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THE NEWSLETTER
O F T H E J O H N S H O P K I N S D E PA RT M E N T O F P S Y C H I AT RY A N D B E H AV I O R A L S C I E N C E S
summer 2014
“If we’re going to say ‘yes’
to helping the community,”
says Robert Findling, “we
need to collaborate.”
New Professorship
from Leonard and
Helen R. Stulman
Foundation
The Leonard and Helen R. Stulman Foundation
supports work in mental health, health and aging.
Leonard Stulman, a Baltimore businessman,
philanthropist and Johns Hopkins alumnus, died
in 2000, but his legacy lives on through the
foundation that he and his wife created.
The foundation established the Leonard and
Helen R. Stulman Professorship in Child and
Adolescent Psychiatry to improve the quality of
and increase access to mental health services
for young people. This new professorship was
dedicated and Robert Findling installed as its
inaugural recipient in April 2014.
Joining Hands for Child Psychiatry
I
n a low voice, as if he’s telling a secret, Robert
Findling says, “The supply of child psychiatrists
is not even close to meeting the demands that
are out there. Depending on how you look at it,
there’s more than a 50 percent shortage.”
But Findling, who heads child and adolescent
psychiatry at Johns Hopkins, isn’t deterred by
these seemingly dire statistics. In fact, he’s working
to meet the challenge head-on. Recently, he
was named the Leonard and Helen R. Stulman
Professor in Child and Adolescent Psychiatry.
Thanks in part to this gift, Findling is spearheading
an effort to improve access to psychiatric care for
young people.
“To do this, we must collaborate,” he says. “We
are thinking locally and recognizing that what we
do can have an impact globally.”
To start, Findling has been working to build
partnerships among three Baltimore entities:
The Johns Hopkins Hospital, Johns Hopkins
Bayview Medical Center and the Kennedy Krieger
Institute (KKI), which is dedicated to helping
patients with developmental, brain, spinal cord and
musculoskeletal disorders.
After just six months, he says, “We are
referring patients between the groups in a much
more facile way, so it’s better for children and
families. Sometimes when you get care from two
organizations, they don’t really speak to each other.
Now information can more readily flow.”
The three-part collaboration also supports
Findling’s efforts to boost psychiatric services
by increasing staff. When he needed a training
director for child psychiatry residents learning
about the psychiatric diagnosis and treatment
of children, adolescents and their families, he
identified Roma Vasa, an autism researcher and
child psychiatrist at KKI. Now, Vasa pursues
her educational endeavors at Johns Hopkins and
clinical research at KKI.
“These kinds of changes will help stabilize,
build and secure a durable, clinical child psychiatry
practice,” says Findling.
With more personnel, there can also be
an increase in research, and Findling says the
area he most wants to explore is prevention.
“Most psychiatric conditions develop during
mid- to late-adolescence, and that tells me
there is an opportunity to intervene and
prevent them,” he says.
Most of the early symptoms that present to a
child and adolescent psychiatrist are not specific—
irritability, hostility or distractibility—much like a
fever, cough or abdominal pain might present to a
pediatrician.
“You don’t wake up one morning with a serious
psychiatric illness,” Findling says. “We want to
look at what’s going on and how we can intervene
and prevent it. Why wait until someone is in
extremis before you intercede, which is what we
currently do in psychiatry.”
In a tone filled with optimism, Findling says,
“We have only one goal here: to help children. Our
job is to serve them. That’s the privilege of having
this endowed professorship.” n
“The supply of child psychiatrists is not even close to meeting the
demands that are out there. Depending on how you look at it,
there’s more than a 50 percent shortage.”
Genetic Links
One Small Step for OCD
Treatment, One Large Step
for OCD Research
C
“
onsidering that obsessivecompulsive disorder is one of
the world’s more disabling
conditions,” says Gerald Nestadt,
“we know very little about its
underpinnings.” But Nestadt, who
has devoted most of his career to
understanding the disorder, recently
came closer than ever to pinpointing
a genetic cause.
For the last five years, the Johns
Hopkins psychiatric epidemiologist
and inaugural recipient of the
Rudolf and Evanne Hoehn-Saric
Professorship for ObsessiveCompulsive Disorder and Anxiety
Disorders Research led a group
of researchers in the second-ever
genome-wide association study of
OCD.
After scanning the genomes of
more than 1,400 people with OCD
and more than 1,000 close relatives
of people with the disorder, Nestadt
and his colleagues identified a strong
signal associating OCD with a gene
called protein tyrosine phosphokinase
(PTPRD). While the study was not
quite a “home run,” Nestadt says
they got very close.
Previously, PTPRD was shown
in animals to possibly be involved in
learning and memory, traits related
to OCD in humans. Moreover, some
cases of attention-deficit hyperactivity
disorder (ADHD) have been
associated with the gene, and OCD
and ADHD have some symptoms
in common. Nestadt says the gene
also works with another gene family,
“The cause of OCD
is due to a complex
pattern of genetic and
environmental factors,”
says Gerald Nestadt.
Curbing Doubts
SLITRK, which has been
associated with OCD in
animals.
OCD affects an
estimated 1 to 2 percent
of the U.S. population,
and the World Health
Organization has
called it one of the
more disabling medical
conditions worldwide.
Some of the least disabling
forms of the disorder
Although Gerald Nestadt and his team are closer
to understanding the genetics of obsessive-compulsive
disorder, he believes that other domains are worth looking
into as well. “Whatever is ultimately causing OCD is actually
causing something before OCD,” he says. “My hypothesis is
that one thing is the trait of doubt.”
In collaboration with other Johns Hopkins faculty, Nestadt is
working on imaging and neuropsychology research to identify
fundamental traits of OCD, including doubt. “We are trying
to define what doubt is, get measurements of it, and test
it using functional magnetic resonance imaging,” he
says. “We are also working on a behavioral test to
see if we can identify doubt and how much
of a doubter someone is” n
Drug Discovery
PAK Inhibitors Pack an
Interesting Punch for
Schizophrenia Research
T
he physicians who discovered the first
effective medication for schizophrenia—
chlorpromazine—did so by luck. The first
antipsychotic, it had initially been used as an
antihistamine and then as an antiseptic. Only by
serendipitous observation did physicians realize that
it improved hallucinations, delusions and other
symptoms related to schizophrenia.
Today, Johns Hopkins psychiatrist Akira Sawa
aims to gain a clearer understanding of the disease’s
pathways to develop drugs that specifically target
its molecular pathology. To this end, he and his
colleagues recently completed a study looking at a
cascade of events that disrupt connections between
brain cells in the schizophrenic brain. They then
examined whether a unique compound could lessen
the disturbing activity.
Working with mice that had brain mutations
involving a gene associated with schizophrenia, Sawa,
Akiko Hayashi-Takagi and colleagues introduced
a drug that is one of a class of compounds known
as PAK inhibitors. The PAK compounds have been
shown in animal studies to provide some protection
during which important neural connections are
unnecessarily destroyed. The researchers were also
able to partially restore disabled neurons so they
could connect to other nerve cells.
“We hope to find drugs that
reverse an existing defect as
well as block future damage.”
“We wish to come across drugs that are able to
reverse an already existing defect as well as block
future damage for good treatment,” says Sawa.
“This compound might have potential to do both.”
Akira Sawa aims to uncover compounds that target the
Even though the results need to be validated by
mechanisms at work in the schizophrenic brain.
determining whether the same PAK cascade occurs
in humans, the findings in “teenage” mice are an
from brain damage due to Fragile X syndrome, a
especially promising step because schizophrenia
disease in humans marked by mental retardation.
symptoms typically appear in late adolescence and
Because the PAK protein can initiate cancer and cell early adulthood, says Sawa. “That we could intervene
growth, PAK inhibitors have also been tested for
in adolescence and still make a difference in restoring
cancer.
brain function in these mice is intriguing.”
After the 35th and 60th days of treatment—
Ultimately, Sawa hopes the compound provides
equivalent to adolescence and young adulthood in
an opportunity for drug discovery and development
the mice—the compound, called FRAX486, appears that intentionally targets the mechanisms causing
to halt an out-of-control biological “pruning” process synaptic disturbance not only in schizophrenia, but
in the brain of the mouse model for schizophrenia
in other brain disorders as well. n
Medication Review
Why We Still Use Lithium
R
can still add an extra hour to the
day’s routine, causing distress and
interfering with daily life. But some
patients are so disabled that they
can’t leave their homes.
“OCD research has lagged
behind other psychiatric disorders
in terms of genetics,” Nestadt says.
“We hope this finding brings us
closer to making better sense of it
and helps us find ways to treat it.” n
ecently, a patient came
to The Johns Hopkins
Hospital from across the
country for treatment of bipolar
disorder. Expecting that there was
something new he could try, he
was at first surprised, and even a bit
disappointed, by his prescription.
But after starting two of the oldest
medications around—including
lithium—he reported feeling better
than he had in years.
“There’s always enthusiasm for
new treatments for bipolar disorder
in hopes they will have fewer side
effects and provide additional
options for treatment,” says Karen
Swartz, who directs Johns Hopkins’
Mood Disorders Consultation
Clinic. “But we want evidencedriven treatments, and even though
lithium is the oldest treatment
for bipolar disorder, it still has
the strongest evidence supporting
its efficacy, which is why it’s a
medication we commonly use.”
Although it was neither doubleblind nor placebo-controlled, the
initial 1949 report by Australian
psychiatrist John Cade describing
lithium’s therapeutic effects in
patients with acute and chronic
mania has not only stood its
ground ever since, but has also
been well validated.
Among the examples Swartz
cites is the 2010 BALANCE trial,
which found that lithium was
more effective at preventing mood
symptoms than valproate, and that
the combination of lithium and
valproate was better than valproate
alone. In a 2013 metanalysis,
lithium was more effective than a
placebo in reducing the number of
suicide attempts and deaths, while
another study found that patients
taking lithium were rehospitalized
for mood symptoms less than
patients taking valproate.
“The caveat,” says Swartz,
“is that you have to make sure
patients are willing to participate
in the treatment.” Because
lithium’s narrow therapeutic
window means patients require
frequent blood level, thyroid and
kidney monitoring, “sometimes
that can make lithium less
appealing,” says Swartz.
Other issues that patients need
to understand include how some
medications, such as ibuprofen, or
medical conditions like a urinary
tract infection or dehydration can
alter their lithium levels.
“We’ve become pretty
sophisticated on how to dose, treat
and monitor lithium,” says Swartz.
“We’ve come to appreciate that
Karen Swartz often starts treatment of
bipolar disorder with lithium because it has
the most evidence behind it.
lower doses can often be just as
effective, so it’s a medication that
more people can tolerate. If we work
with patients and find that they do
just as well with control of their
mood at a lower dose, it can be a
way to decrease their side effects.” n
For information: 410-955-5212
expert opinion
Answering Some Basic
Questions About Medical
Marijuana
Whether you are for or against the use of marijuana as
medicine, 21 states plus the District of Columbia have
legalized the substance for medical use. The laws allow
qualified individuals to purchase and use marijuana products
from dispensaries to treat conditions from pain to anorexia.
Here, Johns Hopkins behavioral pharmacologist and cannabis
researcher Ryan Vandrey discusses some of the benefits
and risks.
What are the benefits of medical marijuana? Isn’t smoking bad for you?
Much like any other drug, there are risks and benefits of medical marijuana, says Ryan Vandrey.
Research has been done with tetrahydrocannabinol, or THC, the primary
psychoactive component of marijuana, in pill form. This research finds that
the medical benefits of marijuana include management of pain, nausea and
spasticity. It is also good for appetite stimulation, especially for people having
chemotherapy or people with AIDS wasting syndrome.
And yes, many physicians have a hard time recommending a drug that is
smoked. Depending on why a person is using it, though, smoking may be
(continued on page 4)
Medical Marijuana (continued from page 3)
better than swallowing. For example, if it is being
used to treat nausea, there is a chance that the person
might not be able to keep the pill form down. Plus, in
certain cases of acute pain, the effects from smoking
are going to happen more quickly. The downside is
that compared to oral administration, smoking is
much shorter-acting, and of course, isn’t good for
your lungs.
symptoms and be unable to quit even though they
want to.
However, when it is used for a medical purpose
as it’s prescribed and discontinued when it’s no
longer needed, the risk of addiction is probably
relatively low.
You are among a small number of scientists who
have made marijuana studies a specialty. Have
your studies showed that people can become
addicted to marijuana?
Data show that about half of adults in the U.S.
have tried marijuana at some point. Most move
on and don’t have a problem with it. A subset of
about 10 percent, however, try it and develop a
problematic pattern of use. There is also the risk of
having an acute panic or psychotic reaction to the
drug, and there’s no way of knowing what kind of
reaction someone is going to have. So, people have
to recognize the risks associated with it. Again, it’s
Yes. Just as with other kinds of drugs, such as
nicotine, people can become addicted, and it can be
abused. Using marijuana can affect a person’s ability
to work, go to school or have relationships. When
people stop using it, they can experience withdrawal
What do people need to know before using
medical marijuana?
much like any other drug.
Do you have worries about the trend to legalize
marijuana?
Yes. My biggest concern at the moment is the lack
of oversight and regulation of the medical marijuana
industry. Right now, there is no way to ensure that
the marijuana being sold isn’t contaminated, and
there’s no oversight making sure that the amount of
THC in one product is the same as the next. In addition, there is no ceiling on the amount of drug that
can be in a single product, and that can be dangerous. As medicine, the dose needs to be consistent
each time it is taken. Medical marijuana needs
oversight and regulation, just as food and other drugs
are regulated. n
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Hopkins
T H E NE W S L ET T ER
summer 2014
O F T H E J O H N S H O P K I N S D E PA R T M E N T O F P S Y C H I AT RY A N D B E H AV I O R A L S C I E N C E S
One Small
Step for OCD
Treatment,
One Large
Step for OCD
Research
PAGE 2
Why We
Still Use
Lithium
PAGE 3
Answering
Some Basic
Questions
About
Medical
Marijuana
PAGE 3