Diagnosis and brain mechanisms of pediatric bipolar disorder

Ellen Leibenluft, M.D.

Section on Bipolar Spectrum Disorders
Emotion and Development Branch
NIMH Intramural Research Program
301-496-8381 irritablekids@mail.nih.gov
I. Controversy about the diagnosis of bipolar disorder in youth
A. BD clearly exists in children. Both it and severe irritability are very impairing. Accurate diagnosis is
important to facilitate the most effective treatments, now and in the future.
B. In adults, bipolar disorder (BD) is characterized by episodes of mania and depression. Episode is
characterized by:
1. change in mood and other symptoms from baseline
2. onset of accompanying symptoms (thinking, sleep, etc.) at the same time as change in mood.
C. Hypothesis: BD in youth is not episodic. Instead, it is characterized by severe, chronic irritability and
ADHD symptoms.
1. Definition of irritability: temper outbursts, between-outburst grumpy mood
2. Treatment implications: use of stimulants and/or SRIs.
II. How to test the hypothesis above?
A. Longitudinal studies. If chronic irritability is a pediatric form of BD, severely irritable youth
should develop manic episodes as they age.
1. Irritability in youth predicts unipolar depression and anxiety disorders in adulthood, not
mania.
2. Manic/hypomanic episodes tend to continue in youth who have them.
B. Family history. Childhood irritability is not associated with family history of BD.
C. Conclusion: Diagnosis of BD most appropriate for those with a history of a clear
manic/hypomanic episode.
D. Treatment: use of stimulants (clear evidence that it helps with irritability, but relatively
contraindicated in BD) and/or SRIs (impact on irritability less clear).

III. Deficits in face emotion processing in pediatric and adult bipolar disorder and in children at risk
A. Definition of endophenotype: heritable biomarker.
1. Should be present in both adults and youth with BD, and in unaffected youth at risk for BD.
2. Why it is important to study youth at risk for BD.
B. Face emotion labeling deficits present in both adult and pediatric BD
C. In pediatric BD, face emotion labeling errors associated with failure to look at the eyes on the
face. They tend to look at the nose or mouth instead.

D.
D. Unaffected children at risk for BD also have face emotion labeling deficits.

E. Adults and children with BD, and children at risk for BD, have the same amygdala dysfunction
when processing emotional faces.

F. Are these deficits an important link in the causal chain of BD, or is this just a good way to probe
the mood regulation system? If kids could identify faces better, would their mood cycling
diminish?

DO YOU HAVE A CHILD WITH

Photos 2009 Jupiterimages Corporation

At the NIH Clinical Center in Bethesda,

Maryland, several research studies are
being conducted into the causes of
bipolar disorder and severe mood
dysregulation (SMD).
These studies seek children and
adolescent participants who have
bipolar disorder or severe irritability.
All evaluations, research procedures,
inpatient (day or full hospitalization) and
outpatient visits are free of cost. Both
parent and child must agree to the childs
participation. Schooling is provided
during inpatient care.
Children and parents are compensated
for participation. Travel and lodging
expenses are paid by NIMH.

Bipolar Disorder or Severe Irritability?

STUDIES OF BIPOLAR DISORDER
Those eligible to participate must be ages 6-17,
have bipolar disorder and be able to perform
research tasks including neuroimaging,
computer tasks, and neuropsychological tasks.
This is an outpatient descriptive study using
brain imaging and clinical assessment. Study
participation begins with an initial outpatient
evaluation that lasts one day. Subsequently,
testing and brain imaging occur at visits which
last two-three days, occur every year, and
continue until age 25. Phone contact occurs
every six months in between visits.
Protocol #: 00-M-0198

BiPOLARKids
Intramural Research Studies at NIMH

FOR FURTHER INFORMATION,

CALL:

Department of Health & Human Services

Naonal Instutes of Health
Naonal Instute of Mental Health

3014968381

Ellen Leibenluft, M.D. or Kenneth Towbin, M.D.

Email: irritablekids@mail.nih.gov
TTY: 1-866-411-1010

STUDIES OF SEVERE IRRITABILITY

Those eligible to participate must be:

Ages 7-17.

Displaying symptoms of chronic anger, sadness, or

irritability, as well as hyperarousal (such as insomnia,
distractibility, hyperactivity) and extreme responses to
frustration (such as frequent, severe temper tantrums).

Able to perform research tasks that include

neuroimaging, computer tasks and neuropsychological
testing.
Participants must currently be in treatment with a physician,
medically healthy, and not currently hospitalized, psychotic,
or suicidal.
A) Non-Treatment Study:
This is an outpatient descriptive study using brain imaging
and clinical assessment. Study participation begins with an
initial outpatient evaluation that lasts one day. Subsequently,
testing and brain imaging occur at visits which last two-three
days, occur every two years, and continue until age 25.
Phone contact occurs every six months in between visits.
B) Treatment Study:
If unstable on current medications participant receives day
or full hospitalization to discontinue medication and
participate in a 12- to 15-week study of the efficacy of
methylphenidate plus citalopram, vs methylphenidate plus
placebo, for decreasing irritability in children with severe
mood and behavioral problems.
If clinically appropriate, participants who received
methylphenidate plus placebo will be offered the
opportunity to receive methylphenidate plus citalopram
at the end of the study.

http://patient info.nimh.nih.gov
Protocol #: 02-M-0021 & 09-M-0034

Photos 2009 Jupiterimages Corporation

NIH RESEARCH STUDY

Does your child have a family

member with Bipolar Disorder?
Consider Participation in a Bipolar Family Study for Children

Researchers at the National Institute of Mental Health

are seeking children who have parents or siblings with
bipolar disorder to participate in non-treatment research.
The purpose of this study is to compare symptoms and
brain function in children at risk vs. children who are not
at risk, with the ultimate goal of being able to predict who
will develop the illness and how to prevent it.
This is an outpatient research study. Participation includes
1-3 visits of 3 hours each at the NIH Clinical Center in
Bethesda, Maryland. As part of the research, a clinical
assessment is provided at no cost to the participant.

NATIONWIDE RECRUITMENT
Those eligible to participate must:
Be between the ages of 6-17
Have parental permission
Have a parent or sibling with
bipolar disorder
Be medically healthy
Participants may or may not have
been diagnosed with a psychiatric
disorder. Those taking medication
may be eligible for participation.

All clinical evaluations, research procedures, and outpatient visits are free of cost. Children and
parents are compensated for participation. Travel and lodging expenses paid for by NIMH.
Participants from across the country may be eligible to participate.

BiPOLARKids
Intramural Research Studies at NIMH

FOR FURTHER INFORMATION, CALL:

3014968381

Ellen Leibenluft, M.D. or Kenneth Towbin, M.D.

Email: bipolarkids@mail.nih.gov
TTY: 1-866-411-1010

Protocol #: 00-M-0198

NATIONAL INSTITUTE OF MENTAL HEALTH

NATIONAL INSTITUTES OF HEALTH, DEPARTMENT OF HEALTH & HUMAN SERVICES
http://patient info.nimh.nih.gov Pediatric Bipolar Research