:06pulling or picking. And here,
• 14:08it's often intentional, like what
• 14:09Catherine described, where you have
• 14:11an out of place hair
• 14:12or maybe a hair that
• 14:12feels a little kinky, or
• 14:14there might be kind of
• 14:14specific triggers that lead to
• 14:16it.
• 14:18And and people tend to
• 14:19have a combination, but they
• 14:20may have more of one
• 14:21type than the other, and
• 14:22that has kind of implications
• 14:24for the therapy we do
• 14:25as well.
• 14:27Pulling and picking sites tend
• 14:28to increase over time, so
• 14:30that's something also you can
• 14:31tell families. Often, they'll be
• 14:33presenting with maybe just pulling
• 14:34from their scalp or, from
• 14:36their eyebrows or eyelashes, but
• 14:38it's likely that those sites
• 14:39will increase over time.
• 14:41And we know that when,
• 14:42the few studies that compared
• 14:43children to adults,
• 14:45we know that in general,
• 14:46when kids are younger, they
• 14:47tend to have less impairment
• 14:49and distress. They tend to
• 14:50be less bothered by it,
• 14:51kind of like with tics.
• 14:53Often the kids aren't bothered
• 14:54by the tics, but the
• 14:55parents may be very bothered
• 14:56by it.
• 14:58And, it tends to be
• 14:59more automatic. So there's more
• 15:01kind of out of consciousness
• 15:02picking and pulling.
• 15:05There are not many longitudinal
• 15:06studies. In fact, the only
• 15:08longitudinal
• 15:09study I know of done
• 15:10in kids was done by
• 15:11Michael Block. So I hope
• 15:12it's okay with him, but
• 15:13I wanted to show one
• 15:14of his older papers.
• 15:17So he did a follow-up
• 15:18study of, his clinical trial,
• 15:20and so he compared kids
• 15:22who he had seen who
• 15:23had an average age of
• 15:24thirteen and then followed them
• 15:25up when they were on
• 15:26average sixteen years old. And
• 15:28what we he found in
• 15:29these kids is in general,
• 15:30they had similar
• 15:32hair pulling symptoms.
• 15:33So the severity of their
• 15:34hair pull these are all
• 15:35hair pulling measures here.
• 15:37But, interestingly,
• 15:39there was as I've kinda
• 15:40described, there was this decrease
• 15:42in automatic pulling.
• 15:44So over time, these kids
• 15:45were, no
• 15:47having more kind of the
• 15:48the focus pulling and less
• 15:50of the automatic.
• 15:51And this is really important.
• 15:53There were higher rates of,
• 15:55depression measured in the CDI
• 15:57and higher rates of anxiety
• 15:59measured by the mask.
• 16:00And people this is a
• 16:01question we often get in
• 16:03clinic. People feel like, well,
• 16:04aren't they pulling or picking
• 16:06because they're, like, nervous or
• 16:07because,
• 16:08and sometimes, yes. Sometimes it's
• 16:10kind of due to anxiety
• 16:12or,
• 16:14kind of mood symptoms,
• 16:15but sometimes it just happens
• 16:17by itself. And this data
• 16:18really suggests that actually,
• 16:20in this case, kind of
• 16:21the hair pulling
• 16:23seems to come earlier,
• 16:25and that the depression and
• 16:26anxiety symptoms are happening later.
• 16:28And so this really suggests
• 16:29that childhood may be a
• 16:30really important time for us
• 16:32to intervene on this.
• 16:34And we haven't done longitudinal
• 16:35follow-up of our samples, although
• 16:37as I was putting together
• 16:38this presentation, I think that's
• 16:39something I should do.
• 16:41But we were able to
• 16:42look at our data,
• 16:43and look, because we have
• 16:45a wide range in our
• 16:45data and kinda look cross
• 16:47sectionally,
• 16:48cross,
• 16:49these, hundred and fifty two
• 16:51individuals who have trick and
• 16:52or skin picking.
• 16:54And what we find is
• 16:55that although kind of these
• 16:56symptoms tend to onset in
• 16:57early adolescence, they tend to
• 16:59peak in our samples in
• 17:01severity in later adolescence. So
• 17:03with trick, when we did
• 17:04this joint point regression,
• 17:06the peak severity was around
• 17:08eighteen years old,
• 17:09and the for excoriation disorder
• 17:11was around sixteen years old.
• 17:12And so this really,
• 17:15suggests,
• 17:16that we may be seeing
• 17:17kids in the clinic when
• 17:19they're really experiencing some of
• 17:20their most severe symptoms and
• 17:21really in,
• 17:23in need of treatments.
• 17:25So how are we doing
• 17:26speaking of treatments, how are
• 17:27we doing treating these conditions?
• 17:30And so these studies are
• 17:31a bit older, but I
• 17:32like to cite them because
• 17:33they are still really the
• 17:34largest surveys we have available
• 17:36of individuals who have these
• 17:37conditions.
• 17:39And the results are pretty
• 17:41sobering.
• 17:42So in these surveys of
• 17:44those who sought treatment, twenty
• 17:46eight to thirty
• 17:47percent felt that their provider
• 17:49had never heard of the
• 17:50disorder. So everyone in this
• 17:52room is doing better than
• 17:53that that twenty eight to
• 17:54thirty percent.
• 17:56Only thirteen to fifteen percent
• 17:58felt that their provider knew
• 17:59a lot or was an
• 18:01expert in excoriation disorder and
• 18:03trichotillomania.
• 18:04And I'm hoping by the
• 18:05end of this, you guys
• 18:06all feel like experts.
• 18:11Fifty four to fifty eight
• 18:12percent felt that their symptoms
• 18:14were unchanged or worse by
• 18:15the treatment that they received.
• 18:17And I wanna pause on
• 18:18this because this is, like,
• 18:19shocking. Right? This is over
• 18:21fifteen percent
• 18:22feel unchanged or worse.
• 18:25I mean, that's like we're
• 18:26almost doing harm. Right?
• 18:28And only four to five
• 18:30percent reported very being very
• 18:32much improved.
• 18:34And the most common treatment
• 18:36received
• 18:37was pharmacotherapy
• 18:39with SSRIs
• 18:40being the most common class.
• 18:41And I'm gonna do a
• 18:42bit of a spoiler because
• 18:43I'm gonna talk about the
• 18:44treatments now. But, really, pharmacotherapy
• 18:46should not be first line.
• 18:48There's much more evidence for
• 18:50behavioral therapies.
• 18:51And,
• 18:53if Michael Block were here,
• 18:54one of the things he
• 18:55often told me is the
• 18:56one thing he feels confident
• 18:58about,
• 18:59the pharmacology of trichotillomania
• 19:01is that SSRIs do not
• 19:02work.
• 19:04So they may help for
• 19:05co occurring conditions, but they
• 19:07there's,
• 19:08substantial evidence that they actually
• 19:09do not help with the
• 19:10hair pulling itself.
• 19:13You would think they might
• 19:14because they're so helpful in
• 19:15OCD and anxiety and depression.
• 19:17But,
• 19:19okay. So,
• 19:20now I wanna present these
• 19:21are actually unpublished results. This
• 19:23is a network meta analysis,
• 19:28led by Louise,
• 19:30and and so this is
• 19:31under review right now. So
• 19:32fingers crossed.
• 19:34And, he has really become
• 19:36an expert kind of working
• 19:37with Michael and doing these,
• 19:38network meta analyses. And what's
• 19:40interesting about these is you
• 19:42can
• 19:42not only look at the
• 19:44level of evidence for different,
• 19:46interventions, but you actually can
• 19:48compare interventions even if there
• 19:50aren't kinda head to head
• 19:51trials
• 19:52of different interventions.
• 19:55And so I'm gonna start.
• 19:56We, you know, over the
• 19:57last two years, we identified,
• 20:00a hundred and thirteen kinda
• 20:02published
• 20:03study
• 20:05studies, a hundred and thirteen,
• 20:07I guess, papers
• 20:08that reported on fifty,
• 20:11six individual,
• 20:12randomized controlled trials of interventions,
• 20:15that are summarized.
• 20:16So,
• 20:18psychotherapies are certainly the most
• 20:20well studied.
• 20:22This is a little hard
• 20:23to see, but the thicker
• 20:24the line, the more studies
• 20:26there are. And I'll just
• 20:27tell you
• 20:28that the most commonly studied,
• 20:30are behavioral
• 20:31therapies. There are nine studies
• 20:33comparing to wait list, and
• 20:35then cognitive behavioral therapies. And
• 20:37so we've actually kinda made
• 20:38those categories. So I'm gonna
• 20:40tell you a little bit
• 20:41how we kind of group
• 20:42these together. So behavioral therapies
• 20:44are kind of habit reversal
• 20:46training
• 20:47and kind of related techniques,
• 20:49primarily just that behavioral components,
• 20:52whereas cognitive behavioral therapies,
• 20:54are often
• 20:56interventions that are kind of
• 20:58enhanced
• 20:58behavioral therapies. So have some
• 21:00sort of kind of cognitive
• 21:02restructuring or third wave components,
• 21:05or they're kind of those
• 21:07cognitive components alone. So like
• 21:08a study
• 21:10of, like, acceptance,
• 21:11ACT, or, DBT.
• 21:15So
• 21:16this is not my area
• 21:17of expertise. I am a
• 21:18child psychiatrist, not a therapist,
• 21:20but I will try to
• 21:21do my best to, kinda
• 21:22explain this. I think
• 21:24it's important to think about
• 21:25kind of the history of
• 21:26these behavioral therapies. So habit
• 21:29reversal training was really the
• 21:30first therapy that was shown
• 21:32to be helpful in trichotillomania
• 21:34and skip picking,
• 21:36and, this involves a few
• 21:37kind of components. So the
• 21:38first step is usually psychoeducation.
• 21:41The next step is this
• 21:42awareness training. And this is
• 21:44really important particularly in these
• 21:45disorders. Right? Because I talked
• 21:47about how a lot of
• 21:48the hair pulling and skin
• 21:49picking can be automatic, so
• 21:50kind of being aware on
• 21:52it if you wanna change
• 21:53that behavior is really important.
• 21:55There's usually a stimulus control
• 21:58component,
• 21:59where you're really addressing kind
• 22:01of, removing a triggering part
• 22:03of the environment. So this
• 22:05might look like, you know,
• 22:06covering up mirrors if that
• 22:07is,
• 22:08a trigger.
• 22:09It might be limiting TV.
• 22:11Sometimes people will pull while
• 22:13they're watching TV or picking,
• 22:14or pick during that time.
• 22:16And then the kind of
• 22:17core of HRT is kinda
• 22:18developing this competing response, so
• 22:21an alternative movement
• 22:23that directly opposes
• 22:24it. And so this was
• 22:25really what was studied for
• 22:27a long time in terms
• 22:28of treating,
• 22:31BFRBs.
• 22:32But more recently, they've kind
• 22:34of been at
• 22:35the addition of additional components
• 22:37to it. So adding sort
• 22:39of cognitive therapy
• 22:41techniques, so not just focusing
• 22:43on the behavior, but also
• 22:44we triggering thoughts that may
• 22:46lead to the behavior,
• 22:48emotional regulation training, and then
• 22:50kind of,
• 22:52mindfulness and acceptance and commitment
• 22:54therapy.
• 22:55So what we found when
• 22:56we kind of group the
• 22:57trials these ways is that
• 22:59we found that, behavioral cognitive
• 23:01behavioral
• 23:02therapy and actually supportive behavioral
• 23:04therapy that was a control
• 23:05in many of the trials,
• 23:08were, beneficial
• 23:09at reducing
• 23:10BFRB symptoms compared to wait
• 23:12list. I just wanna highlight
• 23:14the two groups, as I
• 23:15said, that were kind of
• 23:16are most well studied or
• 23:18kind of these cognitive behavioral
• 23:20techniques versus the behavioral. And
• 23:22in this network meta analysis,
• 23:24we actually do see a
• 23:25statistically
• 23:26significant improvement with adding that
• 23:29cognitive,
• 23:31part to the behavioral therapy,
• 23:33kind of suggesting that that
• 23:34is an important kind of
• 23:35addition. And it makes sense
• 23:37when we talk to patients,
• 23:38they often do describe kind
• 23:40of a cognitive aspect. So
• 23:41kind of targeting that therapeutically,
• 23:44makes sense.
• 23:45We also looked at the
• 23:46delivery formats, and, I think
• 23:48this is important because as
• 23:50I'm gonna talk about, we
• 23:51really, don't have enough trained
• 23:53providers.
• 23:54So most of the studies,
• 23:56focused on kind of looking
• 23:58at individual sessions, but there
• 23:59were quite a few studies
• 24:01here that looked at kind
• 24:02of unguided self help.
• 24:05And when we did the
• 24:06met network meta analysis
• 24:08compared to wait list, individual
• 24:10group, Internet delivered, and unguided
• 24:13self help were actually all
• 24:14more effective.
• 24:16I'm highlighting again the two
• 24:17groups that we have the
• 24:18most data on.
• 24:20Clearly, individual
• 24:22is kind of the best,
• 24:24but I think it is
• 24:25important and in our network
• 24:27meta analysis, it was superior
• 24:29to kind of unguided self
• 24:31help by itself. But I
• 24:32think it is important to
• 24:33recognize that unguided self help
• 24:35does when people are on
• 24:36wait list waiting for their
• 24:38individual therapy that there can
• 24:40be some benefit of that.
• 24:41And so I think that's
• 24:42important to keep in mind
• 24:43when we see patients.
• 24:45So,
• 24:46a big problem,
• 24:48is kind of disseminating these
• 24:49therapies. There's a huge shortage
• 24:51of providers,
• 24:53who know how to provide
• 24:54these kind of,
• 24:55therapies that are specific to
• 24:57treating BFRBs.
• 24:59The TLC Foundation, which is
• 25:01what Catherine was speaking at
• 25:02at the beginning, is, a
• 25:04nonprofit organization
• 25:05for these
• 25:07BFRBs,
• 25:08and they, prior to COVID,
• 25:10it was in person. It's
• 25:11become virtual since then, but
• 25:12they have a training institute
• 25:14for providers.
• 25:16They've also,
• 25:17created kind of a manual.
• 25:18The, training they do is
• 25:20for something,
• 25:22that's like,
• 25:23a cognitive behavioral therapy. It's
• 25:25called comprehensive behavioral treatment for
• 25:27trick and skin picking comb
• 25:28b. It's similar to what
• 25:30you might have heard of,
• 25:31like, CBIT for,
• 25:33for tic disorders.
• 25:35And Heidi and Sharon, who
• 25:37are two of our outstanding
• 25:38clinicians here, kind of both
• 25:40did the training pre COVID,
• 25:41and so they do these
• 25:42specific therapies in our clinic
• 25:44here.
• 25:46And so now I'm,
• 25:47phew, got through that part.
• 25:49Now I'm gonna switch gears
• 25:50to a little more of
• 25:51my comfort zone,
• 25:52which is kind of the
• 25:53pharmacologic
• 25:54treatments. And so here,
• 25:57I'm just highlighting,
• 25:58this is what all the
• 25:59trials we found from the
• 26:00network meta analysis. And the
• 26:01first thing I wanna highlight
• 26:03is I don't know if
• 26:04you can see the numbers
• 26:05on this, and this is
• 26:06taken from the draft of
• 26:07the paper, but I'll just
• 26:09tell you. There are five
• 26:10studies looking at SSRIs,
• 26:12three studies looking at n
• 26:13acetylcysteine,
• 26:16two studies looking at clomipramine,
• 26:18and everything else is one
• 26:19trial.
• 26:20There is really
• 26:22so little research
• 26:24on the pharmacotherapy
• 26:25of these disorders, especially considering
• 26:27how prevalent they are and
• 26:28how many kids they're impacting.
• 26:31Here are kind of the
• 26:32overview of the results. Again,
• 26:34if the confidence intervals don't
• 26:36cross the line, they're statistically
• 26:38significant. So we do have
• 26:39a few treatments in the
• 26:40meta analysis that are statistically
• 26:43separating from placebo.
• 26:45I wanna highlight at the
• 26:46bottom
• 26:47the most well studied group,
• 26:48the SSRIs,
• 26:51essentially no benefit.
• 26:52And so this is one
• 26:53of the take home points
• 26:54for all the child psychiatrists
• 26:56in the room who don't
• 26:57prescribe SSRIs or increase the
• 26:59SSRIs to target hair pulling
• 27:01or skin picking.
• 27:03I'm gonna quickly walk through
• 27:05the data on these other
• 27:06four medications,
• 27:07in case helpful because these
• 27:09are things you might think
• 27:09about,
• 27:11if you have a patient
• 27:11with these disorders. So
• 27:14I'm gonna start with clomipramine,
• 27:16because it was kind of
• 27:17the first one studied.
• 27:19This is a tricyclic antidepressant.
• 27:21It was kind of an
• 27:21obvious choice to look at
• 27:23because it is FDA approved
• 27:24for OCD,
• 27:26in both children and adults.
• 27:28There have been two small
• 27:30trials, and when I say
• 27:31small, I mean very small.
• 27:33Both of them did have
• 27:34some benefit, but, again, the
• 27:36longer term benefit is is
• 27:38less clear. Not everyone continues
• 27:39to respond when some of
• 27:40these, individuals were followed
• 27:43up. And as you know,
• 27:45may know, there are kind
• 27:46of side effects that have
• 27:47to be cons you know,
• 27:48anticholinergic
• 27:49side effects, etcetera, with starting
• 27:50this type of medication.
• 27:52Next, I'm gonna talk about
• 27:53olanzapine.
• 27:54There's only one trial looking
• 27:55at this. This is not
• 27:56a medication that we usually
• 27:58consider in kids because of
• 27:59the obvious kinda side effect
• 28:00profile,
• 28:02but they it was thought
• 28:03to be studied because,
• 28:05it was you know, SSRIs
• 28:06were found not to be
• 28:07effective,
• 28:09which are kind of our,
• 28:10first line treatment and OCD.
• 28:12So I thought, well, maybe
• 28:13this is more like a
• 28:14a tick. Right? We know
• 28:15habit reversal training is helpful.
• 28:17So,
• 28:18let's look at kind of
• 28:19a neuroleptic.
• 28:20So this was a randomized
• 28:21controlled trial of twenty five
• 28:23adults. The mean dose was
• 28:24ten point eight.
• 28:26There was significant weight gain
• 28:27as a side effect as
• 28:28you might expect, but there
• 28:30was kind of a clear
• 28:31separation.
• 28:32So this may be helpful
• 28:33for trick, but, again, it's
• 28:34not something we necessarily use,
• 28:37because of the side effects,
• 28:38especially in kids.
• 28:40Now I wanna turn to
• 28:42NACL cysteine,
• 28:44which,
• 28:45is an antioxidant and glutamatergic
• 28:48modulator. This is something that
• 28:50you can buy over the
• 28:50counter. Right? So you don't
• 28:51need a prescription for this.
• 28:53It's in six hundred milligram
• 28:54tablets. You could buy it
• 28:55on Amazon, I think.
• 28:57It's very it's very well
• 28:59tolerated. There are, very few
• 29:00side effects. So because of
• 29:01that, this is something that
• 29:03we do try,
• 29:04in our patients.
• 29:05And it's been studying a
• 29:06variety
• 29:07of kind of randomized
• 29:09control trials in psychiatry including
• 29:11things like OCD.
• 29:13For trick and skin picking,
• 29:14there are three,
• 29:16clinical trials. All of them
• 29:17were twelve weeks.
• 29:19They have different populations. So
• 29:20the first one was done
• 29:21by John Grant out at
• 29:22US Chicago looking at adults
• 29:24with trich,
• 29:25had a benefit.
• 29:27I wanna kinda note the
• 29:29doses here. So sometimes people
• 29:31will start NAC, but they
• 29:32just start six hundred. The
• 29:33clinical trial dosing is much
• 29:35higher. So if you're gonna
• 29:36try it, you should probably
• 29:37go up to kind of
• 29:38the full dose.
• 29:40Michael Bloch here at Yale
• 29:42then, tried to,
• 29:43replicate this,
• 29:45using very sim a very
• 29:46similar study dye design to
• 29:48the adult trichotillomania.
• 29:49He did not see a
• 29:50separation
• 29:51from placebo,
• 29:54maybe due to a variety
• 29:55of factors. I'm sure you
• 29:56could ask Michael. He's got
• 29:57lots of thoughts on that.
• 29:59And then there was an
• 30:00adult study,
• 30:01later on looking at excoriation
• 30:03disorder.
• 30:05When you meta analyze them
• 30:06together, you do see a
• 30:07nice separation. So this is
• 30:08something we will try. Again,
• 30:10first line should be therapies.
• 30:12And then the last thing
• 30:13I wanna mention is memantine.
• 30:16So this
• 30:18is a medication we don't
• 30:19think about that much in
• 30:20child psychiatry.
• 30:22This, it was thought to
• 30:24be studied because of the
• 30:25benefit of NACL cysteine and
• 30:27potentially targeting the glutamate system.
• 30:30So it's a
• 30:33receptor antagonist. It's FDA approved,
• 30:35for Alzheimer's disease.
• 30:37And this was recently studied.
• 30:40This was published in twenty
• 30:41twenty three in the AJP.
• 30:43Again,
• 30:44say, led
• 30:45led by John Grant. He
• 30:46does a lot of the,
• 30:47pharmacology
• 30:48studies. Looking at a hundred
• 30:49adults, and they actually combine
• 30:50trich and skin picking here.
• 30:52So they had trichotillomania,
• 30:54excoriation, or both. They started
• 30:56at ten milligrams, and then
• 30:57at two weeks increased twenty.
• 31:00They found a huge effect
• 31:01size. Again, single site, only
• 31:03one location.
• 31:05But after eight weeks, sixty
• 31:07point five percent in the
• 31:08memantine group were much or
• 31:10very much improved compared to
• 31:12only eight percent in the
• 31:13placebo group. So a number
• 31:15needed to treat of one
• 31:16point nine. And I know
• 31:18not everyone's used to looking
• 31:19at those numbers. That's a
• 31:20really high number needed to
• 31:21treat. That's high in psychiatry.
• 31:22That's high for all of
• 31:24medicine.
• 31:25And the graphs from the
• 31:26paper kinda show it. So,
• 31:28the first graph
• 31:29looks at,
• 31:31the severity in terms of
• 31:33the NIMH scale. So that's
• 31:34a clinician administered
• 31:36scale. And the second graph
• 31:37looks at the,
• 31:39self report scale,
• 31:40the MGH.
• 31:42And you can see this
• 31:42kind of really nice separation,
• 31:44at eight weeks between the
• 31:46placebo
• 31:46and the memantine groups.
• 31:49And so this is a
• 31:50medication that, you know, we
• 31:51have started trying on patients.
• 31:53Sometimes it is I've had
• 31:55I've had patients who who
• 31:56have found it helpful. It's
• 31:57generally,
• 31:58well tolerated, but it is
• 32:00another option that we use.
• 32:03Okay.
• 32:05So,
• 32:06now,
• 32:08so, you know
• 32:10But I've kind of given
• 32:11you all this data, and
• 32:12you may notice that most
• 32:13of it's adult data. The
• 32:14only clinical trial in kids,
• 32:17in all of BFRBs was
• 32:18Michael's trial,
• 32:20of NACL assisting.
• 32:23And and we do that
• 32:23in trial psychiatry a lot.
• 32:25We use data from adults.
• 32:26There are really no FDA
• 32:28approved medications for these disorders.
• 32:30And so there isn't much
• 32:32when we see patients that
• 32:33we have to offer them.
• 32:34We do what we can.
• 32:36And so I feel kind
• 32:37of strongly that I think
• 32:39there's a really important need
• 32:41to under better understand the
• 32:42etiology of these conditions because
• 32:43we really don't have kind
• 32:45of clear medications,
• 32:48to use. And therapy can
• 32:50be effective,
• 32:51but it's not effective for
• 32:52everyone.
• 32:53It's often harder to do,
• 32:55right, in younger children and
• 32:56things like that. So we
• 32:57do have some limitations.
• 33:00And so one thing we've
• 33:01known I have a genetics
• 33:02background, so I'm very interested.
• 33:04I came to this interested
• 33:05in genetics, but we've known
• 33:06for a long time that
• 33:07these disorders run-in families and
• 33:09families will tell you this.
• 33:10And we know this from
• 33:11family studies and we also
• 33:12know this from twin studies
• 33:14where you can compare identical
• 33:16twins who share a hundred
• 33:17percent of their DNA and
• 33:18have the same environment,
• 33:20and you can compare them
• 33:21to fraternal twins who share
• 33:22fifty percent of their DNA
• 33:23but also have the same
• 33:24environment. They're being kind of
• 33:25brought up in the same
• 33:26household.
• 33:27And in the largest kind
• 33:29of twin study that has
• 33:30been done for trick and
• 33:32skin picking,
• 33:33they found that all of
• 33:34these
• 33:36obsessive compulsive and related disorders
• 33:38were heritable.
• 33:39But they not only kinda
• 33:40give us these heritability estimates,
• 33:42they also did something kinda
• 33:43interesting.
• 33:44And I won't go through
• 33:45the details, but they did
• 33:46this nice kind of latent
• 33:48factor analysis where they basically
• 33:50showed that there seemed to
• 33:51be some genetic factors
• 33:53that are shared across all
• 33:55OCD related disorders. So OCD,
• 33:57hoarding, body dysmorphic trick and
• 33:59skin picking. But then the
• 34:00model that best described the
• 34:02data that they were seeing
• 34:03is then there are some
• 34:04genetic factors that are really
• 34:05specific
• 34:06to trichotillomania
• 34:07and excoriation disorder, and that's
• 34:09that second latent factor that's
• 34:11distinct from these other,
• 34:13OCD related disorders.
• 34:15And that actually most of
• 34:17the genetic factors seem to
• 34:18be shared between trick and
• 34:19skin picking, and that's kind
• 34:20of the premise for looking
• 34:21at them together. And I
• 34:23was very interested in this,
• 34:25but
• 34:26I also felt clinically when
• 34:27I saw patients in clinic
• 34:29that, you know,
• 34:31sometimes
• 34:31that's not the case. Like,
• 34:32I feel like in families,
• 34:34they tend to run individually.
• 34:35Like, you'll see a family
• 34:37where an individual is trick
• 34:38and and their parents also
• 34:39have trick. And so we
• 34:41decided to look at our
• 34:42data, and this is actually
• 34:43led by Doris Chen who's
• 34:44a postgrad.
• 34:46She mainly works on kind
• 34:47of anxiety and an anxiety
• 34:49genetics product with Wendy and
• 34:51Ellie, but she decided to
• 34:52kinda look at this as
• 34:52well.
• 34:54And so we took,
• 34:56our data where we, looked
• 34:58at, probans, and these are
• 34:59all from different families who
• 35:00had trichotillomania
• 35:02only,
• 35:03excoriation disorder only in both
• 35:05conditions,
• 35:07and we compared the family
• 35:08history of these disorders.
• 35:10And as you might expect,
• 35:12the individuals who had
• 35:14trichotillomania
• 35:15had a higher family history
• 35:17of first degree relatives of
• 35:18trichotillomania
• 35:19compared to skin picking, and
• 35:21those who had skin picking
• 35:22had a higher family history
• 35:24of skin picking compared to
• 35:25those who had trichotillomania.
• 35:26And as the this was
• 35:28just recently published, but as
• 35:29the reviewer said, this supports
• 35:31that these conditions breed true.
• 35:33And so kinda how do
• 35:34you put this together?
• 35:36You know, it may be
• 35:38that there are genetic factors
• 35:39that are specific to the
• 35:40conditions,
• 35:41even though we know from
• 35:42kinda the twin studies that
• 35:44there are genetic factors that
• 35:46are clearly shared between them.
• 35:48But
• 35:49it also may be that
• 35:50there are environmental factors. Right?
• 35:52That you may have a
• 35:53genetic liability to develop these
• 35:54BFRBs, but kind of being
• 35:56around one disorder, maybe through
• 35:58parental modeling or whatnot,
• 36:00might be important.
• 36:01And,
• 36:03we did look at family
• 36:04history of a bunch of
• 36:04other conditions in these groups,
• 36:06and there's no differences. It's
• 36:07only within when you look
• 36:08at the trick and skin
• 36:09picking that you see these
• 36:10differences.
• 36:12And so
• 36:14I've basically told you so
• 36:15we know genetic factors are
• 36:16important for BFRBs,
• 36:17but what are those specific
• 36:19genetic risk factors? Right?
• 36:22And currently,
• 36:23there are no genome wide,
• 36:25like, large scale genome wide
• 36:26studies of either the disorders.
• 36:27There are no GWAS studies.
• 36:29Like, there's really limited data.
• 36:31And,
• 36:32this was something when I
• 36:34was a resident here that
• 36:35really struck me, and I
• 36:36really wanted to work on.
• 36:38And we know in child
• 36:39psychiatry, one approach that's especially
• 36:41helpful at helping us find
• 36:42risk genes, which when you
• 36:43think about, like, identifying druggable
• 36:45targets is really kind of
• 36:46the goal,
• 36:48is parent child trio studies.
• 36:50And this allows you not
• 36:51only to look at how
• 36:52genetic factors are inherited,
• 36:55but also kinda new genetic
• 36:57factors or these de novo
• 36:58mutations. And we know that
• 36:59this approach risk
• 37:02genes. This has really been
• 37:03pioneered in the field of
• 37:04autism. I have a paper
• 37:05here when they cross that
• 37:06threshold of a hundred risk
• 37:08genes, but this is now
• 37:09five years old. And now
• 37:10there are hundreds of risk
• 37:11genes that have been associated
• 37:12with autism,
• 37:14and other neurodevelopmental
• 37:15disorders. And this is really
• 37:17already impacting clinical care. Right?
• 37:19Because for families, understanding why
• 37:20they have the condition, understand
• 37:22recurrence risk, understanding medical comorbidities.
• 37:25And so this approach was
• 37:26really pioneered as I said
• 37:28in kind of autism in
• 37:29the field of, neurodevelopmental
• 37:31disorders, but my mentor here,
• 37:33Tom, had shown that you
• 37:34could use this approach. He'd
• 37:36led studies along with others,
• 37:38to find risk genes in
• 37:39OCD and tic disorders, which
• 37:41we know are related.
• 37:42And more recently, we've also,
• 37:44applied this in anxiety disorders
• 37:46and ADHD.
• 37:48And so we were hoping
• 37:49to really apply this in
• 37:51trick and skin picking, and
• 37:52that was kind of the
• 37:54tab study.
• 37:55And I'm showing a photo.
• 37:57This is right when we
• 37:57were starting the study. I
• 37:58was a second year resident,
• 38:00and we had, with the
• 38:02help of Michael and Tom,
• 38:03we'd kind of put this
• 38:04together. And we had decided
• 38:06we were gonna start recruitment
• 38:07at the TLC meeting, and
• 38:08this was pre COVID. So
• 38:09this was out,
• 38:12in San Francisco, and,
• 38:14I had, like we had
• 38:16shipped all these saliva collection
• 38:17kits, and you can see
• 38:18on the table, I printed
• 38:20all the consents
• 38:21organized by child, adolescent, etcetera.
• 38:24And this was kind of
• 38:25the first warning, and I
• 38:26remember setting up the table
• 38:27and being really proud. I
• 38:28was like, I should take
• 38:29a picture of this.
• 38:30And I didn't really know
• 38:32what to expect that day,
• 38:34But it really
• 38:36was amazing
• 38:37how many people I mean,
• 38:38we didn't have money to
• 38:39pay them. I was a
• 38:40trainee.
• 38:41How many people really signed
• 38:42up for the study, and
• 38:43I kinda made a decision
• 38:44that I wanted to contribute
• 38:46to these disorders. Right? That
• 38:48I that I was gonna
• 38:50spend a good chunk of
• 38:51not all my career, but
• 38:52I was gonna try and
• 38:53advance this because I I
• 38:55really felt moved by how
• 38:57excited they were, the participants
• 38:59about this research. And so
• 39:01we started collecting,
• 39:02trios.
• 39:03We collected saliva,
• 39:05from these families for DNA.
• 39:06We
• 39:07collected surveys from them.
• 39:11And and this study has
• 39:13continued,
• 39:14and it's kind of the,
• 39:16premise of my k award,
• 39:17which is finishing its third
• 39:18year now. How hard to
• 39:19believe. And just put together
• 39:21the progress report recently, so
• 39:23I collected the numbers. We've
• 39:24now collected
• 39:26a hundred and fifty seven
• 39:27parent spring trios,
• 39:29so far. I'm highlighting Anna
• 39:30who's worked on this the
• 39:31last two years, but, you
• 39:33know, these recruitment of trios
• 39:34really takes a village. There
• 39:35are lots of trainees who
• 39:37have, contributed,
• 39:38and lots of faculty members
• 39:39who have helped me along
• 39:40the way.
• 39:42With my k award and
• 39:43a variety of other grants,
• 39:44we've,
• 39:45started doing a lot of
• 39:46genetics work,
• 39:48generating genetics data, really trying
• 39:50to find what are these
• 39:51risk genes, what are these
• 39:52risk genetic factors.
• 39:53And I presented some of
• 39:54this data before at a
• 39:56variety of settings in the
• 39:57child's study center. I decided
• 39:58today
• 39:59I would focus on a
• 40:00newer analysis that was led
• 40:01by Sam,
• 40:03who's here, who's a PhD
• 40:04study student working with me.
• 40:06And so
• 40:07this is an analysis. It's
• 40:09not published yet, but, hopefully,
• 40:11it's gonna be submitted soon,
• 40:13where we took we generated
• 40:15genome wide array data in
• 40:16a hundred and ten families,
• 40:21And, you know, you have
• 40:22to do a variety of
• 40:22quality control. We ended up
• 40:24examining a hundred probands with
• 40:25trichotillomania
• 40:27and or excoriation disorder
• 40:28with their parents. And then
• 40:30in these families, we were
• 40:31able to look at transmission
• 40:33of polygenic risk,
• 40:36and look at, rates of
• 40:37rare, copy number variance. And
• 40:40this is just the demographics
• 40:41of the sample. You can
• 40:42see our sample is mostly
• 40:43with female.
• 40:45That's just we recruit everyone.
• 40:46We just happen to get
• 40:47mostly female
• 40:49enrolled.
• 40:50They're on average twenty one
• 40:51years old,
• 40:53but there's a huge range.
• 40:54We have children to later
• 40:56adults.
• 40:56They have a variety of
• 40:57co occurring conditions. We essentially
• 40:59had no kind of exclusion
• 41:01criteria,
• 41:02because so little is known
• 41:03about these thesaurus that we
• 41:04wanted to include as much
• 41:05as we can. They're mostly
• 41:07European ancestry. We're really working
• 41:09on that. You know, we
• 41:10don't have exclusions, but we
• 41:11really do,
• 41:13we're really making efforts.
• 41:15And if other people have
• 41:17suggestions of ways we can
• 41:18try to make these, samples
• 41:19more diverse, I'm
• 41:21I'm very much open to
• 41:22it.
• 41:24They're they're mo about half
• 41:25simplex families, no family history,
• 41:27and about half multiplex families.
• 41:30And with this data, even
• 41:32though there's no GWAS studies
• 41:33of trichotillomania
• 41:34excoriation disorder, we were able
• 41:36to leverage the GWAS studies
• 41:38of other related conditions, and
• 41:39we were able to test
• 41:41if these kids
• 41:43have just by chance,
• 41:45inherited a higher polygenic risk
• 41:47from their parents. And what
• 41:49we found is that for
• 41:50OCD,
• 41:51which makes sense because we
• 41:52kind of characterize it as
• 41:53an OCD related disorder, we
• 41:55find an enrichment, kinda suggesting
• 41:57for the first time at
• 41:58this kind of genetic level
• 42:00that these conditions may be
• 42:01related,
• 42:02to OCD.
• 42:04We also were able to
• 42:05look at rare CMVs,
• 42:07in these individuals,
• 42:09and we found several rare
• 42:11CMVs,
• 42:12in that impact constrained genes,
• 42:15that impact neurodevelopmental
• 42:17CMVs,
• 42:18and that impact,
• 42:20neurodevelopmental
• 42:21risk chains. But if you
• 42:22look at this table and
• 42:23these are all females partly
• 42:25because of our data.
• 42:27But
• 42:28none if you look at
• 42:28the co occurring conditions, none
• 42:30of these, probands have autism
• 42:32or intellectual disability,
• 42:35but we're seeing these genetic
• 42:36changes in that we know
• 42:38are risk genes for neurodevelopmental
• 42:40disorders kind of suggesting potential
• 42:42kind of pleiotropic
• 42:43effects there.
• 42:45We can also, do pathway
• 42:47analyses to understand are these
• 42:49constraints
• 42:50strain genes
• 42:53enriched for particular pathways more
• 42:55than you might expect by
• 42:56chance. We're seeing things like,
• 42:58nervous cyst bigger the circle,
• 43:00the more genes, and the
• 43:01redder, the more statistical significance.
• 43:05We're seeing enrichment for things
• 43:06like nervous system development,
• 43:08and synapse organization, all things
• 43:10that kinda make sense with
• 43:11our neurodevelopmental
• 43:12understanding.
• 43:14And so I said this
• 43:15is work by Sam. I
• 43:16I kinda wanna give a
• 43:18highlight of this. She'll actually
• 43:19if you're interested in this
• 43:20type of work, she's actually
• 43:21presenting this on Friday,
• 43:23at the YCCI,
• 43:25Robert Sherwin All Scholars Day,
• 43:28and,
• 43:29she's giving an oral presentation.
• 43:30And she's actually if you
• 43:31look at the agenda, I
• 43:32think she is the only
• 43:33pre doc with the presentation,
• 43:35so we're really proud of
• 43:36her.
• 43:38And and so in terms
• 43:39of next steps, you know,
• 43:40we're continuing to recruit these
• 43:41families. We're doing a bunch
• 43:42of different genomic analysis, trying
• 43:44to advance our understanding of
• 43:45these genes.
• 43:47I didn't have time today
• 43:49or I had to be
• 43:49selective, but we're also starting
• 43:51to do mechanistic studies when
• 43:52Zong's leading some of that
• 43:54work. In our lab, we've
• 43:55created,
• 43:56kind of brain organized in
• 43:57some of these trichotillomania
• 43:58families,
• 44:00and we're working on that.
• 44:01So maybe the next grand
• 44:02rounds.
• 44:03So we're continuing to do
• 44:04the tab study. I also
• 44:06wanna highlight Michael Block has
• 44:07a clinical trial,
• 44:09looking at, a VMAT inhibitor,
• 44:12valbenazine.
• 44:13So I kinda showed you
• 44:14that benefit,
• 44:15of olanzapine, but, obviously, we're
• 44:17limited because of the side
• 44:18effects. So looking at,
• 44:20valbenazine
• 44:21in terms of, treatment.
• 44:24I'm gonna skip this because
• 44:25I wanna have enough time
• 44:28to kinda end.
• 44:31But I'm not here today
• 44:31to dwell on those hard
• 44:33times in my life.
• 44:34I'm here today to hopefully
• 44:35give you living proof that
• 44:37recovery is possible and things
• 44:38do get better.
• 44:40My senior year of high
• 44:41school, I decided I was
• 44:42tired of keeping this part
• 44:43of my life a secret.
• 44:45I made a Facebook post
• 44:47explaining what trick is and
• 44:48providing links to TLC for
• 44:50more information.
• 44:51The response I received was
• 44:53overwhelming and life changing.
• 44:55Friends and peers began showing
• 44:57more support than I ever
• 44:58could have imagined.
• 45:00Finally, after attending a TLC
• 45:01workshop in New York City
• 45:02one fall day, I decided
• 45:04I was fed up with
• 45:05Trick.
• 45:06Why was I letting this
• 45:08condition control my happiness?
• 45:10Why was I letting it
• 45:11define who I am?
• 45:13From that day on, I
• 45:15stopped feeling sorry for myself
• 45:16and started my journey of
• 45:17really hard work.
• 45:20And I guess I I
• 45:21just wanted to end on
• 45:22that because I I think,
• 45:24again, coming back to kind
• 45:25of these are real people
• 45:27that we're kind of treating,
• 45:28and I think
• 45:30her message of that it's
• 45:31hard work. It is hard
• 45:32work. It's hard work for
• 45:33the patients. It's hard work
• 45:34for the therapists.
• 45:36It's hard work for the
• 45:37researchers, but I think it's
• 45:38really important work that we're
• 45:39all doing on this.
• 45:41And so with that,
• 45:45a big, big thank you,
• 45:47to the individuals and families
• 45:48who participate in these studies.
• 45:49This work is not possible
• 45:51without them. I don't know
• 45:51if any of them are
• 45:52in the audience or listening,
• 45:54but you are the stars
• 45:55of the show.
• 45:56And then,
• 45:57I I also wanna thank
• 45:58everyone in my lab and
• 46:00everyone in, Michael and Tom's
• 46:01labs who, contributed,
• 46:04particularly,
• 46:05to Louise who, I highlighted
• 46:07so much of his work
• 46:08today, and, we're so excited.
• 46:10He came here. I met
• 46:11him as a med student.
• 46:12He started the tab study
• 46:13with me when he was
• 46:13a med student, went back
• 46:15to Brazil, came back as
• 46:16a Fulbright Scholar during his
• 46:18PhD. And now in August,
• 46:20he is joining the faculty.
• 46:22So we're so excited that
• 46:23he's coming. And,
• 46:26and then, of course, Michael
• 46:27and Tom know how I
• 46:28feel about them.
• 46:30And,
• 46:31yeah. And then I you
• 46:32know, I also wanted to
• 46:33mention, I, you know, I
• 46:34chose to talk about this
• 46:35project because, obviously, I really
• 46:37care about it. We have
• 46:38a lot of other projects,
• 46:39and my last grand rounds,
• 46:40I talked about ADHD and
• 46:41anxiety, but there are a
• 46:42lot of other works, we're
• 46:44doing as well with a
• 46:45bunch of collaborators.
• 46:47And so with that, happy
• 46:48to take questions.
• 46:58Yeah.
• 46:59Yeah.
• 47:00Hi. So,
• 47:02I'm actually
• 47:03I said wow at the
• 47:04beginning
• 47:05because of
• 47:07Earlier on because,
• 47:09so this runs in my
• 47:10family, and, like, we really
• 47:12didn't know a lot about
• 47:13it. So this is kind
• 47:14of, in a weird way,
• 47:16exciting because, unfortunately, we do
• 47:18have an aunt that has
• 47:19still dealing with it, and
• 47:20she's completely evolved. And then
• 47:22we have cousin around my
• 47:23age, twenty seven,
• 47:25that is dealing with it.
• 47:27And,
• 47:28earlier on when I was
• 47:29younger, I was dealing with
• 47:30some skin picking issues.
• 47:32So to me, like, to
• 47:33hear this was like, woah.
• 47:34Like, you you just told
• 47:36me things about my family
• 47:37that I was,
• 47:38not aware of.
• 47:40So,
• 47:40thank you so much for
• 47:41that.
• 47:42I guess my question is,
• 47:44is there data that is
• 47:46talking about,
• 47:48like,
• 47:49maybe that shows the correlation
• 47:50of, like, maybe
• 47:52having that influence of your
• 47:53family that,
• 47:55that has trick or skin
• 47:57picking?
• 47:58And
• 47:59that
• 48:00kind of compares
• 48:02parallel to what the genetic
• 48:04portion of it has just
• 48:05because
• 48:06I I'd just be very
• 48:07interested and understanding again, like,
• 48:10my family's
• 48:11issues and then what's, like,
• 48:13the social
• 48:14aspect of, like, seeing that.
• 48:15Yeah. That's a great question.
• 48:17So first of all, thank
• 48:18you for your comment. It's
• 48:19very validating to hear this
• 48:20is useful to people.
• 48:23And then,
• 48:24yeah, you know, there isn't
• 48:26a ton of data.
• 48:29I don't know if Doris
• 48:30is here. Is she here?
• 48:34But,
• 48:35but there,
• 48:37there there have been a
• 48:38few things looking at family
• 48:40factors and looking at kind
• 48:41of the impacts of, like,
• 48:42if your mom has it,
• 48:43but it's definitely an underexplored.
• 48:45And I I tend to
• 48:46think there is kind of
• 48:47a social aspect to it
• 48:48as well,
• 48:49and definitely maybe kind of
• 48:52an accommodation aspect. You know,
• 48:53like, there might be kind
• 48:54of behaviors that we could
• 48:55do, to help improve it
• 48:57as well. But it's very
• 48:59understudied,
• 49:00and I and but I
• 49:01think it it's clearly something
• 49:02I'm interested in and kinda
• 49:04teasing apart. Why does it
• 49:05run-in families? What are kind
• 49:06of what's due to genes?
• 49:07What's due to kinda environment,
• 49:09family factors, etcetera?
• 49:14Hi. I also wanted to
• 49:16say a big thanks.
• 49:18So excoriation
• 49:19is something that I've struggled
• 49:21with in my life since
• 49:22I was young and, like,
• 49:23a teenager.
• 49:25And I I recently saw
• 49:26a picture of myself from
• 49:27ten years ago when I
• 49:28was, like, really struggling with
• 49:29it at, like, the height
• 49:30of it. And
• 49:32everything you're saying rings true.
• 49:34And
• 49:35I was just really interested
• 49:36because
• 49:37I was recently diagnosed as
• 49:38an adult with ADHD
• 49:40and
• 49:41started a course
• 49:42of stimulant medication.
• 49:44And I've heard some evidence
• 49:46that there's a tie between
• 49:48ADHD and these BFRBs.
• 49:51And I was wondering if
• 49:52there's any evidence to suggest
• 49:54that
• 49:56medication that addresses
• 49:57things like ADHD
• 49:59helps with that because this
• 50:00is completely anecdotal, but I
• 50:02noticed
• 50:02a massive reduction in my
• 50:04urge to pick once I
• 50:06started
• 50:07that medication. I I just
• 50:08wanted to hear your thoughts
• 50:09on that.
• 50:10Yeah.
• 50:12So there is an association.
• 50:13ADHD is higher in these
• 50:14disorders.
• 50:16I it's hidden in the
• 50:17slides on one of the
• 50:18tables.
• 50:19It might be a little
• 50:20higher with skin picking than
• 50:21with trick, the ADHD Association.
• 50:25Some people have argued that
• 50:26it that actually might be
• 50:27because of the stimulants, that
• 50:28stimulants might be associated with
• 50:30skin picking, but I actually
• 50:32agree the opposite. I agree
• 50:33with what you said. I
• 50:35my clinical experience, and I'm
• 50:37just gonna give you a
• 50:38clinical experience because I don't
• 50:39I unfortunately don't have data
• 50:41to show it. Mhmm. I
• 50:42think you're right. I think
• 50:43when we treat the ADHD,
• 50:45that often that can be,
• 50:47helpful
• 50:48for the skip pay. And
• 50:48so because this was something
• 50:50I didn't emphasize that much,
• 50:52but because our pharmacotherapies
• 50:53are so limited,
• 50:55we sometimes do really focus
• 50:56on treating if there are
• 50:58co occurring disorders, treating the
• 50:59co occurring disorders. So sometimes
• 51:01when you treat the anxiety
• 51:02or the depression or the
• 51:03ADHD,
• 51:05that that may lead to
• 51:06a reduction in symptoms and
• 51:07may be helpful. But I
• 51:08think there is a group
• 51:09that it's very tightly linked
• 51:11and that actually,
• 51:13the ability and sometimes you
• 51:14even see it, like, they'll
• 51:15be on stimulants and then
• 51:16they'll be they won't pick
• 51:18during the day. And when
• 51:19the stimulant wears off at
• 51:20night, then they'll pick in
• 51:21the evening before bed. And
• 51:22so,
• 51:24I have a few cases
• 51:25like that. So I I
• 51:25think that there is something
• 51:27there, and it's a really
• 51:27interesting point.
• 51:31We have a question from
• 51:32Julie Chilton on the chat
• 51:33and then Bob King.
• 51:35Julie Hey. Julie, would you
• 51:37be on mute?
• 51:39Can you guys hear me?
• 51:41Yeah. Yeah.
• 51:42Okay. Great. Well,
• 51:44fantastic
• 51:45talk. I always,
• 51:47am struggling with what to
• 51:49do when I get,
• 51:51skin pickers or,
• 51:53anything with excoriation
• 51:54disorder in kiddos.
• 51:56I just wondered if you
• 51:58thought space might be appropriate
• 52:01for these guys and and
• 52:03whether Ellie should roll out
• 52:04a new model for that.
• 52:08Well, I can't talk for
• 52:10Ellie, but maybe.
• 52:12I don't know. I have
• 52:13Becca here in his place.
• 52:16But,
• 52:17but there might be I
• 52:18mean, it, again, I think
• 52:19one of the limitations is
• 52:21really when we have these
• 52:22young kids and doing these
• 52:23behavioral treatments. Right? Is it
• 52:25it's really hard with the
• 52:26younger kids. And,
• 52:28I haven't tried actually space
• 52:30specifically for Trich before,
• 52:32only for OCD and anxiety,
• 52:34but
• 52:35but yeah.
• 52:40No. No. If you have
• 52:41thoughts, I don't know.
• 52:43It's it's tough because yeah.
• 52:44Like, it's such a I'm
• 52:45old focused. The behavior and
• 52:47space is so focused, obviously,
• 52:49parent behaviors, but I do
• 52:50think just, again, anecdotally,
• 52:52sometimes there are accommodations that
• 52:53some of, like, the surrounding
• 52:55behaviors, like, supplying,
• 52:56you know, bandies or, like,
• 52:58you know, things that parents
• 52:59can't do to maybe help
• 53:00the child, like, cover up
• 53:02their distress related to, you
• 53:04know, these behaviors. But It's
• 53:06an interesting question. Yeah. Talk
• 53:07to Ellie.
• 53:09It would be interesting to
• 53:10think more about the phenomenology
• 53:13of this,
• 53:16focused versus automatic
• 53:19sort of pulling because that
• 53:20may
• 53:21shed some light on this
• 53:23question of whether
• 53:24paying more attention
• 53:26or less attention
• 53:27would be better. I mean,
• 53:29certainly, Andreas wrote a letter,
• 53:32twenty years ago about, you
• 53:34know, new onset of trichotillomania
• 53:36on on stimulants and so
• 53:38on. And,
• 53:41there, you know, there's this
• 53:42same debate,
• 53:43in Tourette's that goes back
• 53:45fifty years as to whether,
• 53:48stimulants make tics better or
• 53:50worse. The old line was
• 53:51that it made them worse,
• 53:52but there's actually some data
• 53:54from the tax study and
• 53:55some of those things that
• 53:57it may make it better
• 53:58because maybe you can focus
• 54:01your inhibitory,
• 54:03efforts
• 54:04better as opposed to just
• 54:06sort of spacing out and
• 54:08either ticking or
• 54:10obsessing
• 54:11or,
• 54:12or or pulling or scratching.
• 54:14So, I mean,
• 54:16it might be interesting to
• 54:17do a subanalysis
• 54:19of,
• 54:20of of the effects of
• 54:21stimulants by the type of
• 54:24pulling. But Yeah.
• 54:26And clinically,
• 54:27my experience and, again, I
• 54:29think having data, but I
• 54:30I think this is truly
• 54:31a one size does not
• 54:32fit all. I think there
• 54:33probably are groups of people.
• 54:35I have seen it too
• 54:36where it's gotten worse in
• 54:38individual cases, but I think
• 54:40there are group of people
• 54:41where it really helps the
• 54:42stimulant. Right? So I think,
• 54:44and maybe they're different, as
• 54:45you said, kind of phenomenology
• 54:47or biological factors, and maybe
• 54:49they're really not kind of
• 54:50the same disorder. Right? I
• 54:52think that's what I'm hoping
• 54:53that genetics will help us
• 54:54answer as well as kinda
• 54:56understanding the heterogeneity.
• 54:58Final question.
• 55:00We could occasionally, maybe once
• 55:01a year, see
• 55:03very young children, you know,
• 55:05under two
• 55:06who, you know, who were
• 55:07pulling some mostly, they pull
• 55:09their own hair, but sometimes
• 55:11as in, the Trichobe source
• 55:13cases, they'll be pulling mother's
• 55:15hair. Sometimes it's the genitalia's
• 55:17hair. And those are particularly
• 55:19difficult because they're not exactly
• 55:21open to,
• 55:23sophisticated,
• 55:24cognitive restructuring
• 55:26methods
• 55:27at the age one and
• 55:28a half or two.
• 55:29Any thoughts about that group
• 55:31of kids? The baby truck.
• 55:32I didn't talk about baby
• 55:33truck.
• 55:35It is a described kind
• 55:36of phenomenon.
• 55:39I don't have young enough
• 55:40kinda kids in my sample,
• 55:42and I actually personally haven't
• 55:44treated that many of them.
• 55:47But, but you're definitely right.
• 55:48There is this described phenomenon
• 55:50that there's early onset. It's
• 55:52usually not distressing to the
• 55:53child.
• 55:55The parents are usually the
• 55:56ones concerned about it.
• 55:59But
• 56:00but yeah. But I think
• 56:03it trying there is a
• 56:04paper kinda describing it that
• 56:06it it's
• 56:08got some similarities
• 56:09with kind of later onset
• 56:11trick, etcetera. But, again, the
• 56:13distress part is really,
• 56:15different, and that's my memory
• 56:16of the literature. But you
• 56:18are probably more of an
• 56:19expert in this than me.
• 56:21So
• 56:22And we we might fit
• 56:23in one more question. Angie,
• 56:24do you wanna unmute to
• 56:25ask your question?
• 56:28Yeah. I I just wanted
• 56:29to thank you, Emily, for
• 56:31spotlighting this. It's been a
• 56:32pleasure working with you, since
• 56:34since you were a student.
• 56:36It's been a pleasure
• 56:37working with you. And, just
• 56:39to highlight different,
• 56:41aspects of
• 56:42even the cultural aspect of
• 56:44trichotillomania,
• 56:46in doing the trial with
• 56:47the valbenazine,
• 56:48we've had,
• 56:49Muslim,
• 56:50women
• 56:51that hide their trichotillomania
• 56:53under their
• 56:54their,
• 56:56bail.
• 56:57We've had,
• 56:58African American women
• 56:59that, hide their trichotillomania
• 57:02under their wig,
• 57:04or the the,
• 57:05hair pieces,
• 57:07and, just the the
• 57:10the toll that trichotillomania
• 57:12has on the female condition
• 57:14just because of
• 57:15how we are viewed in
• 57:17society,
• 57:18and the the the role
• 57:20that the way we look
• 57:22plays in how we are
• 57:23judged,
• 57:24I think, plays such a
• 57:25big role. And the the
• 57:26fact that you're spotlighting this
• 57:28condition,
• 57:29I think, is
• 57:31tantamount to, you know, kind
• 57:33of
• 57:34focusing,
• 57:35a big spotlight and, you
• 57:37know, doing something for women's
• 57:38health that, I think,
• 57:40has been otherwise under rug
• 57:43swept. And, just thank you.
• 57:47Thanks, Angie.
• 57:48What a great note to
• 57:49to end on. So just
• 57:50join me in thanking the
• 57:51analyst.