>> YOU CAN FIND A COPY OF THE
PROGRAM AND I PROMISE TO KICK
OFF A WONDERFUL DAY AND ALSO TO
HAVE THE OPPORTUNITY FOR
EVERYBODY IN THE PROGRAM TO COME
TOGETHER AND HEAR A LITTLE BIT
ABOUT SOME OF THE AMAZING WORK
THAT'S GONE ON LED BY ELLEN OVER
THE LAST 25 YEARS AND HEAR ABOUT
SOME OF THE ONGOING WORK THAT
FOLLOWS THE INSPIRATIONS SHE
BEGAN HERE AT THE INTERMURAL
RESEARCH PROGRAM.
I'LL BE YOUR HOST FOR THE DAY.
YOU'LL HEAR MORE OF MY WORK WITH
ELLEN HES AN JUST A FEW MINUTES
AND LIKE TO START OFF BY
INTRODUCING DR. SUSA'
INTRODUCING DR. SUSAN AMARA.S'
INTRODUCING DR. SUSAN AMARA.
SUSAN IS THE CURRENT SCIENTIFIC
DIRECTOR AND CHIEF OF THE
LABORATORY OF MOLECULAR AND
CELLULAR BIOLOGY AND ALL OF US
FEEL A GREAT INDEBTEDNESS TO
SUSAN.
WHEN SHE CAME, THINGS WERE IN A
BIT OF DISARRAY AS THERE HAD
BEEN A LOT OF CHANGES AT THE
INTERMURAL RESEARCH PROGRAM AND
SUSAN WAS ABLE TO PULL US ALL
TOGETHER AND LEAD TO A LOT OF OF
THE GREAT THINGS YOU'RE GOING TO
HEAR ABOUT IN THE REMAINDER OF
THE DAY.
I'M TRYING TO THINK IF I CAN
TELL MY FAVORITE FUNNY STORIES
ABOUT ELLEN.
SUSAN, ARE YOU READY?
GOT IT.
I'M TRYING TO THINK IF I HAVE
ONE SHORT -- I WILL SAY THERE'S
BEEN MANY OCCASIONS AND AGAIN,
I'LL TALK ABOUT A FEW OF THESE
WHERE ELLEN HAS SAVED ME AND A
REMEMBER WHEN I FIRST STARTED TO
MOVE INTO ADMINISTRATION AND I
KIND OF THOUGHT THE RULES OF
NAVIGATING WERE FAIR AND
EVERYBODY TREATED EACH OTHER IN
WONDERFUL COLLEGIAL WAYS AND
SHOCKED FIND OUT THAT'S NOT HOW
ADMINISTRATION REALLY WORKS.
I REMEMBER STANDING WITH ELLEN,
THIS IS PROBABLY IN 2002 OUTSIDE
OF BUILDING 1 IN A POURING RAIN
STORM AND ELLEN EXPLAINED TO ME
THIS IS NOT REALLY HOW THINGS
WORKED.
IT WAS A TOUGH PLACE IN GENERAL
AROUND THE WORLD AND YOU NEEDED
TO TOUGHEN UP AND DEAL WITH IT I
REMEMBER THAT LIKE IT WAS
YESTERDAY AND I REMEMBER MANY
OTHER STORIES LIKE THAT.
I INTRODUCED YOU WHEN YOU WERE
OUT --
>> SO, IT'S REALLY A PLEASURE
AND IT'S WONDERFUL TO SEE SO
MANY PEOPLE IN THE AUDIENCE AND
I'M SURE IT'S GREAT TO BE ABLE
TO CELEBRATE ELLEN'S CAREER
WHICH IS AN AMAZING ONE.
SHE'S BEEN REALLY AN
EXTRAORDINARY CONTRIBUTOR TO THE
AREA OF CHILD PSYCHOLOGY AND
STUDY OF IRRITABILITY IN
CHILDREN AND MADE MAJOR
CONTRIBUTIONS.
IT'S MY PLEASURE.
I FIRST MET ELLEN WHEN I WAS
INTERVIEWING FOR THE POSITION
AND YOU WERE ON ONE OF THE
PANELS AND ASKING GOOD QUESTIONS
IN A WONDERFUL WAY.
I APPRECIATED THAT.
I'VE ALWAYS HAD A POSITIVE
OPINION AND REALLY HAVE VALUED A
LOT OF YOUR IDEAS AND YOUR
JUDGMENT DURING THE COURSE OF MY
TIME HERE.
IT'S MY PLEASURE TO ALSO
ACKNOWLEDGE THAT TO MAKE A
CELEBRATION LIKE THIS IT REALLY
DOES TAKE A SMALL VILLAGE AND
WANTED TO BE SURE TO THANK ALL
THE PEOPLE ACTIVELY INVOLVED IN
IN GENERATING THE PROGRAM AND
MAKING ARRANGEMENTS FOR ALL THE
THINGS.
SO REALLY, DANNY AND MARYLAND,
THEY'VE DONE AN AMAZING AMOUNT
OF WORK INITIALLY FORMULATING
THIS PLAN AND EXECUTING IT AND
THERE'S ALSO CHARLENE EDWARDS
AND KALEY AND CELEBRATION OF
ELLEN'S CAREER AND LIFE.
JENNY HERON AND CAROLYN MILLER
AND LISA COLLINS AND WE'RE ALSO
GRATEFUL TO OTHERS OUTSIDE OF
NIMHD, KRISTIN DEMOPOULOS AND
LIEUTENANT DUKE FROM THE NIH
POLICE.
NOT SURE WHAT HIS INVOLVEMENT
WAS --
>> HE LET EVERYBODY IN.
>> GREAT.
AND EVENTS MANAGEMENT AND JOHN
MELVIN AND CHRISTINE WHO SET UP
THE REGISTRATION SITE.
I THINK WE HAVE A GREAT DAY
AHEAD OF US AND CELEBRATING
ELLEN'S CONTRIBUTION TO THE
NATIONAL INSTITUTE OF HEALTH.
THANK YOU.
ALSO, A LITTLE BIT MORE ABOUT
THE PROGRAM WHEN IT'S MY TURN TO
SPEAK AND THE NEXT SPEAKER WILL
BE MARILYN PAO THE NIH CLINICAL
DIRECTOR OF THE INTRAMURAL
RESEARCH PROGRAM AND MARYLAND
HAS DONE MORE THAN ANYBODY NOT A
CLINICALLY ACTIVE INVESTIGATOR
COULD EVER REALIZE TO SUPPORT
CLINICAL RESEARCH AT THE NIMHD
IN GENERAL AND IN PARTICULAR TO
SUPPORT RESEARCH IN CHILDREN.
SUCH RESEARCH IS REALLY
IMPORTANT BECAUSE I THINK WE ALL
KNOW MENTAL DISORDERS BEGIN IN
CHILDHOOD ON THE ONE HAND.
ON THE OTHER HAND, LAUNCHING
RESEARCH THAT STUDIES CHILDREN
AFFECTED BY MENTAL ILLNESSES IS
EXTREMELY DIFFICULT AND WE HAVE
AN AMAZING CHAMPION IN MARYLAND.
SO IT'S WITH GREAT PLEASURE THAT
I CAN INTRODUCE MARYLAND TO SAY
A FEW WORDS ABOUT ELLEN'S
CAREER.
THESE ARE FUN EVENT TO DO IN
THIS JOB.
I HAVE LESS FUN ACTIVITIES BUT I
WANT TO MENTION A FEW
HOUSEKEEPING ITEMS FIRST.
AFTER THE SYMPOSIUM THERE WILL
BE A RECEPTION SPONSORED BY FAES
ON THE FAES TERRACE TO JOIN US
FOR REFRESHMENTS AT THE END OF
DAY.
ALSO, LUNCH WILL BE ON YOUR OWN.
THE RESTROOMS ARE RIGHT OUTSIDE
THE AUDITORIUM.
PLEASE SILENCE YOUR CELL PHONES
WHILE IN HERE AND THERE'S A
CHARGING STATION AT THE BACK OF
THE ROOM FOR PHONES AND
COMPUTERS AND THOUGH I HAVE TO
SAY THE WI-FI'S A LITTLE WONKY
IN HERE AND PLEASE SIGN THE
PHOTOGRAPH IN THE BACK AND IF
YOU DIDN'T HAVE A CHANCE TO
RIGHT ELLEN SOMETHING YOU CAN
CONTRIBUTE THOSE TO KATIE OR
MYSELF AND WE'LL GET THEM TO THE
SCRAP BOOK.
WE'LL PRESENT THAT AT THE END OF
THE DAY.
I DO WANT TO NOTE THAT ELLEN'S
FAMILY IS HERE SO BOB
LIEBENLUFT, HER HUSBAND, AND HER
SON, JACOB, AS WELL AS JACOB'S
FIANCEE, KATIE WELLMAN AND ROBIN
LIEBENLUFT AND JASON GLICK CAME
AND SUE LIEBENLOFT IS HER SISTER
WAS UNABLE TO ATTEND BUT DID
WANT TO BE HERE AND HOPEFULLY
SHE'S WATCHING ON THE VIDEO
LINK.
THOSE ARE THE HOUSEKEEPING I
WANTED TO BE SURE.
IT'S MY PLEASURE TO TALK ABOUT
ELLEN FOR A MINUTE.
YOU'LL NO DOUBT BE HEARING TODAY
ABOUT THE MANY SCIENTIFIC
CONTRIBUTIONS ELLEN HAS MADE TO
THE FIELD OF PSYCHIATRY OVER THE
PASTED AS PARTICULARLY IN CHILD
AND ADOLESCENT PSYCHIATRY.
WE'RE RIGOROUSLY THINKING ABOUT
DIAGNOSTIC CRITERIA AND CLINICAL
TRIALS FOR TREATMENTS ARE
ESPECIALLY NEEDED.
I'M NOT GOING TO GO OVER THE
MILLIONS OF AWARDS SHE'S WON AND
A NATIONAL ACADEMY OF MEDICINE
MEMBER.
YOU'RE GOING TO HEAR TODAY SOME
OF HER MANY MENTEES WHO HAVE
GONE ON TO HAVE SUCCESSFUL
CAREERS OF THEIR OWN.
I WANTED TO TAKE A MINUTE TO
HIGHLIGHT HOW ELLEN HAS SERVED
AS A ROLE MODEL FOR WOMEN IN
RESEARCH AND SCIENCE OVER THE
YEARS.
ELLEN'S INTERESTING AND
INSTRUCTING JOURNEY IS
PARTICULARLY HOPEFUL, I THINK
FOR TRAINEES AND OTHER STAFF
CLINICIANS IN THE AUDIENCE.
SO SHE CLEARLY DEMONSTRATED
EARLY EVIDENCE OF HER LEADERSHIP
AFTER HER EDUCATION AT YALE AND
STANFORD AND HER ADULT
PSYCHIATRY TRAINING AT
GEORGETOWN WHERE SHE'S STILL AN
ASSOCIATE CLINICAL PROFESSOR.
AS MANY CHIEF RESIDENTS DO FOR A
SIGN OF LEADERSHIP, SHE STAYED
ON AS FACULTY SERVING AS MEDICAL
DIRECTOR OF THE MEDICAL HEALTH
IN-PATIENT UNIT FOR GEORGETOWN
FOR SIX YEAR AND DIRECTOR OF
HOSPITAL SERVICES THE LAST COME
YEARS THERE.
I JUST NOTE THAT HER FIRST
PEER-REVIEWED PAPER WAS QUOTE,
STAFF RESPONSE TO THE PREGNANT
SIF A THERAPIST ON AN IN-PATIENT
UNIT.
I DON'T KNOW IF THAT WAS HER
PREGNANCY OR OTHER STAFF MEMBERS
BUT IT'S A SIGN MAYBE WE CAN
INTEGRATE OUR LIVES WITH OUR
WORK.
SHE HAD MORE THAN A DOZEN PAPERS
BEFORE SHE LEFT ACADEMIA WHICH
IS NO SMALL FEAT AS A MEDICAL
DIRECTOR OF AN IN-PATIENT UNIT
AND CAME TO THE NIH AT 60% TIME
FOR FIVE YEARS SERVING AS THE
CHIEF OF THE UNIT ON RAPID
S
AS OPPOSED TO EXPERIENCE WITH
THE ADVERSIVE STIMULUS THAT
RELAT
RELATES TO A RECENT PAPER OF 25
ANXIOUS CHILDREN AND CHILDREN
WITH CLINICAL ANXIETY DISORDER
ALL MEDICATION FREE.
THIS IS A SKIN CONDUCTANTS WITH
NON-PAINFUL STIMULUS AND WHEN
THEY'RE ANTICIPATING A HIGHLY
PAINFUL STIMULUS.
AGAIN, YOU SEE THE INDIVIDUAL
DIFFERENCE.
THERE'S A GREATER DIFFERENCE
HERE IN THE PATIENTS THAN IN THE
HEALTHY INDIVIDUALS.
WHEN YOU MAP THESE TO THE BRAIN
AND LOOK AT THE LEVEL OF PAIN
CHILDREN EXPERIENCE WHAT YOU
FIND THERE'S NO RELATIONSHIPS
WITH ANXIETY, WITH THE LEVEL OF
PAIN BUT THE LEVEL OF PAIN
EXPERIENCE CORRELATES STRONGLY
WITH THE STRUCTURE AND THE
FUNCTION OF THE POSTERIOR INSULA
WHEN IS WHERE WE SHOW
NOCICEPTION IS REPRESENTED IN
HUMANS.
IN CONTRAST, WE SEE DIFFERENT
AREAS INCLUDING THE DORSAL
LATERAL PREFRONTAL CORTEX AND
THE OTHER BRAIN REGIONS WE SEE.
WE ALSO USED THIS PARADIGM TO
DEFINE A NETWORK OF BRAIN
REGIONS AND YOU SEE THEM LISTED
HERE WHERE THE SKIN CONDUCTANT
RESPONSES TO THE ANTICIPATORY
RESPONSE CORRELATED WITH
RELATIONSHIPS AMONG THE
NETWORKS.
I'M GOING COME BACK TO THIS AT
THE END OF THE TALK TO TALK
ABOUT HOW WE USE RESTING
CONNECTIVITY AMONG THESE REGIONS
DEFINED IN THIS ONE STUDY.
SO THE OTHER THING AND THIS IS
THE LAST THING I'M GOING TO TALK
ABOUT IN THIS SECTION, THE OTHER
THING THAT WE'VE LEARNED FROM
DOING A WHOLE RANGE OF THESE
PARADIGMS, YOU SEE THEM
ILLUSTRATED HERE.
HERE'S THE SCREAM PARADIGM AND
THE HEAT PAIN PARADIGM.
THERE'S A WHOLE BUNCH OF OTHER
PARADIGMS ILLUSTRATED HERE AND
THE OTHER THING WE LEARNED IS
EACH ONE OF THESE PARADIGMS HAS
CERTAIN STRENGTHS AND CERTAIN
WEAKNESSES THAT ARE ASSOCIATED
WITH THE PARADIGM AND THIS IS
WORK THAT'S ACTUALLY LED BY
KATERINA KIRKANSKI AND YOU'LL
HEAR FROM HER AND THIS IS THE
WORK YOU CAN ONLY DO IN THE
INTRAMURAL RESEARCH PROGRAM
WHERE CHILDREN COME IN MANY
TIMES AND HEALTHY CHILDREN AND
CHILDREN WITH ANXIETY DISORDERS
AND UNDER GO DIFFERENT
APPROACHES AND WHAT WE'RE
STARTING TO LEARN IS THAT IF WE
MODEL A LATENT FACTOR AND HERE
WE'RE TALKING ABOUT RECOVERY,
RIGHT, BECAUSE I TALKED ABOUT IT
AS ANTICIPATION AND RECOVERY AS
THE TWO MAIN PERIODS WHERE WE
SEE RELATIONS WITH CLINICAL
ANXIETY AND THIS PAPER IS
AVAILABLE ONLINE.
IT HASN'T APPEARED IN THE
JOURNAL YET BUT IT'S VERY HOT
OFF THE PRESS WORK AND WE FIND
THAT THIS FACTOR LOADINGS ON THE
LATENT VARIABLE WE CAN SEE HERE,
WE FIND THIS ARE ROBUSTLY
CORRELATES WITH CLINICAL RATINGS
OF ANXIETY.
THIS IS A CHILD'S CLINICAL
RATINGS WITHIN THE MONTH WHEN
SOME OF THESE TASKS WERE DONE
AND YOU CAN SEE THIS IS AS GOOD
AS WE DO IN TERMS OF
RELATIONSHIP WITH CLINICAL
ANXIETY AND IT ALSO CORRELATES
WITH THE LEVEL OF ANXIETY
CHILDREN RATE WHEN WE GIVE THEM
A CELL PHONE TO RATE THEIR
ANXIETY OVER SEVEN DAYS
CONTINUOUSLY AND THERE'S A
SUGGESTION THAT IT MORE STRONGLY
CORRELATES WITH SKIN CONDUCTANTS
THE FACTOR SCORE COMPARED WITH
RATINGS OF ANXIETY DURING ANY
ONE OF THESE MEASURES.
SO I GUESS THERE'S TWO MAIN
TAKEAWAYS FROM THE FIRST POINT.
NUMBER ONE, THE WORK IS VERY
DIFFICULT TO DO AND IT'S A
UNIQUE ASPECT OF WHAT WE CAN DO
AT THE NIMHD.
BUT NUMBER TWO, IT REALLY STARTS
IN TERMS OF THINKING ABOUT WHAT
ARE THE CLINICALLY RELEVANT
PHENOMENA WE WANT TO STUDY IN
CHILDREN AND HOW CAN WE BRING A
RIGOROUS APPROACH TO THAT STUDY.
THAT'S THE FIRST SNIPPET.
THE SECOND IS TO TALK ABOUT
BEHAVIORAL INHIBITION.
SO BEHAVIORAL INHIBITION IS A
TEMPERAMENT CHILDREN MANIFEST IN
THE FIRST TWO YEARS OF LIFE AND
VERY MUCH LIKE THE THREAT
PARADIGMS ABOUT WHICH I WAS JUST
SPEAKING, WE MEASURE BEHAVIORAL
INHIBITION BY EXPOSING YOUNG
CHILDREN TO SITUATIONS LIKE
THESE.
WE BRING THEM IN THE LABORATORY
AND THEY'RE EXPOSED TO MILDLY
THREATENING STIMULI SUCH AS
INTERACTING WITH FRIENDS THEY
HAVEN'T MET BEFORE OR
ENCOUNTERING A NOVEL TOY LIKE
THIS ROBOT AND THE WORK HAS BEEN
LED BY NATHAN FOX AT THE
UNIVERSITY OF MARYLAND AND
NATHAN, LIKE ME AND LIKE ELLEN,
RECOGNIZES THE IMPORTANCE OF
EVOKING THE PHENOMENON OF THE
BEHAVIORAL INHIBITION AND IT
AFFECT THE SPEECH AND DEGREE TO
WHICH MOVE IN SITUATIONS LIKE
THIS ONE.
CHILDREN WITH BEHAVIORAL
INHIBITION DO NOT SPEAK IN
SITUATIONS LIKE THIS AND TEND TO
REFRAIN FROM MOVING.
SO WE'VE DONE A NUMBER OF
STUDIES WITH NATHAN OVER THE
LAST 25 YEARS.
I'VE BEEN WORKING WITH NATHAN
ABOUT AS LONG AS I'VE BEEN
WORKING WITH ELLEN AND THERE ARE
A FEW IMPORTANT THINGS THAT I
WANT TO HIGHLIGHT ABOUT THE WORK
WITH NATHAN.
THIS IS THE FIRST ONE.
THIS IS 107 CHILDREN THAT WE
FIRST ASSESSED BEHAVIORAL
INHIBITION WHEN THEY WERE 14
MONTHS OF AGE.
AND THEN 26 AND THE DIRECT
MEASURE OF BEHAVIORAL INHIBITION
AND THE NOW ADULT WHO HAD BEEN A
CHILD THE RATINGS OF THEIR
PERSONALITY AND IT'S
PARTICULARLY MEASURES OF THE
LEVEL OF BEHAVIORAL IB HIBITION
AS IT'S RATED IN THE CHILD
BEHAVIOR AND PERSONALITY AT AGE
26.
MOREOVER, WE HAVE LOTS OF DATA
FROM THE INDIVIDUAL CHILD AT AGE
7, 9, 11, 12 AND 15.
MEASURES OF THINGS LIKE SOCIAL
ANXIETY AND THIS IS INDEPENDENT
OF AND BIVARIATE PREDICTS ADULT
PERSONALITY BETTER THAN EVEN THE
CHILD'S OWN RATING OF THEIR
ANXIETY WHEN THEY'RE A CHILD OR
ADOLESCENT.
AGAIN, THE KEY MESSAGE HERE IS
BY DIRECTLY MEASURES EVOKE
BEHAVIOR IN THE LABORATORY WE
GAINED SOMETHING UNIQUE.
NOW, NOT ALL THE CHILDREN WHO
START WITH BEHAVIORAL INHIBITION
GO ON TO DEVELOP
PSYCHOPATHOLOGY.
ABOUT HALF DO.
SOME DEVELOP PROBLEMS WITH
SOCIAL ANXIETY.
WE TYPICALLY SEE THIS IN
ADOLESCENCE AND AS THE CHILDREN
APPROACH ADULTHOOD THEY DEVELOP
A RANGE OF OTHER PROBLEMS
INCLUDING SOCIAL ANXIETY BUT
ALSO OTHER ANXIETY PROBLEMS AND
MAJOR DEPRESSIVE DISORDER.
SO ONE OF THE THINGS THAT WE
HAVE FOUND IS BY MEASURING
ASPECTS OF BRAIN FUNCTION IN
THIS PERIOD WE CAN GAIN INSIGHTS
ON WHICH CHILDREN ARE PROFIT
LIKELY TO DEVELOP SOCIAL ANXIETY
OR MAJOR DEPRESSION AND IS THIS
IS ONE OF THE MOST RECENT
FINDINGS AND LOOKS AT BETWEEN
THE AGES OF 15 AND 26, CHANGES
IN DEPRESSION AND ANG DIE.
-- ANXIETY AND DEPRESSION
MEASURES IN THIS AND ANXIETY AND
WHILE IT RELATE TO DEPRESSION
AND ANXIETY WE FIND DIFFERENT
MEASURES OF BIOLOGY ACQUIRED IN
ADOLESCENCE AND THIS MEASURE WAS
ACQUIRED BETWEEN 15 AND 18
PREDICTS IN A MORE SPECIFIC
MANNER WHAT PROBLEM A CHILD IS
GOING TO HAVE.
THIS FOR REWARD RESPONSIVENESS
AND LEVEL OF ACTIVATION IN THE
STRIATUM AND AMONG THE CHILDREN
WHO ARE LOW IN STRIATAL
ACTIVATION TO THE REWARD THE
ORANGE GROUP HAVE LOW ACTIVATION
BETWEEN 15 AND 18.
THESE CHILDREN HAVE HIGH
ACTIVATION BETWEEN 15 AND 18 SO
THEY HAVE MORE NORMAL
ACTIVATION.
IT'S ONLY IN THE CHILDREN WHO
HAVE BEHAVIORAL INHIBITION 14 TO
24 MONTHS OLD AS WELL AS THE
LEVELS OF ACTIVATION IN THE
STRIATUM AT RISK FOR MAJOR
DEPRESSION IN ADULTHOOD.
WE HAVE OTHER MEASURES THAT S
SHOW.
I'M GOING TO END BY TALKING
ABOUT THE LAST AREA AND I'M H
HOPEFUL THEY'LL TALK ABOUT THE
ONGOING WORK IN THE AREA.
ANOTHER THING THAT HAS BEEN
INSPIRING TO ME IN WATCHING
ELLEN AS SHE HAS APPROACHED THIS
CHANGE IN HER WORK SHE HAS
REMAINED INCREDIBLY INTERESTED
IN CUTTING EDGE APPROACHES.
THE WORK I'LL PRESENT RIGHT NOW
FOLLOWS WORK THAT THEY DID
TOGETHER FOCUSSING IN ON
FRUSTRATION.
THIS LOOKS AT RELATIVELY LONG
CHANGES IN THE BRAIN'S
CONNECTIVITY PROFILE.
THESE ARE UNPUBLISHED DATA ELLEN
HAS DONE WORK LOOKING AT CHANGES
ACROSS THE BRAIN IN THE CONTEXT
OF FRUSTRATION AND ELLEN USES A
SIMILAR DESIGN SUCH AS THE ONE
YOU SEE ILLUSTRATED HERE WHERE
YOU ACQUIRE DATA AND EXPOSURE TO
FRUSTRATION AND ACQUIRE RESTING
STATE DATA.
HERE I'LL TALK ABOUT HAVING
CHILDREN SIT IN THE MRI SCANNER
WE'RE GOING TO ASSESS RESTING
STATE FMRI AND WATCH THE MOVIE
YOU CAN SEE ILLUSTRATED IN THE
UPPER LEFT HAND CORNER AND THIS
IS ABOUT A SIX-MINUTE MOVIE THAT
TELLS A STORY OF THIS AT --
ADOLESCENT GIRL, FRANCIS WHO
SNEAKS FROM CAMP AND ROWS HER
BOAT TO THE MIDDLE OF THE LAKE
AND IT DOESN'T TURN OUT SO WELL.
IT'S ONE OF THE MORE INTERESTING
SCARY MOVIES THAT WORKS WELL IN
THE SCANNER.
THIS IS DATA ON 64 CHILDREN.
30 CHILDREN WHO HAVE ADOLESCENTS
AT 14 YEARS OLD.
30 OF THEM ARE ALL
MEDICATION-FREE.
30 HAVE AN ANXIETY DISORDER AND
34 ARE HEALTHY.
THIS SHOWS YOU ON THE -- THIS
SHOWS YOU ON THE CHILDREN'S
RATED LEVEL OF ANXIETY AND YOU
CAN SEE IS SOMEWHAT NERVOUS OUT
THE ANXIOUS KIDS ARE FAR MORE
NERVOUS AND YOU SEE THE INCREASE
IN THE ANXIETY LEVEL.
HERE YOU SEE THE SKIN
CONDUCTANTS IN THE SCANNER AND
AS YOU WOULD EXPECT ONLY THE
ANXIOUS ADOLESCENCE HAVE THE
SKIN CONDUCTANTS AND HAVE THE
APPROACH TO ANALYSIS THAT ELLEN
HAS BEEN SPENDING TIME THINKING
ABOUT.
WE DO A SIMILAR ANALYSIS USING
THE NETWORK I DESCRIBED IN OUR
WORK ON HEAT PAIN.
SO WE DEFINED THESE REGIONS OF
INTEREST BASED ON THE STUDY AND
HEAT PAIN RELATED TO SKIN
CONDUCTANT RESPONSES TO HEAT
PAIN ILLUSTRATED HERE AND THEN
WE LOOK AT NETWORK
RECONFIGURATION FROM THE RESTING
STATE DATA BEFORE THE MOVIE TO
THE RESTING STATE DATA DURING
THE MOVIE.
AND I'M NOT GOING TO GO OVER THE
DETAILS HERE EXCEPT TO SAY THAT
WHAT WE FIND IN THE LEVEL OF
SKIN CONDUCTANTS AND LEVEL OF
NETWORKS WE FIND THE PATTERNS
DIFFERENT IN ADOLESCENTS WITH
ANXIETY DISORDERS COMPARED TO
HEALTHY ADOLESCENTS.
THE WORK WE HAVE PLANNED GOING
FORWARD EXTENDS THE RESEARCH
WE'RE CONTINUING TO USE THE
FRANCIS MOVIE AND MOTIVATED BY
WORK KATHERINA KIRKANSKI HAS
DONE AND WE'LL SHOW CHILDREN A
FRIGHTENING AND SAD MOVIE AND
WANT TO ATTEMPT TO DISASSOCIATE
CONFIGURATIONS THREAT RESPONSE
AND IR ITABILITY --
IRRITABILITY WE'LL TALK ABOUT.
IN CLOSING I WANT TO SAY A
COUPLE THINGS THE FIRST THING I
WANT TO SAY IS JUST HOW
PRIVILEGED I FEEL TO WORK AT THE
NIH AND TO BE SUPPORTED TO DO
THE WORK THAT I'VE DONE SO FAR.
TO TALK ABOUT THE PEOPLE HERE
FROM ALL OVER THE WORLD AND IT
COULDN'T HAVE BEEN DONE WITHOUT
THE FORCE SO MANY AT THE NIH IN
PARTICULAR MARYLAND AND SUSAN
HAVE GIVEN US.
AND ELLEN AND I THROUGH THE
YEARS NOT ONLY TALK ABOUT
SCIENCE, BUT WE TALK ABOUT LIFE
WE WERE TALKING ABOUT WHAT A
GREAT STAGE OF LIFE THE '60s AND
'70s.
IT'S A GREAT STAGE OF LIFE
BECAUSE I FEEL INCREDIBLY
FORTUNATE FOR SO MANY THINGS AND
PARTICULARLY FORTUNATE THAT I'M
HEALTHY AND SANE ENOUGH TO STAND
HERE REFLECT ON WHAT A WONDERFUL
25 YEARS IT'S BEEN AND WOULD NOT
HAVE HAPPENED WITHOUT THE
STRENGTH, DRIVE AND LEADERSHIP
AND I WANT TO THANK YOU FOR THE
OPPORTUNITY TO BE HERE AND THE
OPPORTUNITY TO TALK AND THANK
YOU, ELLEN.
I'M GOING TO TAKE FIVE MINUTES
IF ANYBODY HAS ANY QUESTIONS?
QUESTIONS?
NO?
[INAUDIBLE]
>> EXCELLENT QUESTION.
THE QUESTION WAS ABOUT POTENTIAL
DIFFERENCES IN SKIN CONDUCTANT
RESPONSE RELATED TO SKIN COLOR
AND THE ANSWER IS YES.
THE DARKER THE SKIN THE LOWER
THE SKIN CONDUCTANT RESPONSE
SEEMS TO BE.
THAT'S ANOTHER WONDERFUL POINT
TO MAKE WE CONSIDER SOME OF
THESE HIGHLY IMPORTANT BUT
INCREDIBLY SENSITIVE ISSUES LUKE
PEOPLE'S ETHNIC BACKGROUND AND
DIVERSE EXPERIENCE IN THE
RESEARCH.
IT TAKES TREMENDOUS CARE AND
THOUGHTFULNESS AND SUPPORT.
SO WE DO NOT TYPICALLY RELY
PRIMARILY ON SKIN CONDUCTANTS IN
OUR STUDIES.
BOTH FOR THE REASONS YOU'RE
DESCRIBING AND FOR OTHER REASONS
THAT CREATE PROBLEMS WITH SKIN
CONDUCTANTS.
THE OTHER THING I WILL SAY IS
THAT THE DIFFERENCES RELATE TO
SKIN COLOR RELATE MORE TO
OVERALL LEVELS OF RESPONDING NOT
STIMULUS RESPONDING.
WHEN YOU CAN CALIBRATE A
STIMULUS AND LOOK AT CHANGES
WHICH YOU CAN DO WITH CHANGES
LIKE THE HEAT PAIN RESPONSE YOU
CAN GET AROUND SOME OF THOSE
ISSUES.
A LOT OF US HAVE OTHER SKILLS
THAT WE SHARE AND THE OTHER
SKILL I HAVE IS THE ABILITY TO
PUT MY FOOT IN MY MOUTH.
I WANTED TO AVOID THAT ONE.
ANY OTHER QUESTIONS BEFORE I
INTRODUCE OUR NEXT SPEAKER?
SO, I'M GOING INTRODUCE OUR NEXT
SPEAKER NOW AND SAY A COUPLE
THINGS ABOUT MELISSA BROTMAN AND
LEADS THE NEUROSCIENCE AND NOVEL
THERAPEUTICS UNIT IN THE
EMOTIONAL DEVELOPMENT BRANCH AND
MELISSA HAS MANY QUALITIES THAT
SET HER APART THAT MAKE HER A
WONDERFUL PERSON TO TALK ABOUT
THE WORK SHE'S DOING.
SHE'S BEEN IN THE BRANCH 20
YEARS SHE IS VERY COMMITTED TO
DOING WORK RELEVANT TO CHILDREN
AND MAKES CLINICAL IMPACT.
I TALKED ABOUT THE WAYS ELLEN
AND I ARE SIMILAR AND MELISSA
ANDRY SIMILAR IN A WAY AT THE
PEAK OF THE THREE OF US, MELISSA
IS ONE OF THE TOUGHEST PEOPLE I
KNOW.
I CHALLENGE YOU TO GIVE MELISSA
A HARD TIME ABOUT ANYTHING AND
NOT SEE HER EMERGE AS A
STRONGER, BETTER PERSON.
AGAIN, THIS IS ANOTHER QUALITY
THAT ELLEN HAS IN SPADES.
I HAVE A LITTLE BIT BUT IT'S
WONDERFUL TO INTRODUCE MELISSA
AS A PERSON WHO REALLY
EXEMPLIFIES THAT.
MEL SEIS.
-- MELISSA.
>> THANK YOU SO MUCH FOR GIVING
THE THE OPPORTUNITY TO CELEBRATE
ELLEN TODAY.
THE TITLE OF MY TALK IS WHAT
MAKES A GOOD RESEARCH QUESTION.
ALL THE WORK WAS SUPPORT ED BY
THE INTRAMURAL PROGRAM OF NIMHD.
A BRIEF ROAD MAP OF WHAT WE'LL
BE TALKING ABOUT TODAY.
FIRST, I WANT TO TALK ABOUT WHAT
MAKES A GOOD RESEARCH QUESTION
AND HOW THE RESEARCH PROGRAM HAS
EXEMPLIFIED THAT.
THEN I WANT TO TALK ABOUT THE
RELATIONSHIP BETWEEN ANGER AND
FEAR AND HOW THINKING ABOUT
ANGER AND FEAR AS BEING TWO
SIDES OF THE SAME COIN HAS SOME
POTENTIAL TREATMENT
IMPLICATIONS.
I'LL TALK ABOUT EXPOSURE THERAPY
FOR IRRITABILITY AND FUTURE
DIRECTION OF THIS WORK AND END
MY TALK WITH MY TOP FIVE
FAVORITE EL ENNENISMS.
FIRST, IT ADDRESSES SOMETHING
NEW AND AN IMPORTANT QUESTION
THAT HAS YET TO BE
SYSTEMATICALLY EXAMINED.
TIS -- IT MUST SOMETHING
CLINICALLY RELEVANT.
THE ANSWER SHOULD INFLUENCE THE
WORLD AND INFLUENCE PATIENTS AND
THE WAY WE DO THINGS AND HAVE A
PROFOUND PUBLIC HEALTH IMPACT.
FINALLY, THE QUESTION HAS TO BE
CLEAR.
IT HAS TO BE CLEAR, FOCUSSED AND
FEASIBLE.
CONCEPTUALIZED INTO A QUESTION
AND THERE ARE ACCESSIBLE METHODS
USED TO ANSWER THAT QUESTION.
FORMULATING GOOD RESEARCH
QUESTIONS IS QUITE A DIFFICULT
TASK.
FORMULATING GREAT RESEARCH
QUESTIONS DOES ALL THOSE THINGS
AND LEADS TO NEW SCIENTIFIC
DIRECTIONS.
THAT IS THE ANSWER TO THE
PRIMARY RESEARCH QUESTION IS NOT
AN END POINT IN AND OF ITSELF.
SO I'M GOING TO TAKE YOU BACK TO
THE 190s.
-- 1990s.
AT THE TURN OF THE CENTURY THIS
WAS THE COVER OF TIME MAGAZINE.
YOUNG AND BIPOLAR.
WHY ARE SO MANY KIDS BEING
DIAGNOSED WITH THE DIAGNOSIS
ONCE KNOWN AS BIPOLAR DISORDER
AND IT WAS TRUE.
IN THE 1990s, THE RATES OF THE
DIAGNOSIS OF BIPOLAR DISORDER IN
YOUTH SKYROCKETED.
THIS IS BECAUSE CHILDREN
PRESENTING WITH SYSTEMS OF
HYPERAROUSAL WITHOUT DISTINCT
MANIA WERE DIAGNOSED WITH B
BIPOLAR DISORDER AND ELLEN ASKED
THE PROFOUND AND ELEGANT
QUESTION, DO YOUTH HAVE A
DIFFERENTIAL DEVELOPMENTAL
PRESENTATION THAN ADULTS WITH
BIPOLAR DISORDER?
THAT IS, LIKE A TAD POLE THAT
EVOLVES INTO A FROG, SHE ASKED
IF THERE'S DEVELOPMENT
DISCONTINUITY IN THE
PRESENTATION OF BIPOLAR
DISORDER.
SHE THEN WENT ON TO OVER THE
NEXT DECADE TO CONCLUSIVELY
ANSWER THAT.
CRITICALLY, THAT ORIGINAL
QUESTION FOCUSSED IRRITABILITY
HAS LED TO A NEW DSM DIAGNOSIS
AND EXAMINING THE NOVELOLOGY AND
PATHOPHYSIOLOGY AND TREATMENT OF
IRRITABILITY IN YOUTH.
IF YOU LOOK AT THE KEY WORD,
IRRITABILITY IN PUB MED IT'S
INCREASED EXPONENTIALLY OVER THE
LAST 30 YEARS FROM WHEN ELLEN
JOINED THE FIELD.
A GOOD QUESTION IS NOVEL,
SIGNIFICANT AND CLEAR AND A
GREAT RESEARCH QUESTION LEADS TO
NEW DIRECTIONS OF RESEARCH.
ONE DIRECTION THAT ELLEN
FOSTERED IN ME WAS THINKING
DEEPLY ABOUT THE RELATIONSHIP
BETWEEN ANGER AND FEAR AND THIS
GREW OUT OF A SERIES OF
CONVERSATION KATERINA, ELLEN AND
I HAD A DECADE AGO.
WE W
WE WERE TRYING TO DEVELOP A
PATHOPHY
PATHOPHYSIOL --
PATHOPHYSIOLOGICAL MODEL.
YOU CAN SEE THE PRIMARY PREMISE
OF DYSREGULATED EMOTION,
ATTENTION INTERACTIONS AND
SENSITIVITY TO THREAT AND THE
PROMINENT ROLE OF THE AMYGDALA.
AND HERE IS THE FINAL PRODUCT
PUBLISHED IN THE AMERICAN
JOURNAL OF PSYCHIATRY IN 2017.
WITHOUT GETTING INTO TOO MANY OF
THE DETAILS, AGAIN, I WANT TO
HIGHLIGHT THIS BIT FOCUSSED ON
ABERRANT THREAT IN YOUTH AND THE
BRAIN REGIONS IN REWARD
PROCESSING AND ABERRANT LET IT
AND THIS STUCK WITH ME THE
RELATIONSHIP BETWEEN REWARD AND
THREAT AND HOW IMPAIRED REWARD
PROCESSING, WHICH CAN MANIFEST
AS ANGER AND IMPAIRED THREAT
PROCESSING WHICH CAN MANIFEST AS
FEAR.
AND IT MADE ME WONDER, WHAT IF
WE THOUGHT OF ANGER AND FEAR AS
TWO SIDES OF THE SAME COIN.
SO FROM A NEUROSCIENTIFIC
PERSPECTIVE ANGER, LIKE FEAR IS
A NORMATIVE RESPONSE BUT IT CAN
BE MALADAPTIVE WHEN IT'S NOT
FLEXIBLY DEPLOYED OR
INAPPROPRIATE TO CONTEXT.
BOTH ANGER AND FEAR ARE
ASSOCIATED WITH INCREASED ANGER
AROUSAL AND MEDIATED BY THE
OVERLAPPING CIRCUITRY OR WHAT WE
HAVE KNOWN AS FIGHT OR FLIGHT
RESPONSE.
ANGER AND FEAR ARE STIMULUS
EVOKED EVENTS WITH A SPECIFIC
TIME COURSE AND THERE ARE MANY
CLINICAL S THAT LINK ANGER AND
FEAR.
WE KNOW THAT YOUTH WITH
IRRITABILITY HAVE LOTS OF
ANXIETY AND YOUTH WITH ANXIETY
TEND TO PRESENT WITH
IRRITABILITY PARTICULARLY WHEN
THEY'RE ANXIOUS AND FROM MY
TRAINING AS A CLINICAL
PSYCHOLOGIST I WAS KEENLY AWARE
OF THE EFFICACY OF EXPOSURE
THERAPY FOR ANXIETY MEDIATED BY
THE SAME OVERLAPPING BRAIN
REGIONS.
SO, WE KNOW THAT WHEN WE ENGAGE
IN COGNITIVE BEHAVIORAL THERAPY
IT NORMALIZES MANY OF THE BRAIN
REGIONS THAT WERE IMPLICATED IN
OUR PATHOPHYSIOLOGICAL MODEL.
I WANT TO TAKE A MOMENT TO TALK
ABOUT EXPOSURE THERAPY.
IT'S A BEHAVIORAL THERAPY
TECHNIQUE SPECIFICALLY DESIGN
FOR THE TREATMENT OF FEAR AND
ANXIETY DISORDERS BASED ON
NEUROSCIENTIFIC PRINCIPLES OF
EXTENSION.
WE KNOW THE CIRCUIT INVOLVED IN
REWARD AND THREAT PROCESSING AND
SPECIFICALLY EXPOSURE THERAPY WE
HAVE PATIENTS REPEATEDLY FACE AN
OBJECT OR SITUATION THAT THEY
PERCEIVE AS THREATENING.
SO FOR EXAMPLE, AN INDIVIDUAL
SAY A SPIDER PHOBIA WE MIGHT
HAVE THEM FIRST LOOK AT A
CARTOON RENDERING OF A SPIDER
AND THEN WORK OUR WAY UP TO AN
ACTUAL REALISTIC SPIDER.
HAVE THEM WATCH A VIDEO OF A
SPIDER AND THE TOP OF THE
EXPOSURE HIERARCHY HANDLE A KNOB
NON-DANGEROUS SPIDER IN VIVO, IN
SESSION.
WE'RE REPEATEDLY EXPOSING THEM
TO THE THREATENING STIMULI BUT
TEACHING THEM TO CHANGE THE
MALADAPTIVE AVOID RESPONSES.
AND GIVEN THE SIMILARITIES AND
THE OVERLAPPING BRAIN REGION
MEDIATING ANGER AND FEAR MADE ME
WONDER IF EXPOSURE THERAPY MIGHT
BE EFFECTIVE FOR THE TREATMENT
OF IRRITABILITY.
SO, INSTEAD OF CREATING A
HIERARCHY OF FEAR INDUCING
STIMULI LIKE WE DO WITH ANXIETY,
WE WOULD CREATE A HIERARCHY OF
ANGER-INDUCING STIMULI FOR YOUTH
WITH IRRITABILITY.
INSTEAD OF INHIBITING THE
MALADAPTIVE RESPONSES WE
APPROACH WHAT MAY BE
OPERATIONALIZED AS SAY A TEMPER
OUTBURST.
WITH ELLEN'S GREAT SUPPORT THIS
IS EXACTLY WHAT WE DID.
WE OPERATIONALIZED AND CREATED
AN EXPOSURE-BASED PSYCHO THERAPY
FOR YOUTH WITH IRRITABILITY
WHEREBY WE GRADUALLY EXPOSED THE
INDIVIDUAL TO ANGER-INDUCING
CUE.
A CHILD I WORKED WITH EARLY ON
WHO GOT ANGRY WHEN ASKED TO
BRUSH HER TEETH WE EXPOSED HER
TO A TOOTH BRUSH AND PUTTING IT
ON HER TOOTH BRUSH AND BRUSHING
HER TEETH.
ANOTHER INDIVIDUAL GOT ANGRY
WHEN HE WAS ASKED TO DO
HOUSEHOLD CHORES AND SIT IN
SESSION AND LOOK AT THE PILE OF
LAUNDRY HIS PARENTS BROUGHT IN
AND PRACTICE OVER AND OVER BEEN
SORTING THE LAUNDRY AND TESTED
THE EFFICACY IN A PAPER LAST
MONTH.
FOCUSSING ON THE CHILDREN
PRESENTING WITH SEVERE AND
IMPAIRING IRRITABILITY ELLEN
OPERATIONALIZED USING THE DSM
CRITERIA SHE CONTRIBUTED TO, WE
RANDOMIZED CHILDREN TO
EXPOSURE-BASED THERAPY.
AND IN FACT IF YOU FOCUS ON THE
MIDDLE PANEL, WE SAW THAT THE
IRRITABILITY SIGNIFICANTLY
DECREASED OVER THE COURSE OF
TREATMENT.
IF YOU LOOK AT THE FAR LEFT
PANEL THE TREATMENT GAINS WERE
MAINTAINED UP TO SIX MONTHS
LATER.
AT LEAST 65% WERE RECOVERED OR
IMPROVED AND PARENTS AND
CHILDREN REPORTED TANGIBLE
CHANGES IN THEIR LIFE.
ONE PARENT SAID THAT THEY CAN
GO BACK TO WORK AND NOW TOLERATE
MY ANGER LIKE A JEDI.
WHAT ARE TAKE-HOME MESSAGES AND
INTERIM CONCLUSIONS?
WE CAN THINK OF ANXIETY AND
IRRITABILITY AS STIMULUS TO HIGH
AROUSAL STATES AND LOOK AT
IRRITABILITY AND ALL THE
CHILDREN TOLERATED THE EXPOSURE.
NONE OF THE CHILDREN DROPPED OUT
AND IT DEMONSTRATED PRELIMINARY
EFFICACY.
HOWEVER, WAS NO ACTIVE
COMPARISON CONDITION INDICATING
IT COULD BE DUE TO EXPECTANCY
EFFECTS AND THE MECHANISMS
MEDIATING THE IMPROVEMENT REMAIN
UNKNOWN.
ELLEN'S ORIGINAL QUESTION ASKING
ABOUT THE DEVELOPMENTAL
PRESENTATION OF BIPOLAR DISORDER
IN YOUTH HAS NOW INSPIRED
ANOTHER DECADE OF RESEARCH AND
EXAMINING MECHANISMS OF EXPOSURE
THERAPY FOR YOUTH WITH
IRRITABILITY.
WHAT WE'RE DOING NOW IS
EXAMINING FUNCTIONAL MAGNETIC
RESONANCE IMAGING BEFORE AND
AFTER EXPOSURE-BASED PSYCHO
THERAPY FOR YOUTH WITH
IRRITABILITY AND EXAMINING
PHYSIOLOGICAL CHANGES THAT IS
HEART RATE VARIABILITY DURING
THE ACTUAL EXPOSURE THERAPY
SESSIONS.
WE'RE MEASURING IRRITABLE MOVE
AND OTHER BEHAVIORS USING MOBILE
APPS WHEN THEIR AT HOME IN THEIR
EVERYDAY LIFE.
WE COMPARED PARENT MANAGEMENT
TRAINING WITH EXPOSURE THERAPY
WITH TWO MENTEES.
SHE TAUGHT ME HOW TO FORM GOOD
RESEARCH QUESTIONS AND I WAS THE
BENEFICIARY OF HER GREAT
RESEARCH.
I WANT TO END WITH MY TOP FIVE
EL ENNEN --
ELLEN
ELLENISMS, WORDS OF WISDOM SHE
SHARED OVER THE YEARS.
FIVE, THE PERFECT IS THE ENEMY
OF THE GOOD.
IN RESEARCH YOU CAN GET STUCK
AND LETTING GO CAN FACILITATE
MOVEMENT FORWARD.
NUMBER 4, SEPARATE THE WHEAT
FROM THE CHAF.
ELLEN CONTINUES TO DEMONSTRATE A
PROFOUND WAY OF DIFFERENTIATING
THE SUBSTANCE FROM THE NOISE.
TAKE THE LONG VIEW.
RESEARCH HAS MANY IN STEPS AND
MANY PEOPLE AND PERSONALITIES TO
IN THE INTERACT WITH.
WHEN IN DOUBT OF YOUR NEXT, STEP
BACK AND TAKE IT ALL IN AND TAKE
THE LONG VIEW.
NUMBER 2, THE MIDDLE IS
CONCEPTUALLY THE HARDEST PART.
THE F VALUE THE STAT AND DATA
CAN BE EASY.
THE OVER ALL GOAL CAN BE CLEAR
BUT LINKING THOSE TWO IS THE
HARDEST.
NUMBER ONE, CLEAR RIGHTING IS
CLEAR THINKING.
ELLEN WOULD ALWAYS HIGHLIGHT THE
CHALLENGES OF BREVITY.
TO DISTILL A MESSAGE TO ITS
CORE.
IS THE REMINDED ME THAT BEING
ACCURATE, CLEAR AND CONCISE CAN
BE HARD BUT THE ABILITY TO DO SO
CAPTURES THE ESSENCE OF WHAT'S
IMPORTANT.
AS I'VE WORKED WITH ELLEN 20
YEARS I WANT TO SHARE MY OWN
MENIAL IMAGE OF ELLEN.
I SAW HER AS A CONDUCTOR
COMPOSING MUSIC AND A COMPOSER
IS DYNAMIC AND PASSIONATE.
THEY COMPOSE AND CONDUCT AND
IT'S AT THE CORE OF THEIR LIVES
AND WHAT THEY LOVE TO DO A
CONDUCTOR IS COURAGEOUS AND
WILLING TO TAKE CALCULATED
RISKS.
A CONDUCTOR IS FOCUSSED THEY
KEEP THEIR EYE ON THE END AND
THEY EVOLVE WITH FRESH IDEAS
COMES EVOLUTION.
THEY'RE RESILIENT AND
PERSISTENT.
THEY LEARN FROM THEIR MISTAKES
AND CELEBRATE THEIR
ACHIEVEMENTS.
FINALLY, THEY INSPIRE NEW
COMPOSERS, CONDUCTORS AND
PERFORMERS AND MOST IMPORTANTLY
THE NEXT GENERATION OF MUSIC.
WITH THAT I WANT TO TAKE A
MOMENT TO THANK ELLEN FOR ALL
SHE'S DONE FOR ME PERSONALLY AND
IN MY CAREER AND THANK THE
INTRAMURAL PROGRAM AND THE
EMOTIONAL AND DEVELOPMENT BRANCH
AND MANY MANY OTHERS INCLUDING
THE CLINICIANS, RESEARCH
ASSISTANTS AND LASTLY THE
PATIENTS AND THEIR FAMILIES FOR
ENGAGING AND SUPPORTING IN OUR
RESEARCH AND I LEFT A COUPLE
MOMENTS FOR QUESTION.
THANK YOU VERY MUCH.
[INAUDIBLE]
>> PATHOLOGICAL DEMAND
AVOIDANCE?
SAY MORE ABOUT THAT.
>> RIGOROUS LEVEL OF SCRUTINY OF
OFFICIAL DIAGNOSIS AND SEEING
THIS IN CHILDREN OFTEN
MISINTERPRETED AS AN
UNWILLINGNESS TO COOPERATE.
>> I'LL TRANSLATE AND IT'S A
VERY BIG THINK IN THE U.K.
THERE'S ARGUMENTS IT SHOULD BE
ENTERED IN THE NOSOLOGY.
IT'S BASICALLY KIDS -- YOU SEE
IT A LOT IN YOUR PATIENTS, WHO
TOTALLY LOSE IT WHEN YOU ASK
THEM TO DO SOMETHING AND PLACE
DEMANDS ON THEM AND ASK THEM TO
STOP USING A VIDEO GAME OR ASK
THEM TO SIT DOWN AT THE DINNER
TABLE AND THIS TERM IS USED IN
THE U.K.
ADULTS WHO EXPERIENCE IT AS
CHILDREN SAY THEY COULD NOT
CONTROL IT.
THEIR BRAIN WOULD NOT LET THEM
COMPLY WITH THE DIRECT REQUESTS.
>> I'M HEARING ABOUT THIS FOR
THE FIRST TIME AND HAVE
THOUGHTS.
I GUESS WHAT I WOULD SAY IS THAT
SEEMS CATEGORICAL.
YOU CAN OR CANNOT DO IT.
S A CLINICAL PATHOLOGIST THERE'S
POTENTIAL FOR INCREMENTAL
MOVEMENT FORWARD AND PARENTS
WOULD SAY TO KIDS I'M TREATING
DEMONSTRATE THIS AND I HAVE SEEN
MAUL GAINS AND MOVEMENT FORWARD.
I WOULD HESITATE TO SAY IT'S ONE
THING THAT COULD BE
CONCEPTUALIZED AND WE CAN MAKE
STRIDES FORWARD IN THE CONTEXT
OF SOMETHING THAT CAN BE
DIFFICULT.
>> JUST A FEW MORE THINGS BEFORE
WE HAVE THE LAST TALK.
SO WE'LL STOP AS SOON AS
DR. KIRKANSKI IS DONE TAKING
QUESTIONS HOWEVER LONG THAT
TAKES AND START AT 1:15 WITH A
RECORDED TALK THAT WILL START
EXACTLY AT 1:15.
SO OUR NEXT SPEAKER IS
DR. KATHERINA KIRKANSKI IN
EMOTIONAL AND DEVELOPMENT BRANCH
AND INTERMURAL RESEARCH PROGRAM
AND KATHERINA'S ANOTHER PERSON
WITH HER BEING HERE JUST WITH
HER PRESENCE AND THE THINGS
SHE'LL DESCRIBE MAKES A
WONDERFUL STATEMENT ABOUT
ASPECTS OF THE INTRAMURAL
PROGRAM.
SO LIKE MELISSA AND LIKE MYSELF,
KATHERINA'S QUALITIES EXEMPLIFY
THE MANY VALUES ELLEN HAS
EMPHASIZED THROUGHOUT HER
CAREER.
THE FOCUS ON PATIENTS, THE
LOGICAL CRITICAL THINKING AND
THE ABILITY TO WRITE.
KATHERINA IS AN AMAZINGLY
SKILLED WRITER AND WE'RE LUCKY
BECAUSE WE'RE GIVEN THE FREEDOM
TO BUILD GROUPS HAVE BOTH
SIMILAR QUALITIES LIKE THE ONES
I WAS JUST DESCRIBING BUT ALSO
BRINGS IN PEOPLE WITH UNIQUE
SKILLS SO THROUGHOUT THE GROUP
SHE HAS QUALITIES SHE SHARES
WITH ME AND ELLEN AND MELISSA
WITH UNUSUALLY STRONG
QUANTITATIVE SKILLS.
AND HER TALK IS GOING TO
ILLUSTRATE THAT AND I THINK IT'S
THROUGH SUPPORT AT PLACES LIKE
THE INTERMURAL RESEARCH PROGRAM
WE BENEFIT FROM THE SKILLS SHE
HAS.
SO, KATHERINA.
>> THREW
>> THANK YOU FOR THE KIND
INTRODUCTION.
>> ALL RIGHT, SO LIKE OTHERS
I'LL START WITH AN OUTLINE TO
FRAME THE TALK AND REALLY FIRST
DEFINING THE PROBLEM SPACE.
ISSUE OFF CONUNDRUM OF
COMORBIDITY AND PSYCHOPATHOLOGY
AND TALK LATENT METHODS THAT
TACKLE THIS ISSUE AND HAVE THE
ABILITY TO PARS MECHANISMS IN
PSYCHOPATHOLOGY AND TALK ABOUT
TWO REPRESENTATIVE STUDIES IN
THE AREA THOUGH YOU'LL HEAR FROM
OTHERS.
THERE'S MANY MORE AND END WITH A
BIT OF A TWIST WITH SOME OF OUR
ONGOING AND FUTURE DIRECTIONS.
AND LIKE OTHER TALKS I'M GOING
TO LEAVE IN THROUGHOUT ELLEN'S
PROFOUND INFLUENCE ON ME AND ON
THE WORK THAT WE'VE DONE AND WE
CONTINUE TO DO.
SO, A HALLMARK IS THINKING ABOUT
THE CLINICAL AND PATIENTS
TYPICALLY PRESENT WITH MULTIPLE
TYPES OF CO-OCCURRING
PSYCHIATRIC DISORDERS AND
SYMPTOMS.
IT'S RARE YOU SEE ONE FORM OF
PSYCHOPATHOLOGY ON ITS EN AND
HEAR ME TALK ABOUT SYMPTOM
DIMENSIONS OR DIMENSIONS OF
PSYCHOPATHOLOGY.
UNTIL RECENTLY UNTIL THE PAST 10
OR 15 YEARS RESEARCH IN
PSYCHOLOGY AND PSYCHIATRY
FOCUSSED ON SINGLE-TARGET
DIAGNOSES.
COMPARING INDIVIDUALS WITH ONE
PSYCHIATRIC DISORDER AND THEY
DON'T TRACK WELL WITH UNDERGOING
BIOLOGY OR BEHAVIOR.
AND WITH THE RECOGNITION OF
COMORBIDITY AND THE CHALLENGES
IT BRINGS ON THE ONE HAND.
WITH PRECISION MEDICINE
APPROACHES TO OUR UNDERSTANDING
OF PSYCHOPATHOLOGY THE QUESTION
COMES HOW DO WE PARS MECHANISMS
OF WHAT ARE DISTINCT BUT
CORRELATED DIMENSIONS?
AND WHEN I CAME TO THE NIMHD IN
2015 TO WORK WITH ELLEN I WAS
FORTUNATE TO ENTER AT A TIME THE
RESEARCH WAS TAKING OFF.
I HAD, HAD ALREADY A
LONG-STANDING INTEREST IN WHY
MOOD AND ANXIETY DISORDERS TEND
TO OCCUR BOTH IN YOUTH AND
ADULTS.
I HAD THE GREAT FORTUNE.
ELLEN WAS INVITED TO CONTRIBUTE
TO A SPECIAL ISSUE OF THE
JOURNAL OF EFFECTIVE DISORDERS
FOCUSSED ON THE NIMHD INITIATIVE
YOU MAY KNOW TACKLES
COMORBIDITIES AMONG OTHER
PROBLEMS BY ATTEMPTING TO
REDEFINE CONSTRUCTS FOR CLINICAL
RESEARCH.
I HAD THE GOOD FORTUNE TO START
TO WORK ON THE PROBLEM STRAIGHT
AWAY WITH ELLEN'S CLEAR MIND AS
PART OF THAT.
AND WHAT WE DECIDED TO DO WAS
USE SYMPTOM-DATA FROM ACROSS THE
ENTIRE MOTION AND DEVELOPMENT
BRANCH.
THESE ARE CHILDREN IN
ADOLESCENTS WITH ANXIETY
DISORDERS, DISRUPTED MOOD
DYSREGULATION AND ADHD WHATEVER
WAS COMING IN THE BRANCH WE
THREW THE QUESTIONNAIRE DATA
INTO WHAT WE CALL A LATENT
PROFILE ANALYSIS TO LOOK AT HOW
SYMPTOMS IN OUR SAMPLE TENDED TO
CO-OCCUR WITH ONE ANOTHER AND
LOOK FROM A DATA-DRIVEN
PERSPECTIVE HOW MUCH ARE
SYMPTOMS SHOWING THE
MULTI-DIMENSIONAL QUALITY.
I WON'T GO INTO LOTS OF DETAIL
ABOUT THIS BUT THIS IS FROM A
LATENT PROFILE ANALYSIS.
THIS IS A LARGE SAMPLE OF YOUTH
OF DATA IN THE BRANCH.
WHAT YOU SEE ON THE X AXIS ARE
DIFFERENT SYMPTOM QUESTIONNAIRE.
WE HAVE IRRITABILITY MEASURES OR
THE LEFT SIDE, SCARED ANXIETY
MEASURES IN THE MIDDLE AND
DEPRESSION AS REPORTED BY THE
CHILD AND ADHD AS REPORTED BY
THE PARENT AND SINCE HAVE BEEFED
UP OUR ASSESSMENT AS A RESULT OF
SOME OF THE WORK.
AND WHAT YOU SEE AND THE Y AXIS
ARE STANDARDIZED SCORES FOR
DIFFERENT CLASSES OR PATTERNS
THAT EMERGED IN THE DATA-DRIVEN
APPROACH TO LOOKING AT THE
SYMPTOM DATA.
AND WHAT YOU CAN SEE I'LL TRY TO
SPELL IT OUT A LITTLE BIT IS
ESSENTIALLY THE DATA ARE
INHERENTLY MULTI-DIMENSIONAL AND
FEW IF EVER OCCUR IN ISOLATION.
FOR EXAMPLE, THE CLASS DOWN HERE
WITH THE DASHED LINE YOU CAN SEE
THEY'VE GOT ANXIETY AND
DEPRESSIVE SYMPTOMS.
AGAIN, THIS IS WHAT THE DATA ARE
TELLING US.
WE HAVE ANOTHER CLASS THAT'S NOT
GOING TO BE A SURPRISE TO
CLINICIANS IN THE ROOM, HIGH
PARENT REPORTED IRRITABILITY AND
ADHD AND TWO OTHER CLASS SHOW
MORE MULTIDIMENSIONAL PATTERNS
SHOWING DIFFERENT SYMPTOMS.
YOU CAN APPRECIATE IF
TRADITIONAL RESEARCH LOOKED AT
SINGLE DIAGNOSIS OR SINGLE
DIMENSIONS OF PSYCHOPATHOLOGY IN
ISOLATION WE'RE MISSING THE BIG
PICTURE AND THE MECHANISMS.
IT'S MORE THAN JUST A NUISANCE.
SYSTEM CO-OCCURRENCE RAISE
QUESTIONS.
IF SYMPTOMS TEND TO GO ALONG
TOGETHER AND SUGGEST THERE'S
PROBABLY COMMON PATHWAYS TO SOME
OR COMMON CORRELATES WE CAN TRY
TO LEVERAGE WHEN WE THINK ABOUT
TREATMENT.
AND OTHERS WILL TALK ABOUT WITH
JULIA LINKE AND I'LL GIVE A
BRIEF OVERVIEW OF METHODS TO
ATTACKAL -- TACKLE THIS AND THE
SYMPTOM SCORES WE OBTAIN ON
QUESTIONNAIRES TO ESTIMATE
PURPORTED THEORETICALLY
UNDERLYING CONSTRUCTS.
THE DATA OR THE CONSTRUCTS
THEMSELVES THE THINGS WE
CONSTRUCT THROUGH OUR
THEORETICAL AND STATISTICAL
MODELS.
ONE TYPE OF MODEL WE'VE BEEN
WORKING WITH THE PAST SEVERAL
YEARS OTHER HAVE AS WELL IS THE
BIFACTOR MODEL AND WELL SUITED
TO CORRELATED SYMPTOM DATA AND
SYMPTOMS THAT GO ALONG WITH ONE
ANOTHER FOR A COUPLE REASONS.
I'LL ILLUSTRATE THIS.
IT TAKES OBSERVED DATA AND SAYS
THERE'S TWO GENERAL SOURCES.
ONE IS A GENERAL FACTOR.
AND SCORING HIGHER VERSUS LOWER
AMONG THE DIFFERENT TYPES OF
THINGS WE ASSESS LIKE SYMPTOMS
AND THAT SEPARATES IT FROM
SYMPTOM-SPECIFIC VARIABILITY
THAT WOULD BE LIKE WHETHER YOU
SCORE HIGHER OR LOWER ON VERY
SPECIFIC TYPES OF SYMPTOMS.
I'LL ILLUSTRATE THIS IN A
MOMENT.
IN STUDY 1, WE USED A FACTOR
TO DISASSOCIATE AND IN STUDY 2
WE FIND INHIBITORY CONTROL
LINKED TO THE RESTING STATE OF
THE BRAIN IS A COMMON MECHANISM
ACROSS DIMENSIONS IN YOUTH
PSYCHOPATH
PSYCHOPATHOLOGY.
THIS IS THE FIRST STUDY.
IRRITABILITY AND ANXIETY
SYMPTOMS FREQUENTLY GO TOGETHER
IN YOUTH.
THROUGH THE PRECISION AND
THINKING WE CRYSTALLIZED THIS TO
THINK IN HOW WE'RE THINKING
ABOUT THE SHARED VERSUS UNIQUE
FEATURES.
WHAT I WANT TO HIGHLIGHT HERE IS
IN THE VERY SCHEMATIC APPROACH,
ONE WAY OF THINKING ABOUT WHAT'S
IN COMMON BETWEEN IRRITABILITY
AND ANXIETY IS THIS OVER ALL
TENDENCY TOWARDS NEGATIVE AFFECT
RESPONSES TO STIMULI IN THE
ENVIRONMENT WHICH INCLUDE
THREATS OF COURSE.
THIS IS THE WORKING CONCEPTUAL
MODEL WE'LL APPLY IN A
QUANTITATIVE WAY WITH THE
BIFACTOR APPROACH.
THIS WAS FIT TO THE DATA.
NOW, THERE COULD BE A WHOLE TALK
IN AND OF ITSELF ON THE SLIDE
AND I'M NOT GOING TO DO THAT BUT
WHAT I'LL TRY TO DO IS GIVE AN
OVERVIEW OF WHAT YOU'RE LOOKING
AT.
SO IN THE MIDDLE HERE THE BOXES
ARE RED ARE PARENT AND YOUTH
RESPONSES ON THE REFLECTIVITY
INDEX THE MEASURE OF
IRRITABILITY IN KIDS AND BLUE IS
THE SCARED CHILD AND PARENT
RESPONSES.
SCARED OUR MOST COMMON MEASURES
OF CHILD ANXIETY.
ON THE RIGHT AS THIS CONVENTION
WE SHOWCASE AND ILLUSTRATE
CONSTRUCTS BY VIRTUE OF BEING IN
CIRCLES.
THIS IS OUR THEORETICALLY
CONSTRUCT CONNECTIVITY AND WHY
SOME FOLKS WOULD BE HIGHER
VERSUS LOWER ACROSS THE
SYMPTOMS.
YOU CAN SEE FROM THE
STANDARDIZED FACTOR LOADINGS
THEY'RE LOADED TO A GENERAL
FACTOR.
THERE WAS EVIDENCE FOR ALL
SYMPTOMS, IRRITABILITY AND
ANXIETY GOING TOGETHER.
NOW, THAT'S SEPARATABLE FROM
WHAT I CALL THE SPECIFIC
FACTORS.
ON THE BOTTOM LEFT YOU SEE AN
ANXIETY-SPECIFIC FACTOR WHICH
WAS DIFFERENT FROM THE NEGATIVE
AFFECTIVITY FACTOR AND THERE'S
ANXIETY-SPECIFIC VARIANTS NOT
CAPTURED WE COULD ESTIMATE AS
WELL.
THERE'S TWO IRRITABILITY
FACTORS.
WE TRIED TO FIT ONE AND AS ELLEN
KNOWS FROM HER RECENT WORK WE
CAN DO IT IN THE DATA SET AND WE
FIT SEPARATE PARENT AND
YOUTH-REPORTED IRRITABILITY.
I KNOW WE'RE HAPPY TO TALK ABOUT
THAT MORE IF THERE'S ANY
QUESTIONS.
AND WE EXTRACT THE SCORES AND
RELATE THEM TO THE BRAIN DATA
LIKE WE WOULD TYPICAL CLINICAL
DATA BUT THE ONLY DIFFERENCE IS
TAKING THE LATENT SCORES WE
CONDUCTED STATISTICALLY AND USED
A WHOLE BRAIN APPROACH WE CAN
TALK ABOUT AS WELL.
NOW, WHAT ARE WE RELATING THESE
CONSTRUCTS TOO?
THREAT ORIENTING HAS BEEN A BIG
THRUST OF THE WORK.
THREAT ORIENTING IS A SPACE
WHERE IRRITABILITY SHOW
COMMONALITIES AND DIFFERENCES.
WE KNOW FROM THE BEHAVIORAL
RESEARCH IN GROUP YOUTH WITH
IRRITABILITY AND ANXIETY TEND TO
TEND THEIR ATTENTION LIKE FACES
AND YOU'LL SEE MORE OF THIS
APPROACH RESPONSE LIKE VERBAL
AND PHYSICAL AGGRESSION IN THE
FACE OF THREAT WHEREAS ANXIETY
THERE'S MORE AVOIDANT RESPONSE.
THIS IS SHOW CAVING THE FMRI
TEST WE RELATED THE BIFACTOR
MODEL TO.
THIS IS WHAT MANY ARE FAMILIAR
WITH AND I WON'T GET TOO MUCH IN
THE DETAILS BUT TALK ABOUT HOW
IT ASSESSES THREAT.
A PARTICIPANT'S JOB IS TO
INDICATE THE DIRECTION OF THE
PROBES LEFT OR RIGHT.
OF COURSE THERE'S INCIDENTAL
MATERIAL PRESENTED ON THE SCREEN
ONE IS THE THREAT INCONGRUENT
CONDITION AND ONE IS AN ANGRY
FACE AND THEN A NEUTRAL FACE AND
IN THE THREAT INCONGRUENT TRIALS
YOU NEED TO SHIFT YOUR ATTENTION
TO COMPLETE THE TRIAL AS
EFFICIENTLY AS POSSIBLE AND
THINK OF IT AS THREAT
INCONGRUENT CONDITION AND
CONTRASTED WHERE THE PROBE IS
FOLLOWING A THREAT FACE.
THE FMRI ANALYSIS WE USE A TASK
CONTRAST OF WHAT ARE THE NEURAL
SUBSTRATES SHIFTING ATTENTION
AWAY FROM A THREAT VERSUS WHEN
THE ATTENTION WOULD HAVE BEEN ON
THE THREAT AND THAT WOULD HAVE
BEEN ABLE TO BE DONE MORE
EFFICIENTLY.
THIS IS THE TASK CONTRAST THAT
I'M SHOWCASING.
THERE'S TWO SETS OF FINDINGS
I'LL HIGHLIGHT.
WHEN IT COMES TO BOLD ACTIVITY
ON THE TASK, ALL THE ACTION WAS
IN THE SPACE OF IRRITABILITY.
IT WAS THE PARENT-REPORTED
IRRITABILITY FACTOR THAT
RELATED.
THIS IS A HIGHLIGHTING OF THE
REGIONS AND RELATED TO INCREASED
ACTIVITY ACROSS WIDESPREAD AREAS
OF THE BRAIN AND REGIONS KNOWN
TO MEDIATE ATTENTION OR MOTOR IN
THE FACE OF THE ABERRANT STIMULI
AND YOU CAN SEE HIGHER PARENT
REPORTED IRRITABILITY WHEN YOU
HAVE TO SHIFT YOUR ATTENTION
AWAY FROM A THREAT.
WE SEE HERE IN THE SCATTER NOT
THE RIGHT INSULA REGION AND THE
PARIETAL LOBULE AND THEY CAME
OUT AS WIDESPREAD AREAS OF THE
BRAIN AND THE INCREASED ACTIVITY
ACROSS DIFFERENT REGIONS
REFLECTS THE HEIGHTENED AROUSAL
THAT CAN BE RELATED TO
IRRITABILITY AND MIGHT MEDIATE
THE MALADAPTIVE APPROACH
BEHAVIOR IN THE FACE OF A DIRECT
THREAT.
INTERESTINGLY, ANXIETY WAS NOT
ASSOCIATED WITH ANY BRAIN
ACTIVITY IN THE TASK WHICH RUNS
COUNTER TO PAST WORK IN THE AREA
THAT DIDN'T USE THE BIFACTOR
APPROACH BUT LOOKED AT AMYGDALA
TASK AND WE LOOKED AT THE
AMYGDALA AND OTHER REGIONS OF
THE BRAIN AND HIGHER SCORES ON
THE ANXIETY FACTOR WERE
ASSOCIATED WITH DECREASED
CONNECTIVITY WITH CORTICOLIMBIC
HUBS IN THE BRAIN.
HERE I'M HIGHLIGHTING THE
BILATERAL CINGULATE AND THE
BILATERAL THALAMUS.
IT MAY BE AND A SUBTLE PATTERN
OF THE ABERRATIONS ASSOCIATED
WITH ANXIETY TO THE MORE
WIDESPREAD CORRELATES OF
IRRITABILITY AND RELATED TO
FUNCTIONAL CONNECTIVITY DATA.
IN ESSENCE WHEN WE USE A
BIFACTOR MODEL THERE'S
A DISASSOCIATION OF BEHAVIOR
ACROSS IRRITABILITY AND ANXIETY.
AND THERE'S SYMPTOM SCORES IN
THE MODEL AND RELATED TO THE
BRAIN.
YOU DON'T SEE THESE ASSOCIATIONS
OR THE DOUBLED ASSOCIATE.
IT'S STRUCTURING PSYCHOPATHOLOGY
THAT BRINGS OUT THE
DISTINCTIONS.
AND NOW I'M GOING TO TELL YOU
ABOUT A DIFFERENT STUDY WITH A
DIFFERENT CONCLUSION FOR STUDY
2.
THIS IS MORE HOT OFF THE PRESS
THAN THE ONE DANNY SHOWED WHERE
IT'S JUST ACCEPTED MAYBE LAST
WEEK AND HERE WE'RE LOOKING AT
INHIBITORY CONTROL AS A
CONSTRUCT OPPOSED TO THREAT
ORIENTING AND LOOK AT THE
GENERAL MODEL OF PSYCHOPATHOLOGY
AND HUGE SHOUT OUT TO A FORMER
POSTDOC NOW A PROFESSOR AT
CATHOLIC UNIVERSITY WHO LED THE
WORK AND JULIA LINKE WHO
CONTRIBUTED A TON TO THE WORK.
INHIBITORY CONTROL IS THE
ABILITY TO STOP THE RESPONSE AND
STOP DOING WHAT YOU'RE DOING IN
THE MOMENT TO SHIFT OR ENGAGE
IN GOAL-ORIENTED BEHAVIOR.
WE KNOW FROM DECADES OF CHILD
PSYCHOPATHOLOGY RESEARCH ADHD IN
KIDS HAS BEEN ASSOCIATED
BEHAVIORALLY WITH DEFICITS AND
THE ABILITY TO DO THIS WHICH
ISN'T SURPRISING GIVEN THE
CLINICAL OBSERVATIONS.
WE ALSO KNOW THERE'S SOME
SIGNALS FOR BOTH IRRITABILITY
AND ANXIETY IN RELATION TO
DIFFERENT FACETS OF INHIBITORY
CONTROL.
THE LITERATURE IS FAIRLY MIXED
AND HASN'T BEEN A STUDY OF
PUTTING THE DIFFERENT TYPES OF
SYMPTOMS TOGETHER TO UNDERSTAND
WHETHER THIS MIGHT BE A COMMON
MECHANISM OR AGAIN MORE SPECIFIC
TO SAY ADHD OR EXTERNALIZING
BEL
BEHAVIOR.
WE WERE FORTUNATE IN THIS STUDY
TO DO WHAT IS HARD TO DO IN
OTHER SETTINGS.
PARTICIPANTS IN THIS STUDY AND
THIS WAS 246 PARTICIPANTS, NOT A
SMALL SAMPLE WHO DID UP TO FOUR
INHIBITORY CONTROL TASKS.
SOME PAINFULLY TEDIOUS LIKE EYE
TRACKING AND FLANKER TEST AND
OTHERS AND WE EXTRACT
PARTICIPA
PARTICIPANTS WE THINK POOLING
THE SHARED VARIANT CAN HELP IN
THE PSYCHOPATHOLOGY.
AND I SHOW THE DIAGRAMS BECAUSE
YOU'LL SEE THEM IN A BIGGER WAY.
THIS IS AN AREA WE'RE INVESTING
A LOT IN AND DOING THIS MORE
ROBUSTLY GOING FORWARD.
THESE ARE BEAUTIFUL DATA AND I
WANT TO HIGHLIGHT HERE THE
NETWORK -- THESE ARE NOTES USED
WITH THE DATA DRIVEN APPROACH A
GRAPH THEORY APPROACH TO
IDENTIFY DIFFERENT MODULES OR
SUB NETWORKS IN THE BRAIN.
IT'S THE RED NETWORK THAT
COMPRISES THE PARIETAL CONTROL
NETWORK IS THE NETWORK
IMPLICATED IN INHIBITORY
CONTROL.
ON THE RIGHT YOU SEE THE TOP 20%
OF CONNECTIONS WITHIN AND ACROSS
THE NETWORKS.
IT'S JUST MEANT AS A WAY TO
UNDERSTAND THE PATTERNS OF
CONNECTIVITY BEING MODELLED
HERE.
AND SO WHAT I'LL TALK ABOUT IS
HOW WE USE THIS RESTING STATE
DATA TO RELATE TO INHIBITORY
CONTROL AND PSYCHOPATHOLOGY.
WHAT WE EXTRACTED AS ONE MEASURE
AMONG MANY IN THE STUDY IS THE
GLOBAL EFFICIENCY OF THIS
FRONTAL PARIETAL CONTROL NETWORK
AND GLOBAL EFFICIENCY INDEXES
THE CAPACITY FOR PARALLEL
INFORMATION PROCESSING SORT OF
THE EFFICIENCY OF INFORMATION
PROCESSING WITHIN THE NETWORK.
WE HYPOTHESIZE INHIBITORY
CONTROL BEHAVIOR WOULD BE
ASSOCIATED WITH INCREASED
EFFICIENCY OF THE NETWORK AND
THAT IN TURN WOULD RELATE TO
DECREASED VULNERABILITY WITH
PSYCHOPATHOLOGY.
THIS IS A BIGGER MODEL I TALKED
ABOUT AND I'LL WALK YOU THROUGH
IT.
IN STUDY 1, THE MODEL FIT THE
DATA WELL.
WHAT WE SEE ON THE RIGHT IS ONCE
AGAIN A BIFACTOR APPROACH
MODELLING ADHD AND ANXIETY AND
IRRITABILITY AND WE ONLY USED
PARENT-REPORT DATA FOR THE
MODEL.
IT'S NOT A PERFECT EXTENSION OF
WHAT I SHOWED BEFORE AND THERE'S
REASONS I CAN TALK ABOUT AND THE
MODEL WE'RE ABLE TO FIT THE DATA
WELL AND THE OTHER THING THAT
WAS A SHOCK TO ME AS FAR AS
BEHAVIORS IS THE INHIBITORY
CONTROL ACTION FIT WELL.
BEHAVIOR ON ALL FOUR TASKS
LOADED SIGNIFICANTLY TO A COMMON
LATENT VARIABLE.
AND WE SEE HIGHLIGHTED IN
YELLOW, IT'S THE GENERAL FACTOR
AGAIN THE COMORBIDITY OR THE
CO-OCCURRENCE OF INHIBITORY
CONTROL SEEMS TO BE MORE HIGHLY
RELATED.
WITH BRAIN DATA WHAT'S MORE
SHOCKING IS IT RELATED TO THE
RESTING STATE OF THE BRAIN IN
THE REGIONS WE HYPOTHESIZED.
INCREASED EFFICIENCY HAS TO DO
WITH CONTROL SCORES AND DID
ANALYSES IN RESPONSE TO REVIEWS
AND SHOWED ALL THE OTHER COLORED
NETWORKS AS WELL AS THE WHOLE
BRAIN, NONE OF THAT IS RELATED
TO INHIBITORY CONTROL.
IT'S SPECIFIC TO THIS ONE
FRONTAL PARIETAL NETWORK
HOWEVER, THE BRAIN DOES NOT
RELATE TO PSYCHOPATHOLOGY THOUGH
IT RELATES TO INHIBITORY
CONTROL.
THAT'S AN AREA WE'RE INVESTING
IN TO TRY TO DO BETTER ABOUT OUR
MEASUREMENT AND SEE IF WE CAN
FIND MORE EVIDENCE FOR THE
BRAIN'S DIRECT RELATIONSHIPS
WITH PSYCHOPATHOLOGY.
THE TAKEAWAYS HERE, BOTH
VARIABLES FIT WELL.
INHIBITORY CONTROL WAS RELATED
TO THE COMMON OR SHARED FACTOR
OF PSYCHOPATHOLOGY NOT ANY ONE
TYPE OF SYMPTOM AND EVIDENCE IT
RELATES TO BRAIN FUNCTION IN THE
TRANS-DIAGNOSTIC YOUTH.
I START THE BEGINNING TALKING
ABOUT THE CHALLENGES OR
CONUNDRUM SYSTEM CO-OCCURRENCE
CREATES FOR CLINICAL SCIENCE AND
CLINICAL NEUROSCIENCE BUT
HOPEFULLY WE TALKED A LITTLE BIT
ABOUT HOW THESE THEORETICALLY
INFORMED AND DATA-DRIVEN
APPROACHES CAN REALLY FIT THE
SYMPTOM STRUCTURE COMING AND
PRESENTING TO US INSTEAD OF
GOING IN WITH SINGLE DIAGNOSIS
OR STRAIGHT UP SYMPTOM SCORES.
THERE'S THING WE CAN DO TO MOELT
MOD
-- MODEL OF THE STRUCTURE WE
AND IN UNDERSTAND BETTER THE
SPECIFIC VERSUS COMMON
MECHANISMS MIGHT ONE DAY HELP US
BE ABLE TO TARGET THE TYPES OF
PRESENTATIONS THAT THE VARIETY
OF PRESENTATIONS THAT WE SEE
CLINICALLY IF WE CAN UNDERSTAND
THESE MECHANISMS IN A MORE
PRECISE WAY.
JUST TO RECAP, IRRITABILITY AND
ANXIETY HAD SPECIFIC BRAIN
CORRELATES THOUGH THEY UNDER LIE
THE SAME BEHAVIORS SEEING THE
SAME NEUROBASIS WERE DRIVING THE
SYSTEMS AND INHIBITORY CONTROL
LINKED TO THE RESTING STATE OF
THE BRAIN PRESENTED COMORBIDITY
OR CO-OCCURRENCE.
AND LAST FUTURE DIRECTIONS.
ONE OF THE HALLMARKS IS KNOWING
THE SOFT UNDER BELLY OF THE
RESEARCH BETTER THAN ANYONE
ELSE.
YOU MIGHT KNOW ABOUT SOME AND
TALK ABOUT THEM FOR HOURS IT
SEEMS AND HONESTLY IT'S ONE OF
THE MOST FUN THINGS TO DO
BECAUSE IT OPENS UP INTERESTING
OTHER DISCUSSIONS.
AND I FEEL LIKE I'VE PRESENTED
MYSELF AS SUCH A FAN OF THE
BIFACTOR MODEL WHICH I AM BUT I
WANT TO HIGHLIGHT THERE'S
LIMITATIONS AND ANOTHER ONE IN
THE LITERATURE THERE'S ISSUES
ABOUT MODEL OVER FITTING.
THERE'S A LOT OF COMPELLING
CONCEPTUAL ISSUES IN THINKING
ABOUT A SYMPTOM DIMENSION AND
CONSTRAINTS ON THE THINKING AND
WE'RE IN THE CONVERSATION OF
TRYING TO PUSH IT FORWARD AND I
VALUE THE OPPORTUNITY TO DO THAT
IN AN OPEN AND NON-JUDGEMENTAL
WAY AND ONE THING I'VE THOUGHT
ABOUT I'VE HAD THE OPPORTUNITY
TO CO-LEAD WITH KEN TOBIN AND
DANNY A GROUP WITH ADOLESCENT
DEPRESSION AND ONE STRIKING
FEATURE THERE THAT'S NO SURPRISE
IS THAT THE VAST MAJORITY, 99%
OF OUR CASES HAVE ANXIETY
DISORDERS AMONG OTHER
COMORBIDITIES.
SO THINKING ABOUT CLINICALLY HOW
TO THINK ABOUT THAT AND HOW TO
DEAL WITH THAT.
IN THINKING ABOUT THE
PERSPECTIVES, THE TWIST OR THE
WAY I'M TURNING THE QUESTION ON
ITS HEAD A LITTLE BIT IS RATHER
THAN THINKING OF IT AS A LATENT
CONSTRUCT LIKE THIS, WHAT IF WE
WERE TO THINK ABOUT IT LIKE A
BALL OF YARN AND AS LIVING
BREATHING, INTERCHANGING DYNAMIC
PROPERTIES AND WHEN WE THINK
ABOUT SYMPTOM CO-OCCURRENCE IT'S
INTERESTING TO THINK ABOUT
DIFFERENT STRANDS AND BALLS OF
YARN CAN BECOME INTERTWINED AND
ENTANGLED AND THAT'S MORE LIKE
WHAT WE THINK ABOUT CLINICALLY
WHEN WE SEE PATIENTS WE THINK
HOW DO THE SYSTEMS INTERACT
WITHIN INDIVIDUAL PEOPLE AND/OR
WORK IS HOW DO WE IN TANGLE SOME
OF THAT.
WE LOOK MORE AT SYMPTOM
INTERACTIONS AND HOW ANXIETY AND
DEPRESSIVE SYMPTOMS INTERACT
WITH ONE ANOTHER AND AT THE
LEVEL OF SPECIFICITY WITH THE
INDIVIDUAL PATIENT AND
ADDITIONAL LAYER SPECIFICITY AND
DYNAMIC FACTOR ANALYSIS AND
TEMPORAL METHODS TO GET AT THE
NEW IDEAS.
SO ONE OF THE SPECIFIC
DIRECTIONS WE HAVE IS THINKING
ABOUT THE ANXIETY SYMPTOMS IN
OUR PATIENTS AS DRIVERS AS THE
DEPRESSIVE SYMPTOMS.
THESE THINGS INFLUENCE ONE
ANOTHER ONE OVER TIME.
LIKE MELISSA'S GROUP WE'RE DOING
INTENSIVE E.M.A. TO GET AT THIS
AND A NEW TASK IN COLLABORATION
THAT GETS AAVOIDANCE CONFLICT
AND HOW WE DEAL WITH THREAT AND
REWARD IN THE ENVIRONMENT AND
THEN WE HAVE TWO FABULOUS
CLINICIANS DOING
TRANS-DIAGNOSTIC ACROSS
DEPRESSION AND ANXIETY C.B.T.
AND KEN AND I HAVE THE
OPPORTUNITY TO SUPERVISE THESE
AND TARGETING THE DEPRESSIVE
SYMPTOMS.
THAT'S WHERE WE'RE GOING BUT I
WANT TO HIGHLIGHT ONCE AGAIN,
ELLEN TOOK A HUGE LEAP OF FAITH
AND A TOOK A HUGE LEAP OF FAITH
COMING HERE.
OUR CONVERSATION IN OUR
INTERVIEW IS ONE OF THE MORE
SALIENT EXPERIENCES OF MY LIFE.
YOU KNOW HOW INTENSE IT WAS FOR
ME WE TALKED ABOUT A LOT.
PUSHING ME TO TAKE THAT NEXT
STEP.
I'D NEVER DONE NEUROIMAGING
BEFORE COMING HERE AND YOU
EXPRESSED THAT CONFIDENCE EVEN
WHEN I DIDN'T TO BE ABLE TO TAKE
THE NEXT STEP SO KNOWLEDGE OF
THIS IS POSSIBLE WITHOUT YOUR
INFLUENCE, YOUR SUPPORT, YOUR
THINKING, YOUR PARTNERSHIP AND
I'M SO EXCITED WE GET TO KEEP
DOING THIS.
THANKS VERY MUCH.
QUESTIONS?
>> THANK YOU FOR THE TALK,
DR. KIRKANSKI.
I WAS WONDERING ABOUT INHIBITORY
CONTROL AND THE GLOBAL
PSYCHOPATHOLOGY FACTOR IF YOU
CAN GO BACK TO THAT SLIDE,
PLEASE.
>> SURE.
>> BY THE WAY I'M CHARLES.
SORRY TO BE SO FORMAL BUT I WAS
ENCOURAGED BY DANNY.
I WAS CURIOUS, SO WHEN I THINK
ABOUT THE CAUSATION BETWEEN
BRAIN AND BEHAVIOR AND A THINK
LIKE PSYCHOPATHOLOGY I WOULD
USUALLY THINK THE BRAIN WOULD BE
WHAT'S DRIVING INHIBITORY
CONTROL WHICH IS THEN DRIVING A
BROADER SYMPTOM.
HAVE YOU TRIED FLIPPING THE
ORDER OF THE MEDIATION ANALYSIS
OR HOW INHIBITORY CONTROL MAY
ACT AS A MEDIATOR BETWEEN THE
GLOBAL EFFICIENCY AND THE
GENERAL PSYCHOPATHOLOGY?
>> 100% CORRECT.
FROM THEORETICAL PERSPECTIVE,
FROM STARTING AT THE PLACE OF
KNOWING ALL PARTICIPANTS HAVE
INHIBITORY CONTROL DATA AND
PSYCHOPATHOLOGY WE WERE ALMOST
FORCED FROM A SAMPLE AND DESIGN
PERSPECTIVE TO DO IT THIS WAY
AND THIS IS THE THEORETICAL
APPROACH.
IT WOULDN'T HAVE MATTERED
BECAUSE THE PREDICTOR IN THE
CASE EVEN IF WERE THE BRAIN
WOULD NOT HAVE RELATED TO
PSYCHOPATHOLOGY BUT IN TERMS OF
THE FUTURE WORK WE WANT TO THINK
ABOUT IT THAT WAY.
IN THE CASE WE HAD TO DO IT
POST
POST-HOC.
>> DOES ANYONE ELSE HAVE
QUESTIONS?
>> IT WAS DONE AT A DIFFERENT
TIME FROM THE BEHAVIOR AND
PSYCHO PSYCH
JOE
PSYCHO PATHOLOGY.
IT'S NOT WHAT WE WOULD WANT
GOING FORWARD.
>> IF YOU DID REGRESSION BETWEEN
THE GLOBAL EFFICIENCY AND
GENERAL FACTOR TURNS OUT TO BE
SIMPLE THAT'S INTERESTING THE
GLOBAL EFFICIENCY IS PICKING UP
EVERYTHING THAT'S NOTED BETWEEN
INHIBITORY CONTROL AND GENERAL.
>> GOOD POINT.
WE SHOULD LIKE TALK MORE ABOUT
THAT FOR SURE BUT YOU'RE TOTALLY
RIGHT.
THERE'S OTHER WAYS -- OTHER
IMPLICATIONS THAT HAS.
WE HAVEN'T THOUGHT AS MUCH
ABOUT.
>> THANK YOU VERY MUCH.
>> RELATED TO THAT, THE DATA IS
PROBABLY STRONGER THAN THE
COGNITIVE DATA THAT YOU USUALLY
GET BUT IN THE DATA AND LARGE
DATA SETS LIKE ABCD.
THE COGNITIVE DATA TENDS TO
RELATE MORE STRONGLY TO THINGS
LIKE RESTING STATE.
>> RIGHT, VERSUS
PSYCHOPATHOLOGY.
IT'S NOT AN ANOMALY IN THE
LITERATURE.
YOU'RE RIGHT.
>> I ALWAYS THOUGHT THAT RELATED
TO THE MESSY NATURE OF
PSYCHOPATHOLOGY.
>> THEN, WHY WOULD IT BE IT'S
RELATED TO THE BEHAVIOR.
>> THERE ARE MORE PATHS TO THE
PSYCHOPATHOLOGY MEASURES WAS MY
THOUGHT.
>> THAT MAKES SENSE.
OKAY.
SO, EVERYONE'S GOOD TO GO TO
LUNCH.
SEE YOU BACK AT 1:15.
SO, IN MANY WAYS THE TALKS FOR
THIS AFTERNOON WILL BE A NATURAL
PROGRESSION FROM SOME OF THE
TALKS THAT WE HEARD THIS
MORNING.
THIS MORNING THE TALKS ALL
INVOLVE PEOPLE WHO ARE ACTIVELY
INVOLVED IN WORK THAT'S ONGOING
AT THE INTERMURAL PROGRAM HERE
IN BETHESDA AND THIS AFTERNOON
WE'LL HEAR A SERIES OF TALKS
FROM A GROUP OF SPEAKERS WHO
HAVE VERY STRONG CONNECTIONS TO
THE IRB BUT ARE INVOLVED IN WORK
THAT IS PROCEEDING OFFSITE.
THE FIRST TALK IS GOING TO BE
FROM JULIA LINKE.
THIS TALK AS WELL AS ONE OF THE
OTHER TALKS IS GOING TO BE
RECORDED.
SO IT'S GONNA RUN AS SOON AS I
FINISH INTRODUCING JULIA AND
WON'T BE QUESTIONS AND ANSWERS
FOR THAT TALK AS WELL AS THE
TALK FOR DR. STRINGARIS.
DR. LINKE IS A PROFESSOR FOR
CHILD AND ADOLESCENT PSYCHOLOGY.
THIS IS A NEW POSITION JULIA
RECENTLY START ED AND WE'RE ALL
THRILLED FOR WORK IN WORK AT THE
IRP AND BRIEFLY IN TEXAS AT THE
UNIVERSITY OF HOUSTON.
LIKE MANY OF THE SPEAKERS FROM
THIS MORNING, JULIA SHARES A LOT
WITH THE GROUP.
HER PASSION, COMMITMENT AND
DIRECTNESS ARE ALL QUALITIES ALL
THE SPEAKERS THIS MORNING SHARE
THERE'S A COUPLE OF FEATURES OF
JULIA'S BACKGROUND IN HER WORK
BOTH AT THE NIMHD AND ALSO WORK
SHE'S PLANNING TO DO AND THE
GROUCH AT NIMHD BENEFIT FROM
THAT.
ONE IS JULIA IS PARTICULARLY
ADAPT AT DEALING WITH COMPLEX
DATA.
HEARD FROM ME AND FROM KATHERINA
ABOUT HER WORK USING GRAPH
THEORY.
SHE'S ALSO PARTICULARLY
PERSUASIVE IN THAT I THINK IT
SPEAKS TO HER ABILITY TO
CONVINCE US THAT THE WAY SHE'S
APPROACHING THINGS IS THE ARE
RIGHT WAY THAT A LOT OF US ARE
USING THE METHODS THAT SHE
BROUGHT HERE.
AND THEN I THINK OF A PAPER I
DID WITH JULIA AND ANDERSON
WINKLER THAT REMAINS ONE OF MY
FAVORITE PAPERS I'VE BEEN
INVOLVE WITH USING CANONICAL
ANALYSIS SHOWING HER ABILITY TO
PUSH THE FIELD IN A FORCEFUL WAY
MUCH IN THE WAY ELLEN HAS BEEN
ABLE TO DO.
I'M EXCITE TOED TO HEAR HER TAL
WHICH WILL END WITHOUT
QUESTIONS.
I THINK WE'RE READY.
>> I'VE BEEN A MENTEE OF ELLEN'S
SINCE 2017 WHEN I JOINED HER LAB
AS A POSTDOCTORAL FELLOW.
BEFORE I WILL SPEAK ABOUT THE
SCIENCE AND THE WORK I WILL
WOULD LIKE TO TAKE A FEW MOMENTS
TO TALK ABOUT MY EXPERIENCE
BEING A PART OF ELLEN'S RESEARCH
GROUP.
SO WHEN I INTERVIEWED FOR THE
POSITION, PEOPLE WERE LIKE SO
THAT YOU KNOW MENTORING IS A
REAL THING IN THIS LAB.
AT THIS MOMENT IN TIME I DID NOT
REALLY UNDERSTAND WHAT THEY WERE
TRYING TO TELL ME BECAUSE ALL I
HAD EXPERIENCED SO FAR ARE WHAT
I WOULD CALL QUEEN BEE KIND OF
LABS.
MEANING WHERE THAT THERE WERE
HIERARCHY AND MANY STRUGGLE BY
THEMSELVES TO BUILD THEIR CAREER
AND WORK FOR THE P.I. AND ELLEN
USED TO MEET WEEKLY WITH THE
POSTDOCS AND BEFORE THE TRAINING
DAY SHE WOULD ALWAYS TAKE TIME
TO CAREFULLY REVIEW POSTERS WITH
THEM AND ALWAYS EMPHASIZED
MENTORING IS NOT A ONE-WAY
STREET AND THAT SHE WOULD LEARN
A TREMENDOUS AMOUNT FROM US AND
IT GOT ME TO TRY MY BEST.
THIS ATTITUDE AT MENTORING
INSPIRED SOMETHING I WOULD CALL
IN LAB CROSS-MENTORING MEANING
THAT POSTDOCS WOULD NOT JUST
OVERSEE OR GIVE THEIR SCRIPTS TO
POSTDOCS YOU COULD MENTOR THEM
AND RESEARCHERS WOULD NOT JUST
DO STUFF FOR THE SENIOR PEOPLE
THEY WOULD LEARN FROM THEM AND
TO ME THIS WAY OF THINKING ABOUT
OUR DAY TO DAY INTERACTIONS OF
LOOKING THE THEM THROUGH THE
LENS OF MENTORING, REALLY MADE A
DIFFERENCE TO THE CULTURE OF THE
LAB AND I LIKED BEING A PART OF
ELLEN'S LAB.
I LOVED BEING PART OF ELLEN'S
LAB.
I HAVE SO MANY FOND MEMORIES.
ONE OF THEM BEING A CHORUS OF 20
OR MORE PEOPLE LOUDLY AND
SURPRISINGLY WELL SING HAPPY
BIRTHDAY TO EVERYONE AT THE LAB
MEETINGS OR HOW WE WOULD GATHER
AT ELLEN'S HOUSE TO CELEBRATE
THE GRADUATES AND NOT JUST TALK
ABOUT ACADEMIC ACHIEVEMENTS AND
CELEBRATE THEM FOR THEIR
UNIQUENESS AND SUPER POWERS.
AND ALSO THE SUPPORT WE WOULD
GATHER TO PRACTICE OF JOB TALKS
OR CHALK TALKS.
I THINK YOU GET WHAT I'M TRYING
TO SAY.
MENTORING IS A GREAT THING, A
GREAT MIND SET BUT HOW CAN WE
ACCOUNT REALLY GOOD MENTORS.
WE CAN GOOGLE AND I WOULD ARGUE
THAT ELLEN HAS DONE ALL THESE
THINGS AS A MENTOR BUT A FEW
THINGS REALLY STOOD OUT TO ME.
ONE OF THEM -- AND I GUESS
EVERYONE WHO'S EVER WORKED WITH
ELLEN PROBABLY AGREES ON THIS,
SHE ASKS SHARP AND GOOD
QUESTIONS SHE HAS A WAY OF
IDENTIFYING ONE THING IN YOUR
SIGNS YOU THOUGHT THROUGH THAT
ARE NOT SO CLEAR AND HELPS
IMPROVE YOUR SCIENCE.
SHE'S PASSIONATE ABOUT HELPING
OTHERS AND I THINK ONE WAY THAT
REALLY SHOWS IS THE SPEED WITH
WHICH SHE RESPONDS TO REQUESTS
AND RECOMMENDATION LETTER OR FOR
A MANUSCRIPT SHE USUALLY GETS TO
WITHIN 24 HOURS WHICH BLOWS MY
MIND.
I ALSO REALLY APPRECIATED HOW
OPEN SHE WOULD SPEAK ABOUT HER
EXPERIENCE AS A WOMAN IN
SCIENCE.
IT HELPED AND OTHER WOMEN
RESEARCHERS STRUGGLING WITH SOME
ASPECT OF THE ACADEMIC SYSTEM.
SHE ALSO CARED ABOUT ME.
ABOUT ALL HER MENTEES ON A
PERSONAL LEVEL AND RESEARCH HAS
BEEN INVEST ED AND THIS ENABLED
SOME OF THE GREAT SCIENCE THAT
HER ACHIEVEMENTS AND PREBLY
BASKETBALL
AND HER ROLE IN THE EMERGENCE IN
THE FIELD OF IRRITABILITY WHICH
IS A COMMON AND IMPAIRING
PROBLEM IN YOUTH THAT'S UNDER
STUDIED AND HER GROUP DEFINED AS
AN INCREASED PRONENESS TO ANGER
RELATIVE TO ONE'S PEERS.
A SIGNIFICANT PORTION OF
IRRITABILITY RESEARCH HAS
EMERGED FROM ELLEN'S LAB OR HAS
BEEN WITH CLOSE COLLABORATORS OF
ELLEN FOR A LONG TIME.
ONE OF THE QUESTIONS IS HOW TO
UNDERSTAND IRRITABILITY IN YOUR
RELATIONSHIP TO OTHER FORMS OF
YOUTH PSYCHOPATHOLOGY IT OFTEN
CO-OCCURS WITH INATTENTION,
HYPERACTIVITY, ANXIETY AND SINCE
THIS IS ALL HAPPENING TOGETHER,
HOW CAN WE IDENTIFY MECHANISMS
THAT ARE UNIQUE, FOR EXAMPLE, TO
IRRITABILITY OR TRULY SHARED
BETWEEN IRRITABILITY OF OTHER
PHENOTYPES.
AND GIVEN ALL THESE REPORTS
ABOUT NON-REPLICABLE FINDINGS
AND WE NEED HUNDREDS OF
THOUSANDS OF PARTICIPANTS TO
FIND BIOMARKERS, I THINK
PHENOTYPING IS STILL CRUCIAL AND
SOMETHING WE NEED TO THINK ABOUT
MORE DEEP DEEPLY TO USE OUR RESS
WELL AND TOOK MANY MY GROUP IN
GERMANY AND MORE IN THE SCIENCE
DEPARTMENT NOW BEFORE I HAD
JOINED ELLEN'S LAB IT SEEMED
NATURAL TO ME TO COMBINE THE
MORE SOPHISTICATED PHENOTYPING
APPROACH.
I HAVE BEEN BECOME ACQUAINTED
WITH IN MY TIME IN ELLEN'S LAB.
IN THE NEXT 20 MINUTES OR SO I'D
LIKE TO TOUCH ON TOPICS I THINK
ARE RELEVANT IN THIS AREA.
FIRST I'M I'LL TALK ABOUT THE
SPECIFICITY IN THE COMMON USE
PSYCHOPATHOLOGY AND THEN LOOK
THROUGH THE LENS OF NEUROSCIENCE
AND LASTLY WOULD LIKE TO ADDRESS
THE QUESTION WHETHER A TYPICAL
STRUCTURE SHOULD BE YOU'D USED
AS A STRUCTURE AND ANXIETY AND
DEPRESSION FREQUENTLY CO-OCCUR.
INTERESTINGLY ALL THE PHENOTYPES
GO TO A TYPICAL MICROSTRUCTURE
AND IF WE LOOK AT ADMITTEDLY
SOMEWHAT CRUDE STUDIES WHAT WE
SEE IS LACK OF SPECIFICITY.
BASICALLY ALL ARE ASSOCIATED
WITH THE PHENOTYPES.
WHICH MAKES YOU WONDER WHAT DOES
IT MEAN?
IT WOULD MEAN THERE'S NOT
SIGNALS AND I WOULD LIKE TO
THINK MORE OF IT AS A HINT THAT
ATYPICAL MICROSTRUCTURE MAY
PRESENT A SHARED MECHANISM OF
ANXIETY, IRRITABILITY AND
INATTENTION AND HYPERACTIVITY.
THAT'S A QUESTION I HAVE BEEN
WORKING ON WITH ANOTHER FORMER
POSTDOC AND WE HAD TWO
INDEPENDENT SAMPLES.
A LARGE WORK OF PHENOTYPIC
INFORMATION AND A SMALLER ONE ON
DIFFUSION IMAGING.
HOW CAN WE MODEL THESE UNIQUE
AND SHARED ASPECTS.
A GROUP HAS SPOKEN OR WILL SPEAK
SHORTLY AFTER ME SO SHE
INTRODUCED US TO THE FACTOR
ANALYSES TO DRAW OUT SHARED AND
UNIQUE ASPECTS OF PHENOTYPES.
THE USE OF THIS MODEL AND THIS
SET AND A QUESTION IS THE
INTERPRETATION OF THE LATENT
FACTORS.
ARE QUE CORRECT IN AND THERE IS
LITERATURE OR TYPE OF LITERATURE
WHERE RESEARCHERS TAKE BROAD
MEASURES OF PATHOLOGY COVERING
PSYCHOTIC SYMPTOMS TO OTHER
SYMPTOMS AND THROW IT IN AND
INTERPRET THE SHARED FACTOR AS
GENERAL PSYCHOPATHOLOGY FACTOR
OR RELATED TO SEVERITY AND SOME
TAKE SPECIFIC PHENOTYPES AND
TEND TO COME UP WITH A MORE
CLEARLY DELINEATED
INTERPRETATION OF THE SHARED
FACTOR.
HERE WE WERE ASSUMING THE SHARED
FACTOR MIGHT PRESENT SOMETHING
LIKE HEIGHTENED INCLUSIVITY OR
INHIBITORY CONTROL.
TO TEST THIS WE CORRELATED THE
LATENT FACTORS THAT ARE
REPRESENTED BY THESE RINGS WITH
INDEPENDENT MEASURES OF
IMPULSIVITY.
INDEED THE IRRITABILITY FACTOR
LOADED MOST HIGHLY ON MEASURES
OF IRRITABILITY.
THE INATTENTION FACTOR ON
MEASURE OF INATTENTION AND
HYPERACTIVITY FACTOR AND THEY
WERE SOMEWHAT ASSOCIATED WITH AN
INDEPENDENT MEASURE OF
IMPLICITIVITY AND IT'S SOMETHING
SHARED WE THINK IT'S THE MEASURE
OF COURSE.
WE ALSO SHARED THE SHARE FACTOR
LOADED EQUALLY HIGH ON THE
MEASURE OF CO-COGNITION
SUGGESTING COGNITIVE AND
EMOTIONAL IMPULSIVITY.
THIS ALIGNED WITH OTHER WORK LED
BY A FORMER MENTEE OF ELLEN WHO
JUST GOT A PAPER ACCEPTED IN
SCIENCE WHERE SHE ALSO SHOWED
THAT THE GENERAL FACTOR THAT
EMERGES OF THE MODEL PUTTING IN
ANXIETY, IRRITABILITY AND ADHD
SYMPTOMS IS ASSOCIATED WITH A
LACK OF INHIBITORY CONTROL.
NOW, I STARTED OFF INTERESTED IN
THE MATTERS SO WHY DON'T WE JUST
TAKE A LOOK AT THAT.
SO BECAUSE THE FINDINGS WERE SO
UNSPECIFIC, IN THE FIRST STEP WE
CALCULATED GLOBAL FRACTION FOR
THE BRAIN AND IT'S A METRIC THAT
TELLS YOU HOW COHERENT THE
FIBERS ARE AND IF WE LOOK AT
THIS ACROSS THE BRAIN, WE SEE'
NEGATIVE ASSOCIATION AND
CONTROLLING FOR THIS GLOBAL
EFFECT WE ALSO FOUND FROM THE
MOTO CORTEX HAS BEEN LINKED TO
THE INHIBITORY CONTROL TASKS.
THE HYPERACTIVITY SPECIFIC
FACTOR ALSO WAS ASSOCIATED
NEGATIVELY WITH GLOBAL F.A. BUT
THERE WERE NO REGIONAL FINDINGS.
ONE THING ABOUT THE ABILITY OF
ADHD, WHEN WE GO FROM EARLY
CHILDHOOD THROUGH ADOLESCENCE
THESE SYMPTOMS TEND TO IMPROVE
AND GET BETTER.
WE WERE WONDERING HOW THESE
FACTORS RELATE.
TOGETHER THE FIRST PREDICTED THE
F.A. FROM H AND POSITIVE
RESIDUALS AS MATURATION AND WE
NO EFFECT WITH REGARD TO THE
SHARED FACTOR BUT EVIDENCE THAT
THE HYPERACTIVITY SPECIFIC
FACTOR WAS LINKED TO A DELAYED
MATURATION OF THE BRAIN'S WHITE
MATTER.
SOW THIS WORK HAS RECENTLY BEEN
ACCEPTED BUT OF COURSE YOU WANT
ROBUST FINDINGS.
WE ALREADY DID THE NEXT STEP AND
GOT A SECOND SAMPLE BECAUSE
UNFORTUNATELY SOMETIMES IT TAKES
A LONG TIME SO WE HAVE A SECOND
SAMPLE ADDING IN ANXIETY AND
INTERESTINGLY WE COULD REPLICATE
A LOT OF THE FINDINGS.
WE CAN SHOW IT'S PROBABLY THE
MOST FRUITFUL TO THINK OF THE
SHARED FACTOR AS NOTHING RELATED
TO A LACK OF INHIBITORY CONTROL
AND THE SHARED FACTOR IS
ASSOCIATED NEGATIVELY WITH
ATROPHY IN THE BRAIN AND
SPECIFIC REGIONS AND AGAIN WE
FOUND THE CORTICOSPINAL TRACK
AND ALSO THE INFERIOR FRONTO
OCCIPITAL AND WE LOOKED AT
FACTOR FINDING AND COULD SHOW
THIS HYPERACTIVITY SPECIFIC
FACTOR RELATED TO DELAYED NACH
RATION OF THE BRAIN WHITE
MATTER.
SO,OVERALL TO HAMMER IT IN, IT
SEEMS CONTROL DEFICITS ARE
SHARED ACROSS DIFFERENT FORMS OF
COMMON USE PATHOLOGY THAT THIS
DEFICIT RELATES TO THE BRAIN'S
WHITE MATTER GLOBALLY BUT ALSO
REGIONALLY AND IN THE CORTICO
SPINAL TRACT AND HAVE EVIDENCE
SUPPORTING HYPERACTIVITY MAY BE
SPECIFICALLY LINKED TO A DELAY
IN WHITE MATTER MATURATION.
THESE ARE SIGNIFICANT FINDING.
NOW, WE SHOULD NOT INTERPRET BY
THE HYPOTHESIS AND SHOULD NOT
FIND ANY EVIDENCE THAT WOULD
LINK A TYPICAL WHITE MATTER
MICROSTRUCTURE TO ATTENTION,
IRRITABILITY OR ANXIETY.
BUT, WE ALSO JUST LOOKED AT THE
BRAIN'S WHITE MATTER AND ONE'S
VERY SPECIFIC WAY.
SO, AS PROMISED EARLIER, I KNOW
INVITE YOU TO LOOK AT THE
BRAIN'S WHITE MATTER IN A
SOMEWHAT DIFFERENT WAY THROUGH
THE SYMPTOMS NEUROSCIENCE
APPROACH AND THEORETICAL
APPROACH AND IN THIS FRAMEWORK
WE LIKE TO THINK OF THE BRAIN AS
A BIG NETWORK CONSTITUTED OF
SMALLER NETWORKS WHICH IN THE
CONTEXT YOU WOULD CALL MODULES
AND THEY'RE MADE UP OF SPECIFIC
BRAIN REGIONS NOT REFERRED TO AS
NODES THAT ARE CONNECTED THROUGH
EDGES AND TO ME THE NICE THING
IF WE APPLY THE APPROACH TO
D.T.I. THERE IS A BIOLOGICAL
COUNTERPART TO THE EDGES BECAUSE
IT'S THE FIBER TRACTS WE'RE
MEASURING.
WE CAN DERIVE DIFFERENT METHODS
TO PROPERTIES OF THE BRAIN
NETWORK TOPOLOGY AND CAN GET
MODULARITY AND LOOK AT HOW
DELINEATED AND NETWORKS WITH THE
BRIN OR NOT AND ABOUT EFFICIENCY
AND HOW MUCH INFORMATION CAN BE
PROCESSED IN PARALLEL.
NOW, WE USE THE METRICS IN OUR
ANALYSIS AND DID NOT FIND
ANYTHING SO CENTRALITY BASICALLY
TELLS US THE CONNECTIONS BETWEEN
THE MODE MAKING THE MIDDLE NODE
CENTRAL AND SAME FOR THE EDGE IF
THE NODES WANT TO COMMUNICATE
THEY ARE WANT TO GO THROUGH THE
EDGE.
THE IDEA IS THAT HIGH CENTRALITY
ALLOWS FOR FLEXIBLE INFORMATION
OR PROCESSING WHEREAS LIKE LOWER
CENTRALITY MEANS MAYBE IT MAY BE
MORE RIGID.
NOW, CORRECTING FOR THE FACT WE
HAD SEVERAL MEASURES
INVESTIGATING AND THERE WERE
SEVERAL EDGES AND REGIONS OR
NODES, WE HAD TWO FINDINGS HERE.
WE SAW THE LATENT ANXIETY
SPECIFIC FACTOR WAS RELATED TO
REDUCED CENTRALITY AND 7% OF THE
200 NODES.
THE USE AS YOU CAN SEE THE RED
DOTS DISTRIBUTED ACROSS AND IT'S
NOT CONFINED TO ONE SPECIFIC
REGION.
AND WE HAD A SECOND FINDINGS
WITH REGARD TO INATTENTION AND
HERE IN THE OPPOSITE DIRECTION
SO 9% OF THE NODES WE LOOKED AT
WERE ACTUALLY ASSOCIATED WITH
HIGHER -- THERE'S HIGHEST
CENTRALITY ASSOCIATED WITH THE
INATTENTION SPECIFIC FACTOR.
TO ME, INTUITIVELY IT MAKES
SENSE THAT IF A LOT OF
INFORMATION PASSES OR IS ALLOWED
TO PASS THROUGH CERTAIN NODES
THAT YOU MIGHT GET LIKE YOU
KNOW, EASILY DISTRACTED AND
INATTENTIVE.
SO, YEAH.
TO SUMMARIZE INATTENTION TO NODE
AND ANXIETY GOES TO A CENTRAL
NETWORK CONFIGURATION WITH FEWER
CENTRAL NODES.
AND WITH THAT, I'D LIKE TO
TRANSITION TO THE LAST AREA THAT
MAY BE OF INTEREST TO YOU AND
THAT'S THE QUESTION SHOULD WE
THINK ABOUT MICROSTRUCTURE AS A
TREATMENT TARGET.
SO I THINK IT'S FAIR THAT THE
LITERATURE WITH REGARD TO
COGNITIVE BEHAVIORAL THERAPY AND
MICROSTRUCTURE IS STILL NASCENT.
IT'S KIND OF OBJECTIVE.
SO, THERE'S BIG HETEROGENEITY
WITH REGARD TO THE DISORDERS AND
TREATMENT PROTOCOL.
NATURALLY, GIVING THE
HETEROGENEITY OF FINDINGS ARE
DIVERGING HOWEVER, I THINK IT'S
FAIR ON A VERY HIGH LEVEL TO
SUMMARIZE THIS IN A WAY TO SAY
THE COHERENCE SEEMS TO INCREASE
AND DIFFERENT TRACTS ACROSS THE
BRAIN DURING THE COURSE OF CBT
AND CBT MAY CHANGE THE
NEUTRALITY OF CERTAIN BRAIN
FUNCTIONS.
THE STUDY IS SMALL AND WE HAVE
19 HEALTHY CONTROLS BOTH GROUPS
UNDERWENT IMAGING TWICE WITHIN
12 WEEKS.
AND THERE WAS EXPOSURE AND
COGNITIVE COMPONENTS.
AND DANNY PINE'S LAB IS WHERE
THE WORK HAS BEEN DONE SO WANT
TO ACKNOWLEDGE THIS.
SO WHEN WE LOOK AT THE DATA WE
SAW SIGNIFICANT BASICALLY TIME
BY DIAGNOSIS OR TREATMENT BY
DIAGNOSIS INTERACTION IN THE
INFERIOR CORTICOSPINAL TRACT AND
ANTERIOR THALAMIC TRACT AND THE
THALAMIC RADIATION.
NOW, INTERACTION CAN SOMETIMES
COME ABOUT IN A LITTLE BIT FUNNY
WAY THAT'S HARD TO INTERPRET.
SO IF IF WE LOOK AS EXPECT THE
ANXIOUS USE HAS LORE -- LOWER
SCORES AFTER THE TREATMENT AND
WE SEE SLIGHTLY HIGHER MEASURES
BUT IT'S NOT STATISTICALLY
SIGNIFICANT AND WE SEE CHANGES
AND IN TRACTS TO THE INHIBITORY
CONTROL DEFICIT BUT WHAT ABOUT
THE ANXIETY SPECIFIC MARKERS ?
WE TALKED ABOUT IT WAS
ASSOCIATED WITH THE NODES AND WE
SAW SIGNIFICANT INTERACTION IN
THE VENTRAL PRE-FRONTAL REGIONS
WHERE WE SAW NORMALIZATION OF
THE CENTRALITY.
SO OVER ALL I THINK IT'S
EVIDENCE THAT WE SHOULD THINK OF
THE MICROSTRUCTURE AS A
TREATMENT TARGET.
SOMETHING THAT IS ALREADY
PARTIALLY TARGETED BY COGNITIVE
BEHAVIORAL THERAPY AND WE ALSO
SAW THERE WERE DEFICITS OR
ABERRANCIES NOT TARGETED BY CBT
SO FAR.
.
AND IT'S PROMISING AND THERE'S
ROOM FOR IMPROVEMENT AND, YEAH.
I GUESS TO SUMMARIZE IF YOU
THINK ABOUT THE ACCUMULATING
EVIDENCE OF CERTAIN BEHAVIORS IN
WHICH WE BASE CLINICAL PHENOTYPE
I THINK THERE IS ABANDONED
EVIDENCE.
IT APPEARS THE FIELD SHOULD
REALLY FOCUS ON ALTERNATIVE
PHENOTYPING APPROACHES AND
ALTERNATIVE FIELDS OF
PSYCHOPATHOLOGY OR COMPUTATIONAL
MODELLING APPROACHES OF LATENT
DIMENSIONAL PSYCHOPATHOLOGY OF
BEHAVIOR HAVE BEEN POSED AS A
WAY FORWARD.
I THINK THERE'S STILL LACK OF
STUDIES APPLYING THE
SOPHISTICATED PHENOTYPING
APPROACHES PARTICULARLY IN
COMBINATION WITH STATE OF THE
ART IMAGING ANALYSES.
BUT I DO THINK THAT WE'RE
INCLUDING THESE APPROACHES COULD
REPRESENT A MUCH NEEDED PUSH
FORWARD IN OUR ENDEAVOR TO FIND
CAUSES OF PSYCHIATRIC DISORDERS
AND ULTIMATELY ADVANCE OUR
TREATMENT OPTIONS.
WITH THAT I WOULD LIKE TO
CONCLUDE MY TALK.
I WOULD LIKE TO THANK YOU FOR
YOUR ATTENTION AND OF COURSE I
THANK YOU FOR BEING A WONDERFUL
MENTOR AND INSPIRING GROUP OF
SCIENTISTS.
>> ALL RIGHT, WITH THAT I'D LIKE
TO TRANSITION STRAIGHT TO THE
NEXT TALK.
WE'RE LUCKY TO HAVE THE NEXT
TALK PRESENTED BY GIOVANNI SALUM
THE CO-PROGRAM DIRECTOR OF THE
STAVROS NIARKOS FOUNDATION FOR
CHILD AND ADOLESCENT MENTAL
HEALTH IN NEW YORK.
HE IS ONE OF THE CLOSEST
HONORARY MEMBERS OF THE MOTION
AND DEVELOPMENT BRANCH.
I DON'T KNOW HOW MANY YEARS
WE'VE WORKED WITH YOU AT LEAST
10.
13 YEARS GIOVANNI HAS WORKED
WITH US WHICH HAS BEEN AN
ABSOLUTE PLEASURE.
I WANT TO LEAVE HIM THE FULL
AMOUNT OF TIME AND SAY TWO OTHER
THINGS.
WE'RE GOING TO END IMMEDIATELY
AFTER HIS TALK AND TAKE A HALF
AN HOUR BREAK AND WE'LL START
BACK -- OH, 15 MINUTES.
WE'LL START BACK AT 2:30 AND THE
TWO QUALITIES I WANTED TO
HIGHLIGHT ABOUT GIGI --
GIOVANNI HAS AND HE STANDS OUT
ONE IS HIS BREADTH OF KNOWLEDGE
IS ABSOLUTELY STAGGERING.
GIOVANNI KNOWS EVERYTHING ABOUT
EVERYTHING THAT HAS TO DO WITH
PEDIATRIC MENTAL HEALTH AND THE
SECOND ONE IS HE'S ONE OF THE
KINDEST PEOPLE I'VE EVER MET AND
IT'S AN HONOR TO HAVE YOU SPEAK.
>> SO THANK YOU FOR THE
INTRODUCTION.
I'M HONORED TO BE HERE TODAY.
I AM I FEEL LIKE NIH HAS BEEN
GREAT TO ME AND CHANGE MID
CAREER TRAJECTORY AND GETTING TO
KNOW SO MANY HERE AND NIH HAS
BEEN A SECOND HOME IN A WAY AND
THAT'S NOT SOMETHING I SAY
LIGHTLY.
I'M FROM BRAZIL SO I FEEL HOME
SICKNESS IN NEW YORK AT THIS
POINT.
AS MY OTHER COLLEAGUES I'LL TALK
ABOUT THE RESEARCH I'VE BEEN
DOING.
I CAME TO NIH IN 2009-2010 AND I
CAME TO WORK WITH DANNY AT THAT
TIME AND GOT TO KNOW ELLEN IN
THE PROCESS OF WORKING WITH
DANNY AND HAVE BEEN VISITING
NIH.
THESE ARE PICTURES.
I WAS DRESSING DIFFERENTLY AND
WAS YOUNG AT THAT TIME.
AND I CAME HERE TO GET HELP TO
UNDERSTAND THE STUDY, THE BRAZIL
COHORT STUDY.
WHEN I CAME HERE, I WAS
COORDINATING THAT STUDY BUS
DOING MY Ph.D. AT THE SAME TIME
AND IN THIS STUDY WE WENT TO 57
SCHOOLS AND INTERVIEWED A
THOUSAND PEOPLE.
THAT'S ONE OF THE FEW STUDIES AT
THAT TIME A LONG TIME AGO AND
SELECTED PARTICIPANTS AND LOOKED
AT MENTAL CONDITIONS AND WHEN I
CAME HERE WE WERE IN WAVE 1 AND
NOW IN WAVE 4 IF WE COUNT
COVID-19 IT'S WAVE 5.
IN THIS STUDY WE DID PHENOTYPING
ON -- WE HAD PSYCHOLOGISTS AND
TWO SPEECH THERAPIST VISITS AND
COLLECTED SALIVA AND IMAGING AND
OTHER QUESTIONNAIRE DATA.
WE REPEATED THE WHOLE PROTOCOL
AND THEN REPEAT THE PROTOCOL.
WE'VE BEEN KEEPING RETENTION OF
AROUND 75% TO 80% AND THIS IS
PARTICULARLY IMPORTANT FOR
MIDDLE INCOME COUNTRIES THOUGH
THEY'RE COMMON IN EUROPE AND IN
THE U.S. THERE'S FEW IN LOW AND
MIDDLE INCOME COUNTRIES AND
SOMETIMES THEY'RE DIFFERENT.
IT'S AND THE MAJORITY OF
CHILDREN LIVE IN LOW-INCOME
COUNTRIES SO IT'S IMPORTANT TO
UNDERSTAND WHAT'S GOING ON AND
LOOK AT THE EXPOSURES AND LOOK
AT THE GAP.
AT THAT TIME WE WERE FOCUSSING
ON BIASES.
THAT WAS OR FIRST WORK TOGETHER.
I WAS DRESSING UP SOMETIMES IN
AN UNPROFESSIONAL WAY AND I
REMEMBER THE FIRST TIME THE
PAPER CAME OUT AND THERE WAS
NOTHING I HAD WRITTEN.
EVERYTHING WAS READ IN THE WORD
DOCUMENT AND THAT WAS THE FIRST
TIME AND SPEAKS TO WHAT WE HAVE
BEEN DOING AND SHOWING IN THE
LINK BETWEEN ANXIETY AND
INABILITY AND REPRESENTED IN THE
WORK AT THAT TIME WE SHOWED WE
REPLICATED THE FINDING THAT
CHILDREN WITH INTERNALIZING
DISORDERS CAN BE CAPTURED IN THE
ENVIRONMENT AND HAPPENS WITH THE
IRRITABILITY EVEN ADJUSTING FOR
ANXIETY.
SINCE THEN, WE HAVE BEEN
COLLABORATING WITH OTHER STUDIES
AND BESIDES GETTING ALL THE
KNOWLEDGE AND LEARNING
EXPERIENCE WITH WRITING AND
GETTING TO KNOW AND BEING
ACCOUNTABLE FOR WHAT YOU WRITE,
WE HAVE BEEN SHAPING THE WORK WE
HAVE BEEN DOING.
THIS IS ONE OF THE VISITS ELLEN
DID.
I DON'T REMEMBER THE YEAR BUT IT
WAS BOB, MICHAEL AND ELLEN.
I REMEMBER MICHAEL SLEEPING IN
THE BACK OF THE CAR IN A SMALL
CITY IN BRAZIL AND FOR US TO
START A COLLABORATION AND TALK
ABOUT THE SCIENTIFIC SIDE THE
THREE MAIN ASPECTS.
THIS IS TRYING TO UNDERSTAND A
DIMENSIONAL ASPECT AND WHAT
REQUIRES ATTENTION AND SYMPTOMS
REQUIRED THAT WOULD BE
IMPOSSIBLE FOR ANY HEALTH SECTOR
TO HANDLE.
HOW IS BEST WAY TO FOCUS
ATTENTION THAT WOULD REQUIRE THE
MOST TRYING TO UNDERSTAND HOW
THAT IS MORE DIFFICULT
PROJECTIONS IN LIFE.
I'LL TALK ABOUT THE IRRITABILITY
IN CHILDREN AND THRESHOLDS IN
ADULTS AND THE IMPORTANCE OF THE
WORK AND THE THRESHOLDS FOR
CLINICAL ATTENTION IN HOW WE CAN
TRY TO UNDERSTAND THAT FROM A
PERSPECTIVE OF EXECUTIVE
FUNCTION FOR EXAMPLE.
THIS START AND I THINK THE PAPER
WAS FROM THE BEGINNING OF THE
SESSION AND IT'S IMPORTANT FOR
CHILD PSYCHIATRY WHICH IS WHEN
YOU DON'T KNOW WHAT'S GOING ON
WE JUST DON'T CALL IT SOMETHING
ELSE.
YOU CALL IT SOMETHING YOU DON'T
KNOW AND LET'S STUDY THAT.
THAT WAS NOT AN EASY DECISION
FOR DANNY AND ELLEN AND AN
IMPORTANT DECISION FOR THE FIELD
TO UNDERSTAND WHAT WAS GOING ON.
THIS HAS A TREMENDOUS IMPACT IN
MANY CHILDREN IN THE WORLD.
SO I REALLY PARTICULARLY APPLAUD
AND THERE'S TRYING TO UNDERSTAND
WHAT'S GOING ON AND NOT JUMPING
INTO OTHER THINGS YOU DON'T KNOW
WHAT YOU'RE TALKING ABOUT.
SO WE DEPARTED FROM THIS
SEMINOLE WORK THAT WOUND UP
BEING REPRESENTED IN THE DSM5
AND UNDERSTAND HOW THE
NEUROLOGICAL STUDIES CAN HELP US
UNDERSTAND THE THRESHOLDS IN A
DATA-DRIVEN WAY THAT COMPLIMENTS
THE CLINICAL DESCRIPTIONS.
THIS IS WORK FROM A Ph.D.
STUDENT AND SO BESIDES THE
GENEROSITY OF ELLEN AND MELISSA
TO HELP ME IN MY CAREER THEY
EXTEND THE BENEFIT TO MY
STUDENTS AND CAME TO US AND WAS
MENTORED HERE AND SO THAT WAS
EVEN -- AND NOW BEING A FATHER
OF A 3-YEAR-OLD YOU UNDERSTAND
HOW NICE IT IS WHEN SOMEONE IS
TAKING CARE OF YOUR CHILD AND
HOW POWERFUL THIS IS.
I DO FEEL THAT IN THE
RELATIONSHIP THAT I HAVE WITH
THE GROUP HERE.
TOGETHER WE DEFINED A METHOD TO
TRY TO UNDERSTAND HOW WE DEFINE
THE THRESHOLDS.
GIVEN THE DIMENSION IS
DISTRIBUTED HOW TO DISTINGUISH
THE ONES THAT REQUIRE MOST
ATTENTION TO THE ONES THAT WOULD
NOT BE THAT EFFECTIVE BECAUSE
IRRITABILITY EVERY CHILDS HAS
TANTRUMS AND WHEN IT'S AN
INDICATOR OR NORMATIVE BEHAVIOR.
UNDERSTANDING FROM THE PHENOTYPE
IN THE LATENT TRAIT WHAT LEVEL
OF EACH RESPONSE CATEGORIES
INFORMS A PROBLEM.
THERE ARE THINGS EVEN THE
PRESENCE IS INFORMED SOMETHING
GOING ON.
WE DEPARTED FROM THIS STRATEGY.
YOU CAN SEE THE PRESENCE OF
SELF-HARM DOESN'T REQUIRE
INTENSITY TO FIRST THINK THIS
MAY BE A PROBLEM.
WHERE ARE SOME THINGS SUCH AS
OUTBURSTS INCENTIVIZE ONE OR TWO
OUTBURSTS ARE SOMETHING TYPICAL
BUT OUTBURSTS EVERY DAY MAY BE
INDICATING SOMETHING REQUIRES
MIN CAL ATTENTION.
THERE IS HOW MANY SYMPTOMS YOU
NEED TO HAVE TO START THINKING
IT'S ONLY ONE SYMPTOM MIGHT BE
AGAIN SOMETHING THAT YOU SEE
MORE FREQUENTLY AND NEED A
COMBINATION OF THE SYMPTOMS TO
UNDERSTAND THIS IS A CHILD
NEEDING A LOT OF HELP.
THAT WAS THE SECOND PART OF THE
PIPELINE WAS THE DATA DRIVEN
ANALYSIS IN THE ANALYSIS AND
COMBINING THAT WITH A METHOD
CALLED RECEIVING OPERATING
CURVES TO TRANSLATE TO A MORE
CLINICAL LANGUAGE CLINICIANS ARE
USED TO SUCH AS THE DSM5 HOW
MANY SYMPTOMS YOU NEED TO HAVE
TO BE PART OF A CLUSTER THAT'S
HIGHLY SYMPTOMATIC.
AND THERE'S TWO PRESENTATIONS
AND A MORE PHASIC LIKE MOOD AND
OUTBURST AND HOW DO WE PUT THOSE
THINGS TOGETHER.
YOU NEED THE AND RULE AND
REQUIRE ONE OF THOSE MEASURES TO
BE PRESENT HERE IN THE STUDY WE
EXPLORED HOW WE CAN PUT THOSE
TOGETHER AND THE IMPACT OF THAT
AND PREVALENCE IN THE COMMUNITY
THAT'S ALSO IMPORTANT PARAMETER
FROM A PUBLIC HEALTH PERSPECTIVE
HOW MUCH OF THE POPULATION WILL
BE AFFECTED BY CONDITION.
AS I MENTIONED AND THERE WAS THE
SECOND AND THIS IS PART OF THE
RESEARCH GROUP I DID IN BRAZIL
AND THAT VISIT WAS PARTICULARLY
IMPORTANT BECAUSE THAT WAS ONE
OF THE FIRST TIME ELLEN SPOKE TO
THE WOMEN IN THE GROUP AND
EVERYONE GOT FEEDBACK IN SAYING
THIS WAS SO IMPORTANT AND I
COULD NOT SPEAK MUCH.
IT WAS REALLY AN IMPORTANT
MOMENT.
WE EXTEND THE WORK ON THIS FOR
ADULTS AND THE MAIN REASON FOR
THAT IS BECAUSE THEIR WORK AARON
AND MANNISH HAVE BEEN DOING, WE
KNOW THE IMPORTANCE OF
IRRITABILITY IN CHILDHOOD IN
PREDICTING ANXIETY, DEPRESSION
INTO ADULTHOOD AND STILL WE KNOW
LITTLE ABOUT HOW IRRITABILITY IN
CHILDHOOD PREDICTS IRRITABILITY
IN ADULTHOOD.
IN PART THE ANGER AND
IRRITABILITY HAVE BEEN
DISSEMINATED IN THE DSM TO SO
MANY CATEGORIES AND THERE'S A
DISCONNECTION BETWEEN THE
CATEGORIES FOR CHILDREN AND
ADULTS AND START THINKING THE
IMPORTANCE OF HOW WE CAN PUT THE
WORK TOGETHER AND HOW THIS COULD
INFORM PSYCHOPATHOLOGY IN A MORE
DEVELOPMENTALLY SENSITIVE WAY.
WE STARTED USING THE SAME
METHODS AND WE STARTED THINKING
ABOUT THE COHORT HOW THAT WOULD
BE IN IN LATE ADOLESCENCE AND DO
THEY MEASURE AND THERE'S
INFORMATION INFORMING THE FACTS
SO HOW CAN WE DO THAT.
I'M SURE THIS IS SCARY.
WE CAN ALSO TEST IF AND TRYING
TO UNDERSTAND IF THE INDICATORS
ARE MEASURING THE SAME THING IN
DIFFERENT STEPS OF DEVELOPMENT.
ONE CONCLUSION OF THE STUDY IS
THEY'RE NOT AND IF WE LOOK AT
LONG DURATION OF IRRITABLE MOOD
AND IT'S NOT THAT COMMON TO SEE
THE MOOD LAST LONG.
IF WE GO TO ADOLESCENCE AND
YOUNG ADULT WE REQUIRE THAT
CONSISTENT WITH THE IDEA OF THE
EXAMPLE.
FOR US TO LOOK AT THE MEASURE IT
REQUIRES EIGHT OF THINK IN HOW
THEY RELATE TO EACH OTHER AND
HOW THE PHENOMENA MANIFEST HAVE
DIFFERENT AGE PERIODS.
WE HAVE OTHER WAYS AND
PROPENSITY SCORE MATCHING AND
THE EFFECT OF COMORBIDITY NOT
REALLY IRRITABILITY AND ONE
THING WE DID WAS WE USED
MATCHING CRITERIA AGAINST THOSE
THAT WOULD NOT MATCH DO
DIAGNOSTIC CRITERIA AND HAVE THE
SAME TYPES OF DISORDERS.
SO IF WE HAVE ADHD THE CONTROL
HAS ADHD.
IF THE CASE HAS ADHD AND PHOBIA
IT'S MATCHING ON THE COMORBIDITY
PROFILES AND MAKE SURE IT'S NOT
ABOUT COMORBIDITY AND YOU CAN
SEE HERE EVEN MATCHING FOR
EVERYTHING POSSIBLE USING
COMPLETELY MATCHED INDIVIDUALS
YOU STILL SEE A HUGE EFFECT OF
IRRITABILITY IN ADULTS AND SEE
THOSE ADULTS ARE INTERESTING
TROUBLE IN THEIR LIVES AND
SYMPTOMS AND IMPAIRMENT IN THEIR
LIVES ABOVE AND BEYOND THEIR
COMORBIDITIES.
THE OTHER THING ALSO THE GROUP
HAS BEEN SHOWING IS USING
ASSESSMENT IF WE PROBE MULTIPLE
TIMES A DAY THE IRRITABILITY
SYMPTOMS YOU'D SEE A LOT OF
IRRITABILITY NOT ONLY CAPTURED
BY QUESTIONNAIRES AND SOMETIMES
JUST QUESTIONNAIRE AFFECTS WITH
ANOTHER SOURCE OF VARIANCE.
THE LAST PART IS TRYING TO
UNDERSTAND TEST-BASED
ASSESSMENTED USING THE
CLASSIFICATION.
-- ASSESSMENT USING THE
CLASSIFICATION.
AND THIS IS A PLOT AND IF WE PUT
TOGETHER THE FUNCTION TASKS AND
CORRELATE THAT WITH THE
PSYCHOPATHOLOGY MEASURES THEY
CLUSTER DIFFERENTLY.
THEY'RE NOT CLUSTERING TOGETHER.
SO THIS REALLY TELLS US THIS IS
CAPTURING INFORMATION
DIFFERENTLY.
IT'S NOT THE SAME SOURCE OF
VARIANTS AND THERE'S A LOT OF
INFORMATION WE CAN EXPLORE ALSO
FROM THE CLINICAL STANDPOINT.
SO WE HAVE BEEN USING THE SAME
APPROACH OF USING THE DERIVED
THRESHOLDS AT THE LEVEL OF THE
TASK ADJUSTING FOR SEX AND AGE
AND DEFINING DIFFERENT
PERFORMANCES AND UNDERSTAND HOW
TO GENERATE GROUPS USING DATA
DRIVEN METHODS THAT ARE IMPAIRED
IN SHOWING THAT THOSE
PARTICIPANTS THAT FULFILLED THIS
PATTERN HAVE A LOT OF IMPAIRMENT
IN THEIR LIVES.
THIS IS GOING TO THE VALIDITY
AND THEY HAVE FRIENDSHIP
IMPAIRMENT AND SCHOOL IMPAIRMENT
AND NOT ONLY IN THE
QUESTIONNAIRE DATA BUT REAL-LIFE
DATA AND WHAT'S THE LEVEL OF
LITERACY AS AN EXAMPLE.
WE SHOWED THOSE GROUPS ALSO HAVE
DECREASED BRAIN THICKNESS IN
CORRECTING IN TIME POINTS AND AN
ASSOCIATION IN STRUCTURES.
I'M GOING TO GO TO THE FINISH OF
THAT AND BEYOND THE IMPACT ELLEN
HAS HAD IN MY LIFE OVER ALL AND
OVER ALL THE NIH TEAM AND FAMILY
AND IT WAS A TRANSITION POINT TO
MY CAREER EVERY TIME I NEED HELP
I CALL ELLEN AND DANNY TO HELP
AND I HAD BEEN THROUGH DIFFERENT
THINGS.
AND IN ALL OF THOSE CRITICAL
MOMENTS I CAN REALLY COUNT WITH
SOMEONE THAT CAN GUIDE ME IN MY
THINKING.
ONE OF THE DIFFERENT THINGS I
HAVE DONE WITH MY CAREER AT SOME
POINT I WANTED TO COME AGAIN
FROM A LOW AND MIDDLE INCOME
COUNTRY AND DO WORK WITH THE
SYSTEM AND TRY TO DELIVER
SERVICES TO CHILDREN MORE AND
HOW CAN I HELP FROM AN ACADEMIC
STANDPOINT AND TO BE HONEST WITH
YOU, I WAS DIRECTOR OF THE
HEALTH FACILITY FOR TWO YEARS
WHEN I WAS STILL PART OF FACULTY
OF THE UNIVERSITY AND AT THE
BEGINNING I THOUGHT, OH, I'M
GOING TO HELP SO MUCH BECAUSE
THERE'S SCIENTIFIC BACKGROUND
AND IT'S GOING TO BE SO
IMPORTANT AND TO BE HONEST I
LEARNED SO MUCH AND A LOT OF THE
THINGS THAT I NEEDED TO BE FOR
THE SYSTEM TO BE EFFECTIVE
REQUIRED LEARNING ON MY END AND
UNDERSTANDING OF THE PEOPLE THAT
HAD BEEN THERE FOR 30 YEARS HAD
A LOT OF THE ANSWERS BUT ONE
THING THAT REALLY MADE A
DIFFERENCE IS THE SCIENTIFIC
THINKING.
IS THERE A WAY TO APPROACH A
PROBLEM AND A WAY TO PUT THINGS
TOGETHER AND THAT'S SOMETHING
MENTORSHIP IS A KEY THING IS HOW
YOU APPROACH AN IDEA AND HOW AU
APPROACH AND HOW YOU THINK ABOUT
THINGS NOT ONLY SCIENTIFIC
PROBLEMS BUT ABOUT PROBLEMS IN A
MORE GENERAL SENSE IN LIFE.
I HAD BEEN A BENEFICIARY OF
ELLEN'S MENTORSHIP AND I'M
GRATEFUL FOR THAT.
THESE ARE SOME OF THE THINGS
WE'VE DONE IN THE CITY.
I'M PROUD OF THE WORK WE'VE DONE
THERE AND CREATED A HUMOROUS NEW
SERVICE AND IMPLEMENTING
ELECTRONIC HEALTH RECORD AND
QUALITATIVE CARE ASSESSMENT THAT
WAS DIFFERENT AND THAT ALLOWED
ME TO TRANSITION TO NEW YORK
CITY AND I HAVE BEEN LIVING IN
NEW YORK CITY THE PAST YEAR AND
A HALF AND I COORDINATE TWO BIG
PROGRAMS AND THERE'S DIFFICULT
PERSONAL TIMES THROUGH MY LIFE
AND SHE WAS ALWAYS THERE TO GIVE
SUPPORT.
I'D LIKE TO FINISH THANKING YOU,
ELLEN.
YOU HAVE BEEN IMPORTANT IN MY
CAREER AND HAVE BEEN A MENTOR
AND FRIEND MULTIPLE TIMES AND
COMING HERE TO NIH AS YOU AN
IMPORTANT POINT IN MY CAREER
TRAJECTORY.
I'M GRATEFUL TO BE HERE
REPRESENTING SO MANY MENTEES AND
THE IMPACT THE INSTITUTE HAS IN
OTHER PARTS OF THE WORLD.
SO I WOULD ALSO LIKE TO TAKE THE
OPPORTUNITY TO THANK OUR
COLLABORATORS AND I SEE
KATHERINA AND MELISSA AND
MONIQUE AND SO MANY OTHERS FROM
ALL PARTS OF THE WORLD.
ALL THE RESEARCH TEAM THAT DID
MOST THE HEAVY LIFTING SO THANK
YOU FOR THE ATTENTION.
DANNY IS ASKING FOR PEOPLE TO BE
BACK AT 2:30.
I'M GOING TO CALL US TO ORDER
AND START IN ABOUT A MINUTE IN
EVERYONE CAN FIND THEIR SEATS.
SO THE NEXT SPEAKER IS DR. WAN
LING TSENG AN ASSISTANT
PROFESSOR AT THE YALE SCHOOL OF
MEDICINE AND CHAIR OF THE CULL
CULTURAL CONSORTIUM ON
IRRITABILITY.
IT'S WONDERFUL TO HAVE WAN LING
TO COME BACK AND WE HAVE SO MANY
FAVORITE CHILDS AND DEFINITELY A
RETURNING FAVORITE CHILDREN.
HIS BACKGROUND IS SIMILAR TO A
LOT OF PEOPLE IN THE GROUPS.
ONE THING UNIQUE ABOUT WAN LING
IS THE CAME TO THE GROUP AS A
DEVELOPMENTAL PSYCHOLOGIST AND
ONE THING ABOUT ELLEN IS THEY
COME FROM ALL DIFFERENT
BACKGROUNDS AND FIELDS AND
THERE'S A NUMBER OF PEOPLE WHO
AS YOU HEARD JULIA TALK ABOUT
HAVE TAUGHT US HERE WITH OUR
FOCUS ON CLINICAL QUESTIONS AS
MUCH AS WE TAUGHT THEM AND I SEE
ASHLEY SMITH DEVELOPMENT
PSYCHOLOGIST AND SOCIAL
PSYCHOLOGIST, AND WAN LING IS A
WONDERFUL REPRESENTATIVE OF SO
MANY GREAT THINGS THEY BROUGHT
TO TEACH US ALL.
>> IT'S MY PLEASURE TO TALK
ABOUT MY CURRENT WORK LOOKING AT
MY AND LOOK AT IRRITABILITY FROM
MULTIPLE LEVELS OF ANALYSIS.
AS I GO THROUGH MY TALK, I THINK
HOPEFULLY IT WILL BECOME OBVIOUS
TO YOU HOW MUCH ELLEN'S WORK AND
MY TIME AT THE NIMHD WITH ELLEN
HAS INFLUENCED MY THINKING AND
RESEARCH PROGRAM.
I WANT TO TAKE YOU THROUGH MY
RESEARCH JOURNEY ON IRRITAB
IRRITABILITY.
MY PASSION FOR WORKING WITH
CHILDREN AND ADOLESCENTS WAS
STARTED WHEN I WAS A CAMP
COUNSELOR EVERY SUMMER IN
COLLEGE IN TAIWAN UNIVERSITY AND
I REMEMBER IT WAS SPECIFICALLY
DESIGN FOR KIDS WHO ARE
UNAFFECTED AND SIBLING AND WHO
HAVE SIBLING WHO HAVE EITHER
MENTAL HEALTH CONDITIONS OR AND
OFTEN TIMES THE UNAFFECTED
SIBLINGS ARE NEGLECTED AND NOT
PAYING MUCH ATTENTION BECAUSE OF
THE SICK CHILD IN THE FAMILY.
WE WANTED TO HAVE A SUMMARY CAMP
DEVOTED TO THE SIBLING TO MAKE
THEM FEEL SPECIAL AND CARED FOR
AND THOUGH THEY WERE UNAFFECTED
MANY OF THEM STRUGGLE WITH
EMOTIONAL AND BEHAVIORAL
PROBLEMS.
MANY FELT THEY WERE NOT GETTING
SUPPORT AND LOVE IN THE FAMILY.
IT WAS DURING A TIME WHERE I
WANTED A CAREER WHERE I WORK
WITH KIDS AND FAMILIES.
SO AFTER COLLEGE, AND I WAS
HIRED IN THE ASSISTANT POSITION
AND WANTED MORE RESEARCH
EXPERIENCE ESPECIALLY IN
DEVELOPMENT PSYCHOPATHOLOGY AND
BEFORE I GET MY DEGREE IN
DEVELOPMENTAL PSYCHOPATHOLOGY
AND I WAS INVOLVED IN MANY
CLINICAL TRIALS AS WELL AS
EPIDEMIOLOGICAL RESEARCH AND
WORKING WITH KIDS WITH NIMHD AND
OPPOSITIONAL DEFIANT DISORDER.
THIS IS HOW MY INTEREST IN THIS
AREA IN ADHD AND ODD STARTED.
THEN I WENT ON TO COMPLETE MY
Ph.D. AT THE UNIVERSITY OF
MINNESOTA AT THE INSTITUTE OF
CHILD DEVELOPMENT AND AT THE
TIME I WAS FOCUSSING ON
[TECHNICAL DIFFICULTIES]
AND I FOCUSSED ON THE EXTERNAL
SIDE OF THINGS AND THE MORE
OUTWARD, MORE OBSERVABLE
BEHAVIORS SUCH AS HYPERACTIVITY
AND IMPULSIVITY AND AGGRESSION.
LITTLE DID I KNOW UNTIL CAME TO
WORK HERE THOSE BEHAVIORS HAVE
AN UNDERLYING MOOD COMPONENT.
THAT'S ONE OF THE MANY MOMENT I
HAD IN MOOD REGULATION.
I DIDN'T DURING MY Ph.D. AND
PRIOR UNDERGRAD EXPERIENCE AND
NOT LOOKING AT THE BRAIN IS A
MISSING PIECE OF THE PUZZLE AND
CAME TO NIMHD AND ELLEN TOOK A
CHANCE ON ME GIVEN I HAD NO
PRIOR FMRI EXPERIENCE OR
NEUROIMAGING EXPERIENCE AND I
ALSO DOUBTING WHY WOULD ELLEN BE
INTERESTED IN ME IN ADHD AND
AGGRESSION WHICH IS NOTHING
ABOUT MOOD IRRITABILITY AND
AGGRESSION AND TOLD ME YOU'RE
THE TYPE OF PERSON WE'RE LOOKING
FOR BECAUSE OF YOUR BACKGROUND
IN ADHD AND AGGRESSION AND
QUANTITATIVE SKILL.
I HAVE NO DOUBT YOU CAN PICK
NEUROIMAGING AND FMRI IN NO TIME
SO I'M GRATEFUL ELLEN TOOK A
CHANCE ON ME AND I STILL
REMEMBER THE DAY SHE CALLED ME
TO OFFER ME THE JOB AND WAS SO
EXCITED TO HEAR FROM HER AND WAS
LIKE WE WOULD LIKE TO OFFER YOU
A POSTDOC POSITION TO COME WORK
WITH US AND I WAS LIKE, YES,
YES, I'LL BE THERE.
I'M GOING TO TAKE THE JOB OFFER
RIGHT AWAY AND SHE STOPPED ME
AND SLOWED ME DOWN AND WAS LIKE,
NO, TAKE YOUR TIME.
DON'T GET BACK TO ME IN THIS
MOMENT.
TAKE A FEW DAYS TO THINK OF IT
AND TALK TO YOUR FAMILY AND YOUR
SIGNIFICANT OTHERS ABOUT IT
BEFORE YOU MAKE A DECISION.
I REMEMBER IT'S ONE OF THE MANY
TEACHING MOMENTS I HAD WITH HER
AND WOULD GIVE ME ADVICE OR
GUIDANCE IN TERMS OF HOW TO
NAVIGATE VARIOUS SITUATIONS.
SO DURING MY TIME AS A POSTDOC
HERE AT NIMHD IS WHEN I GAINED
EXPERIENCE IN FMRI RESEARCH AND
KIDS WITH BIPOLAR DISORDERS AND
FOCUSSING ON SEVER IRRITABILITY
AND SINCE 2019 I'VE BEEN A
FACULTY MEMBER AT YALE STUDYING
IRRITABILITY.
MY LAB IS EFFECTIVE YOUTH LAB.
AND THANKS TO MELISSA WHO HELPED
ME BRAIN STORM THE LAB NAME -- I
OFTEN GET COMPLIMENTS ON THE LAB
NAME.
I'M THE P.I. OF THE LAB OF THE
YAY LAB AND I WILL JUST
HIGHLIGHT THREE LINES OF MY
RESEARCH PROGRAM BUT FOR TODAY,
I'M ONLY GOING TO TALK ABOUT THE
SECOND AND THIRD LINE.
SO GIVEN MY BACKGROUND IN
DEVELOPMENT PSYCHOLOGIY AND LOO
AT THE DEVELOPMENT TRAJECTORIES
AS WELL AS CHANGES IN SYMPTOMS
ESPECIALLY IRRITABILITY I'M
GOING TO FOCUS ON MY RESEARCH ON
BRAIN MECHANISMS OF IRRITABILITY
AND A LOT OF THIS STEMS FROM MY
WORK THAT I CONDUCTED WHEN I WAS
IN ELLEN'S LAB AND THAT
CONTINUED TO INFLUENCE MY
THINKING IN TERMS OF PROBING THE
MECHANISMS OF BRAIN IRRITABILITY
IN MY WORK.
THE THIRD LINE OF RESEARCH I'M
GOING TO TALK ABOUT TODAY THAT
I'M GOING HIGHLIGHT TODAY IS THE
RESEARCH LOOKING INTO THE
ENVIRONMENTAL EFFECT VIA SOCIAL
ENVIRONMENT SUCH AS
CULTURAL-SOCIO FACTOR AND FAMILY
FACTORS AND PHYSICAL ENVIRONMENT
LOOKING AT POLLUTANTS AND
CHEMICALS AS WELL AS CRIME AND
HOW THEY IMPACT IRRITABILITY AND
BRAIN DEVELOPMENT.
SO ULTIMATELY THE GOAL OF MY
RESEARCH PROGRAM IS TO BE ABLE
TO LEVERAGE INFORMATION FROM
MULTIPLE LEVELS OF ANALYSIS
INCLUDING THE BRAIN AND PHYSICAL
ENVIRONMENT AND SOCIAL AND
CULTURAL FACTORS TO BE ABLE TO
IDENTIFY THE MECHANISMS AND
PREDICTORS OF CHILDHOOD
IRRITABILITY AND SO WE CAN
BETTER DESIGN EVIDENCE-BASED
PREVENTION AND INTERVENTION TO
ALLEVIATE AND WE'LL TALK ABOUT
THE BRAIN MECHANISM OF
IRRITABILITY.
IN THIS LINE OF WORK WHERE HE
USE A LOT OF PARADIGMS DESIGN TO
FRUSTRATE KIDS TO OBSERVE THEIR
BEHAVIOR AND SEE HOW THE
PHYSIO
PHYSIOLOGY.
FRUSTRATION IS A NORMATIVE
EMOTIONAL AND BEHAVIORAL
RESPONSE TO BLOCKED GOAL
ATTAINMENT.
THIS IS COLLECTED ABOUT MY FOLKS
HERE AND FRUSTRATION SAY SEB
TRAL NETWORK OF IRRITABILITY AND
FEELING CROUCHY AND HAVING MOOD
CHANGES AND FEELING WORRIED.
GOING BACK TO FRUSTRATION BEING
THE EMOTIONAL RESPONSE TO BLOCK
GOAL ATTAINMENT.
THE PHENOMENON OF NOT GETTING
THE THINGS THAT YOU WANT OR NOT
GETTING THE THINGS YOU'RE EXPECT
ING THIS CONSTRUCT IN THE DOMAIN
THAT INSPIRED OUR WORK STEMS
FROM THIS ANIMAL WORK ACROSS
SPECIES CONSTRUCT WHERE IT WAS
FIRST DEMONSTRATED IN RODENTS
WHERE YOU CAN CHANGE THE REWARD
SCHEJ AND TOWARDS THE AND THE
EXPECTED REWARD IS OMITTED IS
WHEN YOU SEE THE RODENTS AND
ANIMALS START GETTING FRAETED
MEANING THAT THEY SHOW MORE
INCREASED MOTOR ACTIVITIES AS
WELL AS INCREASED AGGRESSION
WHICH IS PARALLEL TO THE TEMPER
OUTBURSTS WE SEE IN IRRITABLE
KIDS.
WE CAN FRUSTRATE KIDS OR
INDIVIDUALS IN THE LABORATORY
SETTING IN THE CLINIC AS WELL AS
IN THE SCANNER TO INDUCE
FRUSTRATION WE'VE DONE THIS IN
THE PAST USING MANY PARADIGMS IN
ELLEN'S LAB AND TALK ABOUT
STUDIES WITH SUCH PARADIGMS IN
HUMAN ESPECIALLY IN CHILDREN AND
ADOLESCENTS AND SEE HOW WE
FRUSTRATE THEM AND MEASURE THEIR
BRAIN ACTIVITIES AND HOW WE
RELATE TO THEIR SYMPTOMS IN REAL
LIFE.
YOU CAN ALSO INDUCE FRUSTRATION
IN SUCH A WAY YOU MEASURE
RESTING STATE OR TAKE OTHER
PHYSIOLOGICAL MEASURES BEFORE
THE FRUSTRATION INDUCTION AND
MEASURE IT DURING THE
FRUSTRATION INDUCTION AND THEN
AFTER THE FRUSTRATION INDUCTION
INTO LOOK AT THE RECOVERY PERIOD
AND SEE HOW PATH YO --
PSYCHOPATHOLOGY CHANGES WITH
FRUSTRATION.
AND THE PROJECT INITIATED WITH
ELLEN AND WAN LING IN THE
AUDIENCE AND TRYING TO DO
CROSS-SPECIES WORK IN HUMANS AS
WELL AS IN MICE TO BE ABLE TO
PROBE ON THE UNDERLYING NEURAL
CIRCUIT OF FRUSTRATION AND THEN
HOME ONCE WE IDENTIFY THE COMMON
NEURAL CIRCUIT WE CAN USE THE
ANIMAL WORK BECAUSE THERE'S SO
MUCH MORE YOU CAN DO IN A MORE
INVASIVE WAY.
AND WE HOPE TO BE ABLE TO
MANIPULATE THE NEURAL CIRCUITS
IN ANIMAL AND USE THE KNOWLEDGE
TO FIND TRANSLATIONAL
INTERVENTION WORK WHERE WE USE
TMS TO SORT OF CHANGE THE
CIRCUITS IN HUMANS AND HOPE THAT
IT WILL LEAD TO DOWN STREAM
BEHAVIORAL CHANGES.
AND THIS IS ONE OF THE GREAT
EXAMPLES WHERE ELLEN IS
TREMENDOUS AND AMAZING MENTOR
BUT ALSO PROVIDES GREAT
SPONSORSHIP WHERE SHE CONNECTS
MENTEES TO MANY DIFFERENT
OPPORTUNITIES AND INTRODUCE
MENTEES TO COLLABORATORS AND
OTHER INVESTIGATORS TO EXPAND
THE MENTEES REPERTOIRE OR
EXPERTISE.
SO, IN THE NEXT FEW SLIDES I'LL
TALK ABOUT TWO STUDIES WE
CONDUCTED USING AT THE
MECHANISMS OF IRRITABILITY.
THIS WORK IS PUBLISHED IN
AMERICAN JOURNAL OF PSYCHIATRY
BACK IN 2019 AND THIS IS THE
MAIN PROJECT THAT I WAS LEADING
DURING MY TIME AT A POSTDOC IN
ELLEN'S LAB AND WHERE WE HAVE
195 KIDS IMAGING FMRI DATA AND
THESE ARE KIDS THAT THIS IS A
TRANSDIAGNOSTIC SAMPLE MEANING
SOME OF THE KIDS HAVE DIAGNOSIS
BUT OTHER KIDS DO NOT AND ALL
THE KIDS WHO HAVE DIAGNOSIS THEY
COULD HAVE AD Ph.D. OR DMDD,
ANXIETY DISORDER, ETCETERA.
WE'RE LOOKING AT IRRITABILITY
ACROSS REGARDLESS OF DIAGNOSIS.
ALL THE KIDS WHO WENT THROUGH
FMRI SCAN WHERE THEY HAVE TO
COMPLETE THE TASK AN
ATTENTION-SHIFTING TASK DESIGN
TO FRUSTRATE THEM BY GIVING THEM
DIRECT FEEDBACK.
WE FOUND AND FIRST CONDITIONED
THEM TO EXPECT FEEDBACK AND
GRADUALLY INTRODUCING FEEDBACK.
WE FOUND IF FOCUS ON THE SCATTER
PLOT ON THE LEFT AND THE HIGHER
IRRITABILITY THE GREATER THEIR
ACTIVATIONS IN THE FRONTAL
REGIONS THEY SHOW ESPECIALLY
FOLLOWING FRUSTRATION AND WE SEE
THIS IN SINGULAR GYRUS AND THE
PREFRONTAL CORTEX AND STRIATUM
NOT SHOWN HERE.
THIS INCREASE FRONTAL STRIATAL
ACTIVATION CHARACTERIZED IN
THESE KIDS CAN WITH HIGH LEVELS
OF IRRITABILITY THE STRIATAL
ACTIVATION IS PARTICULARLY
PROFOUND IB KIDS WITH HIGH
LEVELS OF IRRITABILITY AS WELL
AS YOUNG KIDS 8 TO 18.
PRE-ADOLESCENT IS WHEN WE SEE
THIS ACTIVATION BEING MOST
PRONOUNCED.
AND WANTED TO SEE WHETHER WE CAN
LOOK AT FUNCTIONAL CONNECTOME
FROM THE WHOLE BRAIN AND SEE
WHETHER FUNCTIONAL CONNECTOME
CARRIES IMPORTANT NEURAL SIGNALS
THAT ALLOW US TO IDENTIFY WHICH
KID IS IRRITABLE AND NOT
IRRITABLE.
THIS IS PART OF THE FUNDING
DURING MY TIME HERE AND
CURRENTLY ANALYZING THE DATA I
COLLEC
COLLECTED DATA TO LOOK ACROSS
DIAGNOSTIC BOUNDARIES.
THIS IS ALSO DATA COLLECTED
DURING MY TIME WITH ELLEN BUT WE
DIDN'T START THE DATA ANALYSIS
LOOKING AT THE FUNCTIONAL
CONNECTIVITY UNTIL I MOVED TO
AND WITH THE HELP AND
COLLABORATIONS WITH SOME PEOPLE
IN THE DEPARTMENT OF BIOMEDICAL
ENGINEERING AT YALE WE WERE ABLE
TO DO PREDICTIVE MACHINE
LEARNING WORK.
WHAT WE FOUND IS THAT THE
FUNCTIONAL CONNECTIVITY AND
FORMATION DEPENDING ON WHICH
BRAIN STATE YOU GATHER THE DATA
OF FUNCTIONAL CONNECTIVITY THE
BRAIN STATE MATTERS.
WE FOUND FUNCTIONAL CONNECTOME
ONLY WHEN PARTICIPANTS ARE
FEELING FRUSTRATED BUT NOT WHEN
THEY'RE NOT.
IT CONTAINS THE INFORMATION THAT
ALLOWS US TO PREDICT
IRRITABILITY ESPECIALLY IN THIS
CASE IT'S THE CHILD REPORTED
IRRITABILITY.
IF YOU FEED IT INTO THE
ALGORITHM YOU CAN ASK THE
MACHINE TO COME UP THE SCORE AND
PLOT IT AGAINST THEIR
SELF-REPORTED IRRITABILITY LEVEL
AND WE WERE ABLE TO OBTAIN A
SIGNIFICANT PREDICTION I'M NOT
SURE WHETHER YOU CAN SEE BUT IF
WE TRY TO GET MORE INTERPRETABLE
VISUAL OF THE PREDICTED NETWORK
WHAT YOU CAN SEE HERE, THIS IS
THE DIFFERENT BRAIN REGION AND
DIFFERENT NODES IN THE
PREFRONTAL CORTEX AND THERE ARE
CONNECTIONS BETWEEN PRE FRONTAL
CORTEX TO TEMPORAL AND
SUBCORTICAL REGIONS AND PARIETAL
REGIONS TO THE OTHER SIDE OF
PARIETAL REGIONS AND CONNECTING
TO SUBCORTICAL REGIONS AND
ANOTHER WAY OF PLOTTING WHERE
THE PREDICTIVE NETWORKS ARE.
THE MOST PREDICTIVE ONES ARE
WITHIN THE MOTOR NETWORK AS WELL
AS SUBCORTICAL NETWORK AND
BETWEEN MOTOR AND SALIENCE AND
SUBCORTICAL NETWORK.
TO BRIEFLY SUMMARIZE, WHAT WE
FOUND THE NEURAL NETWORKS
SUPPORTING MOTOR FUNCTION ACTION
PREPARATION ATTENTION CONTROL
AND INTEGRATION OF EMOTIONAL AND
COGNITIVE FORMATION SEEM TO BE
THE MOST PREDICTIVE OF
IRRITABILITY.
I WANTED TO SAY AFTER
CONTROLLING FOR AGE, SEX AND
MOTION AND MEDICATIONS AND
CO-OCCURRING SYMPTOMS SUCH AS
ADHD AND ANXIETY SYMPTOMS SO THE
FINDINGS HERE ARE NOT DRIVEN BY
THOSE CONFOUNDING S --
CONFOUNDING S.
AND IN MY CURRENT WORK I'M
TAKING THIS ONE STEP FURTHER
INSTEAD OF PREDICTING JUST ONE
TIME POINT IRRITABILITY OF
SYMPTOMS AT A SINGLE SNAPSHOT
COLLECTING DATA AND TRYING TO
MAP OUT THE TRAJECTORY OF
IRRITABILITY AND HOPING TO
LEVERAGE THE BRAIN DATA AT
BASELINE TO IDENTIFY SIGNATURES
THAT ALLOW US TO PREDICT WHICH
PARTICIPANT IS GOING TO GO ON TO
HAVE THIS CHRONIC AND LATE
IRRITABILITY TRAJECTORY BECAUSE
THOSE ARE GOING TO BE THE KIDS
MOST AT RISK FOR LATER ANXIETY,
DEPRESSION AND SUICIDALITY.
OKAY.
I'LL JUMP INTO LOOKING AT THE
ENVIRONMENTAL EFFECT OF
IRRITABILITY AND ONE OF THE
ENVIRONMENTAL AFFECTS WE'RE
INTERESTED IN IS THE SOCIO
CULTURAL FACTOR.
THIS WAS INITIATED BY A
CONVERSATION THAT ELLEN AND I
HAD AND I WANTED TO LOOK AT
AREAS OF RESEARCH UNDER STUDIED
AND HAVE NOT BEEN EXPLORED
BEFORE WHICH IS THE CULTURAL
VARIATIONS IN IRRITABILITY.
IN TERMS OF HOW THEY ARE
PRESENTED AND REPORTED AND HOW
THEY MANIFEST, HOW DO KIDS AND
PARENTS EXPERIENCE IRRITABILITY.
ARE THE NORMS DIFFERENT ACROSS
DIFFERENT CULTURE AND BY CULTURE
I ALSO MEAN IT WOULD BE WITHIN
THE U.S. AND LOOKING AT ACROSS
CULTURES AND RACE AND ETHNICITY.
WE START THE CONVERSATION IN
TERMS OF HOW THERE NEEDS TO BE A
NEED TO LOOK AT CULTURAL
VARIATION.
THAT'S WHEN WE ESTABLISHED THE
CROSS-CULTURAL CONSORTIUM ON
IRRITABILITY AND ELLEN AND A
CO-CHAIRED AND LAUNCHED IN MAY
OF 2020 AND HAVE 140 RESEARCHERS
FROM ACROSS THE GLOBE AND
COUNTRIES AND WHERE MEMBERS ARE
FROM.
WE STILL LACK REPRESENTATIONS IN
CONTINENTS AND COUNTRIES AND IF
YOU KNOW ANYBODY INTERESTED IN
IRRITABILITY HAVE THEM REACH OUT
TO US.
THIS IS MEANT TO BE A RESEARCH
NETWORK TO PROVIDE A
COLLABORATIVE STRUCTURE SO THAT
WE CAN SHARE DATA, PULL ACROSS
MULTIPLE DATA SET THAT HAS BEEN
COLLECTED AND TO BE ABLE TO LOOK
AT THE CULTURAL SIMILARITY AND
DIFFERENCES IN HOW IRRITABILITY
IS CONCEPTUALIZED AND REPORT AND
WITH NORMS AND CLINICAL
THRESHOLDS AND WHETHER PARENTS
RESPONSES AND RESPONSE TO TEMPER
TANTRUMS VARY IN HOW THEY'RE
DEALT WITH BY CULTURE AND WE'RE
INTERESTED IN SEEING HOW
SUICIDALITY WHETHER THE
CORRELATES ARE SIMILAR OR
DIFFERENT ACROSS CULTURE.
THIS IS JUST TO GIVE YOU SORT OF
AN OVERVIEW OF SOME OF THE
WORKING GROUPS WE CURRENTLY HAVE
SO BESIDES STANDING STEERING
COMMITTEE WHICH HAS ABOUT 15
MEMBERS AND MEET MONTHLY AND WE
TRY TO FACILITATE MEASURES AND
LOOK AT FRAMEWORK OF PSYCHE
PATHOLOGIES AND DSM AND OTHERS
AND WE HAVE COMMUNITY ENGAGEMENT
SUPPORTING GROUP WHERE WE LOOK
AT COMMUNITY-BASED PARTICIPATORY
RESEARCH TO INVOLVE AFFECTED
KIDS AND FAMILIES IN THE DESIGN
AND FOR THOSE INTERESTED IN
LEARNING MORE YOU CAN USE THIS
URL TO GO TO OUR WEBSITE.
IN THE INTEREST OF TIME, I'M
GOING TO SKIP SOME OF MY CURRENT
WORK ON TRYING TO LOOK AT OTHER
ASPECTS OF ENVIRONMENTAL
INFLUENCE ON IRRITABILITY SO
THIS IS PERINATAL FACTORS AND
WE'RE ALSO INTERESTED IN USING
GEOSPATIAL MODELLING AND
PERSONALIZED EXPOSURE
ASSESSMENTS COLLECTING AIR
SAMPLES, DRINKING WATER AND DUST
AND BLOOD SAMPLES TO LOOK AT
EXPOSURE TO CHEMICALS AND HOW
THAT IMPACTED IRRITABILITY.
I WANT TO END MY TALK BY
BRINGING THIS SLIDE BACK SO THAT
MY SORT OF SIMILAR SENTIMENT
GIOVANNI HAS SAID.
ELLEN REALLY CHANGE MID CAREER
TRAJECTORY AND A LOT OF MY
CURRENT WORK AND PLANNING FOR
FUTURE WORK IS IMPACTED BY THE
WORK THAT I EMBARKED ON AS A
POSTDOC WITH EL JLEN AND THE
CONTINUED CONVERSATIONS AND
THOSE HAVE BEEN SOME OF MY
FAVORITE MOMENTS WHEN I THINK OF
OUR TIME TOGETHER IS TO BE ABLE
TO TALK AND YOU HAVE BEEN A
WONDERFUL MENTOR AND I'VE HAD SO
MANY GREAT FEMALE ROLE MODELS
AND I'M INCREDIBLY LUCKY TO HAVE
SO MANY GREAT FEMALE ROLE MODELS
BUT YOU'RE TRULY THE ONE THAT'S
HAD A GREAT IMPACT ON MY LIFE
NOT JUST IN THE CAREER BUT
PERSONAL LIFE.
YOU HAVE SEEN MY UPS AND DOWNS
AND I'VE HAD A LOT OF PERSONAL
LIFE STRUGGLES THAT SOMETIMES
MAKE ME DOUBT IF I STILL HAVE A
STAY IN ACADEMIA AND CAREER AND
YOU ARE ALWAYS THE ONE TO
SUPPORT ME AND KEEP PUSHING ME
FORWARD I CAN'T SAY THANK YOU
ENOUGH FOR THE KINDNESS AND
SUPPORT YOU HAVE SHOWN ME.
THANK YOU.
>> WE'RE GOING TO HAVE ONE MORE
TALK AND IT'S A PLEASURE TO
INTRODUCE OUR ARGYRIS STRINGARIS
WILL BE A TAPE TALKED.
PROFESSOR OF CHILD AND
ADOLESCENT PSYCHIATRY AT
UNIVERSITY COLLEGE LONDON ALSO
THE PROVOST FOR THE WELL BEING
CHALLENGE AND I'LL BRIEF THING.
WE COULDN'T HAVE PLANNED THIS
BETTER.
HE'S ONE OF THE MOST
ENTHUSIASTIC SCIENCE --
SCIENTISTS AND HE'S BECOME
INCREASINGLY EXCITED ABOUT AN
IDEA AND AS IF IT WOULD BE OKAY
TOE TALK ABOUT THIS IDEA THAT
HE'S EXCITED ABOUT THOUGH IT HAS
NOTHING TO DO WITH WHAT'S IN THE
PROGRAM.
AND CAPTURED THE ENTHUSIASM AND
PASSION THAT THE WORK ARGYRIS
BRINGS AND SHARED NOT ONLY WITH
ME AND ALL THE SPEAKERS BUT
PARTICULARLY WITH ELLEN I
THOUGHT IT WAS A BEAUTIFUL
TESTAMENT TO THE PASSION ELLEN
HAS BROUGHT TO OUR COLLABORATIVE
WORK AND THE WORK SHE'S DONE.
WITH THAT I'LL ASK PEOPLE TO
START THE PRESENTATION.
IT'S A GREAT HONOR FOR ME TO BE
PRESENTING TO YOU HERE.
PED TO TALK ABOUT ELLEN'S
CONTRIBUTIONS TO OUR FIELD.
THE TIME OF MY TALK IS
FUNDAMENTAL FLAWS IN DEPRESSIVE
TREATMENT AND IT'S AN HONOR TO
TALK ABOUT DR. ELLEN LIEBENLUFT.
I'M ARGYRIS STRINGARIS
UNIVERSITY OF PSYCHIATRY AT THE
COLLEGE OF LONDON AND UNIVERSITY
OF ATHENS.
MY TALK IS GOING TO GO THROUGH
THE IMPORTANCE OF ADOLESCENT
DEPRESSION I'M GOING TO TALK
ABOUT ITS TREATMENT.
I'LL TALK ABOUT CONTROL
CONDITIONS AND TALK ABOUT
ADOLESCENT DEPRESSION AND TALK
ABOUT DUBIOUS CONTROL GROUPS OF
PSYCHO THERAPY AND UNDERSTANDING
HUMAN EXPECTATIONS IN THE
PSYCHIATRIC AND PSYCHOLOGICAL
TREATMENTS.
I WANT TO THANK ELLEN, WHO HAS
BEEN MY MENTOR IN THE PAST.
AND THIS IS A PHOTOGRAPH FROM
MANY YEARS AGO AS YOU MAY MAKE
OUT THESE ARE VERY HAPPY TIMES.
I'VE LEARNED A LOT FROM ELLEN.
AS YOU ALL KNOW ELLEN GAVE
MEANING TO THE CONCEPT OF
IRRITABILITY AND NOR GENERALLY
NEGATIVE AND AGGRESSIVE MOOD
WHICH HAS PUBLIC HEALTH
IMPLICATIONS AND NEGLECTED.
SHE FUSED COMMON SENSE I WOULD
SAY TO AN EXTRAORDINARY DEBATE
OF PEDIATRIC BIPOLAR AND
EXCESSIVE -- DANGEROUS PHARMACO
THERAPY THAT CAME FROM POWERFUL
PLACES AT THE TIME AND HAD THE
COURAGE TO STAND UP FOR WHAT
MATTERS TO PATIENTS AND THE
PUBLIC.
SHE WROTE WITH AN STRING OF
PEOPLE AND ANOTHER MENTOR OF
MINE WORKED CLOSELY TOGETHER AND
DR. KENNETH TOBIN WHAT HAS DONE
A LOT OF WORK WITH ELLEN'S TEAM
AND KATHERINA'S TEAM AND OTHERS
WHO HAVE WORKED WITH DANNY AND
MYSELF.
THE MANUSCRIPT IS INCISIVE AND
ORGANIZED THOUGHT AND KEEN SENSE
OF HISTORY AND FALLIBILITY WHICH
IS QUITE RARE IN A SCIENTIST
ACTUALLY.
I'M SORRY I CAN'T BE THERE AND
THE REASON HAS TO DO -- WELL,
THERE'S SEVERAL REASONS BUT THE
REASON IS I WAS WORKING FROM A
HOUSE IN D.C. BECAUSE MY WIFE
HAS PROBLEMS WITH HER PAPERWORK
AND I GOT TO THE METRO STATION
AND REALIZED I DIDN'T HAVE MY
WALLET THE DAY OF MY FIRST
MEETING AND ARRIVED IN QUITE A
STATE.
I DO HOPE THAT YOU AND ELLEN
WILL SEE ELLEN AND ELLEN'S KIND
OF INFLUENCE IN THIS TALK.
ONE LESSON IN DEPRESSION IS
IMPORTANT.
THIS IS A CHART FROM THE WORLD
HEALTH ORGANIZATION AND YEARS
LIVED IN DISABILITY IN
ADOLESCENTS.
ON THE LEFT SIDE ON THE Y AXIS
THE BREAK DOWN BY AGE AND
GENDER.
YOU CAN SEE DEPRESSIVE DISORDERS
TOP THE METRIC BY THE W.H.O.
IF YOU EXTEND THE LIST YOU'D SEE
IRON DEFICIENCY AND ANEMIA AND
DIARRHEA AND DEPRESSION TOPS IT
FOR ADOLESCENT GIRLS.
ALSO FOR ADOLESCENT BOYS IT'S
DIFFERENT.
IT'S QUITE AN EXTRAORDINARY
PROBLEM AT THE MOMENT AND IT IS
AROUND THE WORLD ACCORDING TO
THE WORLD HEALTH ORGANIZATION.
WE DON'T QUITE KNOW WHAT
DEPRESSION IS.
WE HAVE SOME IDEAS BUT IT IS
CERTAINLY SOMETHING QUITE
IMPORTANT.
IF WE HAD MORE TIME SLIDES
DEMONSTRATE IT'S QUITE LIKELY
THAT IT'S PREVALENCE HAS BEEN
INCREASING OVER THE LAST DECADE
OR SO CERTAINLY IN MANY PARTS OF
THE WESTERN WORLD.
WE DON'T QUITE KNOW WHY THAT IS
AND WE DON'T HAVE GREAT
TREATMENTS FOR IT.
SO, BEING A CLINICIAN YOU'LL
KNOW OR THE RAW GUIDELINE FOR
DEPRESSION AND THE BEST KNOWN
ONES ARE THE ONES BY THE
NATIONAL INSTITUTE OF CLINICAL
EXCELLENCE IN THE U.K.
IT'S INTERNATIONALLY VERY
INFLUENTIAL AND ACROSS ALL AREAS
OF MEDICINE, REALLY.
AND THERE'S VERY SMART PEOPLE
THAT INVEST A TREMENDOUS AMOUNT
OF RESOURCES BOTH TIME RELATED
AND MONEY ACTUALLY TO TRY TO
RESOLVE ISSUES OF DECISION
MAKING FOR CLINICIANS.
SO THEY'VE COME UP WITH
GUIDELINES FOR DEPRESSION IF YOU
HAVE MILD DEPRESSION YOU SHOULD
DO ONE OF TWO THINGS THERE'S TWO
THINGS FOR ADOLESCENT DEPRESSION
ONE IS COGNITIVE BEHAVIORAL
THERAPY.
AND PSYCHOLOGICAL AND PERSONAL
THERAPY AND THE COMMITTEE CAME
TO THE IDEA UPON REVIEWING THE
EVIDENCE BASED AND META-ANALYSES
AND SAYING THE SAME THING ABOUT
MODERATE TO SEVERE DEPRESSION
AND MAYBE YOU CAN ADD THERAPY
AND IF YOU'RE DEPRESSION IS
UNRESPONSIVE YOU CAN DO
PSYCHOLOGICAL THERAPY MAYBE
WITHOUT MEDICATION.
YOU CAN SEE IT'S GIVEN TO
PSYCHOLOGICAL THERAPY FOR
ADOLESCENT DEPRESSION AND
THERE'S A COMPARISON THAT IS
JUST THERE AND SEEMS VERY
IMPORTANT AND SAYS PSYCHOLOGICAL
THERAPY OUGHT TO BE PREPARED IN
MOST INSTANCES AND MEDICATION
COULD PERHAPS BE PART.
IT'S NOT EXACTLY THE SAME IN THE
AMERICAN ACADEMY OF CHILDHOOD
AND ADOLESCENT SOCIETY FOR CHILD
ADOLESCENT PSYCHIATRIES BUT THEY
DO SAY THAT THERAPY AND OTHERS
HAVE TREATMENT OPTIONS I CAN USE
ONE OR THE OTHER OR BOTH.
THAT'S WHAT THE GUIDELINES SAY
AND THEY'RE INFLUENTIAL AND FIND
THE SAME GUIDELINES IN AUSTRALIA
AND NEW ZEALAND AND THEY'RE
FOLLOWED AND NATIONAL GUIDELINE
CREATED FOR EXAMPLE, IN GERMANY,
PEOPLE FOLLOW THESE IDEAS A LOT
AND THEY ARE CULTURALLY
DEVELOPING THEIR OWN GUIDELINES
BUT THAT'S THE BASIC
INTERNATIONAL CONSENSUS FOR
PSYCHO THERAPY.
AND THERE'S COGNITIVE AND
BEHAVIORAL PSYCHO THERAPY AND
MEDICATION.
ONLY ONE HEAD-TO-HEAD TRIAL
EXISTS IN ADOLESCENT DEPRESSION.
THAT'S THE TREATMENT FOR
ADOLESCENT DEPRESSION STUDY
WHERE ACTUALLY PSYCHO THERAPY
DID NOT DIFFERENTIATE.
IN FACT THE COMPARISONS RELY ON
THE COMPARISON OF THE RESULTS OF
RANDOMIZED TRIALS OF EACH
MODALITY.
MODALITY IS OTHER MEDICATION OR
PSYCHO THERAPY AGAINST EACH
OTHER.
IN OTHER WORDS, THE COMPARISONS
OF COMPARISONS.
AND TYPICALLY COMPARED TO
PLACEBO AND PSYCHO THERAPY IS
COMPARED TO TALK ABOUT WHAT THE
CONTROL CONDITIONS ARE AND THOSE
COMPARISONS ARE COMPARED TO EACH
OTHER.
IF YOU'RE PATIENT OR CAREER YOU
ASK WHICH TREATMENT SHOULD I OR
MY CHILD BE GIVE AND TAKE AND AS
A HEALTH PROFESSIONAL HEALTH
CARE PROFESSIONAL IF YOU'RE A
DOCTOR YOU'D BE TELLING THEM YOU
CAN TAKE TREATMENT A OR B, WE'LL
TAKE A FIRST AND THEN TAKE MAYBE
TREATMENT B MEDICATION
AFTERWARDS.
AND AS A PUBLIC HEALTH OFFICIAL
THERE'S A BIG INFLUENCE IN THE
PROFESSION.
NOW, NOW DEPRESSIVE STUDIES OR
CONTROL THERE'S THE PLACEBO.
WHAT IS THE EFFECT OF MEDICATION
THE EFFECT OF PSYCHO THERAPIES.
THE NUL CONDITIONS THESE ARE
EQUAL AND WHAT IS BEING TESTED.
AND NOTE MEDICATION THAT COME
FROM PSYCHO THERAPY.
AS I SAID, THIS THOUGH REALIZE
ON WHAT IS TECHNICALLY CALLED
THE ASSUMPTION THAT ALL ELSE IS
EQUAL.
EVERYTHING ELSE IS EQUAL.
SO IT RELIES ON THE QUALITY OF
CONTROLS.
BECAUSE IF I WIPE THIS OUT THE
EFFECT OF MEDICATION IS
ESSENTIALLY THE ACTIVE ARM, THE
DRUG, MINUS THE EFFECT THE
PLACEBO, THE MEDICATION CONTROL
HAS.
HERE EFFECT OF PSYCHOLOGICALLY
ACTIVE TREATMENT COGNITIVE
THERAPY MINUS THE CONTROL ARM OF
A PARTICULAR STUDY OR SET OF
STUDIES.
AND FOR THIS TO BE COMPARED,
THIS QUALITY OR NEAR QUALITY
MUST FAULT THE EFFECTIVE
MEDICATION CONTROLS MUST BE
SIMILAR TO THAT OF PSYCHOLOGICAL
CONTROLS.
OTHERWISE IT WOULD BE DIFFICULT
TO ILLUSTRATE THE PROBLEM THINK
ABOUT SOMETHING LIKE
APPENDICITIS.
I'M NOT TRYING TO MAKE AN
ARGUMENT ABOUT THAT NOW WE JUST
NEED TO ABSTRACT.
I JUST WANT TO MAKE MORE
CONCRETE THE PROBLEM AND
ILLUSTRATION AND NOT TALK
CONCRETELY ABOUT APPENDICITIS
AND TWO TREATMENTS, ANTIBIOTICS
TO SURGERY WHICH HAVE NOT BEEN
COMPARED HEAD-TO-HEAD AND LET
THE ANTIBIOTIC IMPROVEMENT RATE
BE 40% ON THE ANTIBIOTICS AND
ONLY 2% ON THE CONTROL CONDITION
WHICH WOULD BE THE PLACEBO PILL
AND IT'S FOR ILLUSTRATION
PURPOSES AND THE IMPROVEMENT
RATE BE 50% OF THE SURGERY AND
SOME SHAM SURGERY WHERE YOU GET
TO THE SCAR.
SO IT'S CLOSE TO 40% AND WOULD
BE LUDICROUS TO CONCLUDE
THEREFORE YOU WOULD BE TELLING
YOUR PATIENT YOU COULD CHOOSE
EITHER.
IT'S OKAY TO GIVE ANTIBIOTICS OR
GO FOR ONE WHEN ONE IS SO MUCH
STRONGER THAN THE OTHER.
THIS IS NOT ADVICE ON WHAT TO
DO, APPENDICITIS IT'S
ADMINISTRATION IN THE FICTIONAL
SET OF STUDIES BUT SEE THE
PROBLEM THAT IS CLEAR IN ONE
CASE THE DIFFERENCE IN CONTROLS
CREATES A VERY ARTIFICIAL AND
IMPOSSIBLE SORT OF SITUATION.
SO, WHAT DO YOU TELL YOUR
PATIENTS THESE ARE EQUALLY GOOD
TREATMENTS?
I DON'T THINK ANYONE SENSIBLE
WOULD SAY THAT GIVEN THESE
NUMBERS.
SO IF THERE'S VARIABILITY IN THE
CONTROL ARMS AND THEY'RE
DIFFERENT, THE QUESTION IS, IS
IT RANDOM?
DOES IT TELL US SOMETHING HOW
TREATMENTS WORK, FOR EXAMPLE,
WHAT ARE PSYCHOLOGICAL
MECHANISMS OF PLACEBO.
WHY WOULD PEOPLE FIND OTHER
CONTROL GROUPS UNFAVORABLE AND
WHAT IS A CONTROL GROUP?
WHAT IS AN APPROPRIATE COUNTER
FACTOR FOR TREATMENT.
THIS GOES TO TREATMENT THAT GOES
WELL BEYOND THE IMMEDIATE
CLINICAL AND PUBLIC HEALTH NEED
AND TOUCH UPON QUESTIONS OF HOW
HUMANS DEAL WITH EXPECTATIONS
AND A MORE GENERAL QUESTION FOR
ME AND OF THE MORE BASIC SCIENCE
SIDE OF THINGS I DO.
SO WE EXTRACTED THE BASELINE AND
STANDARD DEVIATIONS WHERE
AVAILABLE AND AT THE MEAN OF
TIME POINT 1 AT FOLLOW-UP AND
POINT 2 AT BASELINE AND DIVIDE
THAT BY THE SIMPLE POOLED
STANDARD DEVIATION AND WHAT WE
CALL THE STANDARDIZED MEAN
DIFFERENCE OR THE CHANGE SCORE.
WE LOOKED AT TEST CORRELATION
AND DON'T WANT TO BOTHER YOU
WITH THE TECHNICAL STUFF BUT
LOOK AT THE ABSENCE OF THE
CORRELATION COEFFICIENT BETWEEN
TIME POINT 1 AND 2 WHICH IS
SIMULATED SEVERAL DATA SETS AND
AND LOOKED AT AGGRESSION AND THE
TYPICAL MODEL AND THIS
REPRESENTS HETEROGENEITY AND HAS
A STANDARD OF DEVIATION THE
SO-CALLED AND STUDIES DO NOT
JUST VARY BECAUSE OF SAMPLING
BUT BECAUSE THEY COME FROM A
DISTRIBUTION AND CAN VARY ON THE
DISTRIBUTION.
AND ESTIMATE A MODEL WHERE WE
HAVE MEDICATION CONTROLS AND
PSYCHOLOGICALLY ACTIVE
CONDITIONS AND CONTROL AND
MEDICATION CONTROLS AND PLACEBO
AND THE COGNITIVE AND BEHAVIORAL
THERAPY AND VARIOUS CONTROLS
WHICH COULD BE AS USUAL AND LOOK
AT THE STANDARDIZED MEAN
DIFFERENCE CHANGE FOR EACH
LEVEL.
WITH 81 STUDIES IN TOTAL.
PLACEBO WAS A CONTROL CONDITION
AND ATTENTION CONTROL SUCH AS
PSYCHO THERAPY.
THIS IS THE FIRST RESULT I WANT
TO SHOW YOU.
YOU SEE THE STANDARDIZED MEAN
DIFFERENCE FOR MEDICATION
CONTROL AND THE ESTIMATES THE
MORE EFFECTIVE IT IS.
THE MEDICATION CONTROL IS WITHIN
GROUP TRIAL AND ESTIMATE IS
PRETTY EFFECTIVE.
AS IS MEDICATION ACTIVE BY THE
DRUGS AND HALF DIFFERENTIATE
FROM EACH OTHER.
IF YOU COMPARE THIS IT'S NOT
BAD, WELL ABOVE ONE BUT NOT AS
EFFECTIVE AS MEDICATION CONTROL.
THE MOST FASCINATING DIFFERENCE
IS BETWEEN THIS AND PSYCHO
THERAPY CONTROL AND MEDICATION
CONTROL WHICH IS VAST, YOU CAN
SEE THE INTERVALS ARE NOWHERE
NEAR OVERLAPPING LIKE APPLES AND
ORANGES.
AND THE QUALITY CONTROLS
ASSUMPTION DOES NOT HELP.
THE COMPARISONS OF SUBTRACTING
THIS FROM THAT AND COMPARING
WHICH IS TYPICALLY DONE IN
GUIDELINES DOESN'T HOLD AND
DOESN'T HOLD EVEN IF YOU JUST
ESTIMATE STUDIES WITH TREATMENTS
WE HAVE THE ONES THAT ARE FDA
APPROVED AND YOU HAVE A SIMILAR
EFFECT.
THIS IS QUITE PROBLEMATIC
BETWEEN PSYCHO THERAPY AND
MEDICATION CONTROLS AND NOT AS
ACTIVE AS MEDICATION AND IN THE
CONTEXT OF THE TRIALS AND
PERHAPS MORE ACTIVE THAN PSYCHO
THERAPY.
AND THE CONCEPTS OF THE TRIAL
AND NOT SUGGESTING ONE SHOULD GO
OUT AND SAY OR TAKE PLACEBO.
MY MAIN POINT IS THE DIFFERENCE
BETWEEN THIS AND THIS AND THE
INCOMPARABILITY OF THE TWO
DIFFERENCES.
IF YOU ASSESS COEFFICIENT OF THE
DIFFERENCE AS YOU MIGHT EXPECT
THE DIFFERENCE BETWEEN
PSYCHOPATHOLOGY CONTROL AND THE
P VALUE IS EXTREMELY LOW NOW
NOW, AND POORLY MATCHED TYPES OF
GROUPS AND THINGS LIKE AND
INFORMATION WAS MISSING WITH
VARIABLES FOR EXAMPLE IF YOU
HAVE ENOUGH ATTENTION CONTROL
SUCH AS THERAPY HOW MANY HOURS
AND SESSIONS ARE SPENT AND IT'S
HARD TO EVALUATE THAT.
WHAT IS A GOOD CONTROL?
IT SHOULD SERVE AS COUNTER
FACTUAL.
WHAT WOULD AN INDIVIDUAL LIKE
LIKE IF THEY DID NOT RECEIVE
TREATMENT?
THERE SHOULD BE A TRUE VALUE OF
WHAT AN INDIVIDUAL WOULD LOOK
LIKE HAD THEY NOT RECEIVED THE
TREATMENT.
THAT'S REALLY WHAT THE CONTROL
GROUP IS ABOUT.
WE'RE TRYING TO APPROXIMATE AT
LEAST IN MY OPINION THE VALUE OF
THE CONTROL AND A GOOD CONTROL
AND IT'S A FREQUENT CONTROL AND
IT SOMETIMES DOES NOT AMOUNT TO
MUCH AT ALL PARTICULARLY NOW
GIVEN THE OVERCROWDING SUB
SKRIEPGS AND THE MENTAL HEALTH
SERVICES.
SUBSCRIPTION AND MENTAL HEALTH
SERVICES.
AND BASICALLY NOW THE FINDINGS
I'VE SHOWN, THERE'S A SPACE THAT
SHOWS WHEN WE RESTRICT TO THE
FEW STUDIES THAT HAVE THE SAME
INSTRUMENTS THAT'S THE RESULT OF
THE SAME COULD THERE BE MORE
REGRESSION TO THE MEAN OF THE
PSYCHOPATHOLOGY GROUP AND THE
DIFFERENCE IS ALSO SO LARGE IT'S
QUITE HARD TO IMAGINE AT SOME
DIFFERENCE IN ASCERTAINMENT AND
SOME VALUES WOULD MAKE A
DIFFERENCE FOR THE MEAN IS WHAT
I MEAN BY FLUKE VALUES AND WHEN
WE KIND OF MATCH STUDIES WITH
THE SAME BASELINE SEVERITY WE
GET LARGE DIFFERENCES AND TAKE
THE BASELINE VALUES INTO ACCOUNT
AND THE GUIDELINES I THINK NEED
TO CHANGE.
THIS IS WHERE I'M HOPING TO HAVE
SOME -- I WOULD LIKE PEOPLE TO
VERY VISIT WHAT THEY RECOMMEND
ON THE BASIS OF WHAT YOU'VE SEEN
TODAY IT SEEMS VERY PROBLEMATIC
TO BE COMPARING MEDICATION WITH
PSYCHOLOGICAL THERAPY.
AND ASK WHAT WORKS WITH
DEPRESSION AND IT'S A SOBERING
FINDING.
WE CAN POSE MORE RIGOROUS
CONTROLS ON PSYCHO THERAPY AND
NOT SAYING PLACEBO IS THE BEST
THING.
FAR FROM IT BUT IT'S CLEARLY HAS
SEVERAL ADVANTAGES TO WHAT WE'VE
SEEN IN CONTROL GROUPS AND NEED
TO LOOK AT THE UNDER PINNING OF
CONTROL CONDITIONS.
THIS IS SOMETHING WE DO WITH MY
GROUP LOOKING AT EXPECTANCY OF
THINGS AND COST AND HOW PEOPLE
CREATE COUNTER FACTUALS OF
THEY'VE BEEN DOING AND WE SHOULD
LOOK AT THE ETHICAL IMPLICATIONS
OF THE CONTROL GROUP AND WHAT IT
MEANS FOR THEM PEOPLE WHO ENGAGE
WITH THE TREATMENT AND WHAT IT
TELLS THE PUBLIC IS HAPPENING.
I THINK WE'VE DRAWN INSPIRATION
FROM ELLEN'S WORK FOR BIPOLAR
DISORDER AND THE WORK DONE ON
IRRITABILITY SUBSEQUENTLY.
AND TAKE COURAGE FROM IT.
SO IT'S A GREAT LEGACY.
I WANT TO THANK HER FOR THIS.
I'M SORRY I COULDN'T BE THERE TO
ENJOY THIS WITH YOU, ELLEN, BUT
I AM WISHING YOU ALL THE VERY
BEST.
THANK YOU VERY MUCH FOR
EVERYTHING.
THANK YOU ALL FOR YOUR PATIENCE.
>> ALL RIGHT.
SO WE HAVE SAVED THE BEST FOR
LAST.
IT'S A WONDERFUL TREAT TO
WELCOME UP ELLEN AND I WANT TO
THANK REALLY ALL THE SPEAKERS
AND MARYLAND AND KATIE AND I'M
GRATEFUL AND EXCITED TO HEAR
WHAT ELLEN IN HER ROLE OF
CONTINUING TEACHER TO US.
ELLEN, COME ON UP.
ALL RIGHT.
I HOPE EVERYBODY CAN SEE ME.
IT'S ALWAYS A CHALLENGE.
PEOPLE SEE ME I'M GETTING THE
THUMBS UP.
IF YOU CAN'T SEE ME, JUST MOVE
AROUND.
I'M OVERWHELMED WITH GRATITUDE
THE FACT THIS EVENT IS HAPPENING
AND ALL THE WORK THAT WENT INTO
IT.
ALL THE AMAZING THINGS THAT
PEOPLE HAVE SAID.
I'D LIKE TO THINK OF THIS EVENT
AS A CELEBRATION OF THE WORK AND
SO PARTICULARLY APPRECIATING ALL
THE TALKS THAT WE'VE HEARD AND
ALL THE HARD WORK THAT OUR
SPEAKERS HAVE BROUGHT TO THE
WORK AND HOW MUCH THOUGHT AND
DEPTH AND HARD WORK AND SKILL IT
ALL TAKES I'M GOING TO HAVE A
LOT MORE TO SAY ABOUT GRATITUDE
AT THE ENDS OF MY TALK.
SO I THINK NOW I'LL SORT OF GET
INTO IT.
I WANTED TO USE MY TIME TO
REV
REVIEW MY CAREER FROM A
DIFFERENT PERSPECTIVE AND THE
BEST WAY IS WITH A SERIES OF
QUESTI
QUESTIONS YOU'RE ASKING MY
TITLE, I'M SO GLAD YOU ASKED AND
HOW I WENT FROM IMPOSTER TO
EMPOWERED.
HERE'S THE FOR US QUESTIONS.
FIRST, WHAT WERE THE BIGGEST
BARRIERS TO YOUR SUCCESS.
WHAT WAS THE MOST IMPORTANT
PIECE OF ADVICE THAT YOU IGNORED
WHAT WERE THE LUCKIEST THINGS
THAT HAPPENED TO YOU.
WHAT WERE THE MOST IMPORTANT
THINGS YOU DID TO SUCCEED AND
JUXTA POSING THESE TO EACH OTHER
MAKES THE POINT SOME OF WHAT
HAPPENS TO YOU IS OUTSIDE OF
YOUR CONTROL AND SOME OF WHAT
HAPPENS TO YOU YOU CAN HAVE
CONTROL AND THE CREDIT QUESTION
IS WHAT ARE YOU MOST GRATEFUL
FOR.
SO BIGGEST BARRIERS TO MY
SUCCESS, IMPOSTER SYNDROME IS A
TERM I DO NOT LIKE.
I DON'T THINK IT'S A SYNDROME.
THERE'S VERY LITTLE LITERATURE
ON IT BUT I THINK IT'S A TERM
THAT CAPTURES A VERY DISTINCT
AND COMMON PSYCHOLOGICAL STATE
WHICH IS BEING IN A SITUATION
WHERE YOU FEEL YOU HAVE TO
PERFORM AND FEELING LIKE YOU'RE
NOTE TA
NOT TALENTED ENOUGH, WELL
TRAINED ENOUGH, WHATEVER.
I HAVE HAD THIS THROUGHOUT MY
LIFE.
IT'S DIMINISHED OVER TIME BUT
I'VE DEFINITELY HAD IT AND IN
WAYS THAT I'LL EXPLAIN
INTERACTED WITH GENDER AND
EQUITY WHICH IS PROMINENT WHEN I
WAS COMING UP AND THIS IS ME AT
ALMOST AGE 6.
THIS IS MY SISTER, SUE, WHO
UNFORTUNATELY COULDN'T BE HERE
TODAY BECAUSE HER HUSBAND HAS
COVID BUT IS TWO AND A HALF
YEAR OLDER AND MY PARENTS WERE
FIRST GENERATION IN THE COUNTRY
AND TO GO TO COLLEGE.
MY FATHER WAS A PHARMACIST AND
MOTHER WAS A REGISTERED NURSE.
I DID START LIFE WITH CERTAIN
ADVANTAGES.
I WAS BORN INTO A WHITE
MIDDLE-CLASS FAMILY WITH HIGHLY
EDUCATED PARENTS.
WHEN I TALK ABOUT GENDER
INEQUITY IT'S OF COURSE ON THIS
BASELINE THAT I DID HAVE SOME
ADVANTAGE GOING INTO THINGS.
IN 1970 WHEN WE WERE PUTTING IN
APPLICATIONS TO COLLEGE AND
HEARD MY BEST FRIEND'S FATHER
WHY PUT SO MUCH MONEY IN COLLEGE
SHE'LL ONLY BE WASHING DIAPERS
ANYWAY.
IF HE COULD BE HERE TODAY, I
MEAN, REALLY.
IN 1970 I WAS ACCEPTED TO YALE
MUCH TO MY SURPRISE AND OF
COURSE THAT'S WHEN PRIVILEGE
ENTERED MY LIFE VERY BIG TIME.
I GOT A FABULOUS EDUCATION AT
YALE AND MADE LIFE LONG FRIENDS.
BUT FROM A GENDER PERSPECTIVE IT
WAS A STRANGE PLACE.
YALE WAS FOUNDED IN 1701 AND THE
FIRST CO-EDUCATIONAL CLASS WAS
IN 1969 WHICH MEANS I WAS IN THE
SECOND CLASS OF WOMEN TO GO TO
YALE.
MY ENT TERRING CLASS HAD 230
WOMEN AND THERE WERE ALMOST 800
MEN AND ONLY TWO TENURED WOMEN
AND IF YOU'RE A WOMAN OF COLOR
YOU CAN IMAGINE AND 65% OF WOMEN
HAD A CLASS AND I REMEMBER
HAVING TWO, IN WHICH THEY WERE
THE ONLY WOMEN.
WHEN I WAS AT YALE I DECIDED I
WANTED TO BECOME A PHYSICIAN.
I WANTED TO BE A PEDIATRICIAN OR
A PSYCHIATRIST.
I WAS A PSYCHOLOGY MAJOR AND I
WAS VERY HAPPY WITH THAT
AMBITION.
I FELT VERY GOOD AND POSITIVE
ABOUT MY FUTURE.
THE WHOLE IDEA OF BECOMING A
RESEARCHER AND I THINK IT HAD
SOME EXTENT TO DO WITH MY
IMPOSTER SYNDROME WHICH WAS BIG
TIME AT YALE INTERRUPTING WITH
THE GENDER INEQUITY AROUND ME.
I DIDN'T KNOW HOW TO NETWORK.
I COULDN'T SEE MYSELF NETWORKING
AND I WAS HAPPY AND WASN'T
THINKING ABOUT THAT BUT WHEN I
THINK BACK I THINK THAT'S PART
OF THE SITUATION.
I DID GO AHEAD AND APPLY TO
MEDICAL SCHOOL.
ADMISSION OFFICERS AT MULTIPLE
SCHOOLS SAID YOU'RE GOING TO
WANT TO GET MARRIED AND HAVE
CHILDREN.
WHAT WILL YOU DO WITH YOUR
MEDICAL DEGREE THEN?
AT THAT TIME IT WAS COMMONLY
SAID WOMEN SHOULDN'T GO TO
MEDICAL SCHOOL BECAUSE WE'D BE
TAKING UP SLOTS A MAN COULD
OTHERWISE HAVE AND THEY WOULD
PRACTICE MEDICINE THROUGHOUT
THEIR LIFE TIME AND WE WOULD
DROP OUT.
I WANT TO GO TO 1992 TO TALK
ABOUT HOW THINGS HAD EVOLVED
SHORTLY AFTER I CAME TO THE
NIMHD AND SOMEWHAT EMBLEMATIC OF
WHAT WAS GOING ON AT DIFFERENT
DESTINATIONS.
THIS WAS A REPORT FROM AN
INTRAMURAL WOMEN SCIENTISTS
LOOKING AT GENDER INEQUITIES IN
ALL THE VARIABLES AND LED TO THE
WOMEN SCIENTIST ADVISORS WHICH
STILL EXIST TODAY AND MONITOR
FOR EQUITY ON ALL PARAMETERS.
AT THE NIMHD WE SHOULD GIVE A
HUGE SHOUT OUT TO SUSAN AND
MARYLAND AND JAN AND CHRISTINE
FOR ALL THEY DO AND HAVE DONE IN
TERMS OF DIVERSITY.
THANK YOU.
YES.
WHAT THEY'VE DONE FOR DIVERSITY
AND EQUITY AND CONTINUE TO DO
ACROSS A NUMBER OF PARAMETERS
HERE AT THE NIMHD.
SO LESSONS LEARNED, MONDAY'S
MARTIN LUTHER KING DAY AND
THINGS CAN AND HAVE CHANGED.
MORE FOR WOMEN IN TERMS OF RACE
HOPEFULLY WE ALL WORK TOWARDS
THINGS CHANGING MORE.
I'VE BEEN BELIEVED WITH A
FABULOUS SUPPORT SYSTEM THROUGH
MY LIFE AND IMPORTANT ASPECTS OF
THE SUPPORT SYSTEM MADE A HUGE
DIFFERENCE DURING MY CAREER.
WOMEN SCIENTISTS SCIENTISTS I H
IMPORTANT MENTORS AND MY OTHER
FEMALE COLLEAGUES HERE AND I
LOVE WATCHING HOW WOMEN LAWYERS
ASSERT THEMSELVES AND I LEARNED
A LOT FROM THAT.
A LOT OF ALLIES YOU -- MANY
WHEN WHO SUPPORTED ME AND MY
HUSBAND WE JUST CELEBRATED OUR
40th WEDDING ANNIVERSARY.
WE GOT MARRIED WHEN WE WERE 12
HE SAYS WHICH ISN'T EXACTLY TRUE
BUT I OVER THE YEARS HAVE COME
TO REALIZE THAT IF YOU'RE IN A
PARTNERED RELATIONSHIP AND ARE
VERY INVESTED IN A CAREER
OUTSIDE THE HOME THAT IT'S SUPER
IMPORTANT THAT YOUR PARTNER VIEW
YOUR TALENT AND AMBITION AND
DESIRE TO DO WHATEVER YOU WANT
TO DO OUTSIDE THE HOME AS
SOMETHING THEY AFFIRMATIVELY
LOVE ABOUT YOU.
NOT AS AN ADD-ON.
I'VE ALWAYS HAD THAT WITH BOB
AND IT'S MADE A TREMENDOUS
AMOUNT OF DIFFERENCE ALL THE
TIME AND I LOVE YOU.
THAT'S FOR BOB.
THANK YOU.
YOU DESERVE IT.
I'LL TALK ABOUT DEVELOPING MY
PERSONAL AND SCIENTIFIC VISION
WHEN YOU SEE INEQUITY YOU WANT
TO ADDRESS ITS BUT THERE'S TIMES
WHEN IT'S REALLY IMPORTANT TO
THINK ABOUT THE PERSON LOOKING
FOR THE NORTH STAR IN THE MIDST
OF THE MILKY WAY AND TO DO THAT
YOU HAVE TO FOCUS AND BLOCK OUT
THE INTERNAL AND EXTERNAL NOISE.
THAT'S A THEME I'M GOING TO COME
BACK TO.
WHAT WAS THE MOST IMPORTANT
PIECE OF CAREER ADVICE YOU
IGNORED.
YOU CAN'T GET A PART-TIME JOB
DOING RESEARCH.
I WENT TO MEDICAL SCHOOL AND
GOT HIRED IN GEORGETOWN AND
DEVELOPED MY EXPERIENCE AS A
COMPLINGS AND T
CLINICIAN AND TEACHER AND BOB
AND I WERE DEVELOPING OUR OWN
PERSONAL VISION AND MY SON WAS
BORN IN 1984 LOOKING BEMUSE D
THIS IS MICHAEL LOOKING LIKE A
HAPPY AND CONTENT PACKAGE AND
THEY LOOK DIFFERENT NOW MICHAEL
AND HIS HUSBAND AND MY
DAUGHTER-IN-LAW SO SAY HIGH TO
THEM.
MY BIG SUPPORT SYSTEM.
AFTER MICHAEL WAS BORN I STARTED
THINKING THROUGH THINGS AND
REALIZED I WAS BEGINNING TO
PLATEAU IN MY CAREER DEVELOPMENT
IN GEORGETOWN AND RUNNING AN
IN-PATIENT UNIT IS 24/7 AND WAS
DIFFICULT TO RECONCILE WITH TWO
YOUNG CHILDREN AT HOME AND
IMPORTANTLY AND PEOPLE HAVE
TALKED ABOUT THIS, SOMETHING WAS
MISSING FROM MY LIFE AND HAD TO
DO WITH WRITING.
THIS IS A BOOK BY VIRGINIA WOLF
A FEMINIST CLASSIC PUBLISHED IN
1929 ABOUT THE STRUGGLES THAT
WOMEN WHEN HE WANT TO BE
PROFESSIONAL WRITERS, THE
BARRIERS THEY FACE.
I NEVER WANTED TO BE A
PROFESSIONAL WRITER AND WASN'T
INTO WRITING FICTION AND IT WAS
ALL EXPOSATIOR EXPOSATOREE -- O
AND THIS WAS GIVEN TO ME BY A
TEACHER AND I DON'T WRITE MUCH
AT GEORGETOWN AND I WANTED TO
HAVE A JOB WHERE WRITING WAS
MORE A PART OF IT AND I SHOULD
SEE IF I LIKE DOING RESEARCH SE
GIVEN MY SITUATION AT HOME I
LOOKED FOR PART-TIME, MIND YOU,
40 HOURS A WEEK NOT 60 HOURS A
WEEK AND LOOKED FOR A PART-TIME
JOB DOING RESEARCH AND PEOPLE
SAID YOU CAN'T DO THAT SO I
IGNORED IT AND GOT A JOB HERE IN
1898 -- 1989 DOING RESEARCH ON
CIRCADIAN RHYTHMS AND MOOD
DISORDERS AND I STARTED DOING
WORK WITH ADULTS WITH BIPOLAR
DISORDER AND IMMEDIATELY LOVED
DOING RESEARCH AND I COULD SPEND
THE REST OF MY TIME TALKING
ABOUT RESEARCH AND SHOWS WHO
THEY'RE SHE PASSION I'M SURE YOU
KNOW WHAT THOSE THINGS ARE.
WHEN I THOUGHT ABOUT IT OVER
TIME THIS WRITTEN ON PAPERWORK A
POSTDOC GAVE TO ME AS A PRESENT.
GOOD WRITING IS CLEAR THINKING
MADE VISIBLE AND CLEAR SCIENCE
IS CLEAR THINKING MADE VISIBLE
BECAUSE YOU VISUALIZE AND TEST
AND ETCETERA.
THIS IS THE SOUTH RIM OF THE
GRAND CANYON.
THIS IS THE SOUTH RIM AND THE
REST.
WHY AM I SHOWING YOU THE GRAND
CAN
CANYON?
IT'S MY FAVORITE PLACE ON EARTH
AND THERE'S A METAPHOR LURKING
HERE.
THERE'S A TRAIL THAT GOES ALL
THE WAY FROM THE TOP OF THE
SOUTH RIM OF THE GRAND CANNON
DOWN TO THE RIVER.
WHEN YOU LOOK HERE AND HERE WE
ONLY SEE A SMALL PART BUT
THERE'S PLACES WHERE YOU CAN SEE
THE TRAIL AND HAVE TO FOCUS AND
CONCENTRATE AND WHEN YOU FINALLY
SEE IT THERE'S AN AA
THAT'S AN AHA MOMENT AND THERE'S
A NOWHERE ON THE SOUTH RIM OR
WHERE WHERE YOU CAN SEE THE
ENTIRE ANGEL TRAIL THAT GOES TO
THE BOTTOM.
IT'S HIDDEN BY SIDE CANYONS AND
DEEP INNER GEORGE SO YOU SEE IT
HERE BUT YOU CAN'T SEE THE WHOLE
THING.
YOU CAN NEVER SEE THE WHOLE
THING.
AND NOTICE HOW MUCH IT WINDS.
AS DOES OUR LIFE AND LISTEN UP
AND PAY ATTENTION AND DON'T
BELIEVE EVERYTHING YOU'RE TOLD
AND IN LIFE AS IN SCIENCE, JUST
BECAUSE OTHER PEOPLE HAVEN'T
DONE IT, DOESN'T MEAN IT CAN'T
BE DONE.
WHAT ARE THE LUCKIEST THINGS
THAT HAPPENED TO YOU?
IN 2000 IT WAS SAID TO ME YOUR
SHIP HAS COME IN.
HE WAS A TRAINING DIRECTOR IN
THE IRP BEFORE JAN AND
UNFORTUNATELY PASSED LAST YEAR.
THIS STARTED IN 1989 THROUGH
2023 AND THERE'S NOT A
TREMENDOUS AMOUNT OF PRODUC
PRODUCTIVITY AND NOT EVERY TIME
IN LIFE ARE YOU SUPER
PRODUCTIVE.
THERE'S AN INFLECTION POINT
AROUND 2000.
I DIDN'T GROW 10 I.Q. POINTS BUT
SOMETHING WAS HAPPENING.
DENNIS CAME TO THE INTRAMURAL
PROGRAM AND BROUGHT POSITIVE
CHANGES TO THE CLINICAL RESEARCH
PROGRAM AND ALSO BROUGHT WITH
HIM TALENTED PEOPLE.
POST IMPORTA-- MOST IMPORTANTLY
DANNY AND FROM THE FIRST TIME WE
TALKED IT WAS CLEAR WE HAD THE
MAKINGS OF AN INCREDIBLE
COLLABORATIVE RELATIONSHIP.
IN TERMS OF SIMILAR INTERESTS
AND ANALYZING PROBLEMS AND
COMPLIMENTARY STYLES.
I COULD GO ON BUT ACTUALLY THE
DATA SHOW IT AND ONE THING THAT
HAPPENED TO ME WAS YOUR COMING
TO THE NIH.
NOW, THE BIPOLAR DISORDER
CONTROVERSY.
IT PRESENTS IN EPISODES OF MANIA
AND DEPRESSION IN ADULTS AND CAN
BE EUPHORIA OR IRRITABILITY AND
SAME CHANGE YOU HAVE CHANGES IN
MOOD YOU HAVE CHANGE IN APPETITE
AND SLEEP AND OTHER BEHAVIORAL
AND COGNITIVE CHANGES.
WHAT HAPPENED IN AND IN THE LATE
1990s INTO THE 00s, THOUGHT
LEADERS AND CHILD PSYCHIATRY
SUGGESTED BIPOLAR DISORDER IN
CHILDREN PRESENTS AS CHRONIC
SEVERE IRRITABILITY AND ADHD AND
HAS IMPORTANT TREATMENT
IMPLICATIONS AND IN TERMS OF
EPIDEMIOLOGY BECAUSE IT'S
UNCOMMON IN CHILDREN WHEREAS
THIS SEVERE IRRITABILITY AND
ADHD WERE COMMON AND THE RATES
OF CHILDREN RECEIVING THIS
DIAGNOSIS WAS BEING PRESCRIBED
AND IT WAS ON NEWS AND TIME AND
NEW YORKER.
I WAS IN A PARTICULAR POSITION
WHERE I COULD LOOK AT THIS.
THE LAB I WAS IN CLOSED AND I
WAS PUT INTO A LAB WITH A
DEVELOPMENT PEDIATRICIAN.
I HAD BEEN STUDYING BIPOLAR
DISORDER IN ADULTS AND BECAME
AWARE OF THE FACT THERE WAS A
CONTROVERSY IN PEDIATRIC
DISORDER AND STARTED DOING
STUDY.
I WAS INVITED TO A SMALL MEETING
OF RESEARCHERS WHO WERE FOCUSSED
ON THIS.
IT WAS A MEETING BEING HELD AT
NIMHD HEADQUARTERS AND I WAS
VERY INTIMIDATE AND DIDN'T SAY
ANYTHING AND THEY WERE FIGHTING
AND ARGUING WITH EACH OTHER.
IT WAS DRAMATIC BUT NOBODY WAS
STUDYING THE QUESTION AND I WENT
TO WORK THE NEXT DAY AND SAID I
THINK WE SHOULD STUDY THIS
QUESTION AND LAID OUT A SKELETON
OF A RESEARCH PLAN AND DANNY
SAID THAT'S A GREAT IDEA, LET'S
DO IT.
NO ONE DOES IT ALONE.
COLLEAGUES AND MENTEES EXPLAIN
MUCH AND EPISODES OF REALIZATION
AND TALKING ABOUT THE SCIENTIFIC
QUESTION THAT CAN COME
INFREQUENTLY AND UNEXPECTEDLY
AND LISTEN UP AND PAY ATTENTION
WHEN THEY COME.
WHAT ARE THE IMPORTANT THINGS
YOU DID TO SUCCEED.
CHOOSE YOUR QUESTIONS WELL,
BEING SELF-CRITICAL, LEARN TO
DEAL WITH SETBACKS AND DON'T
FORGET THE MOST IMPORTANT THING
WHICH I'M NOT GOING TO TELL YOU
NELL END BECAUSE THEN YOU WOULD
LEAVE.
SO CHOOSE YOUR QUESTIONS WELL.
YOUR CAREER IS LIKELY TO FOCUS
ON A FEW BIG QUESTIONS AND TELL
YOU THE TWO THAT WERE MINE.
THE QUESTION SHOULD BE BIG
ENOUGH YOU CARE ABOUT THE ANSWER
BUT SMALL ENOUGH IT'S TRACTABLE
AND IN CLINICAL RESEARCH IT'S
DIFFICULT TO DO AND SOMETHING
YOU HAVE TO SPEND TIME WITH.
YOU WANT LINEARITY IN SCIENCE
AND BURSTS OF CREATIVITY.
HERE'S THE FIRST IMPORTANT
QUESTION OF MY CAREER DOES
BIPOLAR DISORDER PRESENT IN
CHILDREN AS CHRONIC IRRITABILITY
AND ADHD.
I COULD SEE IN THE QUESTION AND
HAD AN IDEA WHAT I THOUGHT WHICH
WAY IT WENT WAS I COULD SEE
FUTURE RESEARCH AND REASONABLE
RESEARCH PLANS AND THAT WAS
COMFORTING.
WORK ACTIVELY TO BIAS A DESIGN
AND ALL THE DECISIONS YOU MAKE
ALONG THE WAY AGAINST WHAT YOU
THINK IS THE ANSWER.
PEOPLE HAVE MENTIONED KEN.
HE WAS THE CHIEF CLINICIAN DOING
THIS WORK AND I'M NOT A CHILD
PSYCHIATRIST AND THEY TAUGHT ME
A LOT AND BACKED ME UP AND
HELPED MAKE IT ALL HAPPEN.
ALL THE WORK I DID REALLY.
WE WERE TALKING ABOUT OUR BIAS
AND MAKE SURE IT DIDN'T
CONTAMINATE OUR DATA.
KNOW THE SOFT UNDER BELLY OF
YOUR OWN WORK BETTER THAN ANYONE
ELSE.
NEVER LOSE SIGHT OF THE FLAWS
IB -- IN YOUR WORK AND THIS NOT
ABOUT BEATING YOURSELF UP.
THIS IS ABOUT PUTTING THE
EMOTION ASIDE AND GOING ONE THE
LOGIC.
A NUMBER OF PEOPLE HAVE TALKED
ABOUT THAT TODAY AND IF YOU CAN
GET TO THAT POINT THIS IS
ASPIRATIONAL TOO AND IF YOU CAN
GET TO THE POINT WHERE YOU'RE
COMFORTABLE DOING IT WITH
SOMEONE ELSE, THEN IT'S REALLY,
REALLY IMPORTANT FOR YOUR
SCIENCE.
THE ANSWER WAS NO WHICH LEFT THE
WHOLE AREA OF IRRITABILITY.
IT'S VERY COMMON IN CHILDREN
PRESENTING FOR CARE AND UNDER
STUDIED.
HERE'S ALL THE QUESTIONS.
THAT'S THE SECOND BIG QUESTION
IN MY CAREER A COMBINATION OF
OTHER QUESTIONS AND OF COURSE WE
DIDN'T DO ALL THE WORK BY
OURSELVES BECAUSE WE'RE NOT --
WE DON'T HAVE THE EXPERTISE IN
ALL THE AREAS.
THERE'S A LOT DONE IN
COLLABORATION AND PEOPLE WORKING
ON OTHER THINGS.
HOW DO YOU MEASURE IT AND THE
EPIDEMIOLOGY AND TALKED ABOUT
THE BOUNDARIES OF WHAT'S
NORMATIVE.
PEOPLE TALK ABOUT COMORBIDITIES.
GENETICS AND TREATMENT.
THE ONE NEAREST AND DEAREST TO
MY HEART IS MECHANISMS AND
ANIMAL MODELS AND RECENT WORK
AND THAT HELPS YOU GET BRAIN
MECHANISMS AS WAN LING SAID AND
CULTURAL INFLUENCES.
LEARN TO DEAL WITH SETBACKS.
MOST STUDIES HAVE NEGATIVE
RESULTS BUT ALSO TEACH YOU
SOMETHING.
YOU GET MORE PAPER REJECTIONS
THAN PAPERS PUBLISHED AND CAN
MAKE YOU FEEL LIKE SCREAMING.
IT'S ASPIRATIONAL AND EASY FOR
ME TO SAY.
VALUE THE SCIENTIFIC PROCESS.
WHEN SETBACKS OCCUR DO DEEP
THINKING.
IT'S IMPORTANT TO BE KIND TO
YOURSELF WITH A SETBACK AND
FIGURE OUT WHAT TO DO NEXT.
PERSISTENCE IS KRUCRUCIAL.
THE WORK IS SLOW AND HAVE TO
PERSIST AND CELEBRATE YOUR
SUCCESSES AND OTHERWISE ENGAGE
IN SELF-CARE.
THE MOST IMPORTANT THING IS
DON'T FORGET TO THINK.
IN THE MIDST OF EVERYTHING THAT
HAPPENS ON A DAY TO DAY BASIS
IT'S DIFFICULT TO THINK ABOUT
THE HIGHER ORDER KINDS OF
THINGS.
WHERE YOU'RE GOING WITH YOUR
LIFE.
WHERE YOU'RE GOING WITH YOUR
CAREER AND A LITERALLY WOULD
SCHEDULE TIME ON MY CALENDAR TO
THINK ABOUT THESE THINGS AND IT
ISN'T RUMINATING BECAUSE I WOULD
AT THE END I WOULD REQUIRE I
HAVE AN ACTION ITEM.
MY THINKING LEAD TO SOME ACTION
ITEM OR ITEMS.
SO LIMITATIONS OF YOUR WORK WERE
CONSTANTLY TO ADDRESS THEM.
LEARN TO COPE WITH SETBACKS, BE
PERSISTENT AND DON'T FORGET TO
THINK.
WHAT ARE YOU MOST GRATEFUL FOR?
THE OPPORTUNITY TO TRY TO MAKE A
DIFFERENCE IN THE LIFE OF
CHILDREN AND FAMILIES WHO
STRUGGLE WITH MENTAL HEALTH
ISSUES.
IT'S A BLESSING.
IT'S REALLY A BLESSING TO HAVE
BEEN ABLE TO HAVE THIS CAREER TO
SPEND HOURS AND DAYS AND THE
PRIVILEGE OF HAVING A CAREER AT
THE INTERMURAL NIMHD AND THANKS
TO SUSAN AND MARYLAND WHO HAVE
ALSO VERY KINDLY HIRED ME BACK
NOW THAT I'VE RETIRED FROM MY
P.I. POSITION THEY'VE HIRED ME
BACK TO WORK PART-TIME
COLLABORATING ON SOME PROJECTS
AND MENTORING AND DOING PROJECTS
IN THE INTRAMURAL PROGRAM.
I'M GRATEFUL FOR THAT BECAUSE
I'M NOT QUITE READY TO GIVE IT
ALL UP YET.
AND GRATEFUL FOR RESEARCH
PARTICIPANTS, MENTEES,
COLLEAGUES, SUPPORT STAFF.
YOU MET A BUNCH TODAY AND HEARD
FROM THEM AND THERE'S A LOT
OTHERS.
THANKS TO KATHERINA MAKING THE
SLIDE.
IT'S A TEAM EFFORT AND MY FAMILY
WHO MAKES EVERYTHING POSSIBLE.
AND FOR TODAY, THANKS FOR THE
EVENT.
I WON'T HAVE EVERYBODY RELEVANT
HERE BECAUSE DANNY AND MARYLAND
AND KATIE KEPT ME AWAY FROM THE
REAL WORK BUT THANKS TO THE
SPEAKERS AND TO DANNY, MARYLAND
AND KATIE.
SHE WAS THE REAL ENGINE AND GLUE
OF THIS AND SUSAN THANK YOU SO
MUCH FOR EVERYTHING, CHARLENE,
JAN, KATHLEEN, THE STAFF AND
THANK YOU ALL FOR LISTENING.
>> THIS IS FOR YOUR RETIREMENT
AND THIS IS YOUR BOOK.
IT'S NICE TO THUMB THROUGH LATER
ON AND THERE'S LOVELY E-MAILS
FROM FOLKS AND THANK YOU AND
CONGRATULATIONS ON YO YOUR 4767 04:43:13,309 RETIREMENT.