Welcome to the Clinical Center Grand Rounds,
a weekly series of educational lectures for physicians and
health care professionals broadcast from the Clinical
Center at the National Institutes of Health in
Bethesda, MD.
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effort in training today's investigators and discovering
tomorrow's cures.
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I'M PLEASED TO INTRODUCE OUR
SPEAKER TODAY SAMANTHA MELTZER
BRODY, MD MPH, INTERNATIONALLY
RECOGNIZED PHYSICIAN SCIENTIST
IN PERINATAL DEPRESSION. SHE IS
ASSAD MEYMANDI DISTINGUISHED
PROFESSOR AND CHAIR DEPARTMENT
OF PSYCHIATRY, UNIVERSITY OF
NORTH CAROLINA OR UNC AT CHAPEL
HILL AND IS DIRECTING THE UNC
CENTER FOR WOMEN'S MOOD
DISORDEDISORDERS. BORN AND RAISN
CAN TON, OHIO, SHE COMPLETED HER
BACHELORS DEGREE IN BIOLOGY
PSYCHO YES AT THE SIMMONS
COLLEGE BOSS TUNED EARNED
MEDICAL DEGREE NORTHWESTERN
UNIVERSITY MEDICAL SCHOOL IN
CHICAGO, ILLINOIS. SHE PURSUED A
RESIDENCY IN PSYCHIATRY FROM THE
DUKE UNIVERSITY MEDICAL CENTER
AND BECAME CHIEF RESIDENT AT THE
DURHAM VA MEDICAL CENTER. DR.
MELTZER BRODY FOUNDED UNC
PERINATAL PSYCHIATRY PROGRAM IN
2004 AND BECAME CHAIR IN UNC
DEPARTMENT OF PSYCHIATRY IN
OCTOBER 2019. HER WORK FOCUSED
ON DEVELOPING A INTEGRATED
CLINICAL AND RESEARCH PROGRAM IN
WOMEN'S MOOD DISORDERS ACROSS
THE REPRODUCTIVE CYCLE OF LIFE.
LIFE CYCLE. SHE HAS INVESTIGATED
THE EPIDEMIOLOGIC AND BIOLOGICAL
PREDICTORS OF PERINATAL
DEPRESSION GENETIC
NEUROENDOCRINE BIOMARKERS AS
WELL AS IMPACT OF ADVERSE LIVE
EVENTS. DR. MELTZER BRODY HAS
BEEN ACADEMIC PRINCIPLE
INVESTIGATOR FOR NOVEL CLINICAL
TRIALS DEVELOPING EFFECTIVE NEW
PHARMACOLOGIC TREATMENT FOR POST
PARTEM DEPRESSION CALLED
BREXANALON (PHONETIC) NOW FDA
APPROVED. SHE IS CO-PI OF A
LARGE PATIENT CENTERED OUTCOMES
RESEARCH INSTITUTE GRANT TO
STUDY PSYCHOLOGICAL
INTERVENTIONS INCLUDING TRAINING
NON-MENTAL HEALTH SPECIALISTS
FOR PERINATAL DEPRESSION.
FOUNDER AND LEAD OF THE
POSTPARTUM DEPRESSION ACT
TOWARDS AND TREATMENT
CONSORTIUM. AND SHE IS CO-PI ON
A SMART PHONE APP NOW REBRANDED
AS MOM GENES THAT IS A LARGE
SCALE INTERNATIONAL GENETIC
STUDY OF POSTPARTUM DEPRESSION
AND POST PARTEM. LASTLY, DR.
MELTZER BRODY HAS BEEN
COLLABORATING IN PERINATAL
DEPRESSION INITIATIVES IN SUB
SAHARAN AFRICA, MALAI AND ZOOM
BEEIA. SHE IS A PASSION ANALYST
ADVOCATE FOR TRANSFORMATION
MENTAL HEALTHCARE AND LEADERSHIP
ROLES AND PHYSICIAN HEALTHCARE
WORKER MENTAL HEALTH AND WELL
BEING IN THE SCHOOL OF MEDICINE
AND UNC HEALTH. AND SHE RECEIVED
THE 2020 MAX GARDENER AWARD A
UNC SYSTEM AWARD FOR HIGHEST
FACULTY HONOR. SHE'S ALSO
RECIPIENT OF THE 2019 AMERICAN
PSYCHIATRIC ALEXANDER SIMONS
AWARD IN WOMEN'S MENTAL HEALTH.
SHE RECENTLY NAMED TO THE 2021
FORBES VISIONARY LIST OF WOMEN
OVER 50 FOR SHAPING THE FUTURE
OF SCIENCE TECHNOLOGY AND ART
AND THE FORBES LIST OF WOMEN
OVER 50 WORKING TO IMPROVE LEK
COLLECTIVE MENTAL HEALTH. SHE IS
ALSO RANKED IN 2021 BY EXPERT
SCAPE AS NUMBER ONE EXPERT IN
THE WORLD FOR POSTPARTUM
DEPRESSION. MOST RECENTLY IN
JUNE 22 SHE WAS NAMED TO FORBES
LIST OF 16 HEALTHCARE INNOVATORS
YOU SHOULD KNOW. SO THE TITLE OF
DR. MELTZER BRODY'S PRESENTATION
IS FROM BENCH TO BEDSIDE
TRANSLATIONAL APPROACH TO
INNOVATION IN RESEARCH AND
TREATMENT OF PERINATAL
DEPRESSION. WELCOME AND
CONGRATULATIONS.
>>THANK YOU VERY MUCH FOR THE
GENEROUS INTRODUCTION. IT'S
BEEN A GREAT PLEASURE AND HONOR
TO SPEND TIME HERE THE PAST FEW
DAYS AND TO MEET WITH THE
FANTASTIC PEOPLE THAT MAKE UP
THE NIH. I REALLY ENJOY MEETING
WITH THE TRAINEES, THE FELLOWS,
THE CLINICAL FELLOWS AND THE
MEDICAL STUDENTS TODAY AS WELL
AS ALL THE INVESTIGATORS. IT'S
BEEN A REAL PLEASURE AND
PRIVILEGE. I HAVE BEEN TO THE
NIH BEFORE BUT NOT TO THE
CLINICAL CENTER. SO REALLY
THRILLED TO BE HERE. I THINK
THAT YOU WALK INTO THE CLINICAL
CENTER AND THE THOUGHT THAT YOU
ARE AT THE NIH, THIS IS A PLACE
WHERE WE CAN TRANSFORM CLINICAL
CARE TO DECREASE SUFFERING
BECAUSE OF VERGE IS VERY
POWERFUL AND THAT PROMISE OF
THAT TO THOSE OF US THAT DON'T
WORK HERE, IS AN INSPIRATION SO
IT IS A GREAT HONOR TO COME AND
A GREAT HONOR TO BE ABLE TO GIVE
A TALK CALLED GREAT TEMP TALK
WHEN ONE WANTS TO RISE TO THE
OCCASION TO DO THAT. AS
DEPARTMENT CHAIR, I FEEL THAT A
LARGE PART OF MY JOB IS TO BE AN
EDUCATOR AND TRY TO INSPIRE THE
NEXT GENERATION TO MAKE
IMPORTANT CONTRIBUTIONS SO THANK
YOU FOR THIS GREAT HONOR AND
OPPORTUNITY TODAY. I WANT TO
ACKNOWLEDGE MY DISTHROW INSURES
I WAS DISCLOSE INSURES I HAVE
EXTRAMURAL GRANTS FROM NIH AND
PCORI. I HAVE DONE CLINICAL
TRIALS WITH SAGE PER
THERAPEUTICS AND SERVE AS
CONSULTANT FOR WEB MD AND MODERN
HEALTH. SO TODAY I'M GOING TO
TALK ABOUT PERINATAL DEPRESSION.
I'M GOING TO SPEND A LITTLE BIT
OF TIME TALKING ABOUT THE
TRANSFORMATION WE HAVE WITNESSED
OVER THE LAST THROUGH YEARS TO
TELEPSYCHIATRY OR JUST ELECTR
ELECTRONIC VIRTUAL
COMMUNICATION, I UNDERSTAND MANY
PEOPLE AS WE EXPERIENCE AT UNC
MAYBE WATCHING REMOTELY. AND THE
WAY WE COMMUNICATE NOW IS VASTLY
DIFFERENT. OUR ABILITY TO
INCREASE ACCESS AND REACH
PATIENTS IS VERY DIFFERENT THAN
IT WAS. I WANT TO TALK ABOUT
GENETIC SIGNATURE OF POSTPARTUM
DEPRESSION AND THE MOM GENE
STUDY, THE AT BASE STUDY. AND
THEN TALK ABOUT PRECISION
PSYCHIATRY AS APPLIED TO THE
PERINATAL PERIOD USING THAT AS A
MODEL. THEN END WITH THE WORK
THAT'S BEEN DONE ON NOVEL
TREATMENTS WITH BREXANALONE.
HOPING TO GIVE A STORY THAT
ILLUSTRATES POWER OF TEAM
SCIENCE. AND WANT TO ACKNOWLEDGE
THAT ALL OF MY WORK HAS BEEN
DONE BECAUSE OF OUTSTANDING
COLLABORATORS ACROSS A BROAD
RANGE OF DISCIPLINES, I LOVE
WORKING ON TEAMS. I LOVE
WORKING ON MULTI-DISCIPLINARY
TEAMS AND BRINGING TOGETHER
PEOPLE WITH VERY DIFFERENT
BACKGROUNDS AND AREAS OF
EXPERTISE TO CREATE SOMETHING
THAT IS ULTIMATELY GOING TO MOVE
THE FIELD FORWARD. I FEEL
GRATEFUL TO STAND ON THE
SHOULDERS OF THOSE THAT HAVE
COME BEFORE ME AND HAD
OUTSTANDING MENTORS. AND
COLLABORATORS AND SO EVERYTHING
THAT I HAVE BEEN ABLE TO
ACCOMPLISH IS BECAUSE OF
OUTSTANDING PEOPLE TO WORK WITH
MY INTEREST IN PERINATAL
DEPRESSION IS BECAUSE IT IS SUCH
A PROFOUND TIME IN A WOMAN'S
LIFE AND FAMILY'S LIFE, AND
INTERVENING AT THIS TIME FOR
PEOPLE SUFFERING FROM MENTAL
HEALTH CONCERN HAS ALWAYS BEEN
ENORMOUSLY REWARDING. WHEREVER I
HAVE GONE IN THE WORLD, THIS IS
A PICTURE FROM A POSTPARTUM UNIT
IN MALAWI, YOU SEE THAT THERE IS
BOTH THE JOY OF A MOTHER WITH
HER BABY, YOU ALSO SEE WHAT
HAPPENS WHEN SOMEONE IS
SUFFERING FROM A MENTAL HEALTH
CONCERN. AND IT IS VERY, VERY
DIFFICULT TO TRY TO TAKE CARE OF
A NEW BABY WHEN YOU ARE
SUFFERING FROM DEPRESSION.
POSTPARTUM DEPRESSION REMAINS
ONE OF THE GREATEST CAUSE
CONSIST OF MATERNAL MORTALITY
WORLDWIDE AND SOMETHING THAT
REQUIRES ALL OF OUR ATTENTION.
EVERYBODY FORTUNATE TO SPEND MY
CAREER -- I HAVE BEEN FORTUNATE
TO SPEND MY CAREER AT UNC WE
OPENED THE FIRST PERINATAL
PSYCHIATRY UNIT IN THE UNITED
STATES, WHICH IS AN
ACCOMPLISHMENT FOR THE UNITED
STATES BUT CERTAINLY SOMETHING
THAT IS ABOUT 60 YEARS LATER
THAN THE REST OF THE WORLD. SO
THE UK OPENED THEIR UNITS ABOUT
60 YEARS BEFOR BEFORE. AS HAS EE
AND OTHER PLACES. AND THIS IS
LARGELY REFLECTS THE
COMPLICATIONS WE FACE IN WORKING
IN THE U.S. HEALTHCARE SYSTEM.
AND THE FACT THAT WE DON'T -- WE
ARE THE ONLY DEVELOPED COUNTRY
WITHOUT UNIVERSAL MATERNITY
LEAVE. WE ARE THE ONLY DEVELOPED
COUNTRY THAT HAS NOT MADE
MATERNAL MENTAL HEALTH A
PRIORITY AND THERE'S BEEN A
SYSTEMATIC CLOSING OF IN PATIENT
PSYCHIATRY BEDS THAT BEGAN IN
THE '60s AND '70s AND AT
THIS POINT IS AN ABSOLUTE
CRISIS. AS THE CHAIR OF LARGE
PUBLIC ACADEMIC DEPARTMENT OF
PSYCHIATRY, ALL OF THE EMERGENCY
ROOMS ASSOCIATED WITH UNC HEALTH
ARE FILLED WITH PSYCHIATRY AND
MENTAL HEALTH PATIENTSS. THERE
LACK OF ADEQUATE BEDS. AND FOR
MOTHERS THAT NEED A SPECIAL
UNIT, THERE IS AN ABSOLUTE LACK
OF RESOURCES. SO TO BE
POSTPARTUM AND BE ADMITTED TO A
GENERAL PSYCHIATRY UNIT WORKS
POORLY. WE LEARN THAT THE HARD
WAY AND WE ARE ABLE TO OPEN A
UNIT IN 2011. PEOPLE OFTEN ASK
US HOW WE DID IT. AND WE HAD THE
RIGHT PEOPLE AT THE RIGHT TIME
AT THE RIGHT PLACE. SO ONE OF MY
WONDERFUL MENTORS AND DEAR
FRIENDS DR. DAVID OF RUBINO
(PHONETIC) WHO IS HERE MANY
YEARS AND CAME TO BE CHAIR AT
UNC WAS TRANSFORMATIVE AND
ADVOCATING FOR THAT. WE ALSO HAD
THE VERY GOOD LUCK OF HAVING
LEADERSHIP POSITIONS IN THE
HOSPITAL THAT HAD A PSYCHIATRY
INPATIENT NURSING SERVICES AND
THE HOSPITAL CHIEF NURSING
OFFICER WERE ALSO VERY
SUPPORTIVE. IT WAS EVERYONE
COMING TOGETHER AT THE RIGHT
TIME INCLUDING A COLLEAGUE WHO
WAS RUNNING THE GERO PSYCH UNIT
THAT AGREED TO HAVE THREE BEDS
REMOVED TO GO TOWARDS THIS
CAUSE. LIKE EVERYTHING, I THINK
IN ORDER TO BE SUCCESSFUL AT
MAKING CHANGE YOU HAVE TO HAVE
PEOPLE COMMITTED TO DOING THAT
AND YOU NEED PEOPLE COMMITTED TO
FORWARD PROGRESS. WE OPEN THIS.
OUR UNIT AS MUCH AS WE CAN WE
TRY AND HAVE IT FEEL
COMFORTABLE, DESPITE JOINT
COMMISSIONS BEST EFFORTS TO HAVE
IT NOT BE AGAIN WITH BEST OF
INTENTIONS WITH RISK BUT ENDS UP
MAKING PSYCHIATRY UNITS
INHOSPITABLE. WE WORK TO HAVE
OUR PSYCH NURSING STAFF HAVE
TRAINING IN PSYCHIATRY AND OB
RELATED ISSUES AND TO HAVE
MULTIPLE WAYS TO HAVE BABIES
VISIT, THEY CAN ONLY BE ON THE
UNIT WITH ANOTHER ADULT WHO IS
NOT THE PATIENT BECAUSE WE DON'T
-- THEY ARE NOT ABLE TO STAY
OVER NIGHT LIKE MOTHER BABY
UNITS IN OTHER PLACES. BUT THIS
IS PROVIDED AN OUTSTANDING PLACE
TO CONDUCT NOVEL RESEARCH
PROTOCOLS. CERTAINLY HERE AT
CLINICAL CENTER YOU ARE ABLE TO
DO THAT TOO. WHILE THIS UNIT WAS
DEVELOPED FOR CLINICAL TREATMENT
WE HAVE BEEN ABLE TO USE IT TO
DO RESEARCH, I WILL EXPLAIN MORE
ABOUT HOW THAT HAS WORKED. SO
POSTPARTUM DEPRESSION WE HAVE
LOOKED AT IT AS MORE HOMOGENOUS
FORM OF MAJOR DEPRESSION.
PREVALENCE ESTIMATES WE ARE
USING OF 10 TO 15% GENERAL
POPULATION OCCURS IN
REPRODUCTIVE AGE WOMEN. THIS IS
A MAJOR DEPRESSIVE EPISODE SO
WHEN YOU SAY DATA THAT SAYS ONE
IN FIVE OR ONE IN FOUR WOMEN
HAVE WHAT IS NOW OFTEN TERMED
POSTPARTUM MOOD AND ANXIETY
DISORDERS THERE IS AN EFFORT
FROM THE PUBLIC HEALTH COMMUNITY
TO BE VERY INCLUSIVE IN TERMS OF
HOW WE DO POPULATION BASED
SCREENING FOR ANY KIND OF
MATERNAL MENTAL HEALTH ISSUE.
AND THAT GETS A LITTLE BIT
CONFUSING IN TERMS OF ARE WE
TALKING ABOUT MAJOR DEPRESSIVE
EPISODE OR ARE WE TALKING
ANXIETY DISORDER AND SORT OF
LUMPING EVERYTHING TOGETHER. SO
I'M GOING TO BE TALKING ABOUT
POSTPARTUM DEPRESSION, TALKING
ABOUT WHAT WE SEE AS A DSM
DIAGNOSIS OF A MAJOR DEPRESSIVE
EPISODE THAT IS OCCURRING WITH
ONSET VERY PROXIMAL TO
CHILDBIRTH. THAT IS IMPORTANT IF
WE THINK ABOUT UNDERLYING
PATHOPHYSIOLOGY AND EFFORTS TO
DEVELOP INTERVENTIONS SPECIFIC
TO THAT TIME. WHAT CAUSES IT? IT
IS UNKNOWN, IT IS LIKELY
MULTI-FACTORIAL. IT'S BEEN
LINKED TO HISTORY OF DEPRESSION,
INFLAMMATORY SIGNALING
FLUCTUATIONS AND PERINATAL
HORMONES DISREGULATION OF STRESS
PATHWAYS SUCH AS THE HPA AXIS,
GABBA SIGNALING DYSFUNCTION
INCLUDING ALTERED GABBA RECEPTOR
REGULATION. CERTAINLY PETER
SCHMIDT, DAVID RUBINO AND THEIR
TEAM AND OTHERS HAVE HAVE DONE
PIVOTAL WORK FOR MANY, MANY
DECADES LOOKING AT THE
DIFFERENTIAL SENSITIVITY OF
WOMEN'S REPRODUCTIVE HORMONES SO
THE NIH INTRAMURAL PROGRAM HAS
PLAYED A POWERFUL ROLE IN
ADVANCING SCIENCE IN THIS AREA.
WE HAVE SEEN IT IS MORE
HERITABLE THAN NON-PERINATAL
DEPRESSION SO THIS WAS USING
SCANDINAVIAN SAMPLES AND SEEING
IF YOU LOOK AT THE PERINATAL
PERIOD THERE WAS UP TO 54%
HERITABILITY COMPARED TO
DEPRESSION OUTSIDE THE PERINATAL
PERIOD. SOMETHING UNIQUE ABOUT
THIS TIME. WHEN IT HITS IT IS
OFTEN DEBILITATING WITH A BROAD
RANGE OF CLINICAL SYMPTOMS, YOU
WILL SEE LOW MOOD, DECREASED
INTEREST OR ANHEDONIA, MOMS
UNABLE TO ENJOY THE BABY,
CO-ANXIETY OCCURRING AND UNABLE
TO SLEEP WHEN BABY IS SLEEPING,
STAYING UP ALL KNIFE WATCHING
THE BABY BREATHE FOR FEAR OF
SIDS ALL CAN INTERFERE WITH
MOTHER INFANT ATTACHMENT. MOTHER
BABY RELATIONSHIP, HOPELESSNESS
OR THOUGHTS OF SELF-HARM IS
COMMON WHICH IS WHY REMAINS ONE
OF THE GREATEST CAUSES OF
MATERNAL MORTALITY. YOU END UP
WITH GREAT DISRUPTION IN THE
FAMILY UNIT WITH LONG STANDING
NEURODEVELOPMENTAL DELAYS IN
CHILDREN WHOSE MOTHERS HAD
UNTREATED DEPRESSION OVER TIME
AND NUMBER OF STUDIES THAT
KNOWED PEOPLE LONGITUDINALLY UP
TO AGE 18 AND BEYOND AND YOU SEE
DIFFERENCES MAJOR STRESSORS ON
FAMILY WHICH IS WHY IT IS ALWAYS
BEEN TO ME SUCH AN IMPORTANT
TIME FOR INTERVENTION. SO I WANT
TO TALK A LITTLE BIT ABOUT
TELEHEALTH. EARLIER TODAY WHEN
WE WERE MEETING WITH THE MEDICAL
STUDENTS, THE PANDEMIC HIT, THE
PAYERS DECIDED THEY WOULD PAY
FOR VIRTUAL CAR AND WE RAN
AROUND IN TWO WEEKS AND LAUNCHED
VIRTUAL CARE BROADLY. THIS IS
BEEN AMAZING WAY TO INCREASE
ACCESS AND IN MENTAL HEALTH AND
PSYCHIATRY AND BEHAVIORAL HEALTH
IT IS HERE TO STAY, I THINK
WHATEVER REGULATIONS ARE ROLLED
BACK IN OTHER AREAS, THIS IS
GOING TO BE ONE PLACE WHERE IT
REMAINS IN THE MATERNAL MENTAL
HEALTH SPACE IT'S BEEN VERY,
VERY POWERFUL. IF YOU THINK
ABOUT A NEW MOM HAVING TO COME
IN AND HAVE A MENTAL HEALTH
VISIT AND YOU HAVE TO BRING THE
BABY OR KIDS YOU HAVE TO TRAVEL,
YOU ARE ON THE BUS OR THE TRAIN
OR DRIVING HOURS, THE ISSUES
AROUND ACCESS, AROUND GAS,
AROUND ECONOMIC FACTORS, IF YOU
CAN DO A TELEHEALTH APPOINTMENT
ASSUMING YOU HAVE A SAFE PLACE
IN BROADBAND INTERNET ACCESS IT
REALLY CAN DECREASE BARRIERS. SO
ONE OF THE QUESTIONS THAT IS
RAISED, IS IT AS GOOD? IS
TELEHEALTH AS GOOD AS IN PERSON?
I THINK THE DATA COMING OUT
SHOWS WELL IT DEPENDS ON THE
PATIENT POPULATION. IS IT GOOD
ENOUGH? ARE THE ADVANTAGES OF
INCREASING ACCESS OUTWEIGH
WHATEVER DOWN SIDES MAY BE
THERE. BUT SOMEWHAT IRONICALLY
WE HAVE STARTED A STUDY, THIS IS
A $13 MILLION STUDY WITH PCORI
CALLED SUMMIT TRIAL SCALING MA
ATTORNEY HEALTH HEALTHCARE BY
INCREASING ACCESS TO TREATMENT.
I WANT TO SPEND A LITTLE TIME
TALKING ABOUT THIS. BECAUSE I
THINK IT IS ONE, VERY
INTERESTING TO THE TIME WE ARE
LIVING IN NOW. AND TWO, IT JUST
TALKS ABOUT THE TRANSFORMATION
TO ALL OF OUR RESEARCH PROGRAMS
OVER THE COURSE OF THE PANDEMIC
SO WE STARTED THIS PRE-PANDEMIC,
THE QUESTION WAS, IS
PSYCHOTHERAPY DELIVERED BY
TELEMEDICINE, AS GOOD AS IN
PERSON CARE? AND CAN THIS BE
DELIVERED BY NON-SPECIALISTS? BY
TRAINING OB CLINIC NURSES TO DO
A MANUALIZED FORM OF
PSYCHOTHERAPY, COMPARED TO
HAVING A MENTAL HEALTH
SPECIALIST? SO IF YOU WILL, A
TWO BY TWO TABLE, THE PI OF THIS
IS AN AMAZING WOMAN NAMED DR.
DAISY AT THE UNIVERSITY OF
TORONTO. AND SHE REACHED OUT TO
SAY I NEEDED AMERICAN
COLLABORATOR. I WANT TO APPLY
FOR A PCORI GRANT. THIS WAS IN
2018. REALLY WONDERING HOW ARE
WE GOING TO DO POPULATION HEALTH
LEVEL MATERNAL MENTAL HEALTH
INTERVENTIONS? THERE'S NEVER
GOING TO BE ENOUGH MENTAL HEALTH
PROVIDERS TO DO IT. AND SHE HAD
DONE A LOT OF WORK IN LOW
RESOURCE COUNTRIES GLOBAL HEALTH
WHERE YOU DO A LOT OF TASK
SHIFTING. SHE KNEW I HAD AN
INTEREST IN THAT TOO. AND THE
QUESTION WAS, CAN WE DO
TELEMEDICINE, IS THAT MORE
CONVENIENT AND CAN YOU TRAIN
PEOPLE OTHER THAN MENTAL HEALTH
PROFESSIONALS TO DO THIS IF WE
ARE REALLY GOING TO TACKLE THE
POPULATION BASED HEALTH ISSUE OF
MATERNAL MENTAL HEALTH? SO WE
BEGAN THIS, WHAT IS THE
TREATMENT AT SIX TO EIGHT WEEKS
OF BEHAVIORAL ACTIVATION THERAPY
WHICH HAS A STRONG EVIDENCE
BASE. AND IS BEEN SHOWN AS
EFFECTIVE IN TREATING BOTH
PERINATAL DEPRESSION AND ANXIETY
AND HAS BEEN EASY TO LEARN. IT
WAS PICKED FOR ALL THOSE
REASONS. THIS IS OUR TEAM,
DAISY, RICH SILVERS AND MATERNAL
FETAL MEDICINE DOC AT THE SHORT
SHORE HEALTH SYSTEM CHICAGO. AND
THEN TWO OTHER CANADIAN
INVESTIGATORS SIMONE AT WOMEN'S
COLLEGE TORONTO AND CINDY LEIDEN
IN THIS. WE BEGAN MANY
ENROLLING IN IN JANUARY 2020.
THIS IS VERY, VERY FUNNY, AND
THEN WE KNOW WHAT HAPPENED IN
MARCH. WE WERE ABLE TO CONTINUE
THE TELEMEDICINE PART OF THE
STUDY UNINTERRUPTED OVER THE
COURSE OF THE PANDEMIC. IT WAS
WILDLY POPULAR. ONE OF THE
THINGS THAT BECAME A HUGE
BARRIER THOUGH IS THE NURSES ALL
QUIT. SO WE HAVE HAD TO FIGURE
OUT WHO WERE GOING TO BE THE
NON-MENTAL HEALTH SPECIALISTS
AND WE HAVE MOVED TO DULA'S
WHICH IS HELPFUL BUT DESPITE
THIS WE RESUMED IN PERSON CARE
IN AUGUST '21 AND TODAY WE HAVE
VERY HIGH RETENTION RATES, WE
ARE 90% BEING FOLLOWED UP TO A
YEAR OUT, BABIES BEING FOLLOWED
WE HAVE 50% WHO IDENTIFY AS
BIPOC SO WE HAVE WORK TO HAVE
UNDER-REPRESENTED POPULATIONS
INVOLVEINVOLVED. WE ARE NEARINE
END OF RECRUITMENT WHICH IS 1226
MOTHERS ENROLLED, IT WILL BE ONE
OF THE LARGEST PSYCHOTHERAPY
TRIALS IN THE WORLD. SO MY HOPE
IS THAT THIS BEGAN PRE-PANDEMIC
BUT THIS IS GOING TO PROVIDE
REALLY INTERESTING ANSWERS TO IS
TELEMEDICINE TELETHERAPY AS GOOD
AS IN PERSON? AND CAN WE
SUCCESSFULLY USE TASK SHIFTING
MODELS TO DELIVER PSYCHOTHERAPY
INTERVENTION?
WE ARE GOING TO NEED TO FIGURE
HOW TO DETAILS -- DO TASK
SHIFTING WITH A LOT OF THINGS WE
FACE IN HEALTHCARE BECAUSE THE
PEOPLE AROUND THERE, WE ARE
STRUGGLING WITH WORK FORCE
SHORTAGES AND HOW TO MA MANAGE
THAT, WE CAN'T SAY WE DON'T HAVE
THE PEOPLE WE HAVE TO FIGURE HOW
TO USE TASK SHIFTING AS DONE IN
OTHER MODELS. ONE THING WE ARE
DOING A LOT OF AT UNC IS LOOKING
WHO CAN STAFF ORs, WHO CAN DO
THINGS. THE LPNs WHO GRADUATE
FROM TWO YEAR NURSING PROGRAM
ASSOCIATE DEGREES, WHICH WERE
OFTEN TRIED TO BE REPLACED WITH
DSN NURSES ARE GOING TO HAVE TO
CHANGE THAT MODEL IN THERE IS
NOT ENOUGH BSM NURSES TO DO THE,
WHO. SO WE ARE ARE LIVING IN A
TRANSFORMATIONAL TIME BUT WE
HAVE TO BE OPEN TO INNOVATION AS
TO HOW WE ARE GOING TO ADDRESS
THIS. SO I WANT TO SWITCH GEARS
AND TALK ABOUT PRECISION
PSYCHIATRY. THIS IS A PAPER FROM
2017, I THINK IT IS VERY
RELEVANT, THIS TOPIC IS
SOMETHING THAT'S BEEN INSPIRING
TO ME. ONE OF MY VERY GOOD
FRIENDS IS A BREAST CANCER
ONCOLOGIST. AND I HAVE WATCHED
WITH ENVY AS HER FIELD HAS
BECOME MUCH MORE PRECISE. AND
THE ABILITY TO RECOGNIZE THERE
IS NOT ONE KIND OF BREAST CANCER
HAS BEEN TRANSFORMATIVE IN
CHANGING OUTCOMES AND LIFE
EXPECTANCY. IN PSYCHIATRY
UNFORTUNATELY WE ARE STILL
OPERATING SORT OF A ONE SIZE
FITS ALL MODEL. THEN WE WONDER
WHY WE AREN'T ABLE TO TREAT
PEOPLE TO REMISSION IN THE WAY
WE WOULD LIKE. SO PRECISION
MEDICINE, ASPIRATIONALLY IS THE
IDEA OF USING DIAGNOSTIC AND
THERAPEUTIC TECHNOLOGIES THAT
CAN BE TAILORED AND TARGETED TO
BE VERY PRECISE TO WHAT YOU
HAVE. WE ARE STILL FAR AWAY FROM
THAT IN PSYCHIATRY AND IT IS
SOMETHING WE HAVE TO GET BETTER
AT. SO WHEN THE OPPORTUNITY
AROSE TO ENGAGE IN A PRECISION
MEDICINE ENDEAVOR, THAT WAS
SOMETHING WE ARE VERY, VERY
EXCITED ABOUT. SO I WANT TO TELL
THE STORY OF THAT. THE
PROGESTERONE TO ALLO PATHWAY,
WHEN IT CAME TO UNC I DR.
MOREAU, HE WAS A FILL LOW, SHE
IS A BASIC SCIENTIST WITH
STUDYING ALLO PRENANALONE
(PHONETIC) TRAINED BY BOB PURDY,
YOU HAVE A LONG HISTORY OF PEEP
PEOPLE INTERESTED IN
NEUROSTEROIDS AND STEVE PAUL WHO
WAS HERE TO WORK AT HE WILL LIE
LILY AND GET A DRUG YOU MAY HAVE
HEARD OF PROZAC, TO MARKET AND
HAS INVESTED IN MANY THINGS
INCLUDING WHAT I WILL DESCRIBE
WITH BREXANALONE. THE
PROGESTERONE TO ALLO PATHWAY, IS
FASCINATING. YOU START WITH A
MOLECULE AND END UP WITH A
PROGESTERONE IN THE MIDDLE AND
METABOLIZED TO ALLO PREDNANALONE
E A NEUROMETABOLITE THAT
CROSSESSED THE BLOOD BRAIN
BARRIER AND APHONICY COMPOUND.
-- PHI IN THIS CASEY COM IN YOS
SPEC MACHINE. PEOPLE AT UNC WERE
STUDYING IN ALL KIND OF THINGS
FROM PMS TO OTHER THINGS REALLY
INTERESTED IN A POWERFUL
METABOLITE, KNOWN TO HAVE
PRE-CLINICAL MODELS WHAT
APPEARED TO BE ANGE SOW LYTIC
AND ANTI-DEPRESSIVE EFFECTS.
ANXIOL IRK STIRKSC AND
ANTI-DEPRESSIVE EFFECTS. HOLD
THAT FOR A MINUTE. THE
DIFFERENTIAL SENSITIVITY TO
FLUCTUATIONS IN REPRODUCTIVE
HORMONES AGAIN HAS BEEN
SOMETHING THAT WAS STUDIED AT
THE NIH AND CONTINUES TO BE IN
PIVOTAL WOR WORK. PRE-MENTAL
DYSPHORIC DISORDER AND PERINATAL
MENOPAUSE AND PERINATAL
DEPRESSION. WONDERING WHY IF ALL
WOMEN, IF YOU LOOK HERE AT THE
TOP YOUR LEFT MY RIGHT GRAPH YOU
SEE OVER THE COURSE OF
PREGNANCY, ALL WOMEN HAVE
INCREASING LEVELS OF ESTROGEN
AND PROGESTERONE. THAT IS NORMAL
PHYSIOLOGY, YOU CANNOT HAVE A
PREGNANCY SUCCESSFUL WITHOUT
THAT. AT THE TIME OF DELIVERY,
EVERYONE HAS RAPIDLY PLUM METING
HORMONES. EVERYONE WHO
DELIVERS. SO WHY IS IT THAT SOME
WOMEN END UP DEPRESSED AND
OTHERS DON'T? IT IS NOT THE
ABSOLUTE LEVEL OF HORMONE OR THE
RATE THAT IT CHANGES IS THAT
THERE APPEARS TO BE DIFFERENTIAL
SENSITIVITY. THAT IS THE HORMONE
HYPOTHESIS. ONE HYPOTHESIS OF
POSTPARTUM DEPRESSION. CLEARLY
IT IS NOT THE ONLY THING. SO IF
YOU LOOK AT THE CONTRIBUTIONS OF
EPIGENETIC MECHANISMS WHICH
THERE IS LITERATURE AROUND THAT,
IF YOU LOOK AT SYNAPTIC
TRANSMISSION MECHANISMS THAT
THERE'S ALTERATIONS IN SYNAPTIC
TRANSMISSION, OF MANY DIFFERENT
NEUROTRANSMITTERS, IF YOU LOOK
AT NEURAL NETWORK MECHANISMS AND
THERE'S IMAGING STUDIES SHOWING
ALTERED ACTIVITY IN THE AMYGDALA
PREFRONTAL CORTEX CINGULATE
CORTEX AND INSULA, THERE IS
LITERATURE AROUND INFLAMMATORY
MECHANISMS, ALTERED LEVELS OF
IMMUNE SYSTEM FACTORS. AND
STEROID MECHANISMS ALTERED
LEVELS OF ALLO AND DYSFUNCTION
IN NEUROACTIVE STEROID SIGNALING
AND OF COURSE DISRUPTION IN
STRESS MECHANISMS ALTERATIONS OF
THE HPA ACCESS. SO ALL THESE
THINGS THERE IS LITERATURE ON
AND AS WE TREAT WOMEN WITH
POSTPARTUM DEPRESSION WE ARE NOT
SPECIFIC AT ALL. SO UNLIKE
BREAST CANCER WHERE YOU FIND OUT
IF SOMEONE HAS HORMONE RECEPTOR
POSITIVE OR NEGATIVE BREAST
CANCER OR HR 2 NU POSITIVE
BREAST CANCER OR GENETIC SIGNAL
WHICH MARKEDLY DAY ORS TREATMENT
AND LEADS TO DIFFERENT OUTCOMES
WE THROW THE SAME TREATMENT AT
EVERYONE AND WONDER WHY SOME
PEOPLE GET BETTER EASILY AND
SOME DO NOT. THAT IS A MAJOR
SOURCE OF MOTIVATION FOR ME WHEN
I SIT IN FRONT OF A PATIENT AND
THE FAMILY AND THEY ARE
SUFFERING TREMENDOUSLY. IT IS
FRUSTRATING TO NOT KNOW IF YOU
ARE STARTING THE RIGHT TREATMENT
OR NOT, THE GOLD STANDARD UP
UNTIL RECENTLY WHERE THE FOR
PHARMACOLOGIC THERAPY SSRI
ANTIDEPRESSANTS THAT MAY OR MAY
NOT WORK, MAY TAKE MONTHS TO TIE
TRITE UP TO A THERAPEUTIC DOSE
AND WHEN YOU ARE REALLY SICK AND
THE FAMILY IS IN CRISIS THAT
FEELS LIKE AN ETERNITY. SO THIS
WAS PART OF THE MOTIVATION FOR
TRYING TO FIGURE OUT IS THERE A
GENETIC SIGNATURE? AND PAC
CONSORTIUM WAS STARTED IN 2010
WORKING WITH GENETICS COLLEAGUES
OF MINE PATRICK SULLIVAN WHO IS
A WORLD CLASS PSYCH GENETICIST
AT UNC AND PARTNERING WITH
PEOPLE, YOU SEE PETER SCHMIDT'S
PICTURE THERE, AND TEAM HERE AND
OTHER INVESTIGATORS AROUND GLOBE
WHERE WE SAID DO YOU HAVE DATA
ON CLINICAL PHENOTYPIC DATA AND
GENETIC DATA THAT WE CAN START
POOLING TOGETHER TO TRY AND LOOK
AT THE HETEROGENEITY OF
POSTPARTUM DEPRESSION AND
UNDERSTAND ULTIMATELY FROM A
PRECISION PSYCHIATRY POINT OF
VIEW WHAT ARE THE DIFFERENT
SUBGROUPS AND HOW CAN WE
ULTIMATELY GET TO MUCH MORE
REFINED TREATMENT. PEOPLE WERE
ENORMOUSLY GENEROUS. WE CALLED
IT THE PACT CONSORTIUM WHICH IS
A TERRIBLE ACRONYM POST PARTUM
DEPRESSION ACTION CAUSES AND
TREATMENT AND YOU CAN TELL WE
WERE WELL MEANING ACADEMICS NOT
WORKING FOR A MARKETING FIRM
THAT COCAINE UP WITH WE CAME UPH
FORWARD FIVE YEARS LATER APPLE
RELEASED A RESEARCH KIT
PLATFORM. THE IDEA OF BRINGING
SCIENCE DIRECTLY TO THE CONSUMER
ON YOUR SMART PHONE, WE HAD AN
OPPORTUNITY TO PARTNER WITH THEM
TO LAUNCH A GENETIC STUDY OF
POSTPARTUM DEPRESSION. AND
APPLE SUGGESTED TO US THAT PACT
WASN'T A GREAT NAME, MAYBE
CHANGE IT TO PPD ACT POSTPARTUM
DEPRESSION ACTION TOWARD CAUSES
AND TREATMENT. WE WERE ABLE AND
USING SORT OF INTERNAL FUNDS
LOCAL FOUNDATION FUNDS IN A
VERY, VERY FAST SPRINT TO BUILD
THIS APP AND MANAGE THROUGH A
SMALL ACT OF GOD TO GET ETHICS
BOARD APPROVAL AT UNC SO WOMEN
COULD USE THIS FOR FREE, BOTH
INITIALLY IOS THEN ANDROID IN
ENGLISH AND SPANISH OVER TIME TO
ANSWER QUESTIONS ABOUT LIFETIME
HISTORY OF POSTPARTUM
DEPRESSION. AMEND THEN IF THEY
MET CRITERIA TO GIVE A GENETIC
SAMPLE. WE PARTNERED WITH THE
NIH AROUND THIS, THE NIH
GRACIOUSLY PROVIDED SPIT KITS,
FOR PEOPLE ELIGIBLE WOULD SEND
OUT THEN THEIR RETURN TO NIH
BIOREPOSITORY SO THIS IS PART OF
PUBLIC DOMAIN. WE HAVE HAD OVER
12,000 PARTICIPANTS TO DATE. I
WILL TELL YOU WHERE THIS IS
GOING NEXT BUT IT IS A PRETTY
AMAZING PROJECT. IT WAS LAUNCHED
ALSO IN AUSTRALIA AND CANADIANS
MADE ONE. THERE'S MODELS OF IT
IN SWEDEN AND DENMARK ALL TO
GAIN AS QUICKLY AS POSSIBLE
GENETIC SAMPLES. ASKING WOMEN
WITH LIFETIME HISTORIES TO
PARTICIPATE. WHAT HAPPENED NEXT
WHEN IT LAUNCHED IF YOU BUILD AN
APP AND NO ONE KNOWS YOU HAVE AN
APP YOU WON'T GET MUCH ACTION
WITH IT. WE WERE ABLE THE FIRST
STUDY USING APPLE RESEARCH KIT
TO GET A NEW YORK TIMES REPORTER
WRITING ABOUT POSTPARTUM
DEPRESSION INTERESTED. THE VERY
FIRST DAY WE LAUNCHED WE HAD
10,000 PEOPLE THAT SIGNED UP.
THREE DAYS BEFORE WE WERE
SUPPOSED TO START THE NIH
BIOREPOSITORY TOLD US YOU CAN'T
SEND OUT SPIT KITS YOU HAVE TO
BECAUSE OF PERSONAL HEALTH
INFORMATION SO WE HAD TO TURN
OURSELVES INTO A SPIT KIT
DISTRIBUTION FACTORY, ON VERY
LITTLE WARNING AND WE DIDN'T
KNOW WHEN IT LAUNCHED WE WERE
GOING TO HAVE FIVE PEOPLE SIGN
UP BUT WE HAD 10,000 WHO
INITIALLY ALL WERE NOT ELIGIBLE
NOR THE GENETIC PART BUT IT WAS
A BIT OF A WILD TIME IN TERMS OF
HOW THAT WENT. NONETHELESS WE
PREVAILED. AND A FEW YEARS LATER
GOT A CALL FROM AN ADVERTISING
AGENCY OUT OF THE BLUE IN IN LA
NAMED WONG DUTIFUL AGENCY
STARTED BY MR. WONG AND
MR. DUT DUTY. THEY SENT ME AN EL
SAYING WE WANT TO TALK TO YOU
ABOUT YOUR APP. I ALMOST DELETED
IT. THEY SAID WE SEE YOU HAVE
THIS APP AND WE EVERY YEAR PICK
A PRO BONO PROJECT AND YOU HAVE
WON. WE LIKE TO TAKE OUR
ADVERTISING SUPERPOWERS AND PUT
IT TO GOOD USE AN HELP YOU
TRANSFORM YOUR STUDY. WHICH IS
NICE TO SAY WE THINK YOUR
BRANDING SUCKS AND WE THINK WE
CAN DO BETTER. THIS COMPANY HAS
A LOT OF WOMEN EXECUTIVES SOME
THAT HAD POSTPARTUM DEPRESSION
WHICH I UNDERSTAND IS HOW IT GOT
PICKED. AND IT WAS PREBRANDED
AS MOM -- REBRANDED AS MOM GENES
FIGHT PPD. THIS IS ON THE
SATURDAY NIGHT LIVE SKIT I WEAR
MY MOM GENES JEANS IF YOU ARE
OLD ENOUGH TO REMEMBER. THEY
PUMPED A COUPLE DIFFERENT --
PITCHED A COUPLE OF PLANS AND WE
WENT WITH MOM GENES WHICH WAS
PITCHED BY THEIR LA OFFICE.
THEY HAD A SEATTLE OFFICE THAT
PITCHED SOMETHING THAT IS
FABULOUS BUT I CAN'T SAY PUBLIC
WILL AND NEVER STOOD THE ETHICS
BOARD AND I WILL TELL YOU AFTER
IF YOU DON'T MIND PROFANITY.
THIS LAUNCHED IN THE FALL OF
2019 REBRANDED. IT THRIVED OVER
THE COURSE OF THE PANDEMIC. AND
SO WE HAD VERY DUTIFUL RESEARCH
TEAM THAT CAME IN DURING THE
PANDEMIC SENDING OUT SPIT KITS,
THE LAST TRIP I TOOK BEFORE
MARCH OF 2020 WAS A TRIP TO LA,
SORT OF LAUNCHED THIS WHOLE
THING BUT IT BUILT THIS WHOLE
SOCIAL MEDIA COMMUNITY OF MOMS
COMING TOGETHER PARTICIPATING IN
THE APP SENDING IN GENETIC
SAMPLES, AND SO REALLY
FASCINATING TO WATCH THIS PLAY
OUT OVER PANDEMIC. LEADING TO WE
HAVE A FIRST PAPER UNDER REVIEW,
WE JUST GOT THE REQUEST FOR
REVISED RESUBMIT. THIS IS JERRY
(INAUDIBLE) WHO TRAINED IN
BALTIMORE CAME AS POST DOC AS
JUNIOR FACULTY MEMBER FUNDEDD ON
NIH EXTRAMURAL K AWARD. HE WAS
ABLE TO USE ALL THE APP BASED
DATA AND THE PACT CONSORTIUM
AROUND THE WORLD TO GET 70,000
PEOPLE, 17,000 PPD CASE, 53,000
CONTROLS: TO LOOK AT THE FIRST
GENETIC RISK FACTORS FOR
POSTPARTUM DEPRESSION. THIS META
ANALYSIS IS THE FIRST LARGE
SCALE GENOMIC INTERROGATION OF
THE PPD. ALLOWING US TO EXPLORE
THE RELATIONSHIP OF POSTPARTUM
DEPRESSION WITH OTHER GENETIC
TRAITS AND WHAT IS OF INTEREST
IS THAT IT IS SHOWN THIS WORK
IMPORTANT RELATIONSHIPS OF
GENETIC RISK POSTPARTUM
DEPRESSION WITH MAJOR DEPRESSION
OUTSIDE OF THE PERINATAL PERIOD
WITH BIPOLAR DISORDER WITH
INSOMNIA AND OTHER PSYCHIATRIC
DISORDERS. WHEN WE LOOKED AT IT
FURTHER OUR GENETIC VARIANTS IS
ENRICHED FOR SPECIFIC CELL TYPES
MOST NOTABLY GABBANERGIC OR
INHIBITORY NEURONS IN THE
THALAMUS AND HYPOTHALAMUS. WE
SAW SIGNIFICANT DIFFERENCES IN
POSTPARTUM DEPRESSION AND MAJOR
DEPRESSION. SO HERE IS THE DATA
LOOKING AT THE DIFFERENCES
BETWEEN CASES AND CONTROLS. IF
YOU LOOK AT MANHATTAN PLOT IT IS
NOT MAGIC. TEN TO MINUS 8, TEN
TO MINUS 7 SO LIKE MOST GWAS
STUDIES YOU CAN CONCLUDE LARGER
SAMPLE SIZES ARE NEEDED. THERE
IS ANOTHER 5 TO 10,000 TO DUMP
INTO IT SO WE ARE CLOSE. BUT
WHAT IS PARTICULARLY INTERESTING
OTHER THAN THAT TRENDING IS
THIS. IF YOU LOOK AT CELL
ENRICHMENT TYPE AND LOOK AT THE
TOP, LOOKING HERE AT POSTPARTUM
DEPRESSION VERSUS MAJOR
DEPRESSION OUTSIDE THE PERINATAL
PERIOD YOU CAN SEE INHIBITOR
NEURONS IN THE THALAMUS REALLY
SEEM TO BE DRIVING THE CELL TYPE
ENRICHMENT DIFFERENCES BETWEEN
THE TWO. THIS IS VERY RELEVANT
GIVEN WHERE I WANT TO GO NEXT.
WHICH IS THE STORY OF
BREXANALONE A POSITIVE
ALLOSTERIC MODULATOR OF GABBA
WHICH IS INHIBITORY. SO I THINK
THE CONNECTION OF THIS IN THESE
FINDINGS RECENTLY ARE REALLY
COMPELLING AND HELPING TELL
STORY OF WHY BREXANALONE WORKS.
SO I TOLD YOU ABOUT OUR
PERINATAL PSYCH UNIT. WE HAD THE
OPPORTUNITY AND WE ARE CONTACTED
BY STEVE PAUL WHO NOW WAS PART
OF A BRAND NEW START UP CALLED
SAGE THERAPEUTIC. AND HAD
REACHED OUT TO TALK ABOUT
WHETHER WE WERE INTERESTED IN
POTENTIALLY THINKING ABOUT
LOOKING AT THEIR NEW PRO PRY DAY
COMPOUND OF ALLO PREDNANALONE,
THEY HAD A PROPRIETARY
FORMULATION AS TREATMENT FOR
POSTPARTUM DEPRESSION. SO THE
IDEA WAS COULD YOU USE ALLO TO
SEE IF THERE WAS ANY SIGNAL? WE
STARTED THIS WITH THE MOST
MODEST OF EXPECTATIONS. THEY
HAD A PROPRIETARY FORMULATION IT
WAS AN IV DRUG STUDIED IN
TREATMENT REFRACTORY STATUS
LEPTICUS AND THEY WERE LOOKING
FOR OTHER IMPLICATIONS. WE WERE
INTERESTED IN ALLO A LONG TIME,
WE HAD INPATIENT UNIT DOING
CLINICAL TRIALS. AND I WAS VERY
INTERESTED IN LOOKING AT NOVEL
TREATMENTS THAT WOULD GIVE US
SOMETHING DIFFERENT AND
PARTICULARLY WITH THIS BE MUCH
FASTER ACTING THAN WHAT WAS THE
CURRENT BASELINE GOLD STANDARD
FOR PHARMACOLOGIC TREATMENT
LARGELY SSRIs. SO IT IS OF
NOTE IN THE SAME TWO WEEK PERIOD
IN MARCH OF 2019 THAT AFTER WHAT
I WOULD SAY IS A VERY LONG
DROUGHT IN NOVEL INNOVATION
ANTI-DEPRESS ISN'T TREATMENT YOU
HAD FDA APPROVE INTRANASAL
KETAMINE AND SAME TWO WEEKS HAD
BREX APPROVED. PBS FAST ACTING
ANTIDEPRESSANTS FOR DIFFERENT
INDICATIONS AND NIH CA AND HIS
GROUP WITH KETAMINE, POWERFUL
WORK BEING DONE BUT REALLY
INTERESTING IN TERMS OF THE FACT
THAT BOTH OF THESE TWO THINGS
ENDED UP BEING APPROVED IN THE
SAME TWO WEEKS IS AN INTERESTING
COINCIDENCE BUT SPEAKS TO THE
NEED FOR MORE INNOVATION IN THIS
SPACE. SO BREXANALONE IS A
PROPRIETARY FORMULATION OF ALLO,
THE FIRST APPROVED IN CLASS
TREATMENT FOR ADULT PATIENTS
WITH POSTPARTUM DEPRESSION BY
FDA MARCH OF 2019. AND IT WAS
STUDIED WE PICKED A PROTOCOL
WORKED ON PROTOCOL SKETCHED OUT
IN A CONFERENCE ROOM AT UNC FOR
AN OPEN LABEL STUDY TO SEE IF
THERE WAS ANY SIGNAL AT ALL. THE
IDEA WAS TO DO TEN PATIENTS. AND
WHAT WE WERE OVERWHELMED BY WAS
THE INITIAL FIRST PATIENT I WILL
DESCRIBE THAT BY THAT RESPONSE
WHICH LED US TO BELIEVE EITHER
THIS IS LIKE AN ACTIVE DRUG THAT
IS POWERFUL OR ONE HECK OF A
PLACEBO. SO BECAUSE WE HAD OUR
PERINATAL PSYCH UNIT, WE HAD A
WOMAN ADMITTED, SO IT WAS HER
SECOND BABY AND SHE HAD ONE
PREVIOUS EPISODE OF DEPRESSION
WHICH WAS AFTER HER FIRST BABY
WHERE SHE HAD NOT RESPONDED TO
OTHER ANTIDEPRESSANTS AND HAD
BEEN VERY DEPRESSED FOR ABOUT A
YEAR BEFORE IT RESOLVED. SHE
WAS THEN BACK AT BASELINE NOT
DEPRESSED. HAD THE SECOND BABY,
BECAME ACUTELY DEPRESSED,
WITHDRAWN, NOT EATING. NOT ABLE
TO SLEEP. SOCIALLY WITHDRAWN,
HAVING SUICIDAL THOUGHTS. FAMILY
EXTREMELY WORRIED. SHE HAD BEEN
ADMITTED TO OUR UNIT. WE
APPROACH AND ASKED IF SHE WAS
WILLING TO BE IN THIS OPEN LABEL
STUDY. AND BECAUSE SHE HAD HAD
BAD EXPERIENCE WITH SSRIs IN
TERMS OF SIDE EFFECTS AND FELT
BOTH GAVE HER TERRIBLE SIDE
EFFECTS INCLUDING GI THINGS
PREDOMINANTLY, AND WAS NOT
EFFECTIVE, THEY WERE WILLING TO
DO THIS. AND WITHIN 12 HOURS OF
THE 60 HOUR INFUSION HER -- SHE
HAD A COMPLETE AFFECTIVE STATE
CHANGE WHICH WAS REMARKABLE TO
SEE. I DON'T THINK YOU SEE THAT
WITH -- UNLESS YOU ARE SOMEONE
RESPONDING DOCKET MEAN, SHE WENT
FROM WITHDRAWN FLAT AFFECT TO
BRIGHT AFFECT SHE WENT FROM
SOCIALLY ISOLATED TO WANTING TO
TALK TO PATIENTS. SHE WENT FROM
NOT BEING INTERESTED IN EATING
AND HAD LOSS A HUGE AMOUNT OF
WEIGHT RAPIDLY TO WANTING HER
FOOD ON THE UNI UNIT. SO SUDDENY
SHE WENT FROM A DROOPY WILTED
FLOWER OF NOT MAKING IT TO
BRIGHTENED UP CONSIDERABLY, IT
WAS BIZARRE AND FUN TO WATCH.
AND WE WERE LIKE WOW, THAT IS
SOMETHING. AND IT COULD BE
PLACEBO BUT CERTAINLY
INTERESTING TO WATCH. SO THAT
STORY WAS REPEATED WITH THREE
MORE PATIENTS. WITH VERY
IMPRESSIVE RESPONSE AND THEN IN
WORKING WITH SAGE THERAPEUTIC
THEY DECIDED THAT RATHER THAN
COMPLETING THE OPEN LABEL STUDY
OF TEN PATIENTS, THEY WOULD MOVE
TO PHASE 2. AND GET TO THE
BOTTOM OF WHETHER THIS WAS A
POWERFUL PLACEBO RESPONSE OR
NOT. SO IT ENDED UP FDA
APPROVED. BUT LET ME TELL YOU
MORE ABOUT THE SCIENCE BEHIND
IT. IT IS A POSITIVE ALLOSTERIC
MODULATOR OF GABBA A, IT WORKS
INTRAAND EXTRA SYNAPTICALLY.
THIS IS IMPORTANT BECAUSE
COMPARED TO OTHER AGENTS LIKE
BENZODIAZEPINES THAT ALSO HAD
GABBA, THAT BREXANALONE HAS
INTRA AND EXTRA SYNAPTIC
INHIBITION. AND THAT MAKES IT
VERY UNIQUE COMPARED TO BENZOS
WHICH ARE NOT BOTH. THAT IS
VERY IMPORTANT TO NOTE. WE WERE
OFTEN ASKED WOULD YOU GET SAME
RESPONSE WITH BENZO? IF WE WERE
GOING TO GET THE SAME RESPONSE
WITH BENZOWE WOULD HAVE GOTTEN A
LONG TIME AGO BECAUSE WE HAVE
ALL THESE PATIENTS WE TREAT WITH
BENZOS THAT DON'T RESPOND IN
THIS WAY. SO THAT WAS THE
RATIONALE FOR LOOKING AT IT. WE
STARTED WITH THIS PROTOCOL THAT
AGAIN 60 HOURS, WHY 60 HOURS? WE
HAD TO TITRATE UP AND DOWN SO
YOU DON'T HAVE ABRUPT
DISCONTINUATION. YOU HAD TO
REACH STEADY STATE AND WE
THOUGHT WE HAD TO TREAT FOR AT
LEAST 48 HOURS. ARBITRARILY
DECIDED THAT THE LONGEST YOU
COULD GET A MOTHER TO COOPERATE
WOULD BE ABOUT 60 HOURS IN THE
HOSPITAL. SO AGAIN JUST A SENSE
OF EVERYTHING WITH HOW WE COME
UP WITH PROTOCOLS IS OBVIOUSLY
THERE IS THE ART AND THERE'S THE
SCIENCE. THEN THERE IS THE
PRAGMATIC WHAT ARE YOU ABLE TO
ACTUALLY DO. THAT IS HOW THAT
WAS DESIGNED. THERE ENDED UP
BEING THREE STUDIES NEARLY
LOOKING AT TWO DOSES OF BREX, 60
VERSUS 90. ALL WE KEPT THE EXACT
SAME PROTOCOL. YOU COULD SAY
THAT WE SHOULD HAVE LOOKED AT
EASIER WAYS OF DOSING BUT THERE
WAS MOTIVATION TO SEE IF YOU CAN
GET IT OVER THE FINISH LINE AND
SLOWING DOWN AND CHANGING THE
PROTOCOL COULD HAVE LED TO
DIFFERENT RESULTS AND THE PHASE
2 STUDIES WERE VERY, VERY ROBUST
IN TERMS OF DIFFERENCES BETWEEN
ACTIVE DRUG AN PLACEBO. AND THEN
THE PHASE 3 STUDIES ALSO SAW
STATISTICALLY AND CLINICALLY
SIGNIFICANT DIFFERENCES THOUGH
MUCH HIGHER PLACEBO RESPONSE. BY
THE TIME WE WERE DOING PHASE 3
STUDIES WOMEN WERE COMING IN TO
US COMING FROM ACROSS THE
COUNTRY TO PARTICIPATE WITH
THEIR ARM OUT, I'M READY, I WAS
WORRIED WE WOULD NEVER SEE A
DIFFERENCE IN RESPONSE BECAUSE
PHASE 3 STUDIES HAVE BEEN THE
BANE OF THE EXISTENCE FOR
PSYCHIATRY IN TERMS OF COMBATING
AGAINST PLACEBO EFFECTS. BUT
NONETHELESS WE DID BOTH BY THE
HAMILTON DEPRESSION SCORE, THE
PRIMARY OUTCOME MEASURE, A
DEPRESSION SCORE, AND THE
CLINICAL GLOBAL IMPRESSION
INDEX. PEOPLE WERE FOLLOWED FOR
INITIAL -- THE 60 HOUR MARK,
SEVEN DAYS, OUT, THEN FOLLOWED
THROUGH 30 DAYS OVERALL. THAT IS
WHEN THE STUDY ENDED.
WE SAW YOU SEE THIS RAPID ONSET
OF ACTION IN THE FIRST 12 HOURS
AND THEN CHANGES OVER TIME.
THAT ARE REMAIN. THEN YOU CAN
SEE THE HAMD RESPONSE. THE HAM D
THAT PILL TN DEPRESSION SCALE
GOLD STANDARD FOR DEPRESSION AND
IT WAS DEVELOPED AS
ANTIDEPRESSANT AND WE WERE
WANTING TO LOOK AT WHETHER IT
WAS EFFECTIVE FOR DEPRESSION OR
NOT. PRIMARY SIDE EFFECTS ARE
-- WERE SEDATION AS WOULD BE
EXPECTED WITH A POSITIVE
ALLOSTERIC MODULATOR OF GABA.
IT WAS APPROVED WITH FDA REMS
INDICATION MEANING IT HAS TO BE
ADMINISTERED IN A MEDICALLY
SUPERVISED SETTING TO PREVENT
OVERSEDATION. ALL THE TRIALS OF
BREXANALONE AND TREATMENTS
INCLUDING STATUS EPILEPTICUS IF
YOU HAD A TREMOR AND YOU GOT A
PUMP MALFUNCTION MORE OF THE
DOSE ONE PATIENT PASSED OUT. SO
NONETHELESS THAT WAS THE WAY WE
DELIVERED IT NOW. WHEN APPROVED
IT WAS UNCLEAR HOW THE RESULTS
WOULD HOLD UP IF YOU LOOK AT
MORE MODERATE PATIENTS, HOW ARE
YOU GOING TO DELIVER THIS IN A
WAY WITH AN IV DRUG THAT
REQUIRED A MEDICALLY SUPERVISED
SETTING FOR PEOPLE THAT MAY NOT
MEET CRITERIA FOR IN PATIENT
PSYCHIATRY RESULTS. WHAT WOULD
HAPPEN AFTER 30 DAY?
WOULD IT BE LIKE KETAMINE,
NEEDED TO BE REPEATED. NO ONE
KNEW. WE HAVE PUBLISHED IN THE
CONSULT LIAISON JOURNAL RECENTLY
A SERIES CASE STUDY, MY TERRIFIC
COLLEAGUE DR. PATTERSON, MEDICAL
DIRECTOR OF THE PERINATAL UNIT
AND REASONS THE CLINICAL
PROGRAM, 16 PATIENTS WHO
RECEIVED COME IN FOR CLINICAL
PROGRAM, THIS IS PAID FOR BY
INSURANCE COMPANIES, SAGE
THERAPEUTICS PRICED AT SOME
RIDICULOUSLY CRAZY HIGH COST
WHICH HAS BEEN CHALLENGING FOR
THEM. BUT WE HAVE BEEN ABLE TO
LARGELY GET INSURANCE COMPANIES
TO PAY FOR IT. IRONICALLY IN
ALSO IN THE SUMMER OF 2019 JOINT
COMMIT MADE MUCH MORE STRINGENT
GUIDELINES FOR LIGATURE RISK. SO
WE ARE NOW NOT ABLE TO DELIVER
ON PERINATAL PSYCH UNIT STUDYING
FOR FIVE YEARS LEADING TO FDA
APPROVAL WE DELIVER NOW ON A
WOMEN'S HOSPITAL UNIT SORT OF
GYN UNIT. AND WE HAVE BEEN
WORKING TO GET THAT BACK IN
GEAR, THEN THE MAKE HIT AND
EVERYONE WITH IN PATIENT PSYCH
WAS COMPLICATED. BUT THERE IS NO
LACK OF IRONY HOW THAT GOES. AND
SO IF SOMEONE IS SUICIDAL WE
HAVE A SITTER WITH THEM AND THEN
WE WERE ABLE TO WORK WITH
WOMEN'S HOSPITAL COLLEAGUES TO
DELIVER THE IV DRUG THERE. IN
THE CASE SERIES THAT WE
PUBLISHED WE CONTINUE TO SEE A
PERSISTENT EFFECT, MANY OF THE
PATIENTS STOP THIS AND ARE
STARTED ON AN SSRI BECAUSE THERE
CONCERN WHAT HAPPENS ONCE THIS
IS GONE. BUT WE HAVE CONTINUED
TO SEE A PERSISTENT TREATMENT
EFFECT OVER TIME. PAST THE 30
DAYS AND IN THIS CASE WE HAVE
SEEN ONGOING REDUCTION IN
DEPRESSIVE SYMPTOMS AND
FOLLOWING PEOPLE OUT BETWEEN
THREE AND 16 MONTHS AFTER
INFUSION BECAUSE AGAIN THIS IS
JUST CLINICAL CARE AND PEOPLE
COME IN AT ALL DIFFERENT TIMES
TO GET IT. SO OBVIOUSLY AN IV
DRUG THAT NEEDS TO BE
ADMINISTERED ON A PSYCH UNIT IS
NOT CONVENIENT TO SAY THE LEAST.
MOST PLACES HAVE HAD DIFFICULTY
GETTING THIS SET UP, MANY PLACES
HAVE. SO NATIONALLY THERE ARE
CENTERS THAT ARE DOING IT BUT IT
IS NOT WIDELY AVAILABLE, IT IS
ALSO VERY COSTLYLY. SAGE
THERAPEUTICS HAS BEEN DEVELOPING
ZURANOLONE, A NEUROSTEROID, AN
ORAL DRUG, IT IS NOT AN ORAL
VERSION OF BREXANALONE. IT HAS A
DIFFERENT RING HERE THIS LITTLE
RING ADDED. TO BOTH INCREASE
ORAL STABILITY AND THEN ALSO THE
YOU END UP WITH A MUCH LONGER
PATENT OF TEN YEARS IF YOU HAVE
SOMETHING THAT IS NOT AN
ENDOGENOUS COMPOUND. THIS HAS
BEEN STUDIED OVER TIME AND WE
HAVE BEEN -- I HAVE BEEN ONE OF
THE INVESTIGATORS ON THE TRIAL
AS WELL. THE DESIGN IS A DAILY
TREATMENT FOR 14 DAYS. AND
PATIENTS TAKE THAT ONCE A DAY
FOR TWO WEEKS. AND THEN FOLLOWED
THROUGH DAY 15 IS THE PRIMARY
END POINT MEASURE AND THEN THIS
STUDY WOMEN FOLLOWED FOR 45 DAYS
OUT. INCLUSION CRITERIA SAME AS
WITH BREXANALONE. IN BOTH
STUDIES THE ONSET OF SYMPTOMS
HAS TO BE VERY PROXIMAL TO
CHILDBIRTH. IF WE THINK ABOUT
THE PRECISION PSYCHIATRY
APPROACH, IF YOU SCREEN SOMEONE
AT SIX WEEKS POSTPARTUM AND THEY
ARE DEPRESSED, YOU NEED TO KNOW
WHETHER THEY HAVE BEEN DEPRESSED
FOR 20 YEARS AND YOU JUST HAPPEN
TO BE SCREENING AT THAT TIME
POINT OR YOU HAD ONSET
DEPRESSION PROXIMAL TO
CHILDBIRTH OR THEY STARTED WITH
DEPRESSION IN THE FIRST
TRIMESTER BECAUSE OF A
PSYCHOSOCIAL STRESSOR THAT MAY
HAVE TRIGGERED IT. AND YOU
CAN'T PUT EVERYONE ON THE SAME
BUCKET BECAUSE YOU ARE NEVER
GOING TO END UP WITH ONE TRYING
TO FIGURE OUT IF SOMETHING GOING
TO WORK FOR THAT PARTICULAR
INDICATION AND OFTEN YOU MAY BE
MIXING APPLES AND ORANGES IN
DIFFERENT PATHOPHYSIOLOGY. MAJOR
DEPRESSIVE DIAGNOSIS DSM 5,.
SYMPTOMS LATE THIRD TRIMESTER OR
WITHIN THE FIRST MONTH
POSTPARTUM, VERY PROXIMAL TO
CHILDBIRTH THEY HAD TO START.
YOU CAN HAVE A HISTORY OF
DEPRESSION. BUT IN ALL STUDIES
WE REALLY TRIED TO BE VERY
SPECIFIC TO UNDERSTAND THE
PATHOPHYSIOLOGY AND UNDERSTAND
HOW THIS PARTICULAR DRUG ALLO
PREGNAL AALO INE ALLOSTERIC
MODULATOR OF GABA MAYBE
EFFECTIVE OR NOT. WITH
ZURANALONE YOU HAVE FAST ONSET
OF ACTION BUT IT IS NOT 12
HOURS, TAKES 3 TO 6 DAYS BUT
THEN YOU SEE MARKED REDUCTION IN
SYMPTOMS. FOLLOWED OVER TIME.
THEY PERSIST, THIS IS IN
POSTPARTUM DEPRESSION. IF YOU
COMPARE ZURANOLONE IN ORANGE
WITH PLACEBO IN GRAY YOU SEE
DIFFERENCES OVER TIME THAT
PERSIST. ADVERSE EVENTS AND SIDE
EFFECTS YOU CONTINUE TO SEE
SO,OMULENCE IS PRIMARY BUT MUCH
LESS SEVERE WITH ORAL DRUG
COMPARED TO IV DRUG. THIS WAS
SUB PUBLISHED IN PSYCH A FEW
YEARS AGO. CHRISTINE (INAUDIBLE)
WAS SECOND AUTHOR LOOKING AT
THIS AND WE HAVE THE SECOND
PHASE 3 TRIAL PAPER COMING OUT
SHORTLYLY. WHICH BASICALLY
REPLICATES FINDINGS, THIS IS THE
SKY LARK STUDY, THEY USED A
50-MILLIGRAM DOSE WITH THE
SECOND PHASE 3 TRIAL AND
POSTPARTUM DEPRESSION COMPARED
TO A 30-MILLIGRAM DOSE IN THE
FIRST THAT WAS PUBLISHED.
OTHERWISE RESULTS ARE BOTH
ROBUST, FAST ACTING AND EWE YOU
SEE CHANGE OVER TIME. THIS IS
WHAT THE NEWEST DATA LOOKS LIKE
IN THIS NEW PAPER THAT WILL BE
OUT SOON OVER TIME AND YOU SEE
14 DAYS OF TREATMENT FOLLOWED
OUT OVER 45 DAYS. SAGE
THERAPEUTICS ALSO STUDIED THIS
IN MAJOR DEPRESSION OUTSIDE OF
THE PERINATAL PERIOD WITH MORE
MIXED RESULTS BUT NONETHELESS
THEY HAVE IT FILE WITH THE FDA
RIGHT NOW. IT'S BEEN FAST TRACK
WITH THE FDA, FOR INDICATION FOR
BOTH POSTPARTUM DEPRESSION AND
MAJOR DEPRESSION OUTSIDE OF THE
PERINATAL PERIOD AND IF
APPROVED, WILL BE INTERESTING TO
SEE WHAT HAPPENS, HOW IT IS
USED. IT WILL CERTAINLY HAVE
WIDESPREAD INDICATION, THERE
WON'T BE A RIMS. AND THE
DIFFERENCES BETWEEN THE
ROBUSTNESS OF THE POSTPARTUM
DEPRESSION RESPONSE AND
DEPRESSION OUTSIDE THE PERINATAL
PERIOD IS INTERESTING. AGAIN,
SPEAKING TO WHAT IS THE ROLE OF
NEURAL STEROIDS DIFFERENTIAL
SENSITIVITY FOR THOSE THAT
RESPOND, ABOUT 70% OF WOMEN
RESPOND TO BREXANALONE, 30%
DON'T. WHY IS THAT? THERE IS
CLEARLY UNDERLYING MECHANISTIC
DIFFERENCES WE DONE YET
UNDERSTAND. SO WHAT IS NEXT? WE
HAVE AN OPEN LABEL TRIAL
UNDERWAY IN POSTPARTUM PSYCHOSIS
BECAUSE ANYONE WITH BIPOLAR
DISORDER HISTORY OF PSYCHOSIS IS
EXCLUDED FROM THE POSTPARTUM
DEPRESSION TRIALS. DOES IT
WORK? IS IT DIFFERENT? IS
POSTPARTUM PSYCHOSIS A DIFFERENT
DISORDER THAN MAJOR DEPRESSION?
FOR POSTPARTUM DEPRESSION, A
VERY HOT AREA OF STUDY. I ENJOY
TALKING WITH PETER SCHMIDT AND
TEAM ABOUT THE WORK THEY ARE
INTERESTED IN DOING HERE IN
THIS. THEN THE OTHER THING WE
ARE DOING IN COLLABORATING WITH
LESLIE MOREAU AT UNC IS WHY DOES
BREXANALONE WORK? WE KNOW IT IS
A NEURAL STEROID, IT IS A
POSITIVE ALLOSTERIC MODULATOR OF
THE GABA. APPARENTLY THAT ALSO
HELPFUL IN MAJOR DEPRESSION
OUTSIDE THE PERINATAL PERIOD
BASED ON ORAL DRUG STUDIES OF
ZURANALONE. SO WHY DOES IT WORK
WE RESENTLY PUSHILIED A PAPER
LOOK AT -- PUBLISHED A PAPER
LOOKING AT BREX AND LOOKING AT
INHIBITION OF SYSTEMIC
INFLAMMATORY PATHWAYS. LESLIE,
THIS IS HER SCIENCE AND BASIC
SCIENCE LAB, AS I MENTIONED DR.
PATTERSON IS THE INVESTIGATOR
AND SHE'S THE MEDICAL DIRECTOR
OF PATIENT PERINATAL UNIT SO
THIS IS AN EXAMPLE OF TEAM
SCIENCE. WELCOMING IN FOR
CLINICAL BREXANALONH PROGRAM, WE
COLLECT SAMPLES AND SEND IT OVER
TO DR. MOREAU'S LAB. SO THAT WE
WERE ABLE TO STUDY POTENTIAL
CONTRIBUTIONS OF INFLAMMATORY
PATHWAYS. WE WANTED TO TEST
HYPOTHESIS OF WHETHER
BREXANALONE INHIBITS
PRO-INFLAMMATORY MODULATORS AND
MACROPHAGE ACTIVATION. WE SAW
ALTERED REDUCED LEVELS OF
INFLAMMATORY MEDIATORS AND
INHIBITED RESPONSE TO
INFLAMMATORY IMMUNE ACTIVATORS.
SO THIS IS REALLY INTERESTING
WORK. WE SAW ACTIONS THAT IT
CAUSED INLOBBYINGS OF
INFLAMMATORY MEDIATOR INHIBITION
TO TLR 4, TLR 7 ACTIVATORS
SUGGESTING INFLAMMATION MAY PLAY
A ROLE IN POSTPARTUM DEPRESSION
AND THAT THE INHIBITION OF
INFLAMMATORY PATHWAYS CRIBS TO
THERAPEUTIC EFFICACY. HERE IS
LESLIE MOREAU AND DR. PATTERSON.
I LOVE THIS BENCH TO BEDSIDE
MODEL. WHICH IS THIS IS LESLIE
MOREAU AND TEAM RUN BASIC
SCIENCE LAB PARTNERING WITH ONE
OF OUR CLINICIAN EDUCATORS TO
PARTNER IN THIS AND HERE IS THE
DATA YOU SEE LOOKING AT THE
DIFFERENCES PRE- AND POST BEFORE
TREATMENT IN TERMS OF IMMUNE
INHIBITION. SO TO CONCLUDE, THE
PANDEMIC HAS CERTAINLY HAD THIS
PROFOUND IMPACT ON THE ENTIRE
WORLD. I SEE IT AS A GLOBAL
TRAUMA. IT HAS MARKEDLY WORSENED
MENTAL HEALTH AND WE NOW HAVE A
ENORMOUS MENTAL HEALTH CRISIS
FACING THE COUNTRY. ALL OF US
ARE I THINK HAVE TO RISE TO THE
OCCASION AND AS A PSYCHIATRIST
AND A CHAIR OF A LARGE
DEPARTMENT I AM FACED EVERY DAY
WITH HOW WE MEET OUR CLINICAL
MISSION, HOW DO WE MEET OUR
RESEARCH MISSION OUR TRAINING
MISSION, TO ADDRESS THE PUBLIC
HEALTH CRISIS WE FACE?
TELEHEALTH IS TURNING OUT TO BE
QUITE ADVANTAGEOUS FOR
PSYCHIATRY AND BEHAVIORAL
HEALTH, TRYING TO USE THAT
STRATEGICALLY. BEEN PARTNERING
WITH MY HEALTHCARE SYSTEM TO
BRING EXPERTISE TO CONSULT
ACROSS NORTH CAROLINA AND RURAL
AREAS WHERE THERE ARE NO MENTAL
HEALTH PROVIDERS AND THAT HAS
MADE US POPULAR. SO THAT HAS
BEEN AN OPPORTUNITY, THERE'S
BEEN HUGE NEED FOR PEOPLE TO
ENGAGE, WE ARE NOW SEEING RECORD
NUMBERS OF YOUNG PEOPLE APPLYING
IIN PSYCHIATRY FOR RESIDENCY. WE
ARE SEEING MARKED INCREASES IN
PHILANTHROPIC CONTRIBUTIONS, AND
NIH HAS A POWERFUL ROLE TO PLAY
IN THIS. AND THAT THERE IS A
GREAT NEED FOR NEW RAPIDLY
ACTING TREATMENTS THAT WILL
BREXA INHOLONE IS A GREAT
EXAMPLE OF STORY THAT USES THE
UNDERLYING PATHOPHYSIOLOGY TO
DEVELOP A NOVEL TREATMENT AND
STEP TOWARDS ASPIRATIONALLY HOW
WE THINK ABOUT PRECISION
PSYCHIATRY. SO LOVE ONE DAY TO
APPROACH IT IN THE WAY WHICH
APPROACH BREAST CANCER SO YOU
DON'T JUST THROW JELL-O AT THE
WALL AND SEE WHAT HITS. HOW CAN
WE DO BETTER TO CARE FOR MOTHERS
AND THEIR CHILDREN. SO LASTLY
MT. SPIRIT OF GREAT TEACHER TALK
I WANTED TO SHARE QUICKLY THINGS
I HAVE LEARNED ALONG THE WAY,
ONE IS PASSION FOR MAKES A
DIFFERENCE, YOU HAVE TO BE
PERSISTENT IN WHATEVER WE DO
THAT RELATIONSHIPS MATTER A LOT.
I STILL AM IN TOUCH WITH MENTORS
AND COLLABORATORS I HAVE HAD FOR
DECADES THAT KINDNESS AND
GENEROSITY OF SPIRIT GOES A LONG
WAY ASSUMING GOOD INTENTIONS,
NOT TAKING YOURSELF TOO
SERIOUSLY WHICH I THINK IS
REALLY IMPORTANT. AND MAKING
SURE YOU HAVE A LIFE OUTSIDE OF
WORK WHICH I THINK CONTRIBUTES
TO PEOPLE'S HAPPINESS AND
EFFECTIVENESS. SO JUST WANTED TO
THANK ALL COLLEAGUES
COLLABORATORS AND PATIENTS WHO
TRUST US WITH THEIR CARE. IT IS
A REAL PRIVILEGE AND HONOR TO BE
PART OF PEOPLE'S LIVES IN THIS
WAY. AND TO MYRY IF I CAN
COLLEAGUE AT OUR UNC CENTER FOR
WOMEN'S MOOD DISORDERS. THANK
YOU.
[APPLAUSE]
>>NOW YOU CAN SEE WHY DR. BRODY
IS A GREAT TEACHER. REALLY
COMPREHENSIVE AND WONDERFUL. I
DO HAVE ONE QUESTION FOR YOU
FROM THE VIDEOCAST.
>>OKAY.
>>IF PEOPLE WANT THE ASK
QUESTIONS THEY CAN COME UP TO
THE MICROPHONE, I THINK WE HAVE
GOT ONE OR TWO QUESTIONS. SO YOU
MAY OR MAY NOT HAVE TOUCHED ON
THIS, AS SOMEONE WHO HAVE PEOPLE
WITH PMMD IN MY LIFE I WAS
WONDERING ARE PEOPLE WITH PMMD
AT HIGHER RISK OF PERINATAL
DEPRESSION?
>>IT IS A GREAT QUESTION. YOU
HAVE ONE OF THE WORLD'S EXPERTS
ON PMDD SITTING HERE. SO I THINK
THAT THE LITERATURE IS
CONFLICTED IN TERMS OF SOME
WOMEN APPEAR TO HAVE
DIFFERENTIAL SENSITIVITY TO ANY
TIME OF HORMONAL FLUX SO YOU SEE
PEOPLE THAT SAY I HAVE PMDD I
HAD PERINATAL DEPRESSION AND
FOLLOWED ME THROUGH THE
PERIMENOPAUSE TRANSITION. OTHERS
DO NOT. THEY MAY HAVE ONE AND
NOT THE OTHE OTHER. SO THERE ARE
WOMEN WITH PMDD WHO DON'T HAVE
PERINATAL DEPRESSION AND WOMEN
WITH PERINATAL DEPRESSION
WITHOUT PMDDD. DIFFERENT
MECHANISMS LIKELY THERE'S BOTH
PEOPLE THAT MAY HAVE
DIFFERENTIAL SENSITIVITY BECAUSE
THE UNDERLYING PATHOPHYSIOLOGY
IS SPECIFIC TO THAT VERSUS A
DIFFERENT UNDERLYING
PATHOPHYSIOLOGY FOR WHAT IS
TRIGGERING POSTPARTUM
DEPRESSION. SO THE JURY IS OUT.
BUT BEING STUDIED. BUT IT IS
NOT AS SIMPLE ANSWER OF YES NO R
NO.
(OFF MIC)
SOME SOCIAL MEDIA FEED ON IN
NATURE ABOUT THESE THINGS THAT
WE ARE TALKING ABOUT TOO MUCH
NOW ABOUT CHAT GTP AND LARGE
LANGUAGE MODELS. WHEN I SAW
YOUR SUMMIT SLIDES I WAS
WONDERING I KNOW WE ARE GOING TO
STUDY THESE MODELS IN VARIOUS
CONTEXT BUT WHAT ARE YOUR
THOUGHTS ABOUT THAT IN THIS
PARTICULAR AREA YOU ARE TALKING
ABOUT SUM A -- SUCH AS SUMMIT
TRIAL IS? IS THAT GOOD BAD UGLY?
>>I THINK IT IS HERE TO STAY
AND WE HAVE TO LEVERAGE IT FOR
GOOD. SO I THINK THAT HOW WE
REACH PATIENTS TO HELP PEOPLE
HAVE EDUCATION, TO HAVE
SCREENING, TO THEN GET
INFORMATION ABOUT WHERE TO SEEK
CARE, TO GET THINGS OUT OF THE
DARK WHICH IS MOTHERS WILL FEEL
THEY ARE FAILING BECAUSE THEY
DON'T UNDERSTAND WHAT THEY HAVE
AND NO ONE TOLD THEM AND THEY
FEEL LIKE THEY ARE HORRIBLE.
THAT USING SOCIAL MEDIA AND AI
AND OTHER THINGS THAT CAN DETECT
AND YOU CAN DETECT WHO IS AT
RISK FOR THINGS BASED ON ANY
NUMBER OF THINGS, I THINK THOSE
ARE ALL POTENTIAL GOOD. THEN
WILL IS DOWN SIDE. SO IT IS A
REAL -- EVERYTHING IN THAT REALM
IS A DOUBLE EDGE SWORD AND HOW
WE NAVIGATE THAT IS GOING TO BE
I THINK ONE OF THE GREAT
CHALLENGES OF OUR TIME.
>>THANKS SO MUCH. SO FOR PEOPLE
THAT ONSET THIRD TRIMESTER WHAT
YOUR THOUGHTS STARTING TREATMENT
DURING PREGNANCY?
>>WELL, WE DO. WE DON'T USE
ALLO PREGNANOLONE BECAUSE YOU
ALREADY HAVE HIGH LEVELS OF
HORMONES AND THAT WOULD BE
CHALLENGING, IT IS NOT APPROVED
IN PREGNANCY. BUT WE CERTAINLY
TREAT WITH SSRIs, FIRST LINE
TREATMENT IS PSYCHOTHERAPY. WE
DO THAT REGULARLY BUT WE ALSO
TREAT WITH OTHER ANTIDEPRESSANTS
SSRIs, FOR PEOPLE THAT START
GETTING DEPRESSED OR WHO HAVE A
PREVIOUS HISTORY TO TRY AND
MITIGATE AND WARD IT OFF.
DEPENDING ON THE LEVEL OF
SEVERITY, WE GET MORE OR LESS
AGGRESSIVE IF SOMEONE HAS
HISTORY DEPENDING ON WHAT
HAPPENED. BUT YES I THINK
INTERVENING DURING PREGNANCY IS
HUGE. INTERVENING WHEN PEOPLE
HAVE MILD SYMPTOMS TO TRY TO
PREVENT FROM WORSENING IS REALLY
IMPORTANT.
>>THANK YOU VERY MUCH. WE ARE
GOING TO GIVE YOU YOUR AWARD.
[APPLAUSE]
>>I'M THE CHAIR OF THE
MEDICAL EXECUTIVE COMMITTEE AND
ON BEHALF OF THE MEDICAL
EXECUTIVE COMMITTEE WE ARE
DELIGHTED TO PRESENT TO THIS
VERY BEAUTIFUL PLAQUE TO DR.
SAMANTHA MELTZER BRODY FOR
DELIVERING CONTEMPORARY
MEDICINES GREAT TEACHER LECTURE.
THIS WILL BE MAILED TO HER SO
SHE DOESN'T HAVE TO TAKE IT BACK
ON THE PLANE.
>>THANK YOU. I APPRECIATE IT.
IT IS BEAUTIFUL. THANK YOU.